2016 nibib training grantees meeting 9:00 am … · scientific research, project management,...

MONDAY JULY 11 2016

830 AM REGISTRATION AND POSTER SETUP

900 AMWELCOMING REMARKS - Main Auditorium

Christine Kelley PhD Acting Director Extramural Science Programs NIBIB

915 AMMEETING INTRODUCTION - Main Auditorium

Richard Baird PhD NIBIB

930 AM PLENARY SPEAKER - Main Auditorium

Hannah Valantine MD -Senior Investigator NHLBI Laboratory of

Transplantation Genomics and Chief Officer for Scientific Workforce Diversity NIH

Precision Medicine in Action Applying Genomic Tools to Improve Transplant Health Outcomes

1030 AM BREAK and poster viewing

1045 AM

Profesional Development for PIs in Training - Main

Auditorium

Nicole Steinmetz PhD Case Western Reserve University

IDPs time management fellowship and manuscript writing

Omid Farokhzad MD Brigham and Womens Hospital Harvard Medical School

Clinicians Perspective

1215 PM LUNCH - ( Pre-order your lunch at tgmnibibnihgovlogistics)

115 PM POSTER SESSION

215 PM

Career Options Outside Academia- Main Auditorium

Alexander Adam PhD Associate Hamilton Brook Smith amp Reynolds Intellectual Property Law Firm

Walt Baxter PhD Senior Principal Scientist Medtronic Inc

Colin Brenan PhD Founder Chief Commercial Officer HiFiBiO SAS Editor-in-Chief IEEE Pulse

Magazine

Tiffani Lash PhD Program Director NIBIB

Christopher J Medberry PhD Senior Regulatory Affairs Specialist DePuy Synthes Companies of

Johnson and Johnson

345 PM BREAK and poster viewing - Atrium and lobby

400 PMNIBIB SCIENTIFIC PROGRAM PRESENTATIONS - Main Auditorium

NIBIB Program Officials Present their programs

530 PM

NETWORKING SESSION - Main Auditorium lobby

Meet and network with predoctoral trainees postdoctoral fellows Training Program Directors other

grantees speakers and NIH staff

600 PM

630 PMShuttles to hotel

2016 NIBIB TRAINING GRANTEES MEETING

TUESDAY JULY 12 2016

800 AM REGISTRATION AND POSTER VIEWING

830 AM PLENARY SPEAKER ndash Main Auditorium

BREAKOUT SESSIONS

930 AM

Traineesrsquo Session - Main Auditorium

Rosemarie Hunziker PhD NIBIB

Understanding NIH

Training Program Directorsrsquo Session - Room D

NIBIB funding NIHNIBIB program and policy

changes

1030 AM BREAK and poster viewing BREAK and poster viewing

1045 AM

Michael Summers PhD Professor and HHMI Investigator

University of Maryland Baltimore County

Grant-writing from the PIs Point of view

Training Program Directorsrsquo session

hellip continued

1145 AM

Working Lunch Entrepreneurship Panel

Todd Merchak Program Specialist NIBIB

Todd Landsman Engineering Manager Shape Memory

Therapeutics Inc

Michael K Dempsey Entrepreneur in Residence

Accelerator Program Leader CIMIT Harvard University

(Pre-order your lunch at tgmnibibnihgovlogistics)

100 PM

Grant WritingReview Break-out Session - Rooms A C1C2

E1E2 G1G2 H J Small group discussions of grant

applications withTraining Program Directors other grantees

and NIH staff

Adjourn

200 PM

NETWORKING SESSION - Rooms A E1E2 G1G2

Meet and network with predoctoral trainees postdoctoral

fellows Training Program Directors other grantees and NIH

staff

250 PM Take down posters and adjourn

300 PM

Post-meeting Tours (Select one)

NIBIB Intramural Laboratories

NIH Clinical Center

430 PM Shuttle to hotel

Bruce Rosen MD PhD Professor in Radiology Harvard Medical School Director Athinoula A Martinos Center for

Biomedical Imaging

Lessons Learned

2016 Training Granteees Meeting

Training Program Directerrsquos Session - Natcher Room D

930 AM ndash 100 PM

930-1015 AM Richard Baird (NIBIB) ndash NIH Working Groups Policies Programs and Outcomes

1015-1030 AM Coffee Break

1030 -1050 AM Hannah Valantine (NIH OD) ndash Diversity recruitment and retention

1050ndash1110 AM Tobin Sosnick (UChicago) ndash UChicago BEST program

1110-1130 AM Monga Satdarshan (UPittsburgh) ndash Clinical internships

1130- 1150 AM Mike Regnier (UWashington ) ndash Industrial internships

1150-1210 PM Julie Champion (Georgia Tech) ndash Leadership and professional development

1210 ndash 1230 PM Randy Gollub (MGH) ndash Non-academic Metrics and Careers

1230 ndash 1250 PM Joachim Kohn (Rutgers) ndash Multi-institutional Training aining

Hannah Valantinersquos talk may have to be shifted to accommodate her late arrival

2016 TRAINING GRANTEES MEETING SPEAKER BIOS

TRAINING GRANTEES MEETING BETHESDA MARYLAND JULY 11TH amp 12TH 2016

Alexander Adam PhD JD Alexander Adam is an intellectual property attorney at Hamilton Brook Smith amp Reynolds PC in Boston Dr Adam specializes in drafting and prosecuting patent applications in the fields of computer systems electronics imaging software control systems mechanical devices medical devices telecommunications

and clean energy He also has experience in patent litigation due diligence and providing invalidity and non-infringement opinions Alex advises clients on US and international patent strategy Dr Adamrsquos work on patent applications includes laboratory devices for the pharmaceutical industry 3-D modeling for surgical planning computer-controlled prosthetic devices speech recognition technology needle-free injection devices fuel cell technology and medical implants

Dr Adam received his BS in 1992 MS in 1995 and PhD in 2003 all in Biomedical Engineering from Boston University From 2003 to 2006 he held the position of Research Assistant Professor at the Neuromuscular Research Center at Boston University Dr Adam received a JD from Suffolk University Law School in 2009

Dr Adam is a member of the American Bar Association American Intellectual Property Law Association Boston Patent Law Association IEEE Engineering in Medicine and Biology Society and German American Business Council of Boston

Walt Baxter PhD Dr Baxter serves as a Senior Principal Scientist within Medtronicrsquos Neuromodulation Division primarily within the Therapy Delivery business helping to develop novel stimulation leads for positioning electrodes within the nervous system Dr Baxter has patented key ideas and published seminal works detailing the mechanical conditions implanted medical devices are exposed to during their implant lifetimes Prior to joining Medtronic Dr Baxter studied Mechanical Engineering at the Georgia Institute of Technology and later trained within the Cardiac Mechanics Research Group at the University of California San Diego where he developed implemented and validated novel algorithms for elucidating the mechanics of implanted medical devices In addition to his work at Medtronic Dr Baxter chairs the advisory board for the Georgia Institute of Technologyrsquos Department of Biomedical Engineering and serves on the industrial advisory boards at UC Riversidersquos Department of Bioengineering UC Irvinersquos Department of Bioengineering and UC San Diegorsquos Whitaker Institute of Biomedical Engineering where he impacts and fosters meaningful academic-industrial collaboration through his board work Dr Baxter guest lectures in Mechanical and Biomedical Engineering courses at the University of California Irvine University of California Los Angeles University of Southern California and San Diego State University He mentors engineering students at North Carolina State University through a joint Neuroinnovations design program with Duke University Dr Baxter also speaks to student groups on University campuses about careers in the medical device industry where he seeks to attract talented students to the industry He is an elected Fellow of the American Institute for Medical and Biological Engineering where he works to further awareness of how Medical and Biological Engineering impacts the lives of people around the world



Colin Brenan PhD Colin JH Brenan is a serial life sciences entrepreneur and senior executive with 30 years of experience in scientific research project management product development strategic marketing and financing of early-stage life science companies Dr Brenan is currently a Founder and Chief Commercial Officer for HiFiBiO BV Formerly he was Managing Director of the Monsanto-Atlas Seed Fund

Alliance at Atlas Venture where he identified and invested in seed and early-stage life science companies Prior to Atlas Dr Brenan was Director of Strategic Relationships for the Center for Integration of Medicine and Innovative Technology where he implemented CIMITrsquos innovation strategy with external partners raised $6M in funding and launched a start-up (Organ Solutions) from the CIMIT Accelerator

Previous to joining CIMIT Dr Brenan was the Founder Chief Technology Officer and Senior Vice President Business Development for BioTrove Inc (Woburn USA) a life science tools and consumables company spun-out from the Massachusetts Institute of Technology (MIT) and acquired by Life Technologies Inc At Biotrove he was responsible for development of the OpenArrayTM and RapidFireTM products expansion of the intellectual property portfolio from one patent application to 76 issued and pending patents $8M in strategic sales and was the lead or co-lead in raising $30M of investment capital from corporate and venture capital partners BioTrove is a MIT TLO Success Story winner of the 2009 North American Frost amp Sullivan Award for Growth Strategy Leadership of the Year and the acquisition of BioTrove by Life Technologies was voted one of the top ten MampA transactions of 2009 by PriceWaterhouseCooper

Dr Brenan is the inventor on 17 US and 18 foreign patents and published +50 peer-reviewed journal articles book chapters and reports in the fields of bio-microsystems confocal microscopy spectroscopic imaging and microsurgical robotics He has over a decade of experience in consulting for the US National Institutes of Health and is a reviewer for IEEE IEE and AIP journals Dr Brenan is a Senior Member of the IEEE-EMBS the Founder and former Chair of the EMBS Boston Chapter (2002-2007) the EMBS Region 1 Representative (2002-2005) the EMBC 2011 co-Chair and is Editor-in-Chief of IEEE PULSE Magazine (2013-present) He received his BSc (Honors Physics) M Eng (Electrical) and PhD (Biomedical Engineering) from McGill University (Montreal Canada) and completed post-doctoral training at MIT (Cambridge USA)

Michael Dempsey BSEE Mike is an Entrepreneur in Residence at CIMIT His primary responsibility is to lead the CIMIT Accelerator Program which is focused on finding funding and facilitating innovations that are to be handed off to industry within twelve to eighteen months Mike and his team work closely with the project teams to not only advance the technology but also to develop and execute a complete strategy for getting the innovation into practice

Mike has been working in the field of medical devices for more than 25 years during this time he has invented or worked on products that have treated over twenty million people He was a co-founding of Radianse a venture-backed company that develops indoor positioning systems for hospitals Prior to founding Radianse Mike worked as a technical strategist for wireless solutions at Hewlett-PackardAgilent Technologies (now Philips Medical Systems) He has helped to develop and introduce dozens of successful products holds over 40 patents in wireless medical device communications and has ten more patents pending Mike received a special citation from the Commissioner of the FDA for exceptional initiative and leadership to protect the public health He has a BSEE from The University of Michigan



Omid Farokhzad MD Omid Farokhzad is an Associate Professor at Harvard Medical School (HMS) and a physician-scientist in the Department of Anesthesiology at Brigham and Womenrsquos Hospital (BWH) where he directs the Laboratory of Nanomedicine and Biomaterials He is a faculty member of the Brigham Research Institute Cancer

Research Center and a member of the Dana FarberHarvard Cancer Center Programs in Prostate Cancer and Cancer Cell Biology Dr Farokhzadrsquos research is focused on the development of therapeutic nanoparticle technologies most notably he pioneered the high throughput combinatorial development and screening of multifunctional nanoparticles for medical applications Dr Farokhzad has authored approximately 130 papers and holds more than 140 issuedpending US and International patents The technologies that Dr Farokhzad has developed with collaborators at HMS and MIT formed the basis for the launch of four biotechnology companies BIND Therapeutics Selecta Biosciences Tarveda Therapeutics (formerly Blend Therapeutics) and Koan Biotherapeutics which are translating the aforementioned academic innovations toward commercialization and societal impact Dr Farokhzad has served in various capacities on the Board of Directors and the Scientific Advisory Board of these companies

Dr Farokhzad has received multiple awards including the Ernst amp Young Entrepreneur of the year in 2012 the RUSNANOPRIZE in 2013 the Golden Door Award from the International institute of New England in 2014 and the Ellis Island Medal of Honor in 2016 for his scientific societal and economic contributions to America as an immigrant In 2015 he was named as one of The Worldview 100 by Scientific American which recognized visionaries who shape biotechnology around the world Dr Farokhzad was elected to the College of the Fellows of the American Institute of Medical and biological Engineering He was selected by Thomson Reuters among the Highly Cited Researchers in 2014 and 2015 The Boston Globe selected him among the top innovators in Massachusetts and the Boston Business Journal selected him among the Health Care Champions for his innovations

Dr Farokhzad completed his post-graduate clinical and post-doctoral research trainings respectively at the BWHHMS and MIT in the laboratory of Institute Professor Robert Langer He received his MD and MA from Boston University School of Medicine and his MBA from the MIT Sloan School of Management

Rosemarie Hunziker PhD Rosemarie Hunziker PhD is the Director of Tissue Engineering and Regenerative Medicine at the National Institute of Biomedical Imaging and Bioengineering (NIBIB) within the National Institutes of Health (NIH) in the US Department of Health and Human Services (DHHS) Dr Hunziker brings a diverse background to this broad sphere of research After receiving a Bachelor of Science in Microbiology from the Philadelphia College of Pharmacy and Science (now the University of the Sciences in Philadelphia) she set off to study the complex antigenic profile of bovine lymphocytes and earn a Master of Science in Immunogenetics from Ohio State University Her PhD work with Tom Wegmann at the University of Alberta involved analysis of the cell surface immunogens at the maternal-fetal interface Post-doctoral training at the Laboratory of Immunology National Institutes of Allergy and Infectious Diseases (NIAIDNIH) focused on the generation of transgenic mouse models of histocompatibility antigen variants to study mechanisms of immune recognition and tolerance Rosemarie set up the NIAIDs Transgenic Mouse Facility at the FCRDC in Fort Dietrick MD to supply intramural scientists with mouse lines engineered to express their protein of choice After organizing and running that effort for seven years she left NIH to join the Advanced Technology Program (ATP) at the National Institute of Standards and Technology (NIST Department of Commerce) ATP awarded grants to for-profit companies for high-risk RampD There she was a Program Manager in the Chemistry and Life Science Office with responsibilities to monitor and advance the life science portfolio with particular emphasis on Tissue Engineering

After a brief stint in private consulting advising biotechnology companies on strategic use of federal research grants to advance their business goals Rosemarie returned to NIH in 2004 to help accelerate technology transfer at the National Institute of Dental and Craniofacial Research (NIDCR) and oversee the Dental Biomaterials portfolio In January 2007 she moved to her current position at the NIBIB She is committed to nurturing discovery science and realizing the practical benefits of the exciting developments at the forefront of cell-based tools and therapies



Todd Landsman PhD Todd Landsman is the Engineering Manager at DEP Shape Memory Therapeutics Inc (SMT) which was founded to create medical devices and technology based on novel polyurethane shape memory polymers (SMPs) that were

created in a joint effort between Texas AampM University (TAMU) and Lawrence Livermore National Laboratory As the Engineering Manager at SMT he has led the design and development of a peripheral embolization device (PED) for the past two years While working with SMT for the past two years Dr Landsman was also a graduate student at TAMU pursuing his PhD in Biomedical Engineering as a member of the Biomedical Device Laboratory During his dissertation he designed the PED technology and has become an expert on the functionality testing procedures design and material characteristics of the device Dr Landsman received his BS in Mechanical Engineering and his MS in Biomedical Engineering from Cal Poly State University

Tiffani Lash PhD Dr Tiffani Bailey Lash serves as a Program DirectorHealth Scientist Administrator at the National Institutes of Health She manages the research portfolios for the Biosensors Platform Technologies and mHealth programs at the National Institute of Biomedical Imaging and Bioengineering (NIBIB) Dr Lash is also the Program Director for the NIBIB Point of Care Technologies Research Network consisting of three centers charged with developing point-of-care diagnostic technologies through collaborative efforts that merge scientific and technological capabilities with clinical need Prior to her current position Dr Lash worked within the NIHrsquos science policy administration During that time she worked at the National Institute of General Medical Sciences and National Heart Lung and Blood Institute as well as the NIH Office of the Director Dr Lash has been selected as a science policy fellow for both the American Association for the Advancement of Science (AAAS) and the National Academy of Engineering She also has a background in small business innovation and intellectual property Dr Lash earned her PhD in Physical Chemistry from North Carolina State University via a collaboration between the Departments of Chemistry and Chemical and Biomolecular Engineering Her interdisciplinary research interests include microfluidics biopolymers with controlled molecular architecture and biosensor technologies



Christopher J Medberry PhD Dr Christopher J Medberry is Senior Regulatory Affairs Specialist at the DePuy Synthes Companies of Johnson and Johnson currently supporting Biomaterials and Front End Innovation He completed his PhD in Bioengineering at the McGowan

Institute for Regenerative Medicine at the University of Pittsburgh His research focused on the development and application of novel biomaterials including hydrogels and scaffolds derived from nervous tissue extracellular matrix and multiple preclinical models of traumatic central nervous tissue injury to investigate the mechanisms of biomaterial mediated tissue repair His postdoctoral research explored therapeutic approaches that modulate the default healing response to prevent scarring and preserve or restore vision following injury and disease Beyond the laboratory Dr Medberry worked as a Postdoctoral Fellow with the Coulter Translational Research Partners II Program at the University of Pittsburgh where he provided technical expertise and aided in the development of regulatory documents and in industry where he worked on medical device research design and development He most recently completed the AIMBE Scholars Program which is a Policy Fellowship Program at the US Food and Drug Administration As an AIMBE Scholar Dr Medberry utilized his technical background to influence decisions and help create policy within the Office of the Center Director Center for Devices and Radiological Health His long-term goal is to utilize his regulatory and policy background to foster innovative strategies for medical device development that improve patient care and clinical outcomes

Todd Merchak BS Todd Merchak is a Program Specialist in the Office of Program Evaluation and Strategic Partnerships at the National Institute of Biomedical Imaging and Bioengineering (NIBIB) He has been managing the NIBIB Small Business (SBIRSTTR) programs for the past 12 years and helps lead the Institutersquos strategic partnership activities He also serves as a liaison for health disparities research as well as a Science Officer for the Point-of-Care Technologies Research Network Mr Merchak received his BS degree in Biomedical Engineering from Yale University



Bruce Rosen MD PhD Dr Rosen is a Professor of Radiology at Harvard Medical School Laurence Lamson Robbins Professor of Radiology at Harvard Medical School and Professor of Health Sciences and Technology at the Harvard Medical School-Massachusetts Institute of

Technology Division of Health Sciences and Technology He is Director of the Athinoula A Martinos Center for Biomedical Imaging at Massachusetts General Hospital MIT and the Harvard Medical School He received his PhD in medical physics from MIT and his MD from the Hahnemann Medical College in Philadelphia and is board certified in radiology Dr Rosenrsquos research over the past thirty years has focused on the development and application of physiological and functional NMR techniques His studies allow researchers to better interpret fMRI signal changes and develop new ways to probe brain function for instance through event related fMRI studies Dr Rosen leads the activities of several large interdisciplinary and inter-institutional research and training programs that focus on the development of novel biomedical imaging technologies and their application to diverse programs of basic and clinical research including the NIHNCRR Regional Resource Center the Center for Functional Neuroimaging Technologies (CFNT) the Biomedical Informatics Research Network (BIRN) and others A Gold Medal winner and Fellow of the International Society of Magnetic Resonance in Medicine Dr Rosen is author or coauthor of more than 250 peer-reviewed articles book chapters and reviews He has mentored dozens of graduate students and research fellows through the years

Nicole Steinmetz PhD Dr Steinmetz is an Associate Professor of Biomedical Engineering at Case Western Reserve University School of Medicine Cleveland OH where she leads a research laboratory interfacing bio-inspired molecular engineering approaches with medical research and technology development Dr Steinmetz trained at The Scripps Research Institute La Jolla CA where she was a NIH K99R00 awardee and AHA post-doctoral fellow (2007-2010) she obtained her PhD in Bionanotechnology from the University of East Anglia where she prepared her dissertation as a Marie Curie Early Stage Training Fellow at the John Innes Centre Norwich UK (2004-2007) Her early training was at the RWTH-Aachen University in Germany where she obtained her Diploma (Masters) in Molecular Biotechnology (2001-2004) after completing her pre-Diploma from the Ruhr University Bochum Germany (1998-2001) Dr Steinmetz serves on the Editorial Board of Wiley Interdisciplinary Reviews (WIREs) on Nanomedicine and Nanobiotechnology and on the Advisory Editorial Board for the ACS journal Molecular Pharmaceutics Dr Steinmetz has chaired symposia at American Chemical Society Materials Research Society and Foundations of Nanosciences and she served as Chair of the Gordon Conference of Physical Virology (2015) DrSteinmetz has authored more than 100 peer-reviewed journal articles reviews book chapters and patents she has authored and edited books on Virus-based nanotechnology Research in the Steinmetz Lab is funded through grants from federal agencies including National Institute of Health National Science Foundation and Department of Energy as well as private foundations including Susan G Komen Foundation American Cancer Society and American Heart Association



Michael Summers PhD Dr Summers is a member of the National Academy of Sciences an Investigator with the Howard Hughes Medical Institute the Robert E Meyerhoff Chair for Excellence in Research and Mentoring and a University Distinguished

Professor of Chemistry and Biochemistry at the University of Maryland Baltimore County He is also co-Director of an IMSD-MBRS grant entitled ldquoExpanding Participation by Minorities in the Biomedical Sciences an initiative to promote cultural diversity in the biomedical sciences at the graduate level Dr Summers received his PhD in bioinorganic chemistry from Emory University His research over the past thirty years has focused on understanding how viruses assemble mature and selectively package their RNA genomes Combination drug therapies can keep the virus at bay for extended periods even a normal lifespan but current therapeutic regimes are expensive compliance can be difficult and strains that are resistant to combination drug therapies have emerged Thus there are needs to develop new therapeutic approaches that target different viral components His lab is using nuclear magnetic resonance (NMR) to study the structures and functions of the viral proteins and RNA genome of HIV-1 Their studies are yielding information on how the highly conserved viral 5acute-UTR temporally regulates transcription splicing translation packaging reverse transcription and other essential RNA-dependent activities during the viral replication cycle

Hannah Valantine MD Hannah Valantine is the first NIH Chief Officer for Scientific Workforce Diversity and a Senior Investigator in the Intramural Research Program at the National Heart Lung and Blood Institute Prior to starting this position in April 2014 Dr Valantine was Professor of Cardiovascular Medicine and the Senior Associate Dean for Diversity and Leadership at Stanford a leadership position she held since November 2004 She is nationally recognized for her transformative approaches to diversity and is a recipient of the NIH Directorrsquos Pathfinder Award for Diversity in the Scientific Workforce She is currently leading NIH efforts to promote diversity through innovation across the NIH-funded biomedical workforce through a range of evidence-based approaches Dr Valantine maintains an active clinical research program that continues to have high impact on patient care Current research extends her previous finding that an organ transplant is essentially a genome transplant and that monitoring the level of donor DNA in a recipientrsquos blood as a marker of organ damage will detect early stages of rejection She is currently overseeing a multi-site consortium of mid-Atlantic transplant centers to validate these findings clinically toward the development of a non-invasive tool for detecting early signs of organ rejection



Chris Kelly PhD Dr Christine A Kelley is the Director of the Division of Discovery Science and Technology and Acting Associate Director Extramural Science Programs at the NIBIB She received her PhD degree in Cell Biology from Boston University in 1988 Her graduate research focused on the role of

pericytes in the microvasculature From 1988-1996 Dr Kelley conducted postdoctoral and independent research on the function and regulation of smooth muscle and nonmuscle myosin isoforms in the Laboratory of Molecular Cardiology in the National Heart Lung and Blood Institute (NHLBI) In 1996 Dr Kelley became a Health Scientist Administrator in the Vascular Biology Research Group within the Division of Heart and Vascular Diseases in the NHLBI before moving in 1998 to a position as a Health Scientist Administrator in the Bioengineering and Genomic Applications Research Group within the same Division Dr Kelley assumed her current position in NIBIB in March 2002 Zeynep Erim PhD

Dr Zeynep Erim is a Program Officer in the Division of Interdisciplinary Training at NIBIB Dr Erim received a BS degree in Electrical Engineering from Istanbul Technical University in Turkey in 1983 an MS in Biomedical Engineering from Bogazici University in Istanbul in 1986 and a

PhD in Biomedical Engineering from Boston University in 1992 From 1992 to 2001 she held the position of Research Assistant Professor at the Neuromuscular Research Center at Boston University and in 2002 joined the Sensory Motor Performance Program at the Rehabilitation Institute of Chicago as a Senior Research Scientist where she later became Associate Director for Research She also served as Research Associate Professor in the Department of Physical Medicine and Rehabilitation at the Feinberg School of Medicine and as Adjunct Faculty at the Biomedical Engineering Department in the McCormick School of Engineering at Northwestern University Her research interests include biomedical signal processing motor control and rehabilitation engineering Dr Erim joined NIBIB in August 2007

Richard Baird PhD Dr Richard A Baird is the Director of the Division of Interdisciplinary Training at the NIBIB Dr Baird obtained the BS in Electrical Engineering (1975) from the Massachusetts Institute of Technology and the PhD in Electrical Engineering and Computer Sciences (1981) from the University of California Berkeley After a postdoctoral fellowship at the University of Chicago (1981-1984) he became a research scientist (1984-1998) at the RS Dow Neurological Sciences Institute and an adjunct faculty member of the Department of Physiology and Pharmacology at Oregon Health Sciences University in Portland Oregon In 1998 Dr Baird became the Head of the Fay and Carl Simons Center for Biology and Hearing and Deafness at the Central Institute for the Deaf Spencer T Olin Professor in the Department of Speech and Hearing at Washington University and an adjunct faculty member of the Department of Otolaryngology and the Department of Anatomy and Neurobiology at Washington University School of Medicine in St Louis Missouri He also founded and directed the Inner Ear consortium (1999) a group encouraging collaboration among researchers working on the development function and regeneration of the inner ear and supporting state-of-the-art core facilities in digital imaging electron microscopy molecular biology and electronic services In 2002 he became Director of Research of the Harold W Siebens Hearing Research Center at Central Institute for the Deaf Dr Baird joined the NIBIB in October 2005


POSTER NUMBER ABSTRACT (ALPHABETICAL BY FIRST AUTHORrsquoS LAST NAME)

1 Imaging characteristics of pediatric diffuse midline gliomas based on the presence of a poor

prognostic marker histone H3 K27M mutation

Mariam S Aboian David Solomon Erin Felton Sabine Mueller et al

University of California San Francisco

2 Embolization of Arteries for the Treatment of Obesity (BEAT Obesity) 6 Month Safety and

Efficacy Data

Olaguoke Akinwande Clifford Weiss

Johns Hopkins School of Medicine

3 Convex Optimized Diffusion Encoding (CODE) gradient waveforms for bulk motion

compensated cardiac Diffusion Weighted MRI

Eric Aliotta Holden H Wu Daniel B Ennis

UCLA

4 Assessment of Gd‐doped Silica Microshells for Prostate Ultrasound HIFU Therapy Sensitization

and Targeted Drug Delivery

Gregory Anthony James Wang Andrew Kummel PhD Steffen Sammet MD PhD

University of Chicago

5 Radiomics of breast cancer A robustness study

Natalia Antropova Hui Li Karen Drukker Li Lan et al


6 Targeted Nano‐delivery of Immunosuppressive Agents in Transplantation

Baharak Bahmani Mayuko Uehara Qiaobing Xu Reza Abdi

Harvard Medical School

7 High Frequency QRS Analysis (HF‐QRS) has Incremental Diagnostic Accuracy over ST‐Segment

Analysis Alone for the Detection of Myocardial Ischemia

Pelbreton Balfour Jr MD ScM Jorge Gonzalez MD Peter Shaw MD Margarita Peacuterez MD et al

University of Virginia Health System

8 Mixed AntigenAdjuvant Peptide Amphiphile Micelles Improve Group A Streptococcal

Vaccination

John Barrett Joel Collier Matthew Tirrell


9 Platforms for Scattering Angle Resolved Optical Coherence Tomography Based Retinal

Alzheimers Diagnosis

Vikram L Baruah Michael R Gardner John Rector Robert P Striet et al

University of Texas at Austin

10 Removal of Targeted Pathways on Blood‐Derived and not Brain‐Derived Immune Cells

Improves Intracortical Recordings

Hillary W Bedell MS Madhumitha Ravikumar PhD Shushen Lin Ashley Rein et al

Case Western Reserve



11 Targetable Complement‐Modulating Janus Microparticles for Pathogen Clearance

Michael C Bellavia Brandon A Holt Todd Sulchek

The Georgia Institute of Technology

12 Using Near Infrared Imaging to Assess Lymphatic Function in a Rat Osteoarthritis Model

Fabrice C Bernard Thanh N Doan J Brandon Dixon Nick J Willett

Georgia Institute of Technology

13 Probabilistic tractography of the corticospinal tracts using constrained spherical

deconvolution more completely delineates motor pathways in children with cerebral palsy

Adam S Bernstein Theodore Trouard

University of Arizona

14 Tissue Microenvironment Training Program

Rohit Bhargava

University of Illinois at Urbana‐Champaign

15 Developing Single Molecule Sensitive Fluorescent Tools for Studying RNA‐Protein and Protein‐

Protein Interactions in Cells and Tissue

Emmeline Blanchard Dr Rachel Fearns Dr Philip Santangelo


16 Adipose‐derived Mesenchymal Stem Cells Stimulate Elastin Production by Adult Human

Smooth Muscle Cells in a 3D Fibrin Scaffold

Kory J Blose Justin S Weinbaum David A Vorp

University of Pittsburgh

17 Non‐invasive identification of treatment‐responsive HER2+ breast cancer subtypes through

DCE‐MRI textural analysis

Nathaniel Braman Prateek Prasanna Salendra Singh Donna Plecha et al

Case Western Reserve University

18 Speed Versus Accuracy Tradeoffs in SensoriMotor Control and its Neural Correlates

Macauley S Breault Matthew SD Kerr Pierre Sacreacute Sridevi V Sarma et al

Johns Hopkins University

19 Chromosome refolding model of mating‐type switching in yeast

Gabriel Bronk Dr Barış Avşaroğlu Kevin Li Dr James E Haber et al

Brandeis University

20 An in vitro System to Model the Effects of Fibrosis on Liver Development

Matthew Brovold Shay Soker

Wake Forest Institute for Regenerative Medicine

21 [18F]3F4AP a new PET tracer for demyelinating diseases

Pedro Brugarolas

The University of Chicago

22 Development of an In Vivo Bone Fatigue Damage Model using Axial Compression of the Rabbit

Forelimb



Evan G Buettmann Matthew J Silva

Washington University in St Louis

23 Light‐Triggered Release of Bioactive Molecules from DNA Nanostructures

Susie S Cha Richie E Kohman Xue Han

Boston University

24 Multi‐focused HIFU for diffusive heating and control of acoustic cavitation

Vandiver Chaplin Charles Caskey

Vanderbilt University

25 A Novel Bioluminescent Split Reporter Strategy for Investigating the Regulation of SNAP29

Homodimerization in Starvation‐Induced Autophagy

Ian Y Chen Eric Marceau Thillai S Veerapazham Junfeng Ma et al

Stanford University

26 Investigating feedback circuits with 2D intestinal organoid models

Weilin Chen Curtis Thorne Steven Altschuler Lani Wu


27 Portable robot for autonomous intravenous access using 3D near infrared and ultrasound

imaging

Alvin I Chen Max L Balter Timothy J Maguire Martin L Yarmush

Rutgers University

28 Long‐Term Stability of Stimulating Multi‐Contact Nerve Cuff Electrodes on Human Peripheral

Nerves

Breanne P Christie Max Freeberg Kevin M Foglyano Michael E Miller et al


29 Characterization of contraction intensity differences in strain development during isometric

muscle contraction

Crystal L Coolbaugh John E Mendoza Bruce M Damon


30 Fluorescently‐tethered Hsp90 inhibitors provide therapeutic effect and diagnostic information

in breast cancer pre‐clinical models

Brian Crouch Stella Belonwu Helen Murphy Philip Hughes et al

Duke University

31 Functional Electrical Stimulation for Restoration of Proprioception

Ivana Cuberovic Emily L Graczyk Matthew A Schiefer Dustin J Tyler


32 Non‐monotonic temporal evolution of gradient‐echo MRI signal in brain white matter

Kyle S Decker

Duke University

33 Improved quantification of drug delivery using MRI quantitative susceptibility mapping

Kofi Deh Marjan Zaman Pascal Spincemaille Moonsoo M Jin Yi Wang

Weill Cornell Medical College



34 Adaptation of the Dichromic Fluorescence (DCF) strategy to study kinase activation

Elizabeth N DeLassus Duanwen Shen Mingfeng Bai Baogang Xu et al

Washington University St Louis

35 Characterizing and Eliminating Errors in Enhancement and Subtraction Artifacts in DCE MRI

Studies

Jamal J Derakhshan Elizabeth S McDonald Evan S Siegelman Mitchell D Schnall et al

University of Pennsylvania

36 A Microfabricated Submucosa for Assessing the Effects of Matrix Topography on Colorectal

Cancer

Mahesh Devarasetty Aleksander Skardal Shay Soker


37 Implanted Myoelectric Prosthetic Control for Transradial Amputees

Hendrik A Dewald Matthew R Williams Joris Lambrecht Robert F Kirsch

Department of Biomedical Engineering Case Western Reserve University

38 Alterations in the anterior capsule correlate with impaired joint mechanics in a rat elbow

model of post‐traumatic joint contracture

Chelsey Dunham Ryan M Castile Necat Havlioglu Leesa M Galatz et al


39 No changes necessary Zaire Ebolavirus efficiently infects and replicates in Boa Constrictor

cells without cytopathic effet

Greg Fedewa Melissa Spear Ryan Hernandez Sheli Radoshitzky et al

UCSF

40 Biomedical and Cosmetic Applications of Electrochemical Polyion Sensors

Stephen A Ferguson Mark E Meyerhoff

University of Michigan

41 Metabolomics approaches towards a spatial understanding of host‐microbe interactions in

plants

Dimitrios J Floros Pieter C Dorrestein

UCSD

42 Quantitative Microscopy of Dopamine Receptor Signaling in Pancreatic Beta Cells

Daniel JP Foust Brittany Caldwell Antoine G Godin Alessandro Ustione et al

Washington University

43 Measuring growth patterns during neonatal brain development with surface strain analysis

Kara E Garcia Emma C Robinson Dimitrios Alexopoulos Cynthia E Rogers et al

Washington University in Saint Louis

44 Ion Channels Bound to Endogenous Ferritin are Sensitive to Radiofrequecy Waves

Eric Gibbs

Duke University



45 Translational Research in Biomaterials (TRB)

Mark W Grinstaff

Boston University

46 A POMDP Framework for Breast Cancer Screening Decisions

Simon X Han William Hsu Alex Bui

UCLA

47 Multi scale immune profiling of human peripheral blood with single cell RNA‐Seq for immune

system monitoring

Graham Heimberg John Haliburton Hanna Retallack Eric Wong et al

UC San Francisco

48 Beyond the EPR Effect Multi‐targeting Strategies of Nanoparticles to Image Invasive Glioma

Elizabeth Doolittle Peter Bielecki Efstathios Karathanasis


49 Characterizing embryonic stem cell derived multipotent lung stem cells

Amritha Kidiyoor Sean V Murphy Anthony J Atala


50 Tracking Neural Activity In‐Vivo using Polarization

Nathaniel O King


51 Microvascular Engineering Recapitulating the Bone Marrow Niche

Surya Kotha Amie Adams Brian Hayes Kiet T Phong et al

University of Washington

52 Cell‐free compartmentalized protein synthesis inside double emulsion templated liposomes

with in vitro synthesized and assembled ribosomes

Jin Woo Lee Filippo Caschera Kenneth KY Ho Michael C Jewett et al


53 Theranostic Viral Nanoparticles From Imaging to Therapy

Karin L Lee Nicole F Steinmetz


54 Molecular insights into vein remodeling with arterial flow role of COUP‐TFII

Li Li Mercedes Balcells Takaharu Ichimura Ming Tao et al

Brigham and Womens Hospital

55 Dissecting enhancer grammar in the developing Drosophila

Lily Li Zeba Wunderlich

University of California Irvine

56 Label‐Free High Throughput Microfluidic Device for the Isolation and Single Cell Multiplex

Gene Expression Analysis of Circulating Tumor Cells from Breast Cancer Patients

Eric Lin Lianette Rivera Hyeun Joong Yoon Shamileh Fouladdel et al




57 Developing a bacterial surface display system for the generation of targeted outer membrane

vesicles

Jessica S Lin Anton Bryksin Wilbur Lam Thomas H Barker


58 Quantifying the blood flow and oxygen metabolism responses to a neural stimulus combining

multiple MR methods to optimize the modeling of hyperoxia experiments

Eulanca Y Liu Jia Guo David J Dubowitz Richard B Buxton

UC San Diego

59 Polyethylene Glycol Hydrogel Microparticles for Drug Delivery

Allen L Liu Andreacutes J Garciacutea


60 Implementation of a Clinical Ultrasound Coherence Imaging System

Will Long Dongwoon Hyun Stephen Rosenzweig Gregg E Trahey

Duke University

61 Cell density organizes collective migration through changes in actomyosin contractility

Andrew J Loza Sarita Koride Gregory V Schimizzi Bo Li et al

Washington University in St Louis School of Medicine

62 Bioactivity and Adipogenic Potential of a Composite Adipose‐Derived Hydrogel Scaffold for

Soft Tissue Reconstruction

Christopher Mahoney MS Malik Snowden J Peter Rubin MD FACS Kacey G Marra PhD


63 Research maps A semantic framework for causal discovery and experiment planning

Nicholas J Matiasz William Hsu Alcino J Silva Wei Wang et al

UCLA

64 Design and Mechanical Testing of a Novel Magnesium Based Suture Anchor for Soft Tissue

Fixation

Jonquil R Mau Kwang E Kim Antonio Pastrone Dhir Patwa et al


65 ImmunoPET engineering design considerations for imaging cancer immunotherapies

Aaron T Mayer Arutselvan Natarajan Sydney R Gordon Roy L Maute et al

Stanford University

66 Simple Scalable Proteomic Imaging for High‐Dimensional Profiling of Intact Systems

Evan Murray Jae Hun Cho Daniel Goodwin Taeyun Ku et al

MIT

67 TOWARDS MULTIPLEX PROFILING AND CONTRAST ENHANCED RADIONUCLIDE IMAGING OF

BREAST CANCER

Michael A McDonald MD PhD Benjamin MW Tsui PhD Jingyan Xu PhD

Johns Hopkins Medical Institutions

68 Value of intra‐tumoral metabolic heterogeneity and quantitative 18F‐FDG PETCT parameters

to predict prognosis in patients with HPV‐positive primary oropharyngeal squamous cell



carcinoma

Esther Mena Mehdi Taghipour Sara Sheikhbahaei Abhinav K Jha et al

Johns Hopkins

69 Quantitative breast MRI radiomics for cancer risk assessment and the monitoring of high‐risk

populations

Kayla R Mendel Hui Li Maryellen L Giger


70 Influence of Cardiovascular Risk Factors in Brain Networks and Dementia

Manuel Morales Curtis Thorne Steven Altschuler Lani Wu

Harvard‐MIT Health Sciences amp Technology

71 Image Reconstruction Techniques for a Portable Head‐only 15 T MRI System

Michael Mullen Jinjin Zhang Albert Jang Djaudat Idiyatullin et al

University of Minnesota

72 Tracking human neural progenitor cells derived from pluripotent stem cells using

mitochondrial ferritin as an MRI reporter gene

Kazim H Narsinh Shang Gao Hongyan Xu Martin Marsala et al

UC San Diego

73 A Comprehensive Formulation for Volumetric Modulated Arc Therapy Planning

Dan Nguyen Qihui Lyu Dan Ruan Daniel OConnor et al

UCLA Physics and Biology in Medicine Graduate Program

74 Development of Glutamate‐Sensitive Chemical Exchange Saturation Transfer Imaging at 7

Tesla for Application to Multiple Sclerosis

Kristin P OGrady Adrienne N Dula Bailey D Lyttle Benjamin N Conrad et al

Vanderbilt University Institute of Imaging Science

75 Molecular Recognition of Spermine by LnDOTP5‐ Toward a Noninvasive Staging of Prostate

Cancer

Abiola O Olatunde Taylor L Fuss Philip Z Sun Leo L Cheng et al

Massachusetts General Hospital

76 Functional Network Reorganization of Multimodal Integration Regions in Blind Children

Laura Ortiz‐Teran Ibai Diez Tomaacutes Ortiz David L Perez et al


77 Clinically relevant factors affecting catheter motion in Intracardiac Echocardiography (ICE)

Acoustic Radiation Force Impulse (ARFI) Imaging

Jenna K Osborn Young‐Joong Kim Stephanie Eyerly Patrick D Wolf

Duke University

78 Kinetic Analysis of [18F](2S4R)4‐Fluoroglutamine In Mouse Models of Breast Cancer with

Glutaminase Inhibition

Austin Pantel Rong Zhou Hsiaoju Lee Shihong Li et al

Hospital of the University of Pennsylvania



79 Silicon nanowires as a platform for wireless optical modulation of neuronal activity

Ramya Parameswaran Joao L Carvalho‐de‐Souza Ektor Acaron Ledesma Michael J Burke et al

Biophysical Sciences University of Chicago

80 Spatial Response of Double‐Sided Strip High‐Purity Germanium Detectors for SPECT Imaging

Perea Rose Campbell Desmond L Shokouhi Sepideh Peterson Todd E

Physics and Astronomy at Vanderbilt University

81 Reversed Gradient‐Spoiled Diffusion‐Weighted Imaging in the Breast with PSIF

Stephanie L Perkins Bruce L Daniel Brian A Hargreaves Catherine J Moran

Stanford University

82 A Biomimetic Platform Reveals Novel Mechanisms for Regulation of Microvascular Function

via Hemodynamic Shear Stress

William J Polacheck Matthew L Kutys Christopher S Chen

Harvard University

83 High Resolution Steady State Blood Volume Maps in Glioblastoma Using MRI

Joao Prola Netto Csanad Varallyay Prakash Ambady Jenny Firkins et al

Oregon Health and Science University

84 Preventive Neuroradiology in Brain Aging and Cognitive Decline

Cyrus A Raji MD PhD

UCSF Department of Radiology

85 Evaluating force representation in motor cortex of an intracortical BCI sser with chronic

tetraplegia

Anisha Rastogi Brian A Murphy Frank R Willett William D Memberg et al

Case Western Reserve University Department of Biomedical Engineering

86 FEP‐PDMS Hybrid Microfluidic Devices for Light‐Sheet Microscopy

Stephanie Reynolds Thomas Levario Daniel Porto Yongmin Cho et al


87 Chemotherapeutic Treatment Enriches for Cancer Stem Cell Content within Breast Cancer

Spheroids

Daniel S Reynolds Kristie M Tevis Muhammad H Zaman Mark W Grinstaff

Boston University

88 Multimodal‐MRI based study of the effects of methylene blue in the human brain

Pavel Rodriguez MD Mary Woolsey MS Wilson B Altmeyer MD Francisco Gonzalez‐Lima PhD

et al

The University of Texas Health Science Center at San Antonio

89 Lack of β‐catenin in hepatocytes impairs proliferation and promotes liver stem cell‐mediated

repair in response to the choline‐deficient ethionine‐supplemented diet

Jacquelyn O Russell Hirohisa Okabe Sucha Singh Minakshi Poddar et al


90 Tissue‐specific Effects of Inflammatory and Cancerous Esophageal Extracellular Matrix

Hydrogels



Lindsey T Saldin Luai Huleihel Madeline Cramer Maria Quidgley‐Martin et al


91 Perfluorocarbon doped hydrogels for tissue engineering applications

Daniela Y Santiesteban Stanislav Emelianov Laura Suggs

UT

92 Investigating the role of co‐activators in inducible transcription at the single cell level

Andrew W Sawyer Michael T Marr II

Brandeis University

93 MRI evaluation of spinal cord lesions injected with a gelatin‐based matrix in a rat model

Adhvait M Shah Tehya Johnson Myron Spector

Massachusetts Institute of Technology

94 Development of a Pipeline to Integrate High Angular Resolution Diffusion Imaging (HARDI)

and Intracranial EEG Data in Epilepsy Patients

Preya Shah Lohith Kini Ankit Khambhati Brian Litt et al


95 Invadosome formation and function in chemotrophic axon guidance

Caitlin A Short Edwin A Suarez‐Zayas Timothy M Gomez

University of Wisconsin Madison

96 Segmentation of dense cellular microscopy images for quantification of inflammation in lupus

nephritis

Adam Sibley Maryellen Giger Yulei Jiang


97 Discovering Temporal Signatures that Predict Disease Trajectory of Glioblastoma Multiforme

Patients

Nova F Smedley Dr William Hsu Dr Timothy F Cloughsey Dr Benjamin M Ellingson

University of California Los Angeles

98 Fast Sequence Search using SBT

Brad Solomon Carl Kingsford

Carnegie Mellon

99 Design and Prototype Development of a Torsional Ventricular Assist Device (tVAD)

Elaine Soohoo Lewis K Waldman Dennis R Trumble

Carnegie Mellon University Department of Biomedical Engineering

100 Pointwise Mutual Information Quantifies Intra‐Tumor Heterogeneity in Tissue Sections

Labeled with Multiple Fluorescent Biomarkers

DM Spagnolo R Gyanchandani Y Al‐Kofahi AM Stern et al

University of Pittsurgh

101 Imaging approaches to detect amp monitor changes in joint architecture amp brain networks in

TMJ pain

Megan M Sperry Sonia Kartha Ya‐Hsin Yu Eric J Granquist et al




102 Kupffer Cell Subsets Differ Between Young and Aged Murine Livers

Elizabeth C Stahl Bryan N Brown


103 Optimizing unanesthetized cerebral oxygen consumption measures comparison of MRI and

near‐infrared spectroscopy (NIRS) approaches in neonates with congenital heart disease

Jeffrey N Stout Silvina L Ferradal Lilla Zollei Divya S Bolar et al

Massachusetts Institute of Technology HST

104 A Parallel Approach to Energy Minimization of Protein‐Ligand Interaction

Jocelyn Sunseri David Ryan Koes

Carnegie Mellon University ‐ University of Pittsburgh Computational Biology

105 An injectable block copolymer synthetic cartilage

Stefanie A Sydlik Meng Deng Cato T Laurencin Robert S Langer

Carnegie Mellon University

106 A semiautomatic noninvasive technique for quantitative assessment of collateral circulation

Elizabeth Tong MD Max Wintermark MD


107 Transurethral MR‐guided high‐intensity ultrasound system for focal ablation of prostate

cancer

Trivedi Hari Partanen Ari Wood Bradford Choyke Peter et al

UCSF

108 Extracellular Matrix Hydrogel Promotes Tissue Remodeling Arteriogenesis and Perfusion in a

Rat Hindlimb Ischemia Model

Jessica L Ungerleider Todd D Johnson Melissa J Hernandez Dean I Elhag et al

University of California San Diego

109 Phantom feasibility study for utilization of crawling wave elastography to improve diagnosis

of neonatal intracranial hemorrhage

Alexander M Vezeridis Kenneth Hoyt Clark Z Wu Robert F Mattrey

UC San Diego

110 Using online variant calling for more accurate read mapping

Tim Wall Carl Kingsford


111 On‐Axis Acoustic‐Radiation‐Force‐based Quantitative Stiffness Estimation in Phantoms

Kristy Walsh Mark Palmeri Brett Byram


112 Effects of Microenvironmental Mechanosensing on Cell Migration

Christopher Walter Samila Nasrollahi Amit Pathak

Biomedical Engineering

113 Quantitative Gas Transfer using Hyperpolarized 129Xe MRI in

Idiopathic Pulmonary Fibrosis(IPF)



Ziyi Wang Scott H Robertson Jennifer Wang Mu He et al

Duke University

114 Imaging Bacterial Infection with 6‐[18F]‐Fluoromaltotriose and Positron Emission

Tomography

Mirwais Wardak Gayatri Gowrishankar Evgenios Neofytou Mohammad Namavari et al

Stanford University

115 Multimodal Neuroimaging Evalution of the Default Mode Network in Chronic Traumatic Brain

Injury

Jeffrey Ware

University of Pennsylvania Department of Radiology

116 Discovery of Novel Modulators of the α3 Glycine Receptor

Marta Wells Yan Xu Pei Tang


117 In Vivo Monocyte Tracking by PET and Fluorescence

Moses Q Wilks Marc D Normandin Hushan Yuan Charalambos Kaittanis et al


118 Localized Gradient‐reversed Ultrafast Z‐spectroscopy in vivo at 7T

Neil Wilson Kevin DAquilla Catherine Debrosse Hari Hariharan et al


119 Functional Connectivity Structure of Cortical Calcium Dynamics in Anesthetized and Awake

Mice

Patrick W Wright Adam Q Bauer Grant Baxter Matt D Reisman et al

Department of Biomedical Engineering Washington University in St Louis St Louis MO 63130

120 Textile Platform for Musculoskeletal Tissue Engineering

Iman K Yazdi Afsoon Fallahi Huseyin Avci Ali Tamayol et al

Harvard Medical School Brigham and Womens Hospital

121 Genetically Engineered Human Induced Pluripotent Stem Cells to Model Cronos Titin

Rebecca Zaunbrecher Shiv Bhandari Andrea Leonard Kevin Beussman et al


122 Investigating Population Structure in the Drosophila Genome Nexus

Roy N Zhao JJ Emerson



2016 TRAINING GRANTEES

MEETING

ABSTRACT BOOK


1 Imaging characteristics of pediatric diffuse midline gliomas based on the presence of a poor prognostic marker histone H3 K27M

mutation Mariam S Aboian David Solomon Erin Felton Sabine Mueller et al University of California San Francisco Purpose The molecular basis underlying pediatric gliomas is distinct from adult gliomas One unique molecular alteration that has been identified in pediatric gliomas is K27M missense mutation in histone H3 variants and presence of this mutation correlates with poor prognosis The forthcoming 2016 WHO Classification will include ldquodiffuse midline gliomas with histone H3 K27M mutationrdquo as a new diagnostic entity We identify imaging characteristics of these diffuse midline gliomas in pediatric patients based on the presence of histone H3 K27M mutation Materials and Methods We identified 42 pediatric patients (lt20 yrs old) with diffuse gliomas with available MRI imaging Histopathologic subtypes included diffuse astrocytoma anaplastic astrocytoma and glioblastoma We evaluated the imaging patterns of these diffuse gliomas based on their location enhancement pattern and necrosis Results In these 42 patients tumors were supratentorial in origin in 488 of cases infratentorial in 465 and cervical spine in 47 744 of the tumors were midline (thalamus pons or spinal cord) with 719 of these had K27M mutation All tumors in cerebral hemispheres were histone H3 WT and were associated with high amount of necrosis (plt0003) All cervical spine tumors were K27M mutant and had distal subependymal metastases within the lateral ventricles on follow up at 5-13 months Majority of the infratentorial tumors were K27M mutant (83) while only 67 of the thalamus tumors had K27M mutation When comparing histone H3 mutant to WT midline gliomas there was no statistically significant correlation between enhancement or border characteristics infiltrative appearance or presence of edema Conclusion Majority of diffuse midline gliomas originating in the thalamus pons or spinal cord were found to harbor histone H3 K27M mutation Tumors arising in the cervical cord showed propensity for distal metastatic spread In contrast diffuse gliomas in the cerebral hemispheres were uniformly negative for K27M mutation and were more likely to demonstrate necrosis Clinical Relevance We describe the imaging features of a new WHO class of diffuse gliomas Histone H3 K27M mutant gliomas



Efficacy Data Olaguoke Akinwande Clifford Weiss Johns Hopkins School of Medicine Purpose Bariatric Arterial Embolization (BAE) is an endovascular procedure targeting the gastric fundus for the treatment of obesity BAE results in decreased serum ghrelin and weight modulation in animal models BEAT Obesity study was initiated to assess the safety and efficacy of BAE to treat severely obese patients using 300-500μm Embospheres Material and methods Adult otherwise-healthy morbidly obese patients (BMI=40-60 n=7) were enrolled Primary safety and efficacy endpoints were 30-day adverse events (AE) and weight loss Secondary endpoints were serum obesity hormones (Ghrelin Leptin GLP-1 PYY) hungersatiety assessments Quality of Life (QOL) surveys blood pressure lipid profile endoscopy and gastric emptying results Six-month data as collected to date are presented Results Mean age was 364plusmn191 years and BMI was 446plusmn277 kgm2 at enrollment Left gastric artery (LGA) embolization was performed in all patients Additionally the gastroepiploic arteries were embolized in 4 patients There were 3 minor AEs with no major AEs One patient had sub-clinical pancreatitis 2 patients had a small (lt1cm) superficial mucosal ulcers one was healing by 2 weeks and one was healed by 3 months There was 59plusmn24 95plusmn31 and 133plusmn4 excess weight loss at one three and six months respectively Mean percent change of serum ghrelin from baseline was +868plusmn3474 at 1 month and -1749plusmn2898 at 3 months A trend towards improvement in QOL parameters was noted Hungerappetite scores were markedly decreased post-BAE and remained suppressed Conclusion Early follow-up of BAE demonstrates safety weight loss and associated appetite suppression in severely obese patients




Eric Aliotta Holden H Wu Daniel B Ennis UCLA Purpose ndash To implement and evaluate Convex Optimized Diffusion Encoding (CODE) gradient waveforms for bulk motion compensated cardiac Diffusion Weighted MRI (cDWI) with minimum TEs Introduction mdash cDWI has the potential to characterize cardiac microstructure without the need for a Gadolinium-based contrast agent (GBCA) which is important for the large number of patients with poor renal function requiring evaluation by cardiac MRI[1] The clinical utility of cDWI however has been limited by severe sensitivity to cardiac motion Recent reports of motion compensated (MOCO) diffusion encoding gradients with nulled first (M1) and second (M2) moments have demonstrated robustness to bulk cardiac motion[2 3] but they necessarily increase the echo time (TE) compared to monopolar encoding (MONO) Increased TEs reduce SNR and limit spatial resolution We have developed a MOCO cDWI sequence that employs Convex Optimized Diffusion Encoding (CODE) to reduce bulk motion sensitivity and shorten TE compared to existing MOCO schemes Methods ndash Gradient Design CODE diffusion encoding gradients were designed using convex optimization to determine the M1 and M2 nulled gradient waveform that minimizes TE for a target b-value while conforming to hardware constraints (GMax=74mTm and SRMax=50Tms) and pulse sequence timing Healthy Volunteer Imaging Healthy volunteers (N=10) were scanned on a 30T scanner (Siemens Prisma) after providing written informed consent High resolution cDWI were acquired in the left ventricular (LV) short-axis with b=350smm2 15x15x50mm spatial resolution 2x GRAPPA acceleration three orthogonal diffusion encoding directions and three signal averages in a single 15-heartbeat breath hold Both MONO (TETR=67ms1R-R) and CODE-M1M2 encoding (TETR=76ms1R-R) were acquired at eight subject-specific cardiac phases distributed across systole and diastole Reconstruction and Data Analysis Apparent diffusion coefficient (ADC) maps were reconstructed for each cardiac phase Motion corrupted voxels were identified by ADC values exceeding 30x10-3mm2s (the diffusivity of free water at 37degC a thermodynamic upper bound for soft tissues) in the LV The mean myocardial LV ADC and the percentage of motion corrupted LV voxels were then calculated for each phase Statistical analyses were performed using t-tests with Holm-Sidak post hoc corrections Clinical Imaging Patients (N=5) undergoing routine clinical cardiac MRI exams were also scanned after providing written informed consent cDWI were acquired before and after the injection of a GBCA (Gadovist Bayer Healthcare) using the CODE-M1M2 cDWI protocol at a single early systolic phase (100ms delay from the QRS complex via ECG) Mean myocardial LV ADC was calculated after manual segmentation for each patient Results ndash The TE for CODE-M1M2 (TE=76ms) was 19 shorter than modified bipolar MOCO[3] (TE=94ms) for 15x15mm in-plane resolution and b=350smm2 (Figure 1) With MONO the mean ADC values were significantly corrupted (gt30x10-3mm2s plt0004) for 50 of the cardiac phases whereas 0 of the cardiac phases were corrupted with CODE-M1M2 (p=NS) (Fig 2B) CODE-M1M2 measured significantly lower mean ADCs than MONO (19plusmn03x10-3mm2s vs 38plusmn06x10-3mm2s plt0007) and


fewer motion corrupted voxels (14plusmn14 vs 67plusmn21 plt00006) in 100 of the cardiac phases (Fig 2C) The clinical CODE-M1M2 cDWI scans were largely free of bulk motion artifacts (Fig 3) and ADC maps were in agreement with myocardial diffusivities measured in volunteers There was no significant difference between mean ADCs measured pre- and post-contrast (mean ADCPre=146plusmn02x10-3mm2s ADCPost=158plusmn03x10-3mm2s P=NS) Discussion ndash The volunteer study demonstrated that cDWI with CODE-M1M2 mitigated bulk motion artifacts and substantially increased the range of cardiac phases that can accommodate robust ADC measurement While previous approaches which have required careful selection of the sequence timing and several repeated acquisitions[4] CODE-M1M2 was successful for all patients imaged using a single predetermined 100ms ECG delay These findings echo previous reports[3 5 6] of cDWI with M1M2 nulled encoding Myocardial ADC values (14 to 16x10-3mm2s) were also in agreement with these reports The agreement in ADC values between pre- and post-contrast imaging highlights the relatively weak T1 dependence of the sequence for characterizing myocardial microstructure which is important for the interpretation of ADC values in patients that may not receive contrast Conclusion ndash CODE-M1M2 cDWI significantly improved robustness to cardiac bulk motion compared to MONO cDWI CODE-M1M2 cDWI also permits first and second moment nulling with a shorter TE than existing MOCO cDWI methods References 1 Gansevoort RT Correa-Rotter R Hemmelgarn BR Jafar TH Heerspink HJ Mann JF et al Chronic kidney disease and cardiovascular risk epidemiology mechanisms and prevention Lancet 2013382(9889)339-52 2 Nguyen C Fan Z Sharif B He Y Dharmakumar R Berman DS et al In vivo three-dimensional high resolution cardiac diffusion-weighted MRI A motion compensated diffusion-prepared balanced steady-state free precession approach Magnetic resonance in medicine official journal of the Society of Magnetic Resonance in Medicine Society of Magnetic Resonance in Medicine 201372(5)1257-67 3 Stoeck CT von Deuster C Genet M Atkinson D Kozerke S Second-order motion-compensated spin echo diffusion tensor imaging of the human heart Magnetic resonance in medicine official journal of the Society of Magnetic Resonance in Medicine Society of Magnetic Resonance in Medicine 2015 4 Rapacchi S Wen H Viallon M Grenier D Kellman P Croisille P et al Low b-value diffusion-weighted cardiac magnetic resonance imaging initial results in humans using an optimal time-window imaging approach Investigative radiology 201146(12)751-8 5 Nguyen C Fan Z Sharif B He Y Dharmakumar R Berman DS et al In vivo three-dimensional high resolution cardiac diffusion-weighted MRI A motion compensated diffusion-prepared balanced steady-state free precession approach Magnetic resonance in medicine official journal of the Society of Magnetic Resonance in Medicine Society of Magnetic Resonance in Medicine 2013 6 Welsh C Di Bella E Hsu E Higher-Order Motion-Compensation for In Vivo Cardiac Diffusion Tensor Imaging in Rats IEEE transactions on medical imaging 2015


4 Assessment of Gd-doped Silica Microshells for Prostate Ultrasound HIFU Therapy

Sensitization and Targeted Drug Delivery

Gregory Anthony James Wang Andrew Kummel PhD Steffen Sammet MD PhD University of Chicago Purpose To assess the contrast properties and relaxivity of silica microshells with gadolinium oxide (Gd2O3) incorporated into the shell surface or encapsulated in the interior This study also aims to optimize agarose phantom fabrication for in vitro imaging of the microshells Finally we demonstrate the capabilities of our prostate HIFU transducer for single- and multi-element heating Methods Test tube phantoms with varying type and consistency of agarose were created and studied 2 agarose test tube phantoms were created with varying concentrations of two types of silica microshells intact shells with Gd2O3 incorporated into the surface only and ruptured shells which initially contained Gd2O3 in the interior only Test tube agarose phantoms with varying concentrations of gadodiamide (Omniscan) were also created T1-mapping was performed via inversion recovery SE sequences with varying TI and curve-fitting on a voxel-by-voxel basis T2-mapping was performed using multi-echo SE sequences with varying TE and curve-fitting on an ROI basis T1 and T2 relaxivities (r1 and r2) were obtained as the slope of 1ΔT1 and 1ΔT2 respectively versus Gd concentration in the samples Proton-resonance frequency (PRF)-based MR thermography images were obtained upon sonication of a cylindrical agarose-silica phantom with a transurethral prostate HIFU transducer All images were acquired on a Philips Achieva dStream 3T MR scanner (Philips Healthcare Netherlands) Results 2 by weight non-low-electroendosmosis agarose was selected for phantom fabrication to balance gel strength with minimal T2 reduction Compared with equal molar concentrations of gadolinium in gadodiamide surface-doped microshells showed reduced signal enhancement in T1-weighted images while ruptured microshells with encapsulated Gd2O3 showed little enhancement Intact surface-doped shells had an r1 and r2 of 117 and 375 Lmmol-s respectively Ruptured Gd-encapsulating shells had an r1 and r2 of 0806 and 177 Lmmol-s respectively Gadodiamide gel tubes showed an r1 and r2 of 311 and 139 Lmmol-s respectively MR thermography images showed uniform heating from the central four elements of the prostate transducer When heating with a single element at 4 W for five minutes the width of the thermal dose ge 240 EM (43degC) region was measured at 64 mm along the transducer and 61 mm perpendicular to the transducer Conclusion An effective agarose phantom for imaging Gd-doped silica microshells has been developed Surface-doped microshells can be easily visualized at Gd concentrations of 03 mmolL or higher Large agarose-silica phantoms are also suitable for imaging heating patterns of the prostate transducer



Natalia Antropova Hui Li Karen Drukker Li Lan et al University of Chicago Purpose Computer-extracted image phenotypes (CEIPs)features are being investigated as complimentary attributes in the characterization of breast cancer in radiomics radiogenomics research To be clinically useful CIEPs need to be robust across data obtained with MRI scanners of different manufacturers and imaging protocols Methods Our research involved two HIPAA-compliant retrospectively-collected MRI datasets Database 1 included 91 imaged breast cancers from the National Cancer Institute repository (imaged using General Electric equipment) and Database 2 included 332 breast cancers (imaged at our site using Phillips equipment) For each case information on clinical lymph node (LN) status and histopathology on estrogen receptor (ER) progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) were available Each lesion underwent quantitative radiomics analysis yielding CEIPs characterizing tumor size shape morphology enhancement texture kinetic curve assessment and enhancement variance kinetics The robustness evaluation involved comparing feature values and feature performance in the task of distinguishing LN ER PR and HER2 status between two datasets Prior to the evaluation datasets were matched in terms of pathology and tumor size T-test was used to compare average feature values for the entire datasets and for clinical subgroups of interest Superiority testing was used to evaluate the differences in feature performance in the prognostic tasks with area under the receiver operating characteristic curve (AUC) serving as a figure of merit The features that failed to show statistically significant differences in performance were further evaluated with non-inferiority testing Results We failed to find any statistically significant differences in the average value of the features from tumor size category Greater variation in average feature values for the clinical subgroups having less than 20 cases In the prognostic tasks features showed varying levels of robustness The best agreement in performance was seen in the lymph node classification for two features -- tumor morphology and tumor heterogeneity -- with absolute value of the lower bound of the 90 confidence interval for ∆AUClt005 Conclusion Quantitative breast radiomic features show varying robustness in their average values and in performance across MRI scanners Non-inferiority testing revealed radiomic features with robust performance in the classification tasks In practice features showing different performance need to be tuned based on the MRI scanner used during imaging procedure


6 Targeted Nano-delivery of Immunosuppressive Agents in Transplantation

Baharak Bahmani Mayuko Uehara Qiaobing Xu Reza Abdi Harvard Medical School Purpose Although discovery and development of immunosuppressive agents (ISA) have improved the allograft and recipient survival rate in organ transplantation there are drawbacks associated with administration of ISA that has limited their success in eliminating acute and chronic rejection Other side effects of ISA are post-transplant malignancies as well as accelerated cardiovascular disease Innovative drug delivery approaches are required for efficacious delivery of ISA to overcome their severe side effects Nanoparticle-based drug delivery is an exciting platform with tremendous potential and advantages including controlled release targeted delivery and reduced toxicity By enveloping ISA in a biodegradable nanoparticle significantly lower systemic dosage of ISA is required resulting in reduced toxicity enhanced bioavailability and efficacy of the drug We have designed nanoparticles to deliver ISA to the lymph nodes and the allograft to reduce possibility of graft rejection The targeting moiety used in this study is monoclonal antibody MECA-79 which collectively binds to the peripheral node addressin (PNAd) molecules expressed in high endothelial venules (HEV) Method To study trafficking of nanoparticles to lymph nodes we fabricated poly (lactic-co-glycolic acid) (PLGA) nanoparticles loaded with a near infrared fluorescent dye IR 800CW The nanoparticles were synthesized using a single step self-assembly method called nanoprecipitationsolvent evaporation Briefly mixture of PLGA and IR 800CW in the organic solvent was added drop wise to deionized water under vigorous stirring and was stirred to evaporate the organic solvent Nanoparticles were recovered and washed by centrifugation We have used maleimide-PEG-amine to modify the nanoparticles surface and conjugate MECA-79 antibody to the surface of the nanoparticles To study distribution kinetics of particles in vivo and examine nanoparticles internalization and retention at the level of HEV in real time we administered MECA-79 conjugated IR 800-loaded nanoparticles intravenously to the mouse with and without rejected allogenic skin transplant Results and Conclusion The in vivo live fluorescence imaging on mouse using iBox Explorer2 imaging microscope 24 hours post IV administration of nanoparticles suggests that MECA-79-conjugated nanoparticles accumulate at a higher level in the lymph nodes as compared to nanoparticles without MECA-79 antibody (control sample) Our preliminary results provide strong evidence that MECA-79 conjugated nanoparticles traffic much more efficiently to the draining lymph node in the transplanted animals compared to non-draining lymph nodes We have demonstrated successful conjugation of nanoparticles with monoclonal antibodies against PNAd in HEV and targeted delivery to the lymph nodes These nanoparticles present a promising nano-platform for targeted delivery of ISA to the lymph nodes


7 High Frequency QRS Analysis (HF-QRS) has Incremental Diagnostic Accuracy over ST-

Segment Analysis Alone for the Detection of Myocardial Ischemia

Pelbreton Balfour Jr MD ScM Jorge Gonzalez MD Peter Shaw MD Margarita Peacuterez MD et al University of Virginia Health System Purpose High-frequency QRS analysis (HF-QRS) is a novel tool to supplement standard ST-analysis during stress ECG We sought to compare the diagnostic accuracy compared with standard ST-analysis for the identification of any and significant myocardial ischemia by exercise SPECT myocardial perfusion imaging (MPI) Methods We analyzed the diagnostic accuracy of HF-QRS versus ST-depression analysis in 257 consecutive patients who underwent exercise stress SPECT MPI An ischemic HF-QRS pattern was defined as an absolute reduction of ge1 microV and a relative reduction of ge50 between maximal and minimal values of the mean root square of the 150-250 Hz band signal in ge 3 leads Semi-quantitative gated SPECT MPI was the gold standard with sup310 of the LV considered significant ischemia Statistical analysis was performed using chi-square and logistic regression analysis Results The study cohort was 67 male with a mean age of 59 plusmn 12 Myocardial ischemia was present in 45 patients (175) and significant ischemia (ge10 of the left ventricular (LV) myocardium) in 13 patients (51) ST segment and HF-QRS analyses were positive in 9 (35) and 57 patients (222) respectively HF-QRS had substantially higher sensitivities than ST-analysis for any (600 vs 20 p lt 001) and significant (846 vs 385 p lt 001) ischemia while maintaining similar specificities (p=090 for any ischemia) HF-QRS demonstrated incremental diagnostic value to ST-analysis and clinical risk factors and increased the model discrimination (AUC 074 vs 080 plt00001) Conclusions A strategy of exercise stress ECG with HF-QRS analysis can identify significant ischemia with high diagnostic accuracy This novel adjunct non-invasive method may improve CAD risk stratification in low-intermediate risk subjects


8 Mixed AntigenAdjuvant Peptide Amphiphile Micelles Improve Group A

Streptococcal Vaccination

John Barrett Joel Collier Matthew Tirrell University of Chicago Streptococcus pyogenes (Group A Streptococcus GAS) is a Gram-positive bacterium restricted to natural growth in humans GAS frequently elicits diseases that range in severity from mild infections of the pharyngeal mucosa and dermis to life-threatening invasive infections of connective and muscle tissues leading to necrotizing fasciitis impetigo and toxic shock Additionally post-infection sequelae diseases such as acute rheumatic fever and glomerulonephritis arise following localized infections of the nasopharynx and skin respectively Epidemiological studies estimate that each year greater than 500000 worldwide deaths are attributable to GAS infections placing it among the top ten leading causes of death from infectious pathogens In the United States alone more than $600 million is spent annually treating diseases caused by this organism with no effective preventative method established short of prophylactic antibiotic usage Vaccines against GAS remain unavailable despite decadersquos worth of research and development While whole-killed and live-attenuated vaccines have been tremendously effective in preventing pathogenic infections they are also associated with undesirable side effects Subunit vaccines that deliver just the peptide antigen of interest have been shown capable of stimulating an immune response But these peptide antigens are generally weak immunogens on their own and require strong adjuvants (non-specific immunostimulants) to be effective In order to enhance the immunogenicity of peptide vaccines new delivery systems must be designed Peptide amphiphiles are unique biomaterials comprised of peptide-lipid conjugates that undergo self-assembly into micelles in water and have been shown capable of delivering biologically active peptides for a variety of applications Therefore peptide amphiphile micelles provide a novel platform to improve the host immune response to peptide vaccines The J8 peptide is a 29 amino acid conformationally dependent B cell epitope that has been shown to generate an opsonophagocytic high titer antibody response in mice J8 was covalently tethered to a di-palmitic acid tail (J8-diC16) and fabricated into peptide amphiphile micelles in PBS When delivered to mice subcutaneously J8-diC16 was found to induce J8-specific high antibody titers greater than soluble J8 delivered with commercially available adjuvants To further enhance the antibody response mixed micelles comprised of J8-diC16 and amphiphilic adjuvants were synthesized Mixed micelles induced a strong immune response after a single vaccination and higher titers than all other formulations It was also discovered that micelles are capable of activating dendritic cells The research presented in this poster demonstrates the promise peptide amphiphile micelles have in improving the field of vaccine engineering




Vikram L Baruah Michael R Gardner John Rector Robert P Striet et al University of Texas at Austin PURPOSE Studies have recently shown a primary retinal pathology in neurodegenerative diseases Increasing evidence suggests mitochondria tip towards a fission state in failing synapses a precursor to the development of amyloid-beta (Aβ) plaques and neurofibrillary tangles the classic histopathological indications of Alzheimers disease In accordance with Mie light scattering theory mitochondria in fission are hypothesized to backscatter light at greater angles Although sub-cellular changes in the retina are beyond the resolution of standard OCT scattering angle resolved OCT (SAR-OCT) detects variations in backscattering angle not accessible in current retinal imaging approaches In this study cellular and tissue platforms were developed to support SAR-OCT Alzheimerrsquos diagnostic development METHODS To investigate the general feasibility of deducing mitochondrial fission with SAR-OCT fibroblasts were used as a living optical phantom Fibroblasts were chosen due to their hardy nature and fast growth rate enabling rapid experimentation Cells were repeatedly seeded to generate multilayer cultures resolvable by OCT S-nitrosocyteine was used as a NO donor to induce mitochondrial fission Tools for retinal flatmount imaging were developed to support more clinically relevant analysis A novel retinal extraction method was used where the ora-serrata is the incision point optical nerve is cut at the dorsal surface of the eye before extraction and the sclera is peeled leaving the retina adhering to the lens Subsequently the retina is placed in a novel temperature controlled tissue chamber The chamber was designed with Caddock MP825 resistors to supply heat thermoconductive polycarbonate to dissipate heat thermocouples and PID controller to stabilize temperature of fluid bathing the retina gravity fed inflow of solution and vacuum controlled outflow SAR-OCT imaging was correlated to fission state by two photon imaging mitochondria in both multilayer fibroblast cultures and retinal flatmounts RESULTS Repeated seeding generated up to 50 microm thick primary cell cultures Concerning tissue platforms the retinal surgery technique enabled extraction of flatmounts with intact optical discs visible through OCT The tissue chamber maintained solution temperature at 33 plusmn 072deg C Optical distortions due to temperature fluctuations and turbulent flow were imperceptible CONCLUSION The primary cell culture methods described provide a 3-dimensional optical phantom without artifacts that may exist in hydrogel cultures The novel surgical retinal extraction method and tissue chamber design provide highly intact retinal flat mounts and stabilized imaging These methods serve as a platform supporting experiments involving SAR-OCT imaging of retinal mitochondrial fission ultimately to establish non-invasive and early detection of Alzheimerrsquos disease


10 Removal of Targeted Pathways on Blood-Derived and not Brain-Derived Immune Cells


Hillary W Bedell MS Madhumitha Ravikumar PhD Shushen Lin Ashley Rein et al Case Western Reserve Action potentials from individual neurons can be recorded from intracortical microelectrodes affording these devices much potential in basic research and rehabilitation applications Unfortunately the quality of the neural signal decreases over time Neuroinflammatory mechanisms play a major role in intracortical microelectrode failure Two of the biological pathways that contribute to the failure of these devices are the breakdown of the blood brain barrier with subsequent myeloid cell infiltration and the Cluster of Differentiation 14 (CD14) pathway CD14 is a key co receptor involved in the recognition of extravasated serum proteins and cellular damage in the brain resulting from intracortical microelectrode implantation This work aims to delineate the role of the CD14 pathway on infiltrating macrophages versus resident microglia Bone marrow chimera mice were used to selectively inhibit CD14 from either resident microglia or infiltrating myeloid cells Intracortical microelectrodes were implanted into wild type (WT) C57BL6 CD14 knock out mice (Cd14--) and bone marrow chimera mice (Cd14--+ WT bone marrow and WT + Cd14--bone marrow) To evaluate the long-term stability of intracortical microelectrode performance Cd14-- bone marrow chimera mice (Cd14-- + WT bone marrow and WT + Cd14--bone marrow) and WT control mice were implanted with functional intracortical Michigan style microelectrodes in the forelimb-associated motor cortex Electrophysiological recordings were obtained twice a week to assess function of the electrode The percent of channels of the electrode that are recording single units and number of single units per channel were tracked over time for 16 weeks post implant as metrics of recording quality Two weeks post implantation microgliamacrophage activation astrocytic encapsulation blood-brain barrier disruption and neuronal dieback was assessed via immunohistochemistry After two weeks inhibiting CD14 on myeloid cells and not resident microglia reduced blood-brain barrier permeability and increased neuroprotection Up to 10 weeks the four conditions demonstrated comparable percent of channels recording single units for a given day However about 10 weeks after implant the percent of channels recording single units for WT mice significantly decreases compared to Cd14-- and the two chimeric conditions Interestingly the percent of channels recording single units does not significantly decrease over time for the WT + Cd14--BM mice Our study identifies a clear link between specific inflammatoryimmunity pathways and the long-term performance of intracortical microelectrodes Further our results suggest that systemic administration of therapeutic agents to inhibit the CD14 receptor-mediated pathway from blood-derived cells can be sufficient to improve chronic intracortical electrode performance


11 Targetable Complement-Modulating Janus Microparticles for Pathogen Clearance

Michael C Bellavia Brandon A Holt Todd Sulchek The Georgia Institute of Technology Purpose Multidrug resistance in bacteria is a pernicious healthcare problem ndash methicillin-resistant Staphylococcus aureus (MRSA) is well-known but certain Gram-negative (outer cell membrane high surface lipopolysaccharide) strains such as Klebsiella pneumoniae resist almost all known antibiotics [1] Herein we present a multifunctional biomaterial for targeted complement activation towards antibiotic resistant bacteria Goldpolystyrene Janus microparticles with differentially-functionalized hemispheres were designed to target Escherichia coli a model Gram-negative bacterium and simultaneously activate cytotoxic processes via the complement system The complement system is an integral component of the innate immune response and describes a cascade of interacting proteins that opsonize and lyse foreign pathogens This platform could allow for facile conjugation of a targeting moiety such as an antibody specific to E coli lipopolysaccharide (LPS) to better localize complement to the bacteria Materials and Methods Gold was deposited on a single hemisphere of commercially-available carboxylated polystyrene microparticles and the two hemispheres were subsequently functionalized similarly to a previously reported scheme [2] Gold presence on a single hemisphere was verified via energy-dispersive X-ray spectroscopy (EDS) and the proper conjugation scheme was observed with EDS and confocal microscopy The gold hemisphere received a thiol-polyethylene glycol (PEG)-biotin conjugate in lieu of streptavidinylated anti-LPS antibody Anti-bovine serum albumin (BSA) IgG was adsorbed randomly (non-oriented) or bound to a BSA coating (oriented) on the polystyrene hemisphere The particles were then incubated with DH5α Ecoli and normal human serum at ratios of 101 11 and 110 microparticle-to-cell number Next each Ecoli and serum solution was diluted serially tenfold up to 110000 and plated in agar to evaluate the impedance of bacterial growth All plates were incubated for 16 hr at 37degC and any colonies formed were counted manually Results The Janus particles with non-oriented antibody improve upon the cytotoxicity of the serum in a manner directly proportional to serum concentration The oriented antibody particles demonstrate less cytotoxicity with unmodified polystyrene base particles demonstrating minimal cytotoxicity only at the highest microparticle ratio These results suggest the role of antibody orientation in particle-mediated complement classical pathway activation Conclusions We have demonstrated via a particle platform that the orientation of the antibody displayed affects the cytotoxic capability of serum complement As the gold hemisphere can be further modified with a targeting moiety the diversity of the target pathogen is as extensive as the available antibody library Future work will investigate the capability of the particles to localize complement to a particular pathogen strain 1 Magiorakos AP et al Clinical Microbiology and Infection 2012 18(3) p 268-281 2 Tang JL et al Langmuir 2012 28(26) p 10033-10039


12 Using Near Infrared Imaging to Assess Lymphatic Function in a Rat Osteoarthritis

Model

Fabrice C Bernard Thanh N Doan J Brandon Dixon Nick J Willett Georgia Institute of Technology Purpose Osteoarthritis (OA) is disease of the joint that leads to degradation of the cartilage joint destabilization and eventually joint failure The homeostasis of synovial fluid which lubricates the joint is maintained by the presence of blood and lymphatic capillaries in the synovial membrane Inflammation is present in OA well before the development of significant radiographic changes These inflammatory signals may potentially dysregulate lymphatic function and lead to the further progression of OA as lymphatic clearance requires the active contractility of the collecting lymphatic vessels The selective clearance of large molecules through the lymphatic system allows us to use near infrared (NIR) tracer attached to 20kDa PEG in order to image the knee space and assess functional lymphatic clearance from the joint as well as determine the functionality of the downstream lymphatic collecting vessels that drain the joint Methods Two preliminary experiments were performed For joint clearance studies Lewis rats underwent either a sham surgery where only the MCL was transected or a medial meniscal transection (MMT) surgery where the MCL and the meniscus were transected After surgery rats were injected intra-articularly with 20kDa PEG LICOR NIR dye and the joint was imaged at a fixed interval The data was then fitted to an exponential curve and the rate of decay was determined from the curve fit For functional collector vessel testing non-operated rats were injected subcutaneously near the knee joint in order to visualize and image collecting vessels Results Our preliminary findings suggest that there may be altered fluid drainage from the joint as a result of OA This was shown by a decrease in intra-articular dye clearance in MMT animals up to 30 days after surgery After 81 days the MMT and sham animals no significant difference in clearance was observed We also demonstrated the ability to repeatedly image the lymphatics that drain the knee space to capture growth of lymphatic collaterals in response to surgery and quantify collecting vessel pump function Conclusions These experiments have given our group reliable modalities to quantify lymphatic function in the knee space in addition to downstream lymphatic vessels


13 Probabilistic tractography of the corticospinal tracts using constrained spherical deconvolution more completely delineates motor pathways in

children with cerebral palsy

Adam S Bernstein Theodore Trouard University of Arizona Purpose In the last 10 years huge advances have been made in the field of diffusion magnetic resonance imaging (dMRI) Image acquisition time continues to decrease and more advanced algorithms for estimating the microstructural environment of tissues are becoming more practical for clinical imaging However the majority of clinical studies continue to employ the somewhat simplistic diffusion tensor model for both analysis of microstructure and the anatomy of neural pathways The present work presents a preliminary result of using a more complete dMRI collection and processing scheme for applications in children with Cerebral Palsy Methods One 2 year old female subject diagnosed with cerebral palsy was scanned pre (immediately) and post (36 weeks) physical therapy The MRI protocol included a 64-direction b = 1000 smm2 single shot EPI diffusion MRI sequence with 6 b = 0 smm2 volumes interspersed for motion correction The resolution of the dMRI is 225 mm isotropic with a TRTE of 8150109 ms One b = 0 smm2 was collected with a reversed phase encode direction for EPI distortion correction A T1-weighted image was collected for anatomical reference with 09mm isotropic resolution Diffusion-MRI data was processed using FSLrsquos TOPUP and EDDY for distortion correction LPCA denoising was performed using MATLAB 2015b and constrained spherical deconvolution diffusion tensor fitting and probabilistic tractography were performed using MRtrix Results Tractography results from seed points in the cortical spinal tracts in the pons demonstrate increased coverage of the whole primary motor cortex despite the large periventricular lesion when using constrained spherical deconvolution based tractography relative to the tracography results based on the diffusion tensor model Tracts that intersect the lesion using tractography based on constrained spherical deconvolution either terminate or circumvent the lesion Tractography performed using the diffusion tensor model shows only superior-inferior tracts with very little lateral coverage of the primary motor cortex Further no tracts that intersect the lesion make it to the cortex Conclusion Tractography based on a more robust interpretation of dMRI data more completely maps out pathways in the brain and thus correlates better with the phenotype of the extent of motor dysfunction The tractogram produced by the diffusion tensor model suggests that there are no connections with the motor cortex downstream of the lesion or at any of the more lateral regions of the motor strip If this were truly the case the affected children would be expected to demonstrate much more severe motor disability than they do While it has been shown that most whole-brain tractography algorithms find many false-positive tracts the more complete coverage of the motor strip produced by constrained spherical deconvolution (CSD) based tractography suggests that there is hope for dMRI to be used as a non-invasive diagnostic and prognostic test for the evaluation of cerebral palsy



Rohit Bhargava University of Illinois at Urbana-Champaign A quantitative understanding of the tissue microenvironment (TiMe) is now recognized as critical for advancing biomedical science and healthcare ranging from regenerative medicine to managing the burden of cancer To this end the integration of three technological approaches is essential (a) sensing and imaging to measure biochemical and biophysical parameters (b) bioengineering to recapitulate the TiMe and (c) computational modeling to develop the next generation of productive scientific leaders Here we describe a training program in which predoctoral students will integrate the use of the three technological approaches in TiMe-related studies using the biological contexts of disease and development With intensive mentoring and systematic activities focused on professional development trainees will become the next generation of interdisciplinary leaders capable of undertaking fundamental research and enabling translational advances The University of Illinois at Urbana-Champaign has strong disciplinary programs diverse faculty spanning the intellectual arc of the program and appropriate facilities and unique resources in each of these technological areas The program is outlined and key activities will be highlighted


15 Developing Single Molecule Sensitive Fluorescent Tools for Studying RNA-Protein and Protein-Protein Interactions in Cells and

Tissue

Emmeline Blanchard Dr Rachel Fearns Dr Philip Santangelo Georgia Institute of Technology An important tool in exploring intracellular events is a method of quantitatively looking at single molecule interactions in a cellular context Evaluation of what protein-protein or protein-RNA interactions exist provides vital information about events occurring in a cell Common techniques for deciphering cellular interactions such as co-immunoprecipitation for protein-protein or RNA immunoprecipitation for protein-RNA are informative but require measurement outside the cellular environment so lose localization information and have the potential for altered interactions due to the buffers required This research proposes to use and develop methods of detection for these interactions in a cellular environment These methods could be used for numerous applications such as exploring proteins involved in respiratory syncytial virus (RSV) replication or quantitatively detecting abnormal protein-RNA interactions in colon cancer samples For protein-protein interactions proximity ligation assays (PLA) were used Additionally modified RSV was created by Dr Rachel Fearns with a HA tag on the M2-1 protein to allow for better PLA of M2-1 with different viral proteins To detect RNA fluorescent multiply-labeled tetravalent RNA imaging probes (MTRIPs) were created with sequences specific to the RNA of interest and used as fluorescent in situ hybridization (FISH) probes PLA was then performed off an epitope tag on the MTRIP to investigate protein-RNA interactions Using these tools PLA was successfully able to be performed between the modified M2-1 and other viral proteins It was found that at 6 hpi the nucleocapsid (N) matrix (M) and phospho (P) proteins all interacted with the M2-1 protein in the cell N and M however had visibly more interactions with M2-1 than P Presence of viral mRNAs through the use of FISH at 6 hpi also indicated replication is already occurring at this early time point Additionally through the use of MTRIPS and FISH interaction assays between RNA and proteins were able to be performed This was done with MTRIPs specific for the poly-A tail and the RNA binding protein HuR which is abnormally localized in colon cancer Together these tools provide critical information about interactions in a cellular environment By developing and optimizing these disease molecular interactions in a cellular context can be explored gaining more accurate information to develop better detection methods and treatments


16 Adipose-derived Mesenchymal Stem Cells Stimulate Elastin Production by Adult Human


Kory J Blose Justin S Weinbaum David A Vorp University of Pittsburgh

Adult human vascular smooth muscle cells (SMCs) do not normally produce elastin in-vivo but do so in-vitro with treated with transforming growth factor beta-1 (TGF-β1) As human adipose-derived mesenchymal stem cells (hADMSCs) are known to produce TGF-β1 we hypothesized that adult SMCs co-cultured with hADMSCs would produce elastin Constructs were made by embedding 6x104 commercially-sourced SMCs in fibrin gels After two days 9x105 commercially-sourced hADMSCs embedded in fibrin gels were added on top of the constructs Additional experimental constructs were made without hADMSCs and treated with hADMSC conditioned media Positive and negative control constructs lacking hADMSCs were treated with or without TGF-β1 respectively After 28 days of culture constructs were imaged with an Olympus multiphoton microscope to visualize elastin via autofluorescence The hADMSCSMC co-culture experimental group produced a similar elastin network as the TGF-β1 treated positive controls The conditioned media showed a less developed elastin network than the hADMSCSMC co-culture group and positive control group While the negative control did show elastin production in the ninhydrin assay a developed elastin network was non-existent in the autofluorescent images The results of this study show promise for using hADMSCs as a possible elastogenic therapy stimulating new elastin production by adult SMCs in vivo - ideally in the context of elastolytic diseases such as aneurysms Interestingly the underdeveloped elastin network seen in the conditioned media group may indicate that the co-culture of hADMSCs and SMCs allow the cells to communicate and better form an elastic network compared to growth factor treatment alone


17 Non-invasive identification of treatment-responsive HER2+ breast cancer subtypes

through DCE-MRI textural analysis

Nathaniel Braman Prateek Prasanna Salendra Singh Donna Plecha et al Case Western Reserve University

Background HER2+ breast cancer is biologically and clinically heterogeneous PAM50 profiling of HER2+ breast cancer reliably identifies the HER2-Enriched (HER2-E) subtype as most responsive to HER2-targeted antibody therapy (trastuzumab) As this subtype is currently only identifiable using molecular profiling of breast tumor tissue a non-invasive HER2-E identification method could reduce future patient morbidity We present initial findings involving a new computational imaging feature (CIF) that captures the disorder among pixel level gradient directions on dynamic contrast-enhanced (DCE) MRI We show that this CIF is able to discriminate between HER2-E and other HER2+ breast cancer subtypes on DCE-MRI Methods 25 baseline DCE-MRI HER2+ breast cancer cases were split into two cohorts by PAM50-confirmed subtype (10 HER2-E 15 non-HER2-E) 13 CIFs were computed on peak contrast image within expert-annotated lesions This feature set was narrowed down to the 8 most differentially expressed features Pharmacokinetic (PK) parameters (Kep Ktrans Ve) which quantify tumor-associated permeability changes were also computed using Toftrsquos model Consensus clustering was performed using 1) CIFs and 2) PK parameters and peak intensities Results CIFs yielded two distinct clusters corresponding to HER2-E and non-HER2-E groups with 70 sensitivity and 60 specificity Studies sorted to the HER2-E cluster were characterized by under-expression of entropy and over-expression of texture homogeneity features relative to those of the non-HER2-E cluster In contrast PK parameters and peak intensities produced poorly defined groups that were uncorrelated with HER2 subtypes Conclusion CIFs more accurately identified HER2-E status as compared with standard PK parameters on DCE-MRI CIF expression patterns in HER2-E tumors suggest a less disordered imaging phenotype than other HER2+ tumors Future validation studies of the HER2-E CIF signature identified here could potentially enable non-invasive prediction of response to trastuzumab


18 Speed Versus Accuracy Tradeoffs in SensoriMotor Control and its Neural

Correlates

Macauley S Breault Matthew SD Kerr Pierre Sacreacute Sridevi V Sarma et al Johns Hopkins University Purpose The speed-accuracy trade-off (SAT) is well known in phenomenon motor control in which one must exert more focus to complete a task accurately and subsequently at a slower rate For example attempting to accurately trace a line in one quick pass will most likely result in an flawed reproduction Though a well studied topic the neural basis of how the brain controls these tradeoffs is not yet understood due to lack of data Several brain regions including motor cortical areas are involved in motor control and yet it is not possible to record from all regions simultaneously in humans as they make movements To bypass this data limitation several models of motor control have been developed and generally posit that the cerebellum acts as a feedback controller while motor cortical areas act as a feedforward controller We hypothesize that fast movements implement feedforward control whereas slow movements incorporates feedback and as such involve different brain regions Methods Our study involved medically refractory epileptic patients implanted with several depth electrodes for clinical purposes Brain activity was recorded using stereoelectroencephalography (SEEG) electrophysiological data at a sampling rate of 2 KHz from deep and peripheral brain structures Data was collected on 8 subjects performing speed and goal-directed center out motor task using a robotic manipulandum and a computer screen This system allowed for precise tracking of arm movements over a horizontal plane as the subjects manipulated a cursor presented on the screen along with the task stimuli The behavioral task was to move and maintain their cursor from the center (represented by a circle in the center of the screen) to a target (a circle either left right above or below the center) within an instructed fast or slow time (scaled from calibration results in which subjects were told to move to right target from center as quickly as possible) Each trial comprised of a instructionalpriming phase (visual time instruction (fast or slow) move to center target presentation) the movement phase (Go cue reach and hold cursor on target) and a feedback phase (actual movement duration reward (visual $5) or failure (big red X) comparing actual time to instructed time) Perturbations were performed but were not considered for this analysis Behavioral analysis was performed on trajectories between leaving the center and first hitting the target during the movement phase of un-perturbed trials Results Preliminary analyses of the behavioral data shows that trajectories associated with fast movements yield consistent paths while those associated with slow movements produce correlated paths This observation suggests that the subject may be adjusting their trajectory to reach the target optimally possibly due to feedback over the longer trial period Trajectories also varied based on directionality and subjects varied in their approaches to meeting the time constraint Conclusion Differences were observed between fast and slow movements in the behavioral data analysis with differences also seen across directions The SEEG data may reveal the underlying neural differences between these fast and slow movements


19 Chromosome refolding model of mating-type switching in yeast

Gabriel Bronk Dr Barış Avşaroğlu Kevin Li Dr James E Haber et al Brandeis University Chromosomes are folded into cells in a non-random fashion with specific genes occupying well-defined spatial regions This observation raises the question whether chromosome functions such as transcription and recombination are determined by its spatial organization We consider this general question in the specific context of mating-type switching in budding yeast which is a model system for homologous recombination Mating-type switching is induced by a DNA double-strand break (DSB) at the MAT locus on chromosome III followed by homologous recombination between the cut MAT locus and one of two donor loci (HMLa and HMRa) located on the same chromosome Previous studies have suggested that chromosome III in MATa cells undergoes refolding after the DSB that directs recombination to the HMLa donor Here we propose a quantitative model of mating switching predicated on the assumption of DSB-induced chromosome refolding which also takes into account the previously measured stochastic dynamics and polymer nature of yeast chromosomes Using quantitative fluorescence microscopy we measure changes in the distance between the donor (HMLa) and MAT loci after the DSB and find agreement with theory Predictions of the theory are also in agreement with measurements of changes in the usage of HMLa as the donor when we perturb the refolding of chromosome III These results establish refolding of yeast chromosome III as a key driving force in MAT switching and provide an example of a cell regulating the spatial organization of its chromosome so as to direct homology search during recombination



Matthew Brovold Shay Soker Wake Forest Institute for Regenerative Medicine Purpose Congenital liver disorders are rare but devastating diseases that can culminate in the need for pediatric liver transplant The cause for these diseases remains unknown and animal models for these diseases remain imperfect and expensive Many congenital liver disorders result in a profibrotic environment generated largely by activated hepatic stellate cells (HSC) which produce large amounts of cytokines such as TGF-β and extracellular matrix (ECM) proteins such as collagen TGF-β and non-activated HSC have both been shown to be critical during liver development Perturbations in TGF-B signalling can result in biliary duct malformations hallmark of many congenital liver disorders As HSC produce large amounts of TGF-β when activated it follows that the increased production of TGF-β by the activated HSCs could cause biliary duct malformations Our lab has developed a unique in vitro model capable of recapitulating processes of biliary tubulogenesis Here we propose to use this system to model the effects of the fibrotic environment during development Methods Liver organoid models were produced by seeding decellularized liver matrix (DLM) disks with either primary fetal liver progenitor cells or immortalized liver progenitor cells (HepaRG) Primary HSC or LX-2 cells were in several ways (1) HSCrsquos or LX2 only (control) (2) HSCrsquos or LX2 + HepaRG on plastic and on DLM (3) HSCrsquos or LX2 + HepaRG in a transwell for 1-2 weeks HepaRG cells were analyzed for changes in gene expression of pathways critical during development using qPCR Changes in the physical structure of any tubule formation were analyzed with Confocal IFC Results Cocultures resulted in a variation of gene expression in progenitor cells as compared to controls HSCrsquos also displayed variation of gene expression when cultured on different substrates plastic vs DLM Structural changes in tubule formation were not able to be seen most likely due to time restrictions of the co-culture model Conclusions HSCrsquos are affected by substrate illustrating the need for materials that mimic the in vivo micro-environment Activated HSCrsquos do influence gene expression of liver progenitor cells in this model system A larger analysis of additional developmental such as OPN TBX3 Notch etc should be conducted in the future and compared to tissue samples from patients who suffer from these liver disorders Further comparisons will need to be conducted to determine if the changes in expression were due to TGF-β produced by aHSCrsquos environmental TGF-β or autocrine signalling



Pedro Brugarolas The University of Chicago Purpose Central nervous system demyelination represents the pathological hallmark of multiple sclerosis (MS) and is thought to contribute to a variety of other neurological conditions including traumatic brain injury stroke and Alzheimers disease The ability to quickly and quantitatively assess demyelination is crucial for the diagnosis and treatment of these diseases As current imaging approaches for demyelination rely on magnetic resonance imaging which is neither quantitative nor specific for demyelination we have explored the possibility of targeting axonal potassium (K+) channels to image changes in myelination by positron emission tomography (PET) These channels which normally reside beneath the myelin sheath become exposed upon demyelination resulting in leakage of intracellular K+ ions and disruption of action potentials Consequently the K+ channel blocker 4-aminopyridine (4-AP) is used clinically to enhance axonal conduction in MS patients Here we demonstrate that an F-18 labeled derivative of 4-AP can serve as a PET tracer for imaging changes in myelination Methods - Ex vivo C-14 autoradiography to evaluate the tracer distribution in the brain of mouse models of demyelination - Biochemical assays to find fluorinated 4AP analogs and characterize their binding affinity and stability - Radiochemical synthesis methods to prepare [18F]3F4AP - PET imaging and gamma counting in rodents to characterize the tracer in vivo Results Using C-14 autoradiography we found that 4AP and the fluorinated derivative 3F4AP show significantly higher uptake in demyelinated over normally myelinated white matter and can be used to distinguish demyelinated versus control mice A method for preparing [18F]3F4AP was developed comprising of aromatic nucleophilic substitution followed by reduction microPETCT imaging in healthy rats showed that the tracer localizes primarily in non-myelinated areas of the brain with a mean whole brain SUV (0-30 min) of 393 Additional microPETCT and autoradiography studies in demyelinated rats showed that [18F]3F4AP can be used to detect demyelination in vivo non-invasively Conclusion We have developed the first PET tracer whose binding increases in demyelinated brain regions [18F]3F4AP is metabolically stable and is based on an approved MS drug Thus this compound is a promising PET tracer for demyelinating conditions


22 Development of an In Vivo Bone Fatigue Damage Model using Axial Compression of the

Rabbit Forelimb

Evan G Buettmann Matthew J Silva Washington University in St Louis Purpose Many nontraumatic fractures seen clinically in patients with metabolic bone disorders or on antiresorptive treatment show an increased incidence of microdamage accumulation and impaired intracortical remodeling Currently the non-invasive forelimb fatigue model in rodents represents the ldquostate of the artrdquo system to study the biological and mechanical factors governing microdamage accrual and repair in bone However the lack of basal remodeling and Haversian bone in rodents limits their translatability in studying bone damage repair mechanisms The work presented here demonstrates the development of the forelimb loading model in rabbits the smallest mammal with intracortical Haversian remodeling Methods The forelimbs of post-mortem adult female New Zealand white rabbits were loaded in axial compression to determine their basic monotonic (05mmsec displacement ramp) and fatigue (2 Hz haversine) properties In addition single element strain gauges were applied circumferentially around the average longitudinal location of ulnar fracture in order to determine the local bone deformation profile Following time zero characterization stress fractures were created in vivo and animals were allowed to recover for a period of two or five weeks Formation of damage and new bone following mechanical loading was assessed by x-ray microCT and dynamic histomorphometry Results The rabbit forelimb when loaded in axial compression demonstrates a consistent mid-diaphyseal fracture location characterized by a local mixed compression-bending loading environment Forelimb apparent stiffness when fatigue loaded demonstrates a progressive increase until macrocrack formation (+30) at which time apparent stiffness rapidly declines until complete forelimb failure Stress fractures in the rabbit ulna display robust periosteal expansion and woven bone formation two weeks following fracture Five weeks following fracture remodeling is seen around the fracture line and within the woven bone Conclusion Time zero characterization of the mechanical environment of the rabbit forelimb under cyclic axial compression allowed us to successfully create stress fractures in vivo Survival animals experienced no complications associated with loading demonstrating the efficacy of our model Stress fracture creation triggered periosteal bone formation and an intracortical remodeling response as seen in rodents These biological findings support further development of this fatigue model as a means to study the effects of pharmaceuticals on the creation and removal of damage in osteonal bone


23 Light-Triggered Release of Bioactive Molecules from DNA Nanostructures

Susie S Cha Richie E Kohman Xue Han Boston University Rapid advances in DNA nanotechnology allow the creation of intricate nanostructures that can be functionalized with a high degree of spatial control To advance the use of DNA nanotechnology for controlled release of bioactive molecules we report a general strategy using light to liberate encapsulated cargoes from DNA nanostructures with high spatiotemporal precision We designed a multilayered brick-like nanocage structure with a well-defined cavity in its center containing 14 addressable single-stranded DNA extensions Nanostructures were self-assembled in a single step by slowly cooling a heated mixture of DNA components Cargo molecules were prepared by reacting with photolabile cross-linker and subsequently conjugating to oligonucleotides that are complementary to those presented in the cavity of nanocages TEM revealed properly assembled structures with the desired shape and a clearly visible central cavity Photocleavage of the cross-linkers was validated by conjugating an oligonucleotide to the fluorescent molecule Oregon Green (OG) 50 of OG was released after 11s and complete cleavage was achieved after 40s of low-powered light irradiation To quantify loading efficiency the activated OG was loaded into the nanostructures which incorporated a nonlabile dye for comparison UV absorbance spectra analysis showed two distinct absorption peaks corresponding to the two dyes with 74 to 1 ratio suggesting half of the DNA extensions on each cage were bound We then explored the possibility of releasing large proteins from the nanocages using bovine serum albumin (BSA) and streptavidin TEM analysis of nanostructures revealed clearly visible BSA and streptavidin proteins within the cavity of the nanocages Loading efficiency of 93 for BSA and 71 for streptavidin was observed After low power light irradiation for 60s we found uncaging efficiencies of 79 for BSA and 87 for streptavidin To demonstrate that molecules released from the DNA nanocages retain their bioactivity we tested uncaging of the small molecule glutamate by measuring calcium changes in cultured neurons mediated by the neurotransmitter using fluorescence imaging Before light illumination little basal calcium activity was observed Immediately following a 1 ms light pulse illumination we observed an increase in intracellular calcium levels in 1622 In the absence of the DNA nanocages no cells exhibited a change in calcium levels upon light In conclusion we describe a novel strategy to encapsulate a large variety of bioactive molecules inside DNA nanostructures that can be released with high temporal precision using pulses of light


24 Multi-focused HIFU for diffusive heating and control of acoustic cavitation

Vandiver Chaplin Charles Caskey Vanderbilt University 1 Background Thermal therapy with high intensity focused ultrasound (HIFU) requires controlled elevation of temperature in tissue and typically uses array transducers that enable electronic steering and beamforming However peak negative pressures (PNP) used in thermal therapy are capable of causing spontaneous cavitation which can accelerate heating but also poses a risk of mechanical damage due to inertial cavitation A method that reduces PNP while delivering a therapeutic thermal dose is desirable Here we present a multi-focused technique that can produce a volumetric heating rate equal to or greater than a single-focused technique while reducing cavitation by operating at a lower PNP 2 Methods We implemented multi-focus sonication consisting of a triangular focal pattern with 3 foci 4-mm apart and compared it to the native single focus on the Philips Sonalleve V2 MR+HIFU system To assess cavitation and heating abilities of each sonication scheme we sonicated an agarose phantom with known absorption and thermal characteristics (2 agarose 15 graphite) We first measured cavitation activity at non-thermal energy levels (12 MHz PNP range of 03-85 MPa repetition frequency of 1Hz and 1ms duration) by analyzing echoes received on a 10MHz single-element transducer The cavitation signal was isolated by filtering harmonics and integrating broadband noise components We then compared heating during continuous multi- and single focus sonications at matched power using MR thermometry by measuring the peak and average temperature change in an 8x8x9-mm ROI 3 Results After cavitation onset broadband spectral energy associated with cavitation was greater in single- versus multi-focus sonications at all power levels tested confirming that multi-focus sonication reduces cavitation activity During thermal experiments at matched power the temperature rise in the multi-focus case reached a maximum of 47degC compared to 88degC for the single focus case importantly both strategies yielded an average heating rate of 24 deg C min Our findings demonstrate that multi-focal sonication can be used to reduce cavitation without sacrificing volumetric heating rate in thermal therapy minimizing undesirable effects of cavitation


25 A Novel Bioluminescent Split Reporter Strategy for Investigating the Regulation of SNAP29 Homodimerization in Starvation-

Induced Autophagy

Ian Y Chen Eric Marceau Thillai S Veerapazham Junfeng Ma et al Stanford University BackgroundmdashAutophagy plays an important role in cell survival under starvation Recent evidence suggests that the synaptosomal-associated protein 29 kDa (SNAP29) regulates starvation-induced autophagy by coordinating autophagosome-lysosome fusion Current mechanistic model of SNAP29 function fails to capture the fact that SNAP29 exists as both homodimers and monomers Here we report the development of a novel bioluminescent split reporter-based sensor for investigating the regulation of SNAP29 monomer-dimer equilibrium during starvation-induced autophagy Methods and ResultsmdashA bioluminescent sensor for detecting SNAP29 homodimerization using a split firefly luciferase (FLuc) fragment complementation strategy was specifically constructed This sensor is composed of a single plasmid vector construct (pUbi-N-FLuc-SNAP29-pUbi-SNAP29-C-FLuc) expressing two fusion proteinsmdashSNAP29 fused to the N-terminus of FLuc (N-FLuc) and SNAP29 fused to the C-terminus of FLuc (C-FLuc)mdasheach under the regulation of a constitutive human ubiquitin promoter (Ubi) Human cervical cancer (HeLa) cells expressing the bioluminescent sensor and exposed to starvation in Earlersquos Balanced Salt Solution (EBSS) medium showed decreasing homodimerizationFLuc signal over a 3 hour period (27plusmn3 at 3 hour plt005) during which there was decreasing amount of SNAP29 sugar modification via O-GlcNAcylation by Western blot Global knockdown of O-GlcNAcylation for 24 hours in these cells by siRNA targeting O-linked N-acetylglucosamine transferase (OGT) resulted in significantly less homodimerization FLuc signal at baseline and during starvation (248plusmn43 over 3 hours plt005) HeLa cells expressing a mutant version of the sensor in which the wild-type SNAP29 was replaced by a mutant O-GlcNAcylation-resistant SNAP29 (SNAP29QM) likewise showed less homodimerizationFLuc signal at baseline and during starvation (365plusmn35 over 3 hours plt005) ConclusionsmdashO-GlcNAcylation regulates SNAP29 function and autophagy by shifting the monomer-dimer equilibrium towards homodimers Correspondingly the reduction of SNAP29 O-GlcNAcylation during starvation favors SNAP29 monomerization that is needed for effective autophagy With further refinement the bioluminescent SNAP29 homodimerization sensor can provide a sensitive and convenient platform by which small moleculestherapeutics can be screened for their ability to modulate autophagy by affecting the SNAP29 monomer-dimer equilibrium



Weilin Chen Curtis Thorne Steven Altschuler Lani Wu University of California San Francisco The intestinal epithelium is a highly dynamic tissue that carries out important digestive functions Multiple cell types compose the intestinal epithelium and are derived from the intestinal stem cells located at the bases of the crypts Despite a fast turnover rate the epithelium does a remarkable job of maintaining its cell populations To study this phenomenon we are developing an ex vivo model of intestinal crypts We combine this system with high-resolution image profiling at the single-cell level to build a model of the signals that regulate proliferation and establish tissue homeostasis


27 Portable robot for autonomous intravenous access using 3D near infrared and

ultrasound imaging

Alvin I Chen Max L Balter Timothy J Maguire Martin L Yarmush Rutgers University Purpose Venipuncture is the most commonly performed invasive clinical procedure and leading cause of medical injury in the United States Complications are exacerbated in difficult settings where the rate of success depends heavily on the practitionerrsquos skill and the patientrsquos physiological condition Described here is the development of a portable robotic device that improves the accuracy and speed of venipuncture by drawing blood and delivering intravenous fluids in an autonomous manner Methods The device is designed for use in large hospitals diagnostic labs and primary care settings where complications due to difficult venous access greatly compromise the safety and quality of care The device combines near infrared and ultrasound imaging real-time computer vision and pattern recognition software and a miniaturized nine degrees-of-freedom robotic manipulator The underlying technology operates by mapping the 3D position of a selected vein and precisely guiding the needle into its center under closed-loop image and force feedback Results In multiple feasibility studies the device has demonstrated significantly improved vein detection in humans compared to trained manual visualization and 98 accuracy in 35 sec on commercial and customized tissue phantoms simulating human physiological characteristics over a broad demographic range Animal and human clinical trials have been initiated and work is underway to couple the device with on-board microfluidics-based assays to allow critical diagnostic information to be obtained rapidly and at the point of care Conclusion Compared to current clinical standards automated venipuncture may provide healthcare professionals the ability to draw blood and start IV lines with unparalleled accuracy and speed and furthermore may remove the practitioner from contact with exposed sharps thus eliminating the transfection risk Once translated the described device has the potential for adoption in a number of arenas including pediatric geriatric emergency and military use The technology furthermore represents a step in the miniaturization and automation of robotic systems for routine medical interventions


28 Long-Term Stability of Stimulating Multi-Contact Nerve Cuff Electrodes on Human

Peripheral Nerves

Breanne P Christie Max Freeberg Kevin M Foglyano Michael E Miller et al Case Western Reserve University Introduction Nerve cuff electrodes (NCEs) have been applied to femoral nerves to evoke hip and knee movements in motor system neuroprostheses for standing and stepping after paralysis [Fisher 2008] The purpose of our study was to determine the chronic stability of multi-contact NCEs in human neuroprosthesis recipients in terms of charge threshold joint moment and selectivity for multiple years after implantation Methods Stimulation was delivered via four-contact spiral NCEs implanted bilaterally on the femoral nerves of two volunteers with SCI 5-6 years ago Repeated stimulated responses were measured with a 6-DOF load cell on a dynamometer with the knee fixed at 20deg of flexion while pulse width-modulated twitch recruitment curves were generated for every contact Pulse widths were between 0-255μs and amplitude was 08-21mA Mean maximum and just noticeable twitch moments (10 maximum) were derived from Gompertz models fit to the data Charge threshold was defined as the minimum charge required at each contact to produce a just noticeable twitch moment Linear regression was utilized to quantify change in moment and charge threshold over time Two contacts that elicited adverse sensation in Subject 2 were removed from analyses Selectivity is being quantified by repeatedly determining the optimal stimulation parameters that produce the largest moments while minimizing overlap in muscle recruitment [Fisher 2013] Results The mean maximum twitch moment across all contacts was 010+001Nmkg for Subject 1 and 012+002Nmkg for Subject 2 Between both subjects the moment produced by 1114 contacts exhibited no change over time while the remaining three decreased (plt005) to 3668+374 of the original moment Activating multiple contacts simultaneously produced tetanic moments 4x the 0135Nmkg needed to stand [Kagaya 1998] Average charge threshold across all contacts was 7816+448nC for Subject 1 and 4215+266nC for Subject 2 Seven contacts showed no change in charge threshold over time 514 exhibited a significant decrease and 214 increased (plt005) One contact in Subject 1 increased by 833nC between the first and last session and one contact in Subject 2 increased by 312nC Even the highest threshold was well within safe levels multiple years after implantation Conclusion The stimulated responses of NCEs in terms of twitch recruitment and charge threshold appear to be consistent and stable for up to six years after implantation in two human subjects As muscles strengthen and contractile properties change stimulus parameters may need periodic re-optimization at intervals that are being determined in ongoing analyses of stability of selectivity


29 Characterization of contraction intensity differences in strain development during

isometric muscle contraction

Crystal L Coolbaugh John E Mendoza Bruce M Damon Vanderbilt University Noninvasive quantification of regional muscle deformation (eg strain and strain rate) may aid the interpretation of structural and functional alterations in muscle-tendon mechanics associated with performance injury and disease Attempts to apply cardiac magnetic resonance tagging techniques to skeletal muscle however have required constrained experimental preparations ndash numerous contractions at low contraction intensity ndash that limit the functional relevance of the acquired data Harmonic phase (HARP) analysis may improve extraction of muscle motion from tagged images but it is unclear if this technique can be applied to skeletal muscle during higher intensity contractions Purpose To use HARP analysis to measure the magnitude and spatial pattern of strain in the tibialis anterior (TA) muscle during submaximal and maximal isometric contractions Methods Spatial modulation of magnetization (SPAMM) tagged images were acquired in the axial and sagittal planes in the TA muscle of eight healthy volunteers during isometric ankle dorsiflexion contractions at 25 50 75 and 100 of maximal voluntary contraction intensity Two contractions were performed at each intensity level to assess strain measurement repeatability HARP analysis was used to measure the dynamic three-dimensional displacement and strain field in a region bisecting the internal aponeurosis of the TA for each trial Results Our preliminary analysis indicated the direction of strain was consistent with the bulk muscle movement observed during an isometric contraction of the TA Strain magnitudes across the aponeurosis also related positively with muscle contraction intensity except for the 100 intensity condition which may suggest a possible strain rate limitation of HARP analysis Conclusions This study demonstrates the utility of HARP for analyzing in vivo skeletal muscle mechanics under conditions experienced during activities of daily living Future work will extend these imaging techniques to other clinically relevant muscle groups (eg gastrocnemius and hamstring) in previously injured or older subject populations


30 Fluorescently-tethered Hsp90 inhibitors provide therapeutic effect and diagnostic information in breast cancer pre-clinical

models

Brian Crouch Stella Belonwu Helen Murphy Philip Hughes et al Duke University Purpose The purpose of this study is to establish that a single agent can be used to both visualize and treat breast cancer Heat Shock Protein 90 (Hsp90) is a molecular chaperone that stabilizes and protects many lsquoclientrsquo proteins necessary for tumor growth We have previously developed a fluorescently-labeled Hsp90 inhibitor (Hs-27) that binds to ectopically expressed Hsp90 on the surface of cancer cells In this study we demonstrate the theranostic utility of Hs-27 by treating breast cancer cell lines and examining therapeutic endpoints as well as examining uptake of Hs-27 in these same cell lines in vitro and a subset in vivo Methods Hs-27 combines an Hsp90 inhibitor (SNX-5422) with a fluorescein isothiocyanate derivative (excitation 488nm emission 525nm) To establish the therapeutic capabilities of Hs-27 three breast cancer cell lines were treated with Hs-27 and analyzed for client protein expression through western blotting As many Hsp90 client proteins regulate cellular metabolism metabolic endpoints were also investigated using a Seahorse Extracellular Flux Analyzer Hs-27 uptake was evaluated both in vitro and in vivo Three breast cancer cell lines were incubated with Hs-27 and fluorescence images were captured using confocal microscopy An image processing method was used to evaluate these images and establish differences in Hs-27 uptake between various breast cancer receptor subtypes In vivo uptake of Hs-27 was investigated using hyperspectral fluorescence imaging of a dorsal skinfold window chamber model for mice with either breast tumors or no tumor as a control Results Western blotting of breast cancer cells treated with Hs-27 revealed Hsp90 client protein degradation consistent with other potent Hsp90 inhibitors Additionally Hsp70 expression increased as a compensatory method as Hsp90 was inhibited Consistent with decreased Hsp90 client protein expression both glycolysis and oxidative phosphorylation were significantly lower in breast cancer cells In vitro confocal microscopy revealed that Her2 overexpressing cells take up more Hs-27 than either estrogen receptor positive or triple negative cell lines In vivo imaging of window chambers demonstrated that Hs-27 uptake is greater in tumor bearing mice than non-tumor bearing mice Conclusions In this study we provide compelling evidence that Hs-27 has both therapeutic and diagnostic utility in a variety of breast cancer subtypes Hs-27 causes degradation of client proteins and causes metabolic changes in breast cancers that may precede cell death Finally Hs-27 uptake is greater in tumor mice than non-tumor mice highlighting its utility as a diagnostic tool



Ivana Cuberovic Emily L Graczyk Matthew A Schiefer Dustin J Tyler Case Western Reserve University Proprioception is important for executing movements Individuals such as amputees without proprioception rely on vision for movement feedback which increases cognitive burden during task performance Any disruption to vision significantly degrades performance with the prosthesis Thus prostheses are often relegated to supporting functions This study reports on work to provide functional intuitive proprioceptive feedback with direct neural interfaces Two experiments were conducted with one unilateral trans-radial amputee who had Flat Interface Nerve Electrodes (FINEs) implanted on his median and radial nerves in January 2013 Electrical stimulation of the median FINE resulted in sensation of hand motion The subject mirrored his phantom handrsquos position with his intact arm A CyberGlovetrade system captured changes in joint angle Electromyography (EMG) recording of the residual muscles in the amputated limb indicated concomitant level of muscle activation The subject verbally reported the sensation quality Stimuli were biphasic with constant amplitude (07 mA) and frequency (100 Hz) Stimulation phase duration varied from one to five seconds In one session four pulse width (PW) envelopes were used flat ramp up then down ramp up then hold and ramp up then off In the second session only the flat PW envelope was used but its amplitude was set to one of five evenly distributed levels between sensory threshold (120 micros) and the hardware maximum (255 micros) In both EMG envelopes were found by bandpass filtering rectifying integrating and normalizing to a maximum voluntary contraction Calibrated joint angle traces were extracted from CyberGlovetrade data The presence of proprioception and EMG were strongly associated (Fisher exact test plt0001) Further the shape of the pulse width envelope the evoked EMG and measured joint motion are strongly positively correlated The mean normalized cross-correlation coefficient between stimulation PW envelope and EMG was 090plusmn015 PW envelope and joint angle was 084plusmn013 and EMG and joint angle was 077plusmn020 The EMG signal was quantified by normalizing the area under the curve (AUC) of the EMG envelope by trial duration The perceived motion was quantified by the measured range of motion Both duration and PW affect the magnitude of the evoked EMG and extent of perceived motion where PW variation led to a larger dynamic range of perceived motion and better correlation (linear regression r2 gt 095)


32 Non-monotonic temporal evolution of gradient-echo MRI signal in brain white matter

Kyle S Decker Duke University Purpose Gradient-echo signal is traditionally assumed to decay exponentially However this signal may not always decay exponentially if the underlying field distribution is not Lorentzian We show through simulation and ex-vivo MR results that the field distribution for gradient-echo images may not follow a Lorentzian curve in the presence of ordered structures such as fiber bundles located within white matter (WM) of the central nervous system Methods Simulations of a WM fiber bundle were performed in order to investigate microstructural effects on the observed signal decay A susceptibility tensor was assigned to each grid point in the simulation and the forward Fourier transform relationship between susceptibility and magnetic field was used to calculate the magnetic field distribution of the voxel for a range of echo times T2 decay was incorporated into the simulation through the use of a 3-pool model Ev-vivo images of C47BL6 mouse brains were acquired on a 94T 89-mm vertical bore Oxford magnet Two groups of mice with different cuprizone diets were scanned (n=2 total of 4 mice) One group of mice was administered a cuprizone diet for 4 weeks and then allowed to recover for 8 additional weeks This group serves as a remyelination group The second group was administered the cuprizone diet for the entire 12 weeks thus serving as a chronic demyelination group Classification of non-monotonic decaying voxels was performed using regularized logistic regression which was trained on a simulated dictionary of monotonic and non-monotonic decaying signals Results In the simulation at 94T the field distribution becomes significantly broad at larger fiber angles causing deviation from a Lorentzian curve and resulting in non-monotonic signal decay Similar results are seen as the field strength is increased and the g-ratio is decreased both resulting in non-Lorentzian field distributions and non-monotonic signal decay The non-monotonic decay was seen in voxels throughout the major WM regions of the ex-vivo mouse brain The incidence of the non-monotonic decay in WM ROIs was significantly higher in the remyelination group in comparison to the chronic demyelination group Conclusion At high field strengths the observed gradient-echo signal does not decay as expected in areas with sufficient myelination and relatively large fiber angles with respect to B0 We found the magnitude actually increases for certain echo times The observed phenomena are highly indicative of the underlying microstructure and thus may be a useful tool for studying cytoarchitecture both in vivo and ex vivo



Kofi Deh Marjan Zaman Pascal Spincemaille Moonsoo M Jin Yi Wang Weill Cornell Medical College Quantifying the accumulation of drugs or contrast agents (CA) in a subcutaneous tumor implant in an animal model is a common application of magnetic resonance imaging (MRI) in cancer drug research Several MRI data acquisition and post-processing techniques have been developed to facilitate this procedure Generally however these techniques do not account for contributions of non-CA sources such as the background field fat uncertainty in r2 relaxivity and T1 effect to the measured CA concentration The increase in the use of molecular drug targets however creates the need for more accurate quantification of drug delivery Here we investigate the accuracy of quantitative susceptibility mapping (QSM) which accounts for the non-CA contributions to CA concentration measurement 5 SCID mice bearing PC3-PIP tumors in the flank were injected injected either intra-tumorally or intravenously with a dual-modality iron oxidezirconium contrast agent and scanned on both Positron Emission Tomography (PET) and 7 Tesla MRI scanners QSM images are reconstructed from MRI phase images and compared to PET images We observed excellent agreement between QSM and PET estimates of drug accumulation in the tumors We contrast estimates from QSM with estimates obtained using R2 relaxometry to highlight problems with using the latter approach



Elizabeth N DeLassus Duanwen Shen Mingfeng Bai Baogang Xu et al Washington University St Louis The signaling status of different kinases can be an important indicator of cellular homeostasis since kinases regulate many important pathways in the cell Aberrant kinase signaling is implicated in many pathologies including heart disease diabetes and cancer Therefore the ability to monitor kinase activity in real time would be a powerful tool in imaging disease states in which these enzymes are implicated and monitoring response to drugs that modulate kinase activity Research in the Achilefu lab has demonstrated that inducing structural asymmetry in cypate using different adducts including peptides leads to a shift in emission from 800nm to 700nm thus generating dichromic fluorescent molecules Synthesis of an asymmetrical cypate derivative with the structure phosphoserine-cypate-serine (LS455) yields a dichromic molecule which has enhanced 700 nm emission compared to cypate When the serines conjugated to cypate are symmetrical the resulting molecule LS456 has maximum emission similar to cypate at approximately 800nm However in vitro phosphorylation of LS456 by the kinase Akt-1 in MCF-7 breast cancer cells generates asymmetry in the molecule and results in enhanced 700nm emission with a concomitant decrease in 800nm emission This shows that the DCF strategy is a viable way to image kinase activity with potential to be expanded to image this diverse family of important enzymes


35 Characterizing and Eliminating Errors in Enhancement and Subtraction Artifacts in DCE

MRI Studies

Jamal J Derakhshan Elizabeth S McDonald Evan S Siegelman Mitchell D Schnall et al University of Pennsylvania Purpose Dark band artifacts were observed in dynamic contrast enhanced (DCE) MRI subtraction images routinely used clinically to diagnose breast cancer and remained unexplained causing a diagnostic dilemma despite efforts by both site MR physicists and vendor technicians at optimizing the acquisition including using different fat suppression techniques It was hypothesized that the artifacts were caused by a subtle change in signal cancellation between fat and water in the presence of contrast enhancement A related phenomenon termed paradoxical suppression had been previously reported on opposed-phase non-subtraction images only Methods Computer simulations were performed in Matlab for voxels containing 0-100 fat fraction at all off-resonance angles assuming 50 enhancement for glandular tissue and 10 for fat Phantom experiments were performed by using mixtures of methylene chloride (similar chemical shift to water) and fat with chromium acetylacetonate (hydrophobic) as a doping agent to approximate the T1 of glandular tissue and simulate enhancement A time-equivalent volume interpolated breath-hold examination (VIBE) acquisition was engineered by increasing Partial Fourier in both phase and partition-encode directions Phantom experiments were performed using a standard ACR quality control phantom to explore the high contrast spatial resolution and low contrast detectability of the modified sequence Finally a standard minimum TETR clinical VIBE DCE MRI study was bracketed by the modified time-equivalent in-phase VIBE sequence in a clinical DCE MRI study Results Simulations demonstrated and characterized the large variable reduction in expected enhancement as a function of off-resonance angle and fat signal fraction Phantom experiments validated the simulations showing reduction of enhancement up to -160 Fat-suppressed VIBE reduced fat signal to near water level ACR phantom experiments demonstrated improved high contrast spatial resolution and low contrast detectability in the in-phase time-equivalent sequence The in-vivo studies demonstrated elimination of the subtraction artifacts when imaging with a time-equivalent in-phase acquisition Conclusion Errors in enhancement and subtraction artifacts in contrast-enhanced MRI studies are an important clinical problem and have been completely characterized for the first time (chemical shift artifact of third kind) These are present despite optimal fat suppression and both can be eliminated by imaging with a time-equivalent in-phase acquisition


36 A Microfabricated Submucosa for Assessing the Effects of Matrix Topography on

Colorectal Cancer

Mahesh Devarasetty Aleksander Skardal Shay Soker Wake Forest Institute for Regenerative Medicine Recent investigation of colorectal cancer metastasis has identified the tumor microenvironment as a large proponent of metastasis Factors such as tissue stiffness fiber alignment and bundling and cell-cell interactions have been targeted as affecting cancer cell phenotype proliferation and drug susceptibility To study these effects in vitro this study aims to develop a micro-facsimile of colonic submucosal microstructure using cellularized type I collagen (Col I) hydrogels Constructs are fabricated using rabbit colonic smooth muscle cells (RCSMCs) suspended in a Col I hydrogel Although RCSMCs were able to produce contraction throughout a range of Col I concentrations RCMSCs demonstrated increased propensity for aligning fibrillar ECM components in lower concentration Col I hydrogels To assess the effects of RCSMC remodeling on cancer cells we embedded a foci composed of HCT-116 cells (a malignant colorectal cancer cell-line) into the submucosal construct HCT-116 cells produced mesenchymal phenotypes in stiffer high concentration Col I hydrogels and also demonstrated more epithelial expression when cultured in submucosal constructs indicating a connection between smooth muscle cells fiber alignment and cancer cell phenotype To decouple paracrine activity from fiber effects induced by the RCSMCs we performed transwell co-cultures and inhibited fiber alignment using beta-aminopropionitrile (a lysyl oxidase inhibitor) In both cases cancer cells demonstrated amplified mesenchymal expression Our results indicate that RCSMCs remodel the extracellular matrix into a ldquonormalrdquo or healthy environment that induces ldquonormalrdquo or epithelial expression from HCT-116 cells Future directions include probing the biomolecular effects of fiber alignment as well as the integration of cancer-associated fibroblasts into the model to replicate the cellular content found in in vivo tumors



Hendrik A Dewald Matthew R Williams Joris Lambrecht Robert F Kirsch Department of Biomedical Engineering Case Western Reserve University Purpose Our work focuses on the implementation of implanted myoelectric signals (MES) acquisition systems for control of multi-degree of freedom (DOF) prosthetic hands for individuals with transradial amputation Major limitations of existing myoelectric control in prosthetics stems in part from surface MES recording electrodes Existing myoelectric prostheses use surface electrodes to employ a ldquotwo-site two-staterdquo control algorithm capable of driving one DOF at a time More advanced multi-DOF hands require more and often simultaneous commands to provide a more natural and intuitive interface Numerous intramuscular electrodes will provide a more stable and selective acquisition system for the machine learning approach of an Artificial Neural Network (ANN) The overall goal of this study is to create a robust and simultaneous multi-DOF prosthetic control scheme using machine learning techniques and a consistent set of implanted electrodes for specific and independent MES signals Methods Temporary intramuscular fine wire electrodes are used in both control and amputee subjects to record MES activity during a set of cued finger and wrist isometric flexionextension tasks Electrodes are inserted in pronator teres supinator extensor pollicis longus (or abductor pollicis longus) flexor pollicis longus flexor digitorum superficialis extensor digitorum communis flexor digitorum profundus and extensor digiti minimi The collected MES data is used to train an ANN which is then used to control a 3 DOF virtual hand in a series of posture-matching tasks The ANN control performance is compared against a simpler 6-site agonist-antagonist control that serves to mimic the ldquotwo-site two-staterdquo methodology of existing myoelectric prostheses Time to target simultaneity and path efficiency are measured and compared across the two approaches Results Subjects exhibited 100 posture-matching task completion with little to no significant performance difference between agonist-antagonist and ANN control approaches Additional experiments are ongoing to evaluate a larger and more complete data set Conclusion In our work we demonstrated successful virtual hand postural control both using ANN and agonist-antagonist methods Future work beyond the acute fine wire phase will entail the use of permanently implanted intramuscular recording electrodes in the amputee subject group


38 Alterations in the anterior capsule correlate with impaired joint mechanics in a

rat elbow model of post-traumatic joint contracture

Chelsey Dunham Ryan M Castile Necat Havlioglu Leesa M Galatz et al Washington University in St Louis PURPOSE Post-traumatic joint contracture (PTJC) due to elbow injury is a challenging clinical problem due to the anatomical and biomechanical complexity of the elbow Injury to the elbow disturbs joint congruity and the peri-articular soft-tissue leading to decreased range of motion (ROM) Recently our group developed an animal model of PTJC in the rat elbow We evaluated our model biomechanically and morphologically to determine if it mimicked symptoms common to human PTJC METHODS In this IACUC approved study male Long-Evans rats had unilateral elbow surgery to replicate soft-tissue injuries seen in human dislocation followed by immobilization for 42 days Limbs were evaluated at 3 7 21 and 42-day immobilization (IM) and 42-day remobilization (RM) Control animals were allowed unrestricted cage activity Elbow joints were subjected to mechanical testing in flexion-extension and pronation-supination After mechanical testing sagittal sections of elbow joints from 42-day IM and RM were stained with hematoxylin and eosin (HampE) toluidine blue and picrosirius red for histological assessment RESULTS In flexion-extension injured limbs at 42-day IM and RM demonstrated significantly decreased ROM compared to control and contralateral limbs In pronation-supination injured limbs at 42-day IM and RM showed significantly decreased ROM compared to contralateral Preliminary data for injured limbs in flexion-extension was only significantly different from contralateral for 21-day IM 3 and 7-day IM was not significantly different HampE staining of injured limbs at 42-day IM revealed an increase in the amount of adhesions cellularity and thickness of the anterior capsule compared to control and contralateral While at 42-day RM the capsule from injured limbs exhibited increased adhesions and thickness however cellularity decreased Toluidine blue had a similar trend for cellularity Picrosirius red staining showed an increase in anterior capsule collagen density for injured limbs at 42-day IM and RM CONCLUSION We have shown that our animal model of PTJC mimics biomechanical and biological features of the human condition Significant motion loss persisted from 42-day IM to 42-day RM likely due to the increased disorganized collagen and thickness of the anterior capsule Preliminary data showed that significant motion loss developed between 7 and 21-day IM Biological evaluation at these earlier time points is currently under investigation We are also studying how other peri-articular soft-tissues besides the capsule contribute to motion loss Understanding the mechanobiological signaling of peri-articular soft-tissue will help identify specific changes in the elbow responsible for contracture


39 No changes necessary Zaire Ebolavirus efficiently infects and replicates in Boa

Constrictor cells without cytopathic effet

Greg Fedewa Melissa Spear Ryan Hernandez Sheli Radoshitzky et al UCSF Purpose Ebola virus disease is a type of hemorrhagic fever with a high mortality rate no cure no approved vaccination and no approved treatments Caused by members of genus Ebolavirus little is known of these viruses in the wild including their natural reservoirs The glycoprotein (GP2) of reptile Arenaviruses which infect both boa constrictor and pythons possesses both sequence and structural similarity to Ebolavirus GP suggested that Ebolavirus may also be able to infect and replicate in boa constrictor cells Methods To test this we serially passaged Zaire ebolavirus strain Kikwit ldquoR4368rdquo in a boa constrictor cell line JK in parallel to passage in HeLa cells We then deep sequenced the six serial passages to characterize genomic mutations associated with adaptation for growth in JK cells and identify genomic locations under positive selection We also performed anti-GP antibody staining of the passages to characterize viral growth Results We observed that Zaire ebolavirus will infect JK cells yet caused no obvious cytopathic effect Further we found that serial passage of Zaire ebolavirus in JK cells resulted in no mutations being required for infection and replication Deep sequencing coverage (gt10000x) demonstrated the existence of 48 low frequency variants within the initial inoculum viral population and a mean of 70 variants found per passage Conclusion When we attempted to passage Marburg Marburgvirus despite having a similar range of possible hosts it was not able to infect the JK cell line indicating JK is not just a permissive cell line The lack of cytopathic effects is also a hallmark for a reservoir species Egyptian Rousette Bats (Rousettus aegyptiacus) were long thought to be the reservoir for Zaire Ebola virus until it was recently shown that they donrsquot become viremic when experimentally infected Taken together with our data we believe that additional species should be considered as possible reservoirs this pathogen



Stephen A Ferguson Mark E Meyerhoff University of Michigan Heparin is a common anticoagulant used in clinical procedures to prevent clotting during surgical procedures (eg open heart surgery) Conversely protamine is used to neutralize the anticoagulant effect of heparin in the extracorporeal circuit after a surgery is complete The concentrations of these highly charged macromolecules (polyions) are difficult to detect and quantify directly in blood To circumvent this challenge electrochemical polymer membrane-based polyion sensitive ion-selective electrodes (ISEs) have been developed as tools for the detectionquantification of heparin and protamine in simple background electrolytes as well as in whole blood Further polymeric quaternary ammonium salts (polyquaterniums) represent a class of compounds that have found increasing use in industrial and cosmetic applications In particular polyquaterniums are useful in industrial flocculation processes such as wastewaterdrinking water clarification as they form aggregates with oppositely charges species in colloidal solutions thus allowing the combined weight of the aggregate to settle out of solution Also polyquaterniums have been found to be useful as conditioners and antistatic agents in personal care products such as shampoos In this presentation we will summarize research efforts aimed at developing simple electrochemicalpotentiometric polyion detection methods to quantitate concentrations of various polyions in solution and their potential application to microfluidic devices One approach is based on titrating samples with oppositely charged polyions and detecting excess titrant polyion via a titrant polyion-sensitive membrane electrode Another approach is to mix a given volume of sample to a flowing stream of oppositely charged polyion and measure the decrease in response of a reversible potentiometric polyion sensor toward the indicator polyion owing to it being bound by the analyte polyion These new methods may provide a means to determine levels of heparinprotamine concentrations in whole blood during clinical procedures in addition to providing a quality control method for quanitating polyquaterniums in personal care product formulations


41 Metabolomics approaches towards a spatial understanding of host-microbe

interactions in plants

Dimitrios J Floros Pieter C Dorrestein UCSD Purpose Ubiquitous and diverse microbial communities together with their associated genomes make up microbiomes that are often linked to plant and human health outcomes However the investigation of the metabolites associated with these communities and their effects on host metabolome have not been adequately characterized Better understanding of these communities are needed for their rational engineering and utilization in the clinic or for sustainable agriculture My research aims to incorporate analytical chemistry together with emerging bioinformatic and visualization tools to begin ascribing functionality and causal relationships to the members of microbe-host communities Methods While sequencing based Omics approaches like 16S amplicon and transcriptomic libraries allow us to understand the composition and some of the function of microbial communities it is changes in the metabolomes that often play the largest part in defining different phenotypes and pathologies Untargeted high resolution tandem mass spectrometry (MSMS) based metabolomics allows the rapid generation of testable hypotheses about metabolites that may play key roles in these communities Through our labrsquos rapidly maturing molecular networking platform large MSMS datasets can be readily analyzed and interpreted while new visualization tools for LC-MSMS data are making it possible to generate 3D maps of the metabolome Results We have developed methodologies of 3D spatio-chemical visualization of microbe-host interactions which has allowed the observation of microbial specialized metabolites like valinomycin on plant surfaces Additionally molecular networking tools have allowed the comparison of plant species and tissues at the metabolite level including level 2 and 3 annotations (Metabolomics Standards Initiative) When applied to plant metabolites of members of the Solanum family these techniques allowed the rapid comparison and visualization of tissue-type dependent molecular distributions Conclusion This work has successfully developed techniques for layering molecular information onto three dimensional models Molecular networking was also successfully applied to mine the MSMS datasets for plant and microbial metabolites As these studies continue into controlled multi-member communities we will apply these MS-based metabolome mapping tools to understand the direct effectors and impact of microbial communities on plant metabolism



Daniel JP Foust Brittany Caldwell Antoine G Godin Alessandro Ustione et al Washington University Purpose We are interested in resolving the molecular signaling mechanisms and the subsequent physiological responses that mediate insulin secretion in pancreatic beta cells Impaired insulin secretion is indicated in the progression of diabetes mellitus Bettering our understanding of the molecular interactions that modulate insulin secretion could lead to new therapeutic interventions Specifically our lab has previously shown that activation of D2-like dopamine receptors acts to inhibit insulin secretion These receptors are coupled to trimeric G-proteins on the plasma membrane When the receptor is activated it catalyzes the dissociation of the trimeric G-protein into separate G-alpha and G-beta-gamma subunits The dissociated G-alpha and G-beta-gamma subunits interact with downstream effectors to initiate the physiological response The molecular details of interactions between dopamine receptors G-proteins and their effectors are not known in beta cells Studying these interactions could be source of novel therapeutic targets for diabetes Methods We have labeled D2-like receptors and the G-beta-gamma subunit with fluorescent proteins These recombinant proteins are heterologously expressed in MIN6 cells a murine beta cell line We image these cells using single and two-photon excitation Imaging parameters are selected so that data may be analyzed with various statistical analysis tools These tools belong to family methods referred to as fluorescence fluctuation spectroscopy (fluorescence correlation spectroscopy photon counting histogram image correlation spectroscopy etc) In addition to previously developed analyses of fluorescence fluctuations we have developed spatial intensity distribution analysis for detection of fluorescence in two channels (2D-SpIDA) This novel method gives additional sensitivity to heteromeric protein-protein interactions Results Initial results have shown a decreased affinity between D2-like dopamine receptors and the G-beta-gamma subunit upon dopaminergic stimulation Conclusion Fluorescence fluctuation spectroscopy is a useful approach for measuring the interactions of dopamine receptors with their downstream effectors in beta cells


43 Measuring growth patterns during neonatal brain development with surface

strain analysis

Kara E Garcia Emma C Robinson Dimitrios Alexopoulos Cynthia E Rogers et al Washington University in Saint Louis Purpose During the final trimester of fetal development the human cortex undergoes dramatic deformation to produce complex folding patterns Abnormal folding is associated with disorders including autism schitzophrenia and epilepsy yet the folding process remains poorly understood from a physical standpoint To evaluate the proposed mechanisms of folding precise measurements of spatiotemporal growth are needed Using strain as our metric this study seeks to measure spatiotemporal patterns of cortical surface deformation during critical stages of neonatal brain development Methods In collaboration with the Saint Louis Childrens Hospital cortical surface reconstructions were generated from magnetic resonance imaging (MRI) at postmenstrual age 26-38 weeks Multimodal Surface Matching (MSM) was used to automatically align surfaces based on mean surface curvature (Robinson et al 2014) To minimize nonphysical strains we implemented a new MSM functionality based on the theory developed by Knutsen et al 2010 which minimizes strain energy by considering the brain surface as a compressible neo-Hookean material After alignment strain maps were calculated from vertex motion between the younger and older cortical surfaces of an individual subject For detailed visualization of strain magnitude and direction surfaces were exported into MATLAB for post-processing Results Using MSM to align surfaces and minimize anatomical surface strains we were able to (1) precisely match gyri and sulci from an individual across multiple time points and (2) estimate growth patterns for an individual during brain development Inclusion of strain relaxation reduced maximum strains more than three-fold such that all strains fall within the physically realistic range In general we observed higher strains in regions where gyri are forming or in sharp sulci However it is worth noting that some of these variations particularly in the sulci may reflect artifact due to sharp curvatures that increase tendency toward data alignment Conclusions The strain information presented here is the first of its kind for human cortical development in the preterm brain As such this analysis may provide valuable physical measurements to evaluate proposed hypotheses and models of cortical folding While no ground truth data exist to validate our results future work will test MSM output against cases for which the true deformation is known In future studies we may also align surfaces based on alternative data (sulcal depth fMRI) or compare growth patterns across multiple subjects to ascertain trends in normal and abnormal development



Eric Gibbs Duke University Several research groups including our own have recently reported that when the iron-storage protein ferritin is bound to the Ca2+ ion channels TRPV1 or TRPV4 the resulting channel is sensitive to static magnetic fields andor radiofrequency waves (RF) RF or magnetic-sensitive ion channels fill an immediate void in neuroscience and developmental research where present methods of ion channel control require invasively perturbing the in-vivo system RF weakly interacts with biological tissue but is readily absorbed by magnetic materials Ferritin is a protein that accumulates and stores iron as a super-paramagnetic nanoparticle The effects of exposing ferritin to low levels of RF are negligible to the cell as a whole but our group hypothesized that by localizing ferritin to an ion channel RFferritin interactions could influence ion channel behavior We localized ferritin to TRPV1 and TRPV4 ion channels to test this hypothesis TRPV1 and TRPV4 are both Ca2+ ion channels that are important in sensing a cellrsquos physical environment Ferritin was localized to TRPV1TRPV4 using a short peptide sequence (120 amino acids) that promotes ferritin recruitment to ion channels (FeRIC) This sequence is taken from the high-weight molecular kininogen which binds to ferritin during inflammation Our group has done several in-vitro and in-vivo studies that demonstrate FeRIC TRPV1 and TRPV4 respond to RF and minimally perturb cell physiology The gold-standard in ion channel studies is electrophysiology but the RF used to open FeRIC channels interferes with electrophysiology signals so GCaMP imaging was used to study increased Ca2+ activity in the presence of RF After confirming that FeRIC channels were activated in the presence of RF we used the channel to investigate congenital heart defects in chicken embryos It was previously reported that congenital heart defects in chick embryos were caused by heating the egg at a critical point in development It has also been shown that such defects are caused by irregular migration of neural crest cells (NCCs) Our group hypothesized that temperature-induced activity of TRPV4 which expresses in NCCs during development causes irregular migration and heart defects Using FeRIC TRPV1 we showed that defects could be induced at a high rate (1123) when electroporated into NCCs and exposed to RF WT channels and RF led to no defects while only 1 of 22 embryos not exposed to RF but expressing FeRIC TRPV1 had a defect This has important implications for maternal fever and congenital heart defects in humans



Mark W Grinstaff Boston University The mission of the Translational Research in Biomaterials (TRB) training grant is to develop PhD students into interdisciplinary and translational research scientists engineers Through their TRB training they will acquire 1) a fundamental and quantitative understanding of materials polymer chemistry surface science biomaterial-tissue response and molecular and cellular biology 2) exposure to engineering technologies and characterization techniques 3) research experience in interdisciplinary programs that promote discussion and scientific inquiry in areas outside of the studentrsquos ldquocomfort zonerdquo and 4) training in societal impacts of new technology ethics clinical trials and basic business The cornerstones of the TRB program are the curriculum and the program elements that combine interdisciplinary research quantitative science and engineering courses translational-based courses in clinical trials and business student-organized seminar club dinners with a medical doctor training in professional ethics individual development career plans and professional career development workshops These skills are essential in future biomedical careers as graduates join teams with diverse backgrounds that strive to meet a common goal in research development and ultimately commercialization



Simon X Han William Hsu Alex Bui UCLA Purpose Breast cancer is the second most common cause of death from cancer in women in the United States The most reliable and effective way to reduce death is early detection and treatment Routine mammograms are the current recommended method of detection for most women The recommendations however differ in terms of screening frequency starting age and ending age depending on the institution and its implementation of the process Recent research also further suggest an overdiagnosis and overtreatment trend in breast cancer increasing the burden on patient and healthcare system alike These all point to the need to better understand screening frequency In this work we leverage a large breast cancer screening dataset at our institution and apply a decision making framework to formalize optimal screening schedules Methods Information was extracted from our institutional electronic health record (EHR) system Patient data includes mammogram results biopsy results and previous diagnoses We then used this data to instantiate a partially observable Markov decision process (POMDP) a stochastic decision making framework to provide insight into ldquooptimalrdquo policies for screening frequency In a POMDP an agent makes sequences of decisions (policies) that produce the best probabilistic outcome over time on behalf of the patient The probabilities are learned from the patient data at our institution considering trade-offs between early cancer detection and disadvantages of screening (eg false positives) The agent keeps track of patient history by maintaining belief over the status of the patient with the belief updated as additional observations about the patient are made over time Policies are adjusted as beliefs are updated as well Results We solve the POMDP as a finite-horizon discrete-time problem and derive a finite state controller (policy graph) which models the decision making process From the policy graph we generate a decision tree which can quickly inform a user (eg a radiologist) to select the optimal action based on an observation Preliminary results suggest a biennial (once every other year) screening schedule is appropriate for the lowest risk patient population Conclusion We utilize a POMDP framework to explore screening mammogram schedules in breast cancer and demonstrate that it can suggest actions that optimize patient outcome We anticipate that by keeping track of patient history and patient-specific observations over time we can ultimately provide tailored recommendations for the individual patient


47 Multi scale immune profiling of human peripheral blood with single cell RNA-Seq for

immune system monitoring

Graham Heimberg John Haliburton Hanna Retallack Eric Wong et al UC San Francisco Human peripheral blood contains one of the most important and dynamic components of host defense the immune system Within the immune system different cell types interact to maintain homeostasis and respond to environmental stimuli like drugs or antigens Immune responses trigger transcriptional changes across multiple scales modulating the expression of individual genes entire transcriptional programs or even rapidly expanding specific populations of cells Here we report a novel approach to profiling the immune system by using single cell mRNA-seq to capture information about immune activity across these three distinct scales We show that the high information content of singe cell mRNA-seq allows functional immune signatures to be extracted from sampling just thousands of cells from peripheral blood We use data from healthy human donors and ex vivo disease models to computationally design a compact set of gene expression features that systematically describe immune responses With this method for unbiased multi scale immune profiling we are able to positively identify systemic lupus erythematosus from peripheral blood identifying known and novel biomarkers in a disease with no definitive diagnostic This general approach to immune monitoring could lead to more quantitative and general diagnostic tools and may engender a new modality for precision medicine


48 Beyond the EPR Effect Multi-targeting Strategies of Nanoparticles to Image Invasive

Glioma

Elizabeth Doolittle Peter Bielecki Efstathios Karathanasis Case Western Reserve University Purpose Typically targeted nanoparticles treat tumors as monoliths While cancer cells evolve they alter their gene expression patterns and behavior over time and space including the expression of targetable cell-surface biomarkers Brain tumors display a dynamic microenvironment with spatiotemporal heterogeneity Thus a targeting nanoparticle system must take under consideration that a brain tumor is a collection of microenvironments Dispersive glioma cells select ldquopermissiverdquo structures and pathways (perivascular growth along blood vessels or migratory paths across white matter tracts) Considering that glioma-associated vasculature is not as leaky as in other tumor types we employ multi-ligand vascular targeting schemes against vascular biomarkers that effectively direct nanoparticles to primary and invasive glioma sites Methods Imaging studies were performed using orthotopic murine models of glioma A patient derived pediatric high-grade glioma (SJ-GBM2) and a patient derived adult glioma stem cell glioma (T4121) Brain tumors were generated using tumor cells expressing green fluorescent protein reporter gene (GFP) As a case study liposomes an all-purpose nanoparticle were conjugated with different targeting ligands and NIR fluorophore for particle detection Injection of cocktails containing nanoparticle variants into the same mouse allowed for comparison of targeting while controlling for variability in tumor growth and dispersion Particles with separate fluorochromes one targeted and one non-targeted were intravenously injected Ex-vivo fluorescence imaging of the brains was completed at a short time point (hours after injection) to reflect targeted accumulation on a small time scale and at a long time point (1-2 days after injection) allowing for maximum passive (non-targeted) deposition Organs were analyzed using 2D and 3D fluorescence imaging Histological analyses confirmed whole organ imaging data and provided topological details Results Surface ligands were added at varying surface densities (1000-25000 ligands per particle) confirmed by direct protein assay Imaging studies showed that at a short time scale targeting achieved enhanced particle delivery to the brains when compared to non-targeted variants Notably different targets differentiated targeting of the primary site or infiltrating edges and distant invasive sites Based on quantitative measurements of whole brain imaging and histological analyses performance of different targeting schemes will be presented While EPR-driven delivery can result in significant particle accumulation in the well-vascularized primary tumor location deposition of nanoparticles is patchy and near-perivascular However multi-targeting schemes facilitated efficient targeting to dispersive and invasive sites Conclusion The spatiotemporal differences of brain tumors require careful consideration in order to design a nanoparticle targeting strategy to successfully image dispersive glioma



Amritha Kidiyoor Sean V Murphy Anthony J Atala Wake Forest Institute for Regenerative Medicine Introduction The lung parenchyma consists of many different types of mature lung epithelial cells some of which are involved in cell replacement during normal turnover and after injury Regeneration of epithelium has been observed by adult lung stem cells such as basal cells Clara cells bronchioalveolar stem cells (BASCs) as well as alveolar type II cells These cells have limited differentiation potential For example basal cells can differentiate into lung epithelial cell types found in the upper airways whereas BASCs can differentiate into lung epithelial cell types found in the terminal airways and alveoli The current theory supports the presence of highly proliferative multipotent lung stem cells in the lung bud tips in the pseudoglandular stage of lung development that can give rise to all the different airway and alveolar lung epithelial cell types The objective of this study is to identify the potential of embryonic stem cells to give rise to a phenotype representative of the multipotent lung stem cell population found in the developing lung Methods Differentiating ESCs into multipotent lung stem cells- Embryonic stem cells (ESCs) were differentiated towards lung epithelium in a step-wise manner mimicking embryonic lung development RNA was collected from cells at all stages of differentiation Characterizing the multipotent lung stem cell phenotype- RNA collected from cells during the intermediate stages of differentiation was used for qPCR analysis of pulmonary and stem cell markers and a RNA microarray Lung epithelial markers were also detected by immunofluorescence (IF) on cells at this stage Results ESC derived cells expressed markers characteristic of each differentiation stage indicating successful differentiation Further the ESC derived lung progenitor stage cells were found to express lung epithelial markers such as CFTR CCSP FOXJ1 MUC5AC by PCR microarray and IF analyses Conclusion We were able to successfully differentiate ESCs into lung epithelium in a step-wise manner through an intermediate immature lung cell stage Cells at this intermediate stage expressed multiple lung epithelial as well as stem cells markers at the mRNA and protein level indicating a multipotent lung stem cell phenotype


50 Tracking Neural Activity In-Vivo using Polarization

Nathaniel O King Washington University in St Louis Birefringence has been used to track changes in neurons via transmission illumination for decades The changes in the birefringent properties of these neurons has been shown to track with neural activity Additionally the requirement that the light source and imager be on opposite sides of the neural tissue means that this work has only been conducted in-vitro Using a novel division of focal plane sensor we have developed the first in-vivo prep allowing us to track changes in the polarized component of reflected light Tracking activity in the antenna lobe of locusts we found changes in polarization state that align with olfactory stimulus In addition to the olfactory derived responses we observe a wave that propagates at 05Hz We are continuing to investigate the limits of resolution for these odor evoked responses as well as the origins of these slow moving oscillations



Surya Kotha Amie Adams Brian Hayes Kiet T Phong et al University of Washington Purpose Hematopoietic cells dynamically interact with their surrounding microenvironment during their residence maturation and differentiation Individual marrow components have been isolated in 2D in vitro cultures yet their functional contributions to a complete niche are not fully understood In vivo studies are complex and the inaccessibility of marrow architecture has precluded systematic analysis of each component Here we employ an in vitro 3D microfluidic system to study hematopoietic cell trafficking in an engineered vascular niche Methods Our system allows for control of 3D geometric cues hydrodynamic flow multi-cellular compositions and cellular matrix remodeling by combining soft lithography and injection modeling in type I collagen gel (Zheng et al PNAS 2012) Endothelial cells perfused through the embedded microfluidic network form a confluent patent endothelium within the collagen Incorporating hematopoietic cells and fibroblasts within the collagen allows visualization of cell interactions with vasculature To create a competent marrow niche in vitro we embedded cells from fresh human bone marrow screens within the collagen matrix Next we developed a simplified marrow fibroblast niche by incorporating two different human marrow-derived fibroblast cell lines (HS27a and HS5) in the collagen to understand how the marrow microvasculature is influenced by endothelial phenotype Results In our human marrow platform we found that the heterogeneous cell fraction could be cultured in for at least two weeks Electron microscopy showed various cells interacting with and changing the endothelium Throughout perfusion culture we identified different cell populations were released into the circulation over the course of two weeks including CD34+ hematopoietic progenitor cells megakaryocyte erythroid lymphoid and myeloid lineage cells In our simplified marrow fibroblast platform we observed that HS27a and HS5 cells created distinct microenvironments by secreting divergent inflammatory cytokine profiles Both stromal lines reduced endothelial expression of vWF and junctional proteins These modified vessels yielded distinct adhesion and extravasation patterns to perfused monocytes and CD34+ stem cells Conclusions In summary we developed an in vitro 3D microvascular marrow niche and gained insight into hematopoietic cell trafficking between the matrix and the circulation By guiding the interplay of heterogeneous cell populations we have demonstrated the capacity to define distinct microenvironment spaces This platform shows promise for long term culture of a whole marrow population and for the ex vivo generation of hematopoietic cells Further development of this 3D marrow platform will further our understanding of the complexities mediating stem cell trafficking residence and differentiation in health and disease


52 Cell-free compartmentalized protein synthesis inside double emulsion templated

liposomes with in vitro synthesized and assembled ribosomes

Jin Woo Lee Filippo Caschera Kenneth KY Ho Michael C Jewett et al University of Michigan Purpose Assembling biological parts into a functional system using a bottom-up in vitro reconstitution approach offers the possibility of designing artificial cells with the ability of sensing and responding to external stimuli Artificial cells are defined as the encapsulation of biologically active material in a biological or synthetic membrane We describe a robust and general method to produce artificial cells for the purpose of mimicking one or more behaviors of a cell Methods A cell-free expression platform for making bacterial ribosomes encapsulated within giant liposomes was capable of synthesizing sfGFP The liposomes were prepared using a double emulsion template and compartmentalized in vitro protein synthesis was analyzed using spinning disk confocal microscopy Two different liposome phospholipid formulations were investigated to characterize their effects on the compartmentalized reaction kinetics Results At first we encapsulated the cell-free expression system in DOPC based liposomes in buffer but we did not observe any noticeable synthesis of sfGFP We hypothesized that this was due to the fact that some of the important small molecules needed for protein synthesis could cross the membrane We therefore carried out the cell-free expression reactions encapsulated by double emulsion template in a feeding solution that includes energy components which led to protein synthesis When DOPC was switched to POPC a less permeable lipid sfGFP was generated when buffer was present Also a delay was observed in sfGFP generation when the feeding solution was present Conclusion We report the development of experimental conditions necessary to encapsulate the cell-free expression system into liposomes This study was performed as a necessary step towards the synthesis of minimal cells Looking forward our approach may be integrated with more complex designs such as the expression of cytoskeletal and membrane proteins and encapsulation of gene circuits



Karin L Lee Nicole F Steinmetz Case Western Reserve University Trainee Karin L Lee Purpose Each year one million new cases of cancer are diagnosed with the most aggressive being treated with chemotherapy However chemotherapy has side effects when administered systemically and is not effective for long-term treatment due to the development of resistant cells Attachment of chemotherapeutics to nanoparticles decreases side effects while also improving overall payload delivery and efficacy Plant viral nanoparticles (VNPs) are being investigated as carrier systems to deliver therapies to specific cells and tissues VNPs have symmetrical structures are amenable to chemical modification and can be produced in high yields in plants Additionally they are biocompatible biodegradable and non-infectious in mammals Potato virus X (PVX) is a filamentous virus measuring 515 x 13 nm and comprised of 1270 identical coat proteins each containing a solvent-exposed lysine residue As a filamentous nanoparticle PVX offers a novel nanomaterial since synthetic nanoparticles cannot be synthesized at high aspect ratios Therefore we must first investigate its interactions with biological systems Here using multiple imaging techniques we evaluate the impact of surface modifications on the in vitro and in vivo properties of PVX while also developing it for delivery of chemotherapy Methods PVX was modified with fluorescent tags as well as polyethylene glycol or targeting molecules For chemotherapy delivery doxorubicin was attached Modified particles were studied in vitro and in vivo using a combination of confocal and fluorescence microscopy flow cytometry and fluorescence molecular tomography (FMT) Results We formulated PEGylated targeted or drug-loaded PVX particles Using FMT we determined that PEGylated particles exhibited distinct biodistribution compared to native PVX particles the difference in biodistribution correlated to different circulation profiles In vitro PVX particles targeted towards the epidermal growth factor receptor (EGFR) had specific uptake in EGFR+ cells in single and co-culture as measured by flow cytometry and confocal microscopy Lastly doxorubicin was attached to PVX (PVX-DOX) and evaluated for cell efficacy PVX-DOX had decreased efficacy compared to free DOX in a panel of cell lines but maintained its cell killing ability Using fluorescence microscopy we determined that the decrease in efficacy was due to reduced uptake of doxorubicin after loading onto PVX Conclusions Here we developed the filamentous plant virus PVX for use as a cancer therapy We utilized multiple imaging techniques to evaluate its interactions with biological systems with and without surface modifications PVX offers a promising platform with modifiable properties for use in cancer therapy


54 Molecular insights into vein remodeling with arterial flow role of COUP-TFII

Li Li Mercedes Balcells Takaharu Ichimura Ming Tao et al Brigham and Womens Hospital Purpose Veins remodel under arterial flow This occurs in a vein graft for coronary bypass surgery or arteriovenous fistulae (AVF) used in hemodialysis and indeed such changes are required for graft utility Maladaptation of the vein can lead to graft failure Though well-defined the driving molecular mechanisms behind vein arterialization are not clear We examined these events Chicken ovalbumin upstream promoter transcription factor II (COUP-TFII also known as nuclear receptor subfamily 2 group F member 2 NR2F2) is expressed in venous but not arterial endothelial cells In addition serving as a specific venous endothelial cell marker COUP-TF II plays an essential role in the fate decision of endothelial cells during development This study investigates the expression and regulation of COUP TFII in AVF with the overall goal to achieve a better understanding of the molecular mechanisms that drive vein arterialization Methods Venous specimens were collected during revision of malfunctioning AVF from hemodialysis patients with end-stage renal disease COUP TFII and activated Notch 1 staining were evaluated on these specimens using immunofluorescence We also examined the effects of arterial flow on COUP TFII expression in venous endothelial cells in vitro Cultured human saphenous vein endothelial cells were exposed to different shear stress (0 510 40 dyncm2) for 48 hours in controlled perfusion bioreactors Results Human venous segments from malfunctioning AVF showed significant intimal hyperplasia covered with intact endothelium COUP TFII staining was positive on endothelial cells as expected Furthermore significant COUP TFII staining appeared in neointima most expressed by endothelial cells in many neovessels in intimal hyperplasia Activated Notch 1 expression was substantial in intimal hyperplasia similar to the pattern seen with COUP TFII In the cell culture system in the bioreactor COUP TFII expression was observed in venous endothelial cells but was minimal in arterial endothelial cells Under high shear stress (40 dyncm2) venous COUP TFII expression decreased significantly compared to levels seen in static venous endothelial cells Conclusions There is substantial endothelial cell expression of COUP TFII and activated Notch 1 associated with intimal hyperplasia in malfunctioning human AVF In the bioreactor system in vitro protein expression of COUP TFII was decreased in venous endothelial cells exposed to high shear stress Dysregulation of COUP TFII and Notch pathways may be involved in AVF malfunction and vein graft failure The different expression of COUP TFII with arterial flow between conditions in vivo and in vitro suggest that shear stress is not the only driving force for vein remodeling The underlying mechanisms linking COUP TFII expression to vein arterialization requires further investigation



Lily Li Zeba Wunderlich University of California Irvine During development enhancers drive the expression patterns that specify cell fate decisions The complexity of these decisions can be defined as the number of cell fates from which an enhancer has to choose Thus early in development when cells are mostly homogeneous and are simultaneously differentiating into many different cell types the enhancers are driving a relatively complex set of decisions in contrast later in development when cells are more differentiated and are only making decisions between a few cell types the enhancers are driving a much simpler set of decisions Consequently we expect that enhancer architecture in terms of enhancer length number of transcription factor binding sites (TFBSs) and average information content will reflect the complexity of cell fate decisions being made We first consider the differences in the architecture of enhancers in the Drosophila anterior-posterior (AP) and dorsal-ventral (DV) patterning systems These systems have been extremely well-characterized and they exemplify the disparity in decision complexity that enhancers need to drive as the AP axis consists of 14 segments whereas the DV axis consists of six germ layers and sublayers We then consider a larger data set of developmental enhancers and characterize changes in the architecture of the enhancers active over development We find that regulation of more complex decisions is associated with increased enhancer length and number of TFBSs and with decreased average information content This can be explained by the fact that increased numbers of TFBSs can be arranged in more ways allowing for enhancers to drive more patterns of expression and thus increased complexity This examination of enhancer architecture in the context of cell fate decisions helps us understand why enhancer architecture is so diverse with well-characterized enhancers containing as few as two to as many as fifteen TFBSs


56 Label-Free High Throughput Microfluidic Device for the Isolation and Single Cell Multiplex Gene Expression Analysis of

Circulating Tumor Cells from Breast Cancer Patients

Eric Lin Lianette Rivera Hyeun Joong Yoon Shamileh Fouladdel et al University of Michigan The metastasis of cancer is preceded by the dissemination of cancer cells from the primary tumor site to remote sites via the blood circulation The presence of circulating tumor cells (CTCs) in the peripheral blood represents a strong and independent prognostic factor for decreased disease-free and overall survival Immune-affinity based capture although being the most commonly used method for the isolation of CTCs offers low throughput (~1mLhr) and have considerably cell loss caused by the heterogeneous expression of biomarkers on CTCs Various label-free approaches utilizing the physical properties of CTCs have been developed to overcome the limitations Here we present an inertial microfluidic-based separation technique for high throughput and label-free isolation of CTCs yielding the highest throughput with high CTC recovery and high blood cell removal among all the label-free technologies The isolated CTC populations were further analyzed for single cell multiplex gene expression analysis The separation of CTCs in the device is driven by two main forces (i) inertial force that focuses the cells into streamlines and (ii) drag force from Dean flow that migrates the focused cells to various positions based on size Device is optimized with MCF-7 and Panc-1 cell line within PBS buffer solution and diluted blood and is tested in patients with breast cancer on an average of 5 mL of whole blood processed through double devices in series CTCs isolated were analyzed for tumor specific protein markers and genomic characterization is done using singe cell analysis techniques Samples are processed through the inertial microfluidic device and CTCs are enriched in second outlet based on size difference between CTCs and blood cells Device is optimized to operate at an extremely high throughput of 2500 μLmin with high recovery (greater than 90) and high white blood cells (WBCs) removal (5 log orders) In patient samples we identified CTCs in 38 of 40 (95) breast patients with metastatic disease (54plusmn46 CTCmL) with low WBC contamination (663plusmn647 WBCmL) Based on the gene expression both inter and intra patient heterogeneity of CTCs at the single cell level were discovered among the tested patient samples The study of CTCs could have a direct impact upon society by presenting novel ways to address one of the major hurdles in cancer research ndash early detection ndash and will foster the advancement of science and engineering via the exploration of new druggable targets approaches and the further understanding of the pharmacodynamics


57 Developing a bacterial surface display system for the generation of targeted outer

membrane vesicles

Jessica S Lin Anton Bryksin Wilbur Lam Thomas H Barker Georgia Institute of Technology Purpose To develop and optimize a bacterial surface display system to display an antibody that binds selectively to fibrin over soluble fibrinogen and to generate outer membrane vesicles that can be targeted to fibrin clots in wound sites Methods Reduced genome E coli are transformed with vectors containing the PET autotransporter and the myc-tagged fluorescent protein mCherry Flow cytometry with phycoerythrin labelled anti-myc antibody is used to characterize the presence of protein on the surface of the bacteria Microscopy is used to confirm the localization of the protein to the periplasmic space Results Flow cytometry with a myc-tagged mCherry demonstrates that the myc tag is exposed on the surface of the cell only when the vector contains both the PET construct and a signal peptide directing the protein to the periplasmic space Microscopy demonstrates that the mCherry is localized to the periplasmic space only in the presence of a signal peptide Conclusions The bacterial surface display system using the PET autotransporter displays protein on the cell surface and is a promising step towards the development of targeted outer membrane vesicles


58 Quantifying the blood flow and oxygen metabolism responses to a neural stimulus

combining multiple MR methods to optimize the modeling of hyperoxia experiments

Eulanca Y Liu Jia Guo David J Dubowitz Richard B Buxton UC San Diego Purpose To evaluate an approach for measuring cerebral metabolic rate of oxygen (CMRO2) in both baseline and activation states from repeated activations in normoxia and hyperoxia including effects of hyperoxia itself on CMRO2 based on a simplified model for the BOLD signal Background Two general approaches to measuring baseline CMRO2 are currently being investigated measuring responses to hypercapnia and hyperoxia[1-3] and isolating venous blood signal and measuring T2 which depends on venous oxygenation[4] Here we have applied both approaches and used the measured data to test and refine a simplified model for the BOLD signal that includes changes due to CBF CMRO2 and hyperoxia This extended data set makes it possible to estimate the model parameter alpha and to estimate potential changes in CMRO2 due to hyperoxia itself Experimental Methods and Results Eight subjects (4M4F mean age 258 yrs) were examined CBF and BOLD responses measured with a dual echo spiral PICORE QUIPSS II ASL acquisition (TR=2500ms TI1=700ms TI2=1750ms TE=3330ms) The stimulus was an 8Hz flickering checkerboard and an activated ROI in visual cortex was identified with a separate functional localizer experiment Responses in 4 conditions were measured 1) to hypercapnia (mean deltaPaCO2=84mmHg) 2) to 60s activation 3) to hyperoxia (mean deltaPaO2=179mmHg) and 4) to activation during hyperoxia A correction factor of 1094 was applied to ASL measures of CBF in hyperoxia to correct for decreased T1 of blood based on previously reported values[5] In separate experiments baseline O2 extraction fraction E0 was measured with VSEAN[4] (mean value was E0=041+-0097) For this study BOLD and CBF responses were averaged across the subjects to obtain a high SNR dataset to use in evaluating the model and characterizing the physiological responses Modeling Results We tested a simplified model for the BOLD response based on the approximation that the BOLD signal is proportional to the absolute change in deoxy-hemoglobin (dHb) and that dissolved O2 gas is always a small fraction of the arterial hemoglobin-bound O2 This model approximates the more complete models developed in previous work[1-3] In applying the model to the measured data we assumed 1) No change in CMRO2 with hypercapnia 2) Activation deltaR (fractional change in CMRO2) is the same in normoxia and hyperoxia and 3) hyperoxia itself induces an additive change in CMRO2 Assuming a value of alpha the exponent for dHb weighted blood volume change four model parameters were calculated from the four measured responses M a scaling factor (83) deltaR-activation (166) deltaR-hyperoxia (-38) and wO2 (a factor combining the change in arterial PO2 in a hyperoxia experiment with baseline CBF and CMRO2) From wO2 E0 was calculated with the assumption Hb=90 mM We then used the independent measurement of E0 using VSEAN as a constraint making it possible to estimate alpha as well (011) Conclusions A relatively simple BOLD signal model for quantifying CMRO2 during baseline and activation was evaluated in the context of


measuring ASLBOLD activation responses in both normoxia and hyperoxia Using VSEAN a separate measurement of baseline O2 extraction fraction gave an average value of 041 in these subjects in good agreement with literature values This value was used in the modeling of combined ASLBOLD data to allow a fit for the value of alpha (011) Because this model includes the effects of CMRO2 CBF and deltaPaO2 it is possible to fully characterize CMRO2 without special equipment to force specific blood gas changes even when there are associated changes in CBF and CMRO2 induced by hyperoxia itself (estimated to be -92 and -38 respectively in this study) References 1) Gautier and Hoge Neuroimage 601212 (2012) 2) Wise et al Neuroimage 83135 (2013) 3) Blockley et al Neuroimage 122105 (2015) 4) Guo and Wong MRM 681458 (2012) 5) Bulte et al NeuroImage 601 (2012) Acknowledgements NIH grant support NS036722 and NS085478


Allen L Liu Andreacutes J Garciacutea Georgia Institute of Technology Synthetic polyethylene glycol (PEG) hydrogel microparticles (microgels) encapsulating bovine serum albumin (BSA) are synthesized A microfluidic synthesis platform is employed affording good control over particle diameter and monodispersity BSA is introduced into the aqueous PEG flow channel prior to droplet formation and microgel crosslinking The BSA serves as an affinity-based macromolecule to better modulate release of a diffusion-loaded drug Release of a fluorescent model drug loaded into our PEG microgels is investigated in vitro



Will Long Dongwoon Hyun Stephen Rosenzweig Gregg E Trahey Duke University Purpose Short-lag spatial coherence (SLSC) imaging is an ultrasound beamforming method which forms images using the coherence of backscattered echoes SLSC has been shown to significantly improve image quality over conventional B-mode particularly in difficult-to-image patients exhibiting high levels of clutter Previous studies have demonstrated improved visualization of a variety of clinically relevant structures however such studies have been limited to analyses of single images Given the real-time nature of ultrasonic imaging clinical translation of SLSC requires evaluation of its temporal stability and real-time performance This study extends previous work to implement real-time SLSC imaging on the Siemens SC2000 clinical scanner Development of this framework aims to provide a means to assess the feasibility and clinical utility of real-time ultrasound coherence imaging Methods An SC2000 scanner is modified to acquire channel data and bypass internal processing for software beamformation Due to bandwidth limitations channel data is collected using synthetic receive sequencing in which transmit firings are repeated to sequentially acquire echo data from each channel To satisfy real-time requirements SC2000 parallel receive capabilities are leveraged to acquire multiple channels in parallel Subaperture beamforming in hardware is furthermore used to reduce channel data throughput Images are beamformed on a pixel-by-pixel basis via GPU processing Average spatial correlations between closely spaced channels are calculated to form each pixel in SLSC B-mode pixels are found by taking the log-compressed magnitude of summed channel IQ data Following beamformation images are routed from the GPU to the scanner back-end for display Results Real-time SLSC was successfully implemented with the Siemens 6C1 curvilinear array Using this framework channel data can be acquired with 35 MHz sampling and 161 parallel receive B-mode and SLSC images (171 lines at 9 cm depth) are processed and displayed with frame rates ranging from 10 to 38 fps for subapertures of 3 to 12 elements respectively Acquisitions from phantom and in vivo fetal scans demonstrate the systemrsquos real-time capabilities In low SNR conditions videos show improved contrast and CNR in SLSC over B-mode consistent with previous findings Conclusion Real-time coherence imaging was implemented on a clinical ultrasound scanner Channel acquisition and GPU beamforming enable real-time display of B-mode and SLSC images at frame rates of up to 38 fps Ultimately clinical evaluation of such a system will provide valuable insight into the feasibility and utility of real-time SLSC imaging



Andrew J Loza Sarita Koride Gregory V Schimizzi Bo Li et al Washington University in St Louis School of Medicine Purpose Collective migration of cells underlies embryonic development tissue regeneration and tumor invasion Despite this widespread importance there is still an incomplete understanding of the physical and biological mechanisms that allow multiple cells to organize their motion and furthermore how these properties shape the specific types of collective migration that emerge Using iterative hypothesis testing between simulation and experiment we track the motion of thousands of cells to determine how the fundamental properties of cell density adhesion and actomyosin contractility combine to produce collective migration Methods In this project we combine mathematical simulation cell culture and in-vivo approaches Time-lapse imaging was performed on large regions of confluent MCF10A monolayers spanning a range of cell densities Stable cell lines with altered adhesion and contractility were developed using lentiviral transduction Simulations were carried out using a vertex model of cell migration In vivo tests were performed on the developing drosophila follicular epithelium through 3D confocal time-lapse microscopy Results We find that adhesion competent cells undergo an initial paradoxical decrease in organization with increasing density followed by an increase in organization at the highest densities This trend reflects two processes First the high degree of organization at low density is produced by regulated actomyosin contractility Enhancing or diminishing actomyosin contractility or uncoupling cells through by reducing cell-cell adhesion reduces organization Second the organization that appears at high density arises through adhesion and contractility independent mechanisms Furthermore these two mechanisms of organization produce collectives with distinct patterns Contractility mediated collective migration produces broad collective groups with cells moving in line with neighbors to either side Packing mediated collective migration results in streaming patterns with cells following those in front and sliding past neighbors on either side We test these predictions in-vivo using the drosophila follicular epithelium a population of cells that undergoes a highly organized motion during egg development providing insights into the initiation and maintenance of motion during this process Conclusions This work demonstrates how commonly altered cellular properties can prime groups of cells to adopt migration patterns that may be harnessed in health or exploited in disease High cell density and low cell-cell adhesion as might be seen in cancer transforms groups from broad collectives to small narrow streams potentially increasing invasive ability Diminishing cell density as might occur at a wound front leads to large broad collectives with a distinct leader-follower structure that may accelerate wound healing


62 Bioactivity and Adipogenic Potential of a Composite Adipose-Derived Hydrogel Scaffold

for Soft Tissue Reconstruction

Christopher Mahoney MS Malik Snowden J Peter Rubin MD FACS Kacey G Marra PhD University of Pittsburgh Introduction Soft tissue reconstruction for the repair of congenital deformities or defects from tumor resectionstrauma often require adequate replacement of adipose tissue Standards of care include vascularized flaps or prosthetic implants consisting of silicone or saline Although tissue flaps can have favorable results complications may lead to flap failure infections pulmonary embolisms and morbidity of the donor site Autologous fat grafting using lipoaspirate is minimally invasive in reconstructive surgery but results are unpredictable due to resorption up to 10 volume retention These limitations serve as motivation for developing therapies to regenerate adipose tissue within the tissue engineering field Materials and Methods Abdomen whole fat was donated from a non-diabetic female (age 41 BMI 263) undergoing elective cosmetic surgery at the University of Pittsburgh Medical Center The decellularization process includes four main phases consisting of alcohol rinses delipidization and disinfection of the adipose matrix After processing the matrix was snap frozen using liquid nitrogen and then lyophilized A Mini Wiley Mill breaks down the lyophilized matrix into a powder for pepsin digest and hydrogel formation PLGA (5050) was used as the base polymer to encapsulate fluorescent dexamethasone in microscopheres using a single emulsion mixing technique Adipose-derived stems cells (ASCs) were acquired using an isolation protocol on abdominal fat donated from a non-diabetic female (age 38 BMI 248) undergoing elective cosmetic surgery Adipocyte quantification of ASCs study was conducted in a 12-well tissue culture plate along with Transwell tissue culture inserts to suspend the composite hydrogel above the cells in culture medium The following culture conditions were used for comparison cells with adipogenic medium cells + composite hydrogel with adipogenic medium cells + composite hydrogel without adipogenic medium (maintenance medium) and cells in maintenance medium (n=3) Cells were kept incubated at 37 degC and 5 CO2 At day 7 and 14 mature adipocytes were stained using the AdipoRedtrade Reagent Assay Results and Discussion Immunohistochemistry of matrix sections show that endogenous proteins were retained after the decellularization process SEM images of the lyophilized hydrogel indicates porosity throughout the structure As expected higher concentrations of MS in hydrogel displayed a lower presence of porosity which may generate challenges for progenitor adipocytes migration into the scaffold The 14-day differentiation study demonstrated higher amounts of adipogenesis in groups containing hydrogel and hydrogel with microspheres when compared to the positive control of ASCs alone It is also important to note that adding the hydrogel to ASCs in maintenance medium resulted increased differentiation compared to the ASC in maintenance medium Conclusion The objective of this research project is to develop a composite hydrogel scaffold from discarded human adipose tissue for an enhanced adipogenic effect in the form of microspheres containing dexamethasone for the application of soft tissue engineering The decellularization process has been found to be a reproducible process with consistent material production These bioactivity studies allowed for further characterization of the


composite hydrogel A 14-day differentiation study confirmed the scaffoldrsquos potential to increase proliferation and differentiation of adipose stem cells into adipocytes Overall the results warrant further investigation of the composite and its possible use in the regeneration of soft tissue


Nicholas J Matiasz William Hsu Alcino J Silva Wei Wang et al UCLA Purpose Biomedical researchers perform experiments to identify causal mechanisms Their success depends on the quality of the experimentsrsquo designs and the resultsrsquo interpretations However the model space for causal mechanisms is so large that it is unreasonable to expect researchers to consider all possible causal interpretations of the evidence in the literature A causal system with only seven variables mdash for example one showing how EGFR mutation affects contrast enhancement in T1-weighted MRI of gliomas mdash can be represented by over one billion possible causal graphs To explore this vast model space exhaustively researchers need the computational power of machines however as long as researchers remain ldquoin the looprdquo of the scientific method they also need to explore this model space using a framework whose semantics and epistemics they recognize Methods Using a distilled taxonomy of experiments and evidence we operationalized the strategies biologists use to identify causal mechanisms and expressed these strategies as the research map framework A research map is a graphical representation of causal assertions and the evidence for these assertions it integrates findings from multiple studies according to empirical principles in science consistency and convergence We have started to develop a complementary medicine map framework tailored to evidence in clinical trial articles Whereas research maps can inform basic scientistsrsquo experiment planning medicine maps can inform physiciansrsquo treatment of patients We are also exploring how these representations can be used to specify constraints on traditional causal models (eg causal graphs) We are using state-of-the-art satisfiability solvers to process these constraints to find all causal interpretations of available evidence thus informing the process of experiment planning Results We implemented this framework in ResearchMaps a web application with over 400 registered users across four continents ResearchMaps allows users to create and visualize research maps for published articles as well as query an integrated global map of all entries in the database We have also started to develop MedicineMaps which implements the complementary medicine map framework The growing databases of these applications are providing data with which to evaluate our constraint-based experiment-planning approach Conclusion Work in causal discovery is yielding robust formalisms for modeling causality Our frameworks offer semantically rich representations for encoding causal information that can be used to plan experiments and define traditional causal models These ldquometa-scientificrdquo tools can facilitate the scientific method by guiding biologistsrsquo efforts to obtain new evidence while formalizing the evidence already published


64 Design and Mechanical Testing of a Novel Magnesium Based Suture Anchor for Soft

Tissue Fixation

Jonquil R Mau Kwang E Kim Antonio Pastrone Dhir Patwa et al University of Pittsburgh Purpose Metallic and polymeric suture anchors have been used successfully for soft tissue fixation to bone (ie rotator cuff repair) However there are advantages and disadvantages of each of these biomaterials Titanium anchors could migrate and loosen as well as interfere with magnetic resonance imaging Complications with polymeric suture anchors include osteolysis and breakage during insertion Thus we aim to develop a metallic suture anchor using Mg-based alloys which is biodegradable has the desirable mechanical properties and could promote bone remodeling Methods The finite element method was used to determine the optimal threading for a Mg-based suture anchor (65 mm x 165 mm) A parametric analysis including thread pitch of 20 mm 25 mm 30 mm and thread depth of 04 mm 07 mm and 10 mm was conducted A simulation of suture anchor pullout from polyurethane foam was conducted for each combination of design parameters The design combination with the lowest von Mises stress was selected as the optimal design and manufactured Then the suture anchor underwent experimental pullout from polyurethane foam by an applied uniaxial load and the ultimate load and ultimate elongation were recorded Polymeric suture anchor served as the control Results From the parametric analysis the thread pitch of 30 mm and thread depth of 10 mm were found to be optimal From the mechanical test the stiffness ultimate load and ultimate elongation were found to be 185 plusmn 13 Nmm 379 plusmn 34 N and 24 plusmn 02 mm respectively for the Mg-based suture anchor and 107 plusmn 13 Nmm 210 plusmn 13 N and 19 plusmn 02 mm respectively for the polymer suture anchor The stiffness ultimate load and ultimate elongation were significantly different between the Mg-based and polymeric suture anchors (plt005) Conclusion With these promising results we believe it may be a superior alternative and are conducting an in-vivo animal study to evaluate its performance


65 ImmunoPET engineering design considerations for imaging cancer

immunotherapies

Aaron T Mayer Arutselvan Natarajan Sydney R Gordon Roy L Maute et al Stanford University Cancers have evolved to upregulate tolerogenic immune checkpoints such as PD-L1 to suppress and evade the immune system Although therapeutic antibodies targeted to block these immunosuppressive signaling pathways have exhibited remarkable success many patients still do not respond to treatment Imaging scientists are racing to validate biomarkers and develop tools to enable clinical response prediction patient stratification and therapeutic monitoring of cancer immunotherapies ImmunoPET offers the potential means to noninvasively assess dynamic immune checkpoint expression and the complex pharmacokinetics of antibody based drugs Unfortunately antibodies as imaging agents pose unique challenges including long blood circulation half-lives and high non-specific background The engineering of small high-affinity protein binders can potentially overcome these limitations and provide an accurate means to assess biomarkers for clinical checkpoint blockade We have developed high affinity consensus (HAC)-PD1 [size = 14 kDa kD = 100pM] the first engineered binder to be employed for human PD-L1 immune checkpoint imaging Here we sought to optimize ImmunoPET imaging of human PD-L1 expression in a pre-clinical model and assess the impacts of common radiotracer design parameters including chelate glycosylation and radiometal on tumor specific uptake and biodistribution Five HAC-PD1 radiotracer variants were developed and assessed by small animal PETCT studies NSG mice were inoculated with subcutaneous tumors engineered to either be constitutively positive (CT26 hPD-L1) or negative (ΔmPD-L1 CT26) for human PD-L1 expression and imaged with 20-60 microCi (~10 microg) of each HAC-PD1 radiotracer variant (3-6 micegroup) Of the design parameters tested aglycosylating the radiotracer resulted in the greatest improvement in image quality showing significantly reduced nonspecific signal The Cu64 variants accurately visualized PD-L1 expression with Cu64-NOTA-HACA-PD1 exhibiting the highest tumor specific uptake [hPD-L1+ tumor 23plusmn01 IDg hPD-L1- tumor 09plusmn03 IDg] and lowest background Ga68 variants which are more amenable to widespread clinical access showed favorable biodistribution profiles including Ga68-DOTA-HACA-PD1 which had the highest observed target tumor to background ratios for muscle [152x] lungs [63x] spleen [52x] pancreas [78x] small intestine [92x] large intestine [52x] bone [68x] and brain [682x] The tracers primarily underwent renal clearance Notably all HAC-PD1 radiotracer variants enabled much earlier detection of human PD-L1 expression (1h post injection) than previously reported radiolabeled antibodies (gt 24h post injection) This work provides a template for assessing ImmunoPET tracer design parameters and strongly supports the translation of small engineered protein radiotracers for imaging human immune checkpoints


66 Simple Scalable Proteomic Imaging for High-Dimensional Profiling of Intact Systems

Evan Murray Jae Hun Cho Daniel Goodwin Taeyun Ku et al MIT Measuring diverse molecular and structural traits over multiple length scales remains a major challenge in biology For decades two-dimensional molecular phenotyping techniques have been utilized for investigating tissue samples These techniques ensure similar reaction conditions by sectioning and limiting the length scale through which reactive moleculesnotmdashsuch as fixatives molecular probes and antibodiesmdashneed to diffuse Clearing techniques such as CLARITY are able to preserve the three-dimensional spatial arrangement of endogenous molecules and enable fluorescence imaging of intact biological systems (Chung et al Nature 2013) However slow diffusion of reactive molecules and molecular probes over system-wide length scales can cause uneven fixation and staining respectively Here we introduce a simple method for the scalable high-dimensional phenotyping of animal tissues and human clinical samples This method termed SWITCH synchronizes tissue fixation across the entire system to uniformly secure the tissue architecture and native biomolecules The preserved samples are robust to heat and chemical treatment and can be subjected to multiple rounds (gt20) of relabeling We have performed 22 rounds of labeling of a single tissue in combination with precise image co-registration By attenuating reaction kinetics SWITCH can also be applied to labeling reactions to improve probe penetration depth and overall staining uniformity With SWITCH we performed combinatorial protein expression profiling in the human cortex as well as examined the geometric structure of fiber pathways within mouse brains SWITCH enables the extraction of high-dimensional protein expression information and may expedite our understanding of biological systems over multiple levels


67 TOWARDS MULTIPLEX PROFILING AND CONTRAST ENHANCED RADIONUCLIDE

IMAGING OF BREAST CANCER

Michael A McDonald MD PhD Benjamin MW Tsui PhD Jingyan Xu PhD Johns Hopkins Medical Institutions PURPOSE Multiplex profiling of the molecular needs of breast cancer (metabolism perfusion angiogenesis hypoxia pH apoptosis cell proliferation receptor status and signaling pathways) can facilitate early cancer detection and improve specificity relative to the current practice of imaging with single nonspecific agents Radionuclide multiplexing has potential for early adoption and can bridge recent achievements in metabolomicsproteomics with precision medicine The combination of energy-resolved image processing methods with single photon counting detector technology can facilitate multiplexing and also permit contrast-enhanced radionuclide imaging potentially leading to both decreased radiation dose and decreased contrast agent dose Our current research involves 1) multiplexing radionuclides at ultralow radiation dose and 2) development of contrast-enhanced radionuclide imaging methods including Compton scatter-based imaging and dynamic contrast enhancement of scatter for improved sensitivity of breast cancer detection METHODS Sequential andor simultaneous Tc99m In111 and I123 phantom imaging studies were conducted in small animal- and clinical SPECT scanners Energy spectra and contrast-enhanced images were acquired demonstrating attenuation of I123 by iodine- and gadolinium-based CT and MRI contrast agents as well as by Fe Pd Ag and Bi particulates Simulated nuclear mammograms from a 4-D anthropomorphic breast phantom were acquired on NaI(TI) scinitillator (Dilon 6800 Dilon Technologies Newport News VA) and CZT solid-state detector (LumaGEM 3200S Gamma Medica Northridge CA) modeled commercial breast imaging systems using analytical and Monte Carlo methods (GATE SimSet) RESULTS Multiplexing of radionuclides using scintillation-based detectors is shown to be degraded by poor energy resolution and downscatter Contrast agent detection at ultralow dose (50 uCi I123) through breast tissue equivalent material is demonstrated in a clinical SPECT scanner Subtraction imaging shows potential for imaging at sub-mM contrast agent concentration Similar analysis using simulated CZT-based detectors with higher energy resolution show significant improvement in resolving multiple energy peaks for Tc99m In111 and I1213 Subtraction images acquired before during and after contrast agent administration demonstrate the possibility of tumor localization using dynamic contrast and scatter enhancement techniques CONCLUSION Preliminary results demonstrate the advantages of utilizing energy discriminating detectors for radionuclide multiplexing and contrastscatter enhancement including dynamic enhancement Simulated breast tumor imaging is being used for the development and validation of novel dual- and triple energy constrained expectation maximization based image reconstruction techniques On-going studies involve further improvement in sensitivity and specificity of breast tumor detection via development of a novel dual-modality breast imaging device incorporating CZT-based single photon counting detector technology for co-registered X-ray spectral- and molecular tomosynthesis


68 Value of intra-tumoral metabolic heterogeneity and quantitative 18F-FDG

PETCT parameters to predict prognosis in patients with HPV-positive primary

oropharyngeal squamous cell carcinoma

Esther Mena Mehdi Taghipour Sara Sheikhbahaei Abhinav K Jha et al Johns Hopkins Objective To evaluate the impact of intra-tumoral metabolic heterogeneity and quantitative FDG-PET imaging parameters for predicting patient outcomes in primary oropharyngeal squamous cell cancer (OPSCC) METHODS This is an IRB-approved HIPPA-compliant retrospective study investigating 105 patients (mean age 58plusmn97 yo) HPV-positive OPSCC Maximum and peak standardized uptake value (SUVmax SUVpeak) total metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were measured for each primary head and neck tumor and when available for metastatic lymph nodes and distant sites Intra-tumoral metabolic heterogeneity of the primary tumor was calculated as the area under a cumulative SUV-volume Histograms curve (AUC-CSH) The median follow-up time was 354 months (range 3-92 months) Outcome endpoint was event free survival (EFS) including recurrence-free and overall survival KaplanndashMeier survival plots and Cox regression analyses were performed RESULTS Of the 105 patients included in the study 19 patients relapsed and 11 of them deceased during the study period Univariate analysis demonstrated that optimum SUVmax (p=0006 HR=58 95CI 16-205) SUVpeak (p=0025 HR 33 95CI 11-94) total MTV (p=0004 HR= 31 95CI 11-90) and total TLG (p=0033 HR= 29 95CI 11-77) were associated with EFS and remained significant in multivariate analysis AUC-CSH indexes were associated with EFS using either PET gradient-based (p=0034) and 50-Threshold (p=0022) segmentation methods on multivariate analysis KaplanndashMeier survival analysis using optimum cut point of 167 SUVmax and 148 ml for total MTV were significant predictors of EFS By stratifying SUVmax and AUC-CSH index in three subgroups patients with higher degree of intratumoral heterogeneity and higher SUVmax values were associated with worse outcome (log-rank p=0026) Similarly patients with higher intra-tumoral heterogeneity tumors and higher MTV values had worse prognosis (log-rank p= 0022) CONCLUSION Quantitative FDG-PET parameters such as SUVmax and MTV and AUC-CHS indexes as well as an integrated subgroup stratification of FDG avidity total tumor burden and intra-tumoral heterogeneity appear to provide prognostic survival information for patients with primary OPSCC patients


69 Quantitative breast MRI radiomics for cancer risk assessment and the monitoring of

high-risk populations

Kayla R Mendel Hui Li Maryellen L Giger University of Chicago Breast density is routinely assessed qualitatively in screening mammography However it is challenging to quantitatively determine a 3D density from a 2D image such as a mammogram Furthermore dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) is used more frequently in the screening of high-risk populations Purpose The purpose of our study is to segment parenchyma and to quantitatively determine volumetric breast density on pre-contrast axial DCE-MRI images (ie non-contrast) using a semi-automated quantitative approach Methods In this study we retroactively examined 3D DCE-MRI images taken for breast cancer screening of a high-risk population We analyzed 66 cases with ages between 28 and 76 (mean 488 standard deviation 108) DCE-MRIs were obtained on a Philips 30 T scanner Our semi-automated DCE-MRI algorithm includes (a) segmentation of breast tissue from non-breast tissue using fuzzy c-means clustering (b) separation of dense and fatty tissues using Otsursquos method and (c) calculation of volumetric density as the ratio of dense voxels to total breast voxels Results We examined the relationship between pre-contrast DCE-MRI density and clinical BI-RADS density obtained from radiology reports and obtained a statistically significant correlation [Spearman -value of 066 (p lt 00001)] Conclusion We observed a significant correlation between pre-contrast DCE-MRI density and radiologist-assigned BI-RADS density Therefore we believe that pre-contrast DCE-MRI breast segmentation could be useful in future feature assessment such as texture analysis and DCE contrast enhancement assessment We conclude that pre-contrast DCE-MRI images can be used to obtain a clinically relevant measure of breast density Our method within precision medicine may be useful for monitoring high-risk populations



Manuel Morales Curtis Thorne Steven Altschuler Lani Wu Harvard-MIT Health Sciences amp Technology Purpose It is important to understand the preventable and treatable causes of dementia Evidence is accumulating to suggest that cardiovascular disease (CVD) risk factors may be instrumental in the development of dementia The objective of the present study is to elucidate the relationship between specific CVD risk factors and dementia Two approaches will be taken to investigate the relationship between CVD risk factors and dementia (1) examine the effects of CVD on resting-state fMRI brain networks in patients with mild cognitive impairment (MCI) and (2) identify the relationship between microinfarcts and MCI by assessing the possible pathophysiological causes behind microinfarcts Methods To validate our network modelling approach network modelling of resting-state fMRI time series data was conducted in ε4 variant of the APOE allele associated with Alzheimerrsquos disease as well as non-carriers using independent component analysis (ICA) to categorize the various resting-state networks and identify population differences Future cohorts will include MCI patients with and without cardiovascular risk factors Results Full correlation resting-state network matrices were calculated using ICA network modelling The edge strengths of these network matrices were used in a machine learning algorithm and group differences were found Interpretation of group differences was problematic due to the high sensitivity of the network matrices to head motion cardiac and breathing cycles and scanner artefacts Conclusions Motion correction methods of head motion cardiac and breathing cycles will have to be developed to improve the performance of the ICA network modelling


71 Image Reconstruction Techniques for a Portable Head-only 15 T MRI System

Michael Mullen Jinjin Zhang Albert Jang Djaudat Idiyatullin et al University of Minnesota Purpose To develop a magnetic resonance imaging (MRI) technique and an image reconstruction algorithm for studying the human brain with a small head-only magnet that produces a non-uniform magnetic field The MRI signals to be reconstructed are obtained using either 1) a spatiotemporally-dependent RF pulse (see [1]) or 2) a conventional RF pulse but with an array of coils driving a ldquoshimmedrdquo volume over the brain Methods To simulate the behavior of magnetization for various pulses and magnetic field topologies an empirical description known as the Bloch equations were used What is known as the encoding matrix which describes the magnetization at a given point over time is numerically determined in this manner The signal is then related to a summation over this encoding matrix To overcome complications arising from the non-uniform magnetic field the two aforementioned methods of obtaining a signal were used In case 1 the RF pulse compensates for the magnetic field inhomogeneity while in case 2 the shimmed volume possesses a nearly uniform magnetic field due to coil array One method of reconstruction is the Maximum Likelihood Estimation (MLE) which compared the signal corresponding to an approximate image to that of the simulated signal A likelihood function is defined in such a way as to be maximized when the difference between the two goes to zero Another method of reconstruction took advantage of the sparsity of the encoding matrix in the spatial Fourier space Results For both methods of inhomogeneity compensation in a small magnet the reconstruction techniques discussed successfully constructed images showing the viability of image acquisition in such an MRI technique The latter reconstruction algorithm proved to be more reliable in terms of efficiency and accuracy Note these results have only been verified on simulation results and phantoms not yet on true brain scans However the results up to this point are promising and are indicative that this approach should work in this regime as well Conclusions In summary this project moves forward in demonstrating the feasibility of a portable head-only MRI system which can produce reliable brain images The ability to perform small-scale MRI will open exciting new possibilities for neuroscientists to study the brain and human behavior in a diverse range of conditions References [1] Jang A Kobayashi N Moeller S Vaughan J T Zhang J and Garwood M (2015) 2D Pulses using spatially dependent frequency sweeping Magn Reson Med doi 101002mrm25973 Funding NIH 2T32 EB008389 NIH R24MH105998 and NIH P41EB015894




Kazim H Narsinh Shang Gao Hongyan Xu Martin Marsala et al UC San Diego Introduction An unmet challenge to successful translation of stem cell therapies into patients is the ability to non-invasively monitor cellular behavior and movement following transplantation Imaging tools can potentially provide critical information regarding the homing engraftment and proliferation of the delivered cells MRI can track cells by direct labeling with iron-oxide nanoparticles or gadolinium chelates but these agents become diluted after mitotic cellular divisions thereby limiting long-term visualization and may fail to discriminate between living versus dead cells Genetically- engineered ferritin constructs can be used as MRI reporter genes to overcome these limitations (1) Upon cellular expression ferritin forms a superparamagnetic iron core that generates hypointensity in T2- and T2-weighted images Because the ferritin gene cam be stably passed to daughter cells long-term tracking studies of cellular therapeutics may be performed Here we report the use of a modified mitochondrial ferritin construct with improved MRI sensitivity over wild-type ferritins to monitor the engraftment and survival of human neural progenitor cells after their transplantation into rat striatum Materials and Methods We inserted an engineered human mitochondrial ferritin gene (2) into a lentiviral construct already containing green fluorescent protein (GFP) under a human ubiquitin promoter We then transduced human embryonic stem cell-derived neural progenitor cells (hESC-NPCs) with the lentiviral construct to generate hESC-NPC lines that stably expressed mtFt Twenty adult male athymic nude rats underwent stereotactic implantation of mtFt-expressing hESC-NPCs into their striata while nontransduced hESC-NPCs were stereotactically implanted into the contralateral striata as a control On day 7 14 28 90 and 180 after implantation in vivo MRI was performed at 117 T using a 3D gradient- recalled echo (GRE) sequence with TETR=7100 ms and 117 μm isotropic voxels Ex vivo imaging at 117 T was also performed Immunohistochemistry was performed on the fixed rat brain tissue using rabbit polyclonal antibody against mtFt mouse anti-nuclear proteinh-nuc antibody (anti-hNUMA) specific to a human antigen and goat anti-GFP antibody Results and Discussion After injection into rat brain cortex hESC-NPCs expressing mtFt were clearly detected as hypointense regions on T2- weighted GRE images The contralateral side demonstrated normal signal intensity Immunohistochemical analysis confirmed that the hypointense regions contained transplanted cells expressing GFP Truncated mtFt localized to the cytoplasm and loaded more iron than wild-type mtFt or human ferritin The ferritin-expressing cells identified by MRI were confirmed as hESC-NPCs by immunohistochemical staining for a human specific nuclear antigen This optimized MRI reporter gene has significant potential for long-term monitoring of the success of stem cell transplantation studies References 1 Genove G DeMarco U Xu H Goins WF Ahrens ET Nat Med 2005 (43)450ndash4 2 Iordanova B Hitchens TK Robison CS Ahrens ET PLoS One 2013 8(8)e72720



Dan Nguyen Qihui Lyu Dan Ruan Daniel OConnor et al UCLA Physics and Biology in Medicine Graduate Program Purpose Volumetric modulated arc therapy (VMAT) is a widely employed radiotherapy technique showing comparable dosimetry to static beam intensity modulated radiation therapy (IMRT) with reduced monitor units and treatment time However the current VMAT optimization has various greedy heuristics employed for an empirical solution which jeopardizes plan consistency and quality We introduce a novel direct aperture optimization method for VMAT to overcome these limitations Methods The comprehensive VMAT (comVMAT) planning was formulated as an optimization problem with an L2-norm fidelity term to penalize the difference between the optimized dose and the prescribed dose as well as an anisotropic total variation term to promote piecewise continuity in the fluence maps A level set function was used to describe the aperture shapes and the difference between aperture shapes at adjacent angles was penalized to control MLC motion range A proximal-class solver was adopted to solve the large scale optimization problem and an alternating minimization was implemented to solve the fluence and aperture shapes simultaneously Single arc comVMAT plans utilizing 180 beams with 2deg angular resolution were generated for a glioblastoma multiforme (GBM) case a lung (LNG) case and 2 head and neck casesmdashone with 3 PTVs (HampN3PTV) and one with 4 PTVs (HampN4PTV) The plans were compared against the clinical VMAT (clnVMAT) plans utilizing two overlapping coplanar arcs for treatment Results The optimization of the comVMAT plans had converged within 600 iterations comVMAT plans were able to consistently reduce the dose to all organs-at-risk (OARs) as compared to the clnVMAT plans On average comVMAT plans reduced the max and mean OAR dose by 659 and 745 respectively of the prescription dose Reductions in max dose and mean dose were as high as 145 Gy in the LNG case and 153 Gy in the HampN3PTV case PTV coverages measured by D95 D98 and D99 were within 025 of the prescription dose By comprehensively optimizing all beams the comVMAT optimizer gained the freedom to allow some select beams to deliver higher intensities yielding a dose distribution that resembles a static beam IMRT plan with beam orientation optimization Conclusions The novel non-greedy VMAT approach simultaneously optimizes all beams in an arc and then directly generates deliverable apertures The single arc VMAT approach thus fully utilizes the digital linacsrsquo capability in dose rate and gantry rotation speed modulation In practice the new single VMAT algorithm generates plans superior to existing VMAT algorithms utilizing two arcs


74 Development of Glutamate-Sensitive Chemical Exchange Saturation Transfer

Imaging at 7 Tesla for Application to Multiple Sclerosis

Kristin P OGrady Adrienne N Dula Bailey D Lyttle Benjamin N Conrad et al Vanderbilt University Institute of Imaging Science Purpose Glutamate is the principal excitatory neurotransmitter in the brain and dysfunctional glutamate regulation is implicated in the pathogenesis of chronic neurodegenerative processes In multiple sclerosis (MS) glutamate-mediated excitotoxicity leads to neuronal death and magnetic resonance spectroscopy studies have detected altered glutamate metabolism in MS and linked gray matter glutamate levels with cognitive impairment Pathology in gray matter is subtle and difficult to detect and there is a need for the development of imaging biomarkers that will enable detection of early molecular changes prediction of future cognitive impairment and evaluation of treatment response Recently glutamate-sensitive chemical exchange saturation transfer (GluCEST) has been explored and we extend the application of GluCEST at 7T in the brain for healthy controls and MS patients We hypothesize that the GluCEST signal will be altered in MS patients and we examine correlations with measures of cognitive impairment Methods A 2D multi-shot TFE sequence (factor=3 094 x 094 x 10 mm resolution) was applied in thirty-five healthy controls (ages 22-56) and 24 MS patients (ages 30-44) at 7T CEST data were acquired using a 425 T pulse train of ten 10 ms RF pulses (total saturation duration = 100 ms) at 49 frequency offsets between -50 and 50 ppm and at one offset far off resonance (=800 ppm) for reference A T1-weighted image was obtained for segmentation CEST data were corrected for B1 inhomogeneity and z-spectra were centered with a B0 correction derived from a Lorentzian fit Several methodologies for quantifying GluCEST were compared including [Msat(-)-Msat()] Msat(-) computed at = 30 ppm where an exchange effect between glutamate amine protons and bulk water has been reported Correlations between GluCEST and cognitive function were investigated in MS patients Results and Conclusions Preliminary analysis of GluCEST data was performed on a subset of healthy (n=7) and MS (n=6) subjects (age range of 30-37) The mean GluCEST contrast for gray matter in each MS subject correlates significantly with the Global Deterioration Score (overview of cognitive function) with a Spearmanrsquos correlation coefficient of 0912 In ongoing work we will further optimize our approach for processing and quantifying the GluCEST data and will examine correlations with additional cognitive measures using our complete set of subjects Acknowledgments NIHNIBIB K01EB009120 KL2 TR 000446 CTSA Grant (RR024975) DoD W81XWH-13-0073 NIHNIBIB 5T32EB001628-14


75 Molecular Recognition of Spermine by LnDOTP5- Toward a Noninvasive Staging of

Prostate Cancer

Abiola O Olatunde Taylor L Fuss Philip Z Sun Leo L Cheng et al Massachusetts General Hospital Purpose Spermine is an important biomarker of prostate health and its concentration is inversely correlated with the presence of cancer In vivo quantification of spermine by MR spectroscopy is limited because the chemical shift of the spermine protons (ca 18 ppm) overlap with signals from other metabolites in this region LnDOTP5- a stable anionic lanthanide (Ln(III)) macrocyclic complex forms a sufficiently stable ternary complex with the positively charged spermine The ion-pair interaction results in the selective shift of the spermine MR resonances with the magnitude and direction of the shift dependent on the pseudocontact contribution of the lanthanide Here we report the affinity of different LnDOTP5- complexes for spermine and the effect of complex formation on spermine MR resonances in D2O serum solutions and intact human prostate tissue Method Intact Tissue Frozen tissue was scanned using high-resolution magic angle spinning (HRMAS) MRS on a Bruker AVANCE spectrometer operating at 600 MHz (141T) A 4 mm zirconia rotor with Kel-F inserts created a 10 μl sample space for tissue samples and D2O was added for field locking After an initial scan 5 μl LnDOTP5- was added to one rotor and 5 μl of D2O was added to another rotor as control Both rotors were kept overnight at 4ordmC and then rescanned the next day Spectra were recorded at 4ordmC with the spectrometer frequency set on the water resonance Spectra were measured with HRMAS with a spin rate of 3600Hz (plusmn10Hz) and analyzed using an in-house developed MatLab based program D2O and Serum Samples Prepared samples of 10 mM spermine and 10 mM citrate in D2O or serum were analyzed with MRS on the same Bruker spectrometer D2O was added to serum samples for field locking Eu(III) Yb(III) and Tm(III) complexes were evaluated at 4ordmC and 37ordmC Results and Conclusion Spermine forms stable 11 complexes with LnDOTP5- (K gt 10^-5 M) and the lanthanide-induced shift can be large with shifts up to 100 ppm for the spermine-TmDOTP5- The results of experiments exploring the effects of ions such as Zn(II) Ca(II) and phosphate as well as the observed changes in citrate and lactate in tissue has enhanced our understanding of the ion-pair interactions of spermine-LnDOTP5- complex in physiological conditions In the presence of competing anions (phosphate lactate and citrate) the shift of spermine-LnDOTP5- complex is reduced due to the spermine-metabolite interactions in serum and D2O The ion-pair interaction provides a means for distinguishing metabolite-metabolite interactions in tissue


76 Functional Network Reorganization of Multimodal Integration Regions in Blind

Children

Laura Ortiz-Teran Ibai Diez Tomaacutes Ortiz David L Perez et al Massachusetts General Hospital PURPOSE Cross-modal neuroplasticity has been proposed as a mechanism by which individuals without sight recruit visual-related cortices to process sensory information from other perceptual modalities We have previously observed in adults with blindness compared to healthy subjects that multimodal integration regions are prominent sites of neuroplastic reorganization This study uses network-based functional connectivity analyses to investigate network connectivity differences in blind children compared to controls We hypothesize that in addition to connectivity differences in visual and other sensory cortices blind subjects show functional connectivity changes that centralize within multimodal integration regions MATERIAL AND METHODS We studied 13 children with blindness (N=9 boys) ages between 7-12 years old (mean=96plusmn13) and 15 sighted controls (N=6 boys) (mean=103plusmn14) Subjects were scanned on a 3T MRI scanner acquiring BOLD and high-resolution 3D T1WI Following pre-preprocessing whole brain weighted-degree functional connectivity and step-wise connectivity graph theory analyses were applied RESULTS In weighted-degree analyses corrected for multiple comparisons blind children exhibited enhanced connectivity in bilateral ventral premotor middle cingulate cortexsupplementary motor area and right temporal parietal junction Several of these connectivity changes positively correlated with age Using step-wise connectivity analysis blind children compared to controls demonstrated increased functional streams along certain multimodal integration regions such as the anterior insula and temporoparietal junction bilaterally and right lateral occipital cortex CONCLUSIONS Blind children show increased functional connectivity in multimodal integration areas compared to controls and older children showed greater increases within these regions


77 Clinically relevant factors affecting catheter motion in Intracardiac

Echocardiography (ICE) Acoustic Radiation Force Impulse (ARFI) Imaging

Jenna K Osborn Young-Joong Kim Stephanie Eyerly Patrick D Wolf Duke University Purpose Acoustic Radiation Force Impulse (ARFI) Imaging is an ultrasound-based imaging technique that utilizes a high intensity acoustic wave to remotely displace tissue with a momentum transfer The displacement of the tissue can be tracked using conventional ultrasound and can be used to visualize variations in tissue elastic properties In intracardiac echocardiography (ICE) catheter ARFI imaging momentum is also transferred to the catheter causing a kickback motion The motion could potentially degrade the integrity of the induced displacement measurements as all are made relative to the transducer To address these issues in a clinical setting the relevant factors were examined Methods A 3 kPa homogeneous elastography phantom was imaged using an 8F SoundStartrade ICE catheter with custom ARFI imaging sequence (30 pushes 15 mm focus 6 MHz transmit frequency) on a Siemens SC2000trade scanner All pushes were directed toward the center line and were temporally equivalent to current clinical sequences used in other protocols The fulcrum length the distance from a mechanically fixed point to the tip of the catheter was varied from 30 mm to 50 mm Different mechanical steering configurations in the same dimension as the kickback motion were tested for possible improvements The kickback displacements were measured 10 mm from the focal point to isolate the kickback motion from the induced ARFI displacements The sequential pushes were aligned in time to evaluate the accumulation of the kickback over the sequence Results and Conclusions For fulcrum lengths greater than 40 mm mechanical oscillations were seen with different frequencies and amplitudes depending on the fulcrum length The mechanical steering did not significantly improve the accumulated displacements over the angles tested For the imaging parameters tested kickback motion is 2-3 μm per push recovering to a net 04 μm per push by the end of tracking This motion could be a source of bias in ICE catheter ARFI imaging and a solution is desired


78 Kinetic Analysis of [18F](2S4R)4-Fluoroglutamine In Mouse Models of Breast

Cancer with Glutaminase Inhibition

Austin Pantel Rong Zhou Hsiaoju Lee Shihong Li et al Hospital of the University of Pennsylvania PURPOSE Alterations of cellular metabolism in malignancy represent opportunities for nuclear probe development As an alternate nutrient source to glucose tumors may utilize glutamine the most abundant amino acid in blood Inhibitors of glutamine metabolism represent potential therapeutic targets Inhibitors of glutaminase the enzyme responsible for the conversion of glutamine to glutamate are in early clinical trials [18F](2S4R)4-Fluoroglutamine ([18F]Fluoroglutamine) an analog of glutamine for PET imaging has been evaluated in pre-clinical studies Based on cellular data we hypothesize that tumors with elevated glutaminolysis (triple-negative breast cancer (TNBC) tumors) which have lower intracellular glutamine pool size would have lower [18F]Fluoroglutamine distribution volumes compared to tumors with low glutaminase activity (MCF-7 tumors) Additionally glutaminase inhibition would increase the distribution volume for [18F]Fluoroglutamine METHODS TNBC cells (HCC1806) were subcutaneously inoculated in the flank of athymic nunu mice After adequate growth imaging was performed on a dedicated small animal PET scanner [18F]Fluoroglutamine was injected into the lateral tail vein at the start of dynamic image acquisition and images were obtained for 60 minutes at 5 minutesframe A glutaminase inhibitor was then administered per protocol while a control mouse received a saline-based vehicle solution Mice were then reimaged using the same protocol A mouse inoculated with MCF-7 cells was also imaged Image analysis was performed using AMIDE data analysis software Kinetic analysis was performed using PMOD RESULTS Logan plot analysis revealed linearity from which distribution volumes of [18F]Fluoroglutamine were estimated Preliminary Logan plot analysis of the two TNBC tumor-bearing mice demonstrated an increased volume of distribution post-glutaminase inhibition with individual estimates of ~10 and nearly 50 change No increase in volume of distribution was seen in the vehicle-treated TNBC mouse The untreated mouse with the MCF-7 tumor demonstrated a volume of distribution at least 50 larger than the TNBC untreated tumors CONCLUSION Preliminary kinetic analysis identified increased volume of distribution of [18F]Fluoroglutamine post glutaminase inhibition in a mouse model of breast cancer with elevated glutaminase activity Furthermore the volume of distribution of this radiotracer was greater in tumors with low glutaminase activity compared to tumors with elevated glutaminase activity Kinetic modeling of [18F]Fluoroglutamine represents a promising tool to measure the impact of glutaminase-directed therapy


79 Silicon nanowires as a platform for wireless optical modulation of neuronal

activity

Ramya Parameswaran Joao L Carvalho-de-Souza Ektor Acaron Ledesma Michael J Burke et al Biophysical Sciences University of Chicago The development of minimally invasive methods to modulate electrical activity in cellular systems with high spatiotemporal resolution has been a significant challenge for many years now Shapiro et al and Carvalho-de-Souza et al have recently demonstrated that IR light and gold nanoparticles can stimulate neurons photothermally Here we explore an inorganic platform that when interfaced with neurons can modulate neural activity via a photovoltaic effect We demonstrate that coaxial pin Silicon nanowires consist of both a radial p-n diode component and an axial Au-Si diode component caused by the diffusion of the gold nanoparticle catalyst along the nanowire side-walls during growth In culturing these nanowires with primary rat dorsal root ganglion cells we show that upon localized laser stimulation at the cell-nanowire interface they can efficiently induce action potentials in individual neurons These findings provide us with a novel method to optically modulate neuronal activity in a wireless manner and thus a potential therapeutic strategy for patients suffering from neurodegenerative diseases


80 Spatial Response of Double-Sided Strip High-Purity Germanium Detectors for SPECT

Imaging

Perea Rose Campbell Desmond L Shokouhi Sepideh Peterson Todd E Physics and Astronomy at Vanderbilt University Purpose Single Photon Emission Computed Tomography (SPECT) is a nuclear medicine imaging technique that allows mapping of the biological distribution of an injected radiotracer We are developing a dual-headed small-animal SPECT system using double-sided strip High-Purity Germanium (DSS HPGe) detectors HPGe provides superior energy resolution (lt1 FWHM at 140 keV) which allows for good scatter rejection and facilitates dual- or multi-isotope imaging The electrode strip configuration allows sub-strip positioning of events Reconstructed images in our prototype small-animal SPECT system exhibited artifacts which we attributed to a combination of mis-positioning of events near the strip edges and loss of events (due to charge sharing and multiple-strip events) The objective of this study is to develop and deploy advanced signal processing techniques to enhance the performance of our DSS HPGe detectors which will lead to improvements in the sensitivity spatial resolution and image contrast of our SPECT scanner Methods The detector used in this study consists of an HPGe crystal 90 mm in diameter with 16 x 16 orthogonal stripsThe strip widths are 475 mm with 025 mm gaps between strips The depth of interaction is estimated from the arrival time differences of the signals on the two sides of the detector The detector and readout were fabricated by PHDs Co in Knoxville TN To study the detector response and acquire data to develop methods to recover multi-strip events we have scanned a detector with a focused beam (~25x25 microm2 131 keV) at the Advanced Photon Source (APS Argonne National Lab) We obtained three different data types using the detector acquisition software list-mode data (fully shaped digitized binned into sub-pixels two-strip events only) raw data (fully shaped and digitized not binned all events) and waveform data Preliminary Results The preliminary data reveals efficiency losses that extend more than 100 micrometers beyond the gap region as well as variations in spatial resolution across the strip area using our current processing From the waveform data events show a clear signal on the collecting strip and fast transient signals induced on neighboring strips Future Work Our next steps are to perform a full detector scan at APS to develop distortion and efficiency correction techniques for improvement to our current position estimation method as well as explore advanced signal processing methods to further improve performance Improvements in event estimation should remove artifacts and lead to better contrast and sensitivity in SPECT images


81 Reversed Gradient-Spoiled Diffusion-Weighted Imaging in the Breast with PSIF

Stephanie L Perkins Bruce L Daniel Brian A Hargreaves Catherine J Moran Stanford University Purpose Breast MRI protocols including contrast-enhanced and non-contrast scans are routinely used to aid in the diagnosis of breast cancer Diffusion-weighted imaging (DWI) is a non-contrast scan that may aid in distinguishing between benign and malignant breast lesions when used as an adjunct to contrast-enhanced breast MRI PSIF is a reversed gradient-spoiled sequence with diffusion weighting that has been shown to increase SNR improve spatial resolution and reduce distortion in the breast relative to traditional DWI However known challenges of using PSIF in the breast include sensitivity to motion fat-water separation and decreased tissue-lesion contrast relative to DWI The goal of this work was an initial attempt to overcome these challenges Methods Sagittal PSIF scans were performed in a fat-water phantom and in volunteers on a GE Discovery MR750 3T scanner Imaging parameters were modified from typical DWI to fit scans within a breath-hold The amount of spoiling applied across the voxel was changed between scans to vary the diffusion weighting The amount of diffusion weighting was examined qualitatively by plotting the mean signal in fat water and lesion ROIs as a function of cycles of spoiling The effects of k-space ordering (sequential vs elliptical-centric) on motion artifacts that appear at higher cycles of spoiling were also analyzed A radiologist with breast MRI experience also provided an initial assessment of the images to give feedback on the motion artifacts fat-water separation and tissue-lesion contrast Results In the phantom the mean fat ROI signal remained constant as the cycles of spoiling was increased but the mean water ROI signal decreased In vivo motion artifacts at higher cycles of spoiling appeared to affect the fat-water separation and thus the mean signal in the ROIs Using elliptical-centric k-space ordering instead of sequential ordering removed motion artifacts seen in the phantom but not completely in vivo The effect of cycles of spoiling on tissue-lesion contrast was not consistent across subjects in vivo Conclusion The phantom results of decreased water ROI signal with increased cycles of spoiling provides motivation for continued investigation although parameter optimization taking into account motion artifacts and fat-water separation needs to be resolved Future work will include analyzing the effect of applying cycles of spoiling in different directions on the motion artifacts and fat-water separation and comparing image contrast between traditional DWI and PSIF scans to determine the cycles of spoiling necessary for adequate diffusion weighting


82 A Biomimetic Platform Reveals Novel Mechanisms for Regulation of Microvascular

Function via Hemodynamic Shear Stress

William J Polacheck Matthew L Kutys Christopher S Chen Harvard University Regulation of vascular permeability is critical to cardiovascular function and misregulation of vascular permeability contributes to a host of cardiovascular diseases Hemodynamic shear stress is a key determinant of vascular homeostasis and known to be a critical regulator of vascular permeability However the molecular mechanisms that regulate vascular permeability in response to shear stress remain poorly understood due to the lack of experimental systems that recapitulate hemodynamically controlled blood flow through an endothelial lumen surrounded by 3D ECM Here we introduce a microvasculature-on-chip model that leverages the physical and biochemical control of in vitro systems and integrates 3D ECM and vessel architecture to investigate the effects of shear stress on vascular barrier function in a precisely regulated physiologically relevant microenvironment We further implement the platform and CRISPR-based gene editing in primary cells and cell lines to identify novel mechanisms that govern shear-regulated vascular barrier function



Joao Prola Netto Csanad Varallyay Prakash Ambady Jenny Firkins et al Oregon Health and Science University Purpose Glioblastoma (GBM) is the most common infiltrative primary malignant brain tumor Magnetic resonance imaging (MRI) using gadolinium based contrast agents (GBCAs) is routinely used in the diagnosis and evaluation of therapeutic response DSC perfusion MRI has been tested in multiple studies and its value in brain tumors has been shown however due to certain limitations it is not used widely in the clinical practice Steady state (SS) imaging using ferumoxytol tries to overcome these limitations providing high resolution cerebral blood volume (CBV) maps The primary objective of the study will compare SS-CBV with DSC-CBV parametric maps using visualization variables Secondary objectives of the study are correlation with histology and immunohistology association of CBV with overall survival differentiation of progression from pseudoprogression and assessment of late ferumoxytol enhancement Methods This prospective imaging study was approved by the local institutional review board Subjects with suspected or confirmed diagnosis of GBM are eligible The subjects undergo 3 consecutive days of MRI scans first day with and without gadolinium second day with and without ferumoxytol and a third day with no contrast to study late ferumoxytol uptake Research scans are done at specific time points at various stages of disease After acquisition patient data is de-identified and post processing and analyses are done in a dedicated workstation Comparison between SS-CBV with DSC-CBV maps will be done using four visualization variables each using a 3 point scale Results 9 patients have been enrolled with 18 time points of scans 5 before surgery 5 after surgery and before chemoradiation therapy (CRT) 5 after CRT and 3 by the time of recurrence 5 patients are still being followed In all the patients the SS CBV maps were superior to DSC CBV maps in the visualization criteria (assessment of overlay accuracy with T1w post contrast scans confidence in identifying the lesion corresponding areas on CBV maps assessment of CBV in small lesions and separation of tumor from larger blood vessels) Conclusion This preliminary data shows the feasibility of the SS CBV maps with ferumoxytol in patients with GBM Initial analyses of the obtained maps showed superiority of SS CBV maps when compared to DSC CBV maps



Cyrus A Raji MD PhD UCSF Department of Radiology Preventive neuroradiology is a new concept supported by growing literature The main rationale of preventive neuroradiology is the application of multimodal brain imaging toward early and subclinical detection of brain disease and subsequent preventive actions through identification of modifiable risk factors An insightful example of this is in the area of age-related cognitive decline mild cognitive impairment and dementia with potentially modifiable risk factors such as obesity diet sleep hypertension diabetes depression supplementation smoking and physical activity In studying this link between lifestyle and cognitive decline brain imaging markers may be instrumental as quantitative measures or even indicators of early disease The purpose of this article is to provide an overview of the major studies reflecting how lifestyle factors affect the brain and cognition aging In this hot topics review we will specifically focus on obesity and physical activity



tetraplegia

Anisha Rastogi Brian A Murphy Frank R Willett William D Memberg et al Case Western Reserve University Department of Biomedical Engineering Background Intracortical brain computer interfaces (iBCIs) have emerged as a promising assistive technology for restoring hand grasping in individuals with tetraplegia To date most iBCIs intended for human use have utilized only kinematic information from the motor cortex However during natural hand grasping the motor cortex encodes a combination of kinematic and kinetic information Previous studies in nonhuman primates have investigated the feasibility of utilizing kinetic neural information identified during executed force production as control signals for iBCIs Here we further elucidate how force-related information is represented in the motor cortex in an individual with chronic tetraplegia Specifically we characterize the extent of neural modulation that occurs during observed imagined and attempted forces Methods Participant T8 of the BrainGate2 Clinical Trial (55-year-old male C4-level spinal cord injury) was asked to observe imagine and attempt producing four discrete force levels with the dominant hand Full broadband neural recordings were obtained from two 96-channel microelectrode arrays (Blackrock Microsystems Salt Lake City UT) in the dominant precentral gyrus We characterized the modulation of two time-varying features (spike firing rates high frequency spike powers) during force production These features were also used as inputs to a linear discriminant analysis (LDA) classifier to discriminate the observed imagined and attempted force levels offline Results amp Conclusions The number of neural features tuned to force production as well as offline discrimination performance was greatest during attempted force and least pronounced when force production was observed Additionally tuned features exhibited various temporal profiles with some tuned to the preparatory phase of force production others tuned to active force production and still others tuned to both phases These results suggest that force-related information is retained in motor cortex in individuals with tetraplegia and that it is feasible to incorporate cortical activity during attempted force production into iBCIs that restore hand grasping function


86 FEP-PDMS Hybrid Microfluidic Devices for Light-Sheet Microscopy

Stephanie Reynolds Thomas Levario Daniel Porto Yongmin Cho et al Georgia Institute of Technology Purpose Live model organisms such as Caenorhabditis elegans (C elegans) are often handled and imaged in a high-throughput manner using microfluidic devices Live imaging methods can include epifluorescence and confocal microscopy but these can exhibit significant photobleaching and phototoxicity Light-sheet microscopy (LSM) has recently been developed to limit the effects of photobleaching and phototoxicity LSM utilizes a water-immersion lens in order to create a refractive-index-matched imaging axis for biological specimens (nwater = 1333) However microfluidic devices cannot be used with LSM because typical devices are constructed with optically-incompatible materials including glass coverslips (nglass = 147) Furthermore the space between the two LSM objectives is rather small preventing the use of large glass coverslips within the chamber Thus the purpose of this work is to develop microfluidic devices that are appropriately sized and optically compatible with LSM Fluoroethylene propylene (FEP) sheets satisfy the refractive index requirements (nFEP = 1344) and can be easily cut to size However standard FEP has a very low surface energy and bonding with poly(dimethylsiloxane) (PDMS) is weak but corona-treated FEP (Type C or Type C20) has some adhesive properties making it ideal for this application Methods Corona-treated FEP (Type C) is treated with APTMS in DI water rinsed with DI water and dried with air Crosslinked PDMS is plasma treated for 1 minute and then placed on top of the corona-treated side of the FEP Device was placed on a hot plate and temperature was ramped from RT to 260degC A slight pressure was applied to secure the bond of FEP to PDMS Results While our procedure still needs to be optimized our preliminary results suggest that pressure-withstanding capabilities of the FEP-PDMS hybrid devices exceed 15 psi and are stable when submerged in water Further proof-of-concept studies are still needed Conclusion This FEP-PDMS device is a step toward integrating microfluidics with LSM for high-throughput imaging of C elegans and other model organisms



Spheroids

Daniel S Reynolds Kristie M Tevis Muhammad H Zaman Mark W Grinstaff Boston University Purpose Most in vitro tumor models fail to recapitulate the abnormal multicellular architecture of in vivo tumors or accurately predict in vivo cellular responses to therapeutics Here the purpose of this study was to assess the response of breast cancer cells to two front-line chemotherapies (paclitaxel and cisplatin) within an in vitro 3D collagen-embedded spheroid tumor model which reflects the multicellular architecture of in vivo tumors compared to a 3D collagen diffusely-embedded single-cell model and a 2D monolayer Furthermore because failure to completely eradicate the highly malignant cancer stem cell (CSC) subpopulation is thought to be a driver of cancer relapse we also investigated the presence of CSCs across the three in vitro models Methods The triple-negative breast cancer cell line MDA-MD-231 was used in this study For the 2D monolayer cells were cultured on tissue-treated polystyrene In the 3D diffusely-embedded model cells were embedded within 4 mgmL collagen gels at a seeding density of 105 cellsmL For the embedded spheroid model spheroids composed of 104 cells were formed following our published procedure and embedded in 4 mgmL collagen gels The treatment regimen for all models began 24 hours after initial seeding and consisted of 72 hours of drug exposuremdash10 ngmL for paclitaxel (Indena) and 15 microgmL for cisplatin (Sigma-Aldrich)mdashfollowed by removal of drug and an additional 72 hours of culture Viability following drug treatment was assessed using a colorimetric MTS cell proliferation assay (Sigma) and oxoplates (Precision Sensing) CSC content was quantified using three methods 1) ALDEFLUOR Stem Cell Identification Kit (Stem Cell Technologies) 2) Mammosphere Assay and 3) RT-qPCR analysis of two CSC-related genes (ALDH1A3 and SOX2) Results Viability measurements of the in vitro models revealed cells within the 2D monolayer condition to be the most sensitive to chemotherapeutic intervention and cells remaining within the core of the spheroid which we termed the lsquocorersquo population to be the least sensitive Moreover the drug sensitivity of the 3D single-cell diffusely embedded model was similar to that that of cells which had invaded away from the spheroid termed the lsquoperipheryrsquo population CSC quantification studies revealed CSC content to be inversely related to drug efficacy The ALDEFLUOR assay mammosphere assay and RT-qPCR analysis of the untreated in vitro models showed the spheroid core population to have an enriched CSC subpopulation Moreover the high sensitivity of the TaqMan assay provided the means to assess ALDH1A3 and SOX2 expression across our in vitro models following treatment with either paclitaxel or cisplatin Specifically treatment with paclitaxel led to a statistically significant increase in both ALDH1A3 and SOX2 expression across all in vitro models compared to the untreated conditions suggesting that paclitaxel treatment enriches for CSCs Treatment with cisplatin significantly increased both ALDH1A3 and SOX2 expression within the 2D monolayer and 3D diffuse systems but did not increase these genes within the core or periphery populations Conclusion In summary we describe a tumor model that recapitulates the cell-cell and cell-matrix interactions found within the native tumor and its microenvironment The results show that paclitaxel or cisplatin alone do not effectively combat


tumor growthmdashconsistent with many clinical outcomesmdashand support the further evaluation of dual therapies involving cisplatin or paclitaxel in combination with ALDH inhibitors in order to target CSCs which are linked to chemoresistance recurrence metastasis and progression

88 Multimodal-MRI based study of the effects of methylene blue in the human brain

Pavel Rodriguez MD Mary Woolsey MS Wilson B Altmeyer MD Francisco Gonzalez-Lima PhD et al The University of Texas Health Science Center at San Antonio Purpose USP methylene blue USP (MB) is a FDA-grandfathered drug used in clinics to treat methemoglobinemia and as a surgical stain Oral MB crosses the blood brain barrier and acts on the mitochondria to sustain or enhance ATP energy production MB has shown efficacy in animal models of Parkinsonrsquos and Alzheimerrsquos disease (AD) MB also increased oxygen consumption brain glucose uptake and fMRI evoked responses in the rat brain A phase II clinical trial showed that daily oral doses of 300mg MB slowed the progression of AD compared to placebo using neurocognitive assessments Our aim was to use task-based and task-free functional MRI (fMRI) to assess the efficacy of MB on cognitive and physiologic measures in the human brain Methods Study Design Randomized double-blinded placebo-controlled clinical trial (Phase II) divided into two stages Primary Outcome Measures bull Working memory fMRI task and behavioral measures bull Episodic memory fMRI task and behavioral measures bull Sustained attention task fMRI and behavioral measures bull Visuomotor task cerebral blood flow (CBF) bull Resting Functional Connectivity fMRI measures bull Resting CO2 Challenge Secondary Outcome Measures bull Neuropsychological Battery Stage 1 (NCT01836094) bull Arms MB (n=15) and Placebo Healthy Young (n=13) mean age 28-30 bull Intervention 280mg MB or placebo oral x 1 bull Time Frame 1 hour after completion of baseline fMRI tasks Stage 2 (NCT02380573) bull Arms MB Mild Cognitive Impairment (MCI) and Healthy elderly (40 total) Placebo MCI and Healthy Elderly (40 total) ages 65-89 bull Intervention MB (94 mg x 3 daily) or placebo oral with phenazopyridine (975 mg daily all subjects) bull Time Frame baseline 2 weeks plusmn 3 days 12 weeks plusmn 7 days for all primary outcome measures Follow up secondary outcome measures will be obtained at 2 weeks and 12 weeks Statistical analysis Repeated measures analysis of variance (ANOVA) to assess Drug x Time between-group interactions Results In healthy young subjects MB significantly increased fMRI response in the bilateral insular cortex during the sustained attention task and in the prefrontal parietal and occipital cortex during the working memory task MB treated subjects had a 7 increase in short-term memory retrieval (P=001) MB was also associated with a reduction in CBF in a task-related network during the VMT and with stronger resting-state functional connectivity in multiple regions linking perception and memory functions Conclusions A low dose of MB can increase short-term memory retrieval modulate sustained attention working memory resting-state and task-related visuomotor neural networks in the human brain The findings support our ongoing investigations in elderly and MCI populations (Stage 2)


89 Lack of β-catenin in hepatocytes impairs proliferation and promotes liver stem cell-mediated repair in response to the choline-

deficient ethionine-supplemented diet

Jacquelyn O Russell Hirohisa Okabe Sucha Singh Minakshi Poddar et al University of Pittsburgh Purpose Despite the liverrsquos capacity for regeneration liver disease is the 12th leading cause of death in the United States Treatments for chronic liver disease remain limited thus the purpose of this work is to elucidate mechanisms of liver regeneration Typically liver regeneration is mediated by proliferation of hepatocytes When hepatocyte proliferation is impaired liver stem cells (LSCs) are activated and are thought to mediate regeneration by differentiating into hepatocytes However the role and origin of LSCs remains controversial The choline-deficient ethionine-supplemented (CDE) diet model of liver injury is known to induce proliferation of LSCs However since the CDE diet does not block hepatocyte proliferation recent evidence has supported repair primarily driven by hepatocyte self-duplication in the CDE diet model As a member of the WNT signaling pathway β-catenin plays an important role in liver regeneration by promoting hepatocyte proliferation Therefore we hypothesize that β-catenin loss in hepatocytes would impair hepatocyte proliferation and lead to biliary-derived LSC-mediated hepatic repair in the CDE diet model Methods To determine the role of β-catenin in hepatocyte proliferation we placed mice with genetic deletion of β-catenin in both biliary epithelial cells (BECs) and hepatocytes (Albumin-Cre β-catenin KO mice) on the CDE diet To investigate whether liver regeneration is mediated by LSCs in this model we performed genetic fate tracing in mice by utilizing adeno-associated virus serotype 8 carrying thyroid binding globulin-driven Cre (AAV8-TBG-Cre) to simultaneously delete β-catenin and permanently label hepatocytes with EYFP (AAV8 β-catenin KO mice) Importantly in this model BECs contain β-catenin and do not express EYFP Results Albumin-Cre β-catenin KO mice display increased morbidity mortality and defective hepatocyte proliferation when compared to wild-type (WT) littermates after 2 weeks of CDE diet Similarly when AAV8 β-catenin KO mice were given two weeks of CDE diet they displayed increased liver injury and a lack of hepatocyte proliferation compared to β-catenin WT littermates Notably in AAV8 β-catenin KO mice given two weeks of CDE diet followed by a two week recovery on normal diet we detected clusters of hepatocytes which expressed β-catenin and did not express EYFP indicating that they originated from the BEC compartment We did not observe expansion of EYFP-negative hepatocytes in control mice where hepatocytes retained β-catenin expression Conclusions Our results demonstrate that loss of β-catenin in hepatocytes impairs hepatocyte proliferation after CDE diet-induced liver injury and supports the hypothesis that LSCs mediate liver regeneration when hepatocyte proliferation is blocked


90 Tissue-specific Effects of Inflammatory and Cancerous Esophageal Extracellular Matrix

Hydrogels

Lindsey T Saldin Luai Huleihel Madeline Cramer Maria Quidgley-Martin et al University of Pittsburgh Purpose Despite the known importance of the microenvironment in cancer progression cancer biology tools to recapitulate the microenvironment have largely remained unchanged collagen gel and Matrigel have dominated the cancer biology literature for the past 50 and 33 years respectively The stimulus of the present study was to develop a new cancer biology technology disease-specific ECM hydrogels A novel approach was used to develop normal inflammatory and neoplastic ECM hydrogels from decellularized normal inflammatory and neoplastic adenocarcinoma (EAC) esophageal tissue and to identify mechanisms by which these ECM hydrogels influence cell behavior We identified and isolated matrix-bound nanovessicles (MBVs) from ECM and showed their ability to rapidly and markedly affect cell phenotype We will characterize MBVs derived from the three ECMs Important and unanswered questions are 1) What is the profile of extracellular miRNA contained within the ECM via MBVs to drive EAC progression 2) How does diseased ECM activate an important cell type in an inflammatory driven cancer the macrophages via dynamic reciprocity Methods Normal inflammatory and EAC tissue from a rat model of EAC were decellularized using the same protocol assessed for absence of nuclei and formed into hydrogels as previously described SDS-PAGESilver Stain were used to characterize the protein profiles and scanning-electron microscopy was used to visualize the nanostructure of the three ECM hydrogels The activation state (M1M2) of human naiumlve macrophages exposed to the three ECM hydrogels in vitro was determined by gene expression (qPCR) and secreted products (ELISA) Small RNA sequencing was used to identify the miRNA profiles contained within normal inflammatory and neoplastic ECM MBVs Results The three ECMs showed distinctive fiber networks and chromatographic protein profiles Metaplastic and neoplastic ECM distinctively activate macrophages to a dual ``pro-inflammatory (TNFalpha high) and ``immunomodulatory (IL1RN high) state with expression that increased as ECM tumorigenicity increased MBVs were isolated from the three ECMs as a potential mechanism to regulate cell behavior Top differentially regulated MBV miRNAs were notably related to epithelial-mesenchymal transition a known mechanism of EAC progression cancer and macrophage activation suggesting the direct role of the ECM to reciprocally and dynamically instruct cell behavior Conclusion A novel ECM hydrogel ldquoprogression seriesrdquo was developed from normal inflammatory and neoplastic EAC tissue A better understanding of diseased ECM MBV miRNA cargo profiles and disease-specific activation of macrophages will guide regenerative strategies for patients of this increasingly devastating form of cancer



Daniela Y Santiesteban Stanislav Emelianov Laura Suggs UT Purpose Stem cell (SC) angiogenic therapies seek to promote angiogenesis needed for restoration of injured ischemic tissues Although initial SC studies showed promise clinical translation has proven challenging due to high amounts of SC death upon implantation The high amount of SC death can in part be attributed to the hypoxic implantation site and lack of host integration into scaffolds used for SC delivery In order to produce clinically relevant tissues maintaining survival of cells until blood vessel ingrowth occurs is essential To achieve this we have developed a nanoparticle-doped PEGylated fibrin gel that 1) allows for short-term increased oxygen (O2) levels and 2) long-term control over hydrogel porosity which can impact stem cell differentiation nutrient diffusion and improve host integration Methods All studies utilized human adipose stem cells (hASCs) A PEGylated fibrin hydrogel was used for the scaffold because it offers good SC viability and proliferation Perfluorocarbon nanodroplets (PFCnDs) with a stabilizing shell were synthesized and incorporated into hydrogels A 1064 absorbing dye (Epolig 3072) was encapsulated within the PFCnDs to allow for external triggering via lasing To assess effects of lasing on cell viability ASCs within gels were stained (LIVEDEAD) 24 hours after lasing and imaged with a Zeiss LSM 710 confocal microscope PFCnDrsquos ability to deliver appropriate O2 for maintaining ASC viability was assessed by culturing ASCs within doped hydrogels under hypoxic conditions (1 O2) for 48 hours Results Conducted studies demonstrate the promise of a PFCnD- doped scaffold to enhance SC angiogenic therapies PFCnDs allow for short-term oxygen delivery that allows for increased SC survival under hypoxic conditions (1 O2) PFCnD doped hydrogels had significant higher viability than control groups at 72 hours PFCnDs also allow for long-term control over porosity and mechanical properties of the hydrogel Lasing of PFCnDs causes phase -changes of the particles resulting in expansion which alters the hydrogel within close proximity and creates porous structures Based on nD concentration and lasing energy one could dictate the extent of porosity created LIVEDEAD staining was performed to ensure that lasing does not have any cytotoxic effects on cells Conclusions The combination of increased oxygen and dynamic hydrogel properties are expected to lead to more effective stem cell angiogenic therapies as cells have increased viability and the changes in hydrogel properties can facilitate ingrowth of blood vessels and improve host integration


92 Investigating the role of co-activators in inducible transcription at the single cell level

Andrew W Sawyer Michael T Marr II Brandeis University The tight control of gene expression is achieved largely through the ordered assembly of large multiprotein complexes at the promoters of mRNA genes For genes that respond to cellular stress signals the amount of gene expression must be tightly coupled to the stress condition We have been investigating the role of co-activators in the cellular response to heavy metals using the metallothionein genes as a model Previous work from our lab showed that upon destabilization of TFIID a core co-activator we find an unexpected increase in transcription of these genes in response to heavy metal These previous studies were done using methods that operate at population level and this can obscure the heterogeneity in the system To investigate this we are using RNA FISH to examine the transcriptional dynamics following heavy metal treatment in the presence or absence of various co-activators We find that the responding population is extremely heterogeneous with huge variations in the number of RNAs per cell In addition the induction of transcription is not uniform with only a fraction of the cells transcribing at any given time We also find that upon destabilization of TFIID there is an increase in total RNA similar to what was seen at the population level However with the single cell approach we find that the regulation changes not only in terms of number of RNAs per cell but also in the uniformity of the response across the population There is a much tighter distribution in the number of RNAs per cell


93 MRI evaluation of spinal cord lesions injected with a gelatin-based matrix in a rat

model

Adhvait M Shah Tehya Johnson Myron Spector Massachusetts Institute of Technology Introduction Spinal cord injury (SCI) is a devastating condition affecting roughly 253000 patients in US As a result of the injury several functional impairments in breathing bladder control and limb movements drastically reduce the patientrsquos quality of life Current treatments include administering steroids and rehabilitation The root cause ndash traumatic loss or degeneration of neural tissue ndash is not targeted Our overall goal is to assess the effectiveness of an injectable gelatin-based matrix with specific growth factors in spinal cord tissue repair It is imperative to include in the precinical animal investigation the non-invasive imaging modality that in addition to be able to provide longitudinal assessments in the animal model will also be able to be employed in an ultimate human trial In this work employing a rat model we present ex-vivo spinal cord MRIs with a proof of principle that critical characteristics of the injury site can be evaluated by MRI and correlated with behavioral assessment of spinal cord injury Materials and Methods Twelve lewis rats (300 g) underwent survival surgery that induced a 1 mm T8 hemiresection injury to their spinal cord On Day 0 the control group was injected with 15 μl of gelatin-hydroxyphenyl propionic acid (Gtn-HPA) matrix (Gel only groupn=6) and the experimental group was injected with 15 μl of Gtn-HPA matrix with epidermal growth factor (Gel + EGF group dose = 6 μgrat) Behavioral behavioral data were employed from historical untreated controls Every week until sacrifice rats underwent open field locomotor test and their hindlimb function was rated as per the Beattie Basso Brashnahan (BBB) scale from 0 (complete paralysis) to 21 (normal gait) The rater was blinded to the groups After 4 weeks they were sacrificed by transcardial perfusion and relvant spine region was preserved in 4 PFA at 4degC After sacririce T2-weighted coronal MRI images of the spinal cords with injury site were obtained in a 7T Bruker Scanner (resolution = 75 μm slice thickness = 250 μm) Lesion volume was calculated using ImageJ Results amp discussion We were able to obtain high-resolution MRI images showing the lesion site and the surrounding tissue in greater detail giving further insights (Figure 1) For Gtn-HPA + EGF group average lesion volume was calculated to be 1253 mm3 which was found to be lower than Gel only group 1527 mm3 (p = 005) (Figure 2) After 4 weeks the Gel+EGF group rats showed greater functional improvement from 53 to 135 average BBB score (Δ = 82) while the Gel only group showed improvement from 53 to 11((Δ = 57) (p = 005 Figure 3) Results from MRI correlate with the results from functional assessemnt of the rats using BBB scale Conclusion Our work provides a proof of principle that Gtn-HPA gel with EGF reduces the lesion volume contributing to greater protection of the surrounding healthy tissue Moreover our preliminary work suggests that MRI can be used as a tool to non-invasively study important critical parameters of the lesion site such as lesion volume Encouraging results motivate us to further test various doses of EGF and relevant factors to induce tissue regeneration in our animal model We aim to test a combinatorial approach with Gtn-HPA gel EGF and a cell types such as bone-marrow derived mesenchymal stem cells


94 Development of a Pipeline to Integrate High Angular Resolution Diffusion Imaging

(HARDI) and Intracranial EEG Data in Epilepsy Patients

Preya Shah Lohith Kini Ankit Khambhati Brian Litt et al University of Pennsylvania Purpose Diffusion tractography is an MRI-based technique which can probe the brainrsquos structural connectivity and identify white matter abnormalities in epilepsy patients Intracranial EEG (iEEG) data which is commonly recorded in patients with intractable epilepsy can provide valuable information about the brainrsquos functional connectivity Integration of the two data types may allow us to better understand the relationship between structural and functional epileptic networks in the brain and more robustly identify areas of seizure onset and spread With this motivation we have developed a pipeline to facilitate combined analysis of diffusion tractography and iEEG connectivity data For our structural data we utilize High Angular Resolution Diffusion Imaging (HARDI) an advanced diffusion imaging method which can produce reliable tractography results in regions of crossing white matter pathways Methods We have collected CT T1 MRI HARDI and iEEG data for five patients with intractable epilepsy A pipeline was designed using data from one patient implanted with 78 subdural electrodes HARDI data was acquired on a Siemens Trio Magnetom 3T scanner using 116 diffusion weighted directions 20times20times20mm voxel size and b-values of 300 smm2 700 smm2 and 1000 smm2 Tractography was performed using q-space diffeomorphic reconstruction Structural connectivity matrices were generated using the number of tracts connecting each region Functional connectivity matrices were generated by calculating cross-correlations between iEEG electrode recordings Results Via thresholding and coregistration we successfully localized and determined coordinates of the patientrsquos 78 electrodes By creating cylindrical regions around each electrode we were able to perform HARDI tractography using electrodes as seed regions The tractography reveals evidence of connectivity between the electrode regions and the brainrsquos major white matter pathways Moreover we generated a functional adjacency plot using ictal iEEG connectivity data In this framework both structural and functional connectivity are characterized using electrodes as nodes Therefore these data can be used as the basis for future direct quantitative comparison of HARDI and iEEG data Conclusion We have outlined a process to enable multimodal analysis of brain connectivity in epilepsy To our knowledge this is the first attempt to directly integrate HARDI and iEEG data We hope to use the process to further analyze epileptic networks in our growing repository of patient data We believe that a combined structural-functional approach can be extremely valuable in better localizing seizure onset predicting pathways of seizure spread and ultimately informing clinical decision making



Caitlin A Short Edwin A Suarez-Zayas Timothy M Gomez University of Wisconsin Madison Invadosomes are F-actin rich adhesions which protrude the membranes of some migrating cells and promote degradation of the extracellular matrix Although invadosomes have predominantly been studied in cancer and immune cells they have recently been identified in neural crest cells in the developing zebrafish and pathfinding growth cones of Xenopus laevis spinal neurons (Santiago et al Development) Our lab found that similar to non neuronal cells invadosome formation in neuronal growth cones requires Tks5 and that active Src (pY418-Src) localizes to these sites Our previous work largely examined invadosomes in 2D culture however in vivo growth cones may receive cues from a variety of directions in 3D to modulate their growth and form networks In this work we employ confocal and structured illumination microscopy (SIM) of developing motoneurons (MN) in both 2D and 3D extracellular protein environments to test the roles of candidate morphogens and investigate the formation and function of growth cones invadosomes in neuron growth and axon guidance We hypothesize that growth factors such as BDNF and SDF-1 are released from peripheral tissues during development to induce invadosome formation in MNs to guide them through the basement membrane of the spinal cord and into the periphery Preliminary data suggests that axons are guided along a gradient of BDNF in collagen gels Invadosome-dependent penetration of collagen is being examined by manipulating the activity of Tks5 Src kinase and the actin regulatory Rho GTPase cdc42 Future work will continue to elucidate the molecular induction of growth cone invadosomes


96 Segmentation of dense cellular microscopy images for quantification of inflammation in

lupus nephritis

Adam Sibley Maryellen Giger Yulei Jiang University of Chicago Purpose To develop a computerized segmentation method for densely packed cells in microscopy images This enables analysis of the process of B cell activation by T follicular helper cells in lupus nephritis and in inflamed human tissue in general We primarily desire accurate localization of cells and accurate representation of their boundaries to enable shape and distance analysis of interacting cells Methods and materials T follicular helper cells are critical for B cell activation in germinal centers and are often observed in human inflamed tissue However it is not known whether they contribute to in-situ inflammation Using confocal laser scanning microscopy with immunofluorescent antibody staining we have previously developed a method to quantify image cell interaction by segmenting image channels corresponding to the different cell types and using shape and distance metrics We seek to validate this model in a mouse model of tonsil germinal centers On 42 cellular images of interacting cells in a mouse model we used a quincunx wavelet transform with gaussian filtering applied to the wavelet coefficients at each scale The coefficients at each scale are then multiplied together to produce a wavelet multiscale product Thresholding this product produces a robust segmentation of key features in the cell We then apply an iterative morphological opening with a circular structuring element and as processing proceeds a selection criterion based on solidity Objects above a solidity threshold are removed from consideration at each iteration In order to differentiate the objects mean shift clustering is performed on the centroid features of connected object populations This reliably identifies object clusters corresponding to actual cells without requiring foreknowledge of the number of cells present Final object segmentations are a combination of segmented objects in the differentiated clusters Intra-cluster outliers are removed based on centroid area solidity and boundary saliency features Results Our segmentation results compare favorably against our previous method using the watershed transform By visual inspection this method produced poor cell localization and poor cell shape characterization Conclusions With increased accuracy of our cellular segmentation method for dense tissue we can better quantify cell position and shape in our images This method will aid in segmentation of cells in dense tissue in human renal biopsies to quantify inflammation in lupus nephritis


97 Discovering Temporal Signatures that Predict Disease Trajectory of Glioblastoma

Multiforme Patients

Nova F Smedley Dr William Hsu Dr Timothy F Cloughsey Dr Benjamin M Ellingson University of California Los Angeles Purpose Patients with glioblastoma multiforme (GBM) experience poor prognosis Surgery and adjuvant therapies following diagnosis improves median survival by 6 months Unfortunately tumor recurrence is essentially inevitable and subsequent rounds of therapies have mostly proven ineffective The decision to treat or not treat is informed by a patientrsquos clinical history and disease trajectory While a variety of clinical and imaging observations (eg Karnofsky performance score (KPS) tumor volume) are reviewed by a neuro-oncologist the relationship between temporal patterns captured in these observations and overall survival is not well understood Our goal is to utilize sequential pattern mining approaches to identify temporal signatures that are predictive of irreversible patient decline after observing the pattern Methods Between September 1999 to August 2014 a UCLA cohort of 314 newly diagnosed GBM patients were followed from time of diagnosis until May 11 2015 During this period tumor volume from radiological images surgery chemotherapy radiation and several forms of neurological evaluations were collected The dataset has a total of 9297 clinical visits and 23963 events Representing each patient as a sequence of events frequent sequences were mined using the cSPADE algorithm Several forms of constraints including temporal gaps between events and data discretization were utilized to identify meaningful frequent sequences or patterns Patterns were then analyzed through the Kaplan-Meier (KM) estimator to identify changes in survival days from when the pattern was observed Significant differences in survival was controlled by the false-discovery rate method Cox proportional hazard regression using covariates from patient demographics and genomics (eg MGMT methylation IDH1 mutation) identified the predictive value of each sequence Results cSPADE found 309 patterns consisting of 598 single events 183 two-event sequences and 18 three-event sequences A total of 87 patterns were identified to be significant predictors of survival Examples of these patterns include a) an overall neurological score of -1 on the same day as a decrease in KPS from the last clinical visit b) a tumor volume increase followed by a tumor volume increase within the next month and c) a decrease in KPS followed by the same KPS within the next month Conclusions This work presented a set of sequential patterns extracted from a relatively large cohort of GBM patients throughout their history of clinical observations These patterns were able to predict patient decline in addition to being intuitive and understandable



Brad Solomon Carl Kingsford Carnegie Mellon Purpose An enormous amount of DNA and RNA short read sequence data has been published worldwide By aggregating and analyzing this data as a whole it would be possible to investigate genetic variation and condition- and disease-specific gene function in ways the original depositors of the data did not anticipate Unfortunately the scale of the data is so large that it is not even possible to search for a single query sequence in reasonable computational time Methods We developed a novel data structure the Sequence Bloom Tree to address this gap between data and analysis We demonstrate SBTrsquos efficiency by building an index on 2652 human RNA-seq experiments and searching this index for all 214293 known human transcript in under four days using only megabytes of RAM and a single CPU We also benchmark SBTrsquos average query time and index size to several existing tools such as Sailfish STAR and SRA-Blast Results We find that an average single transcript search takes SBT 20 minutes using 239 MB of RAM and a single thread The comparable search times using SRA-BLAST or STAR is 22 days or 921 days respectively although both tools return alignments while SBT does not SBT and STAR can also be batch queried with SBT roughly 4056 times faster than STAR SBT achieves this speedup while using 4 of the original data storage cost in a directly searchable index These significant speed and size benefits come at a minor accuracy loss with an average true positive rate of up to 085 when using Sailfish gene expression estimates as a ground truth Conclusion Currently it is difficult to access all the relevant data relating to a particular research question from available sequencing experiments SBTs enable the efficient mining of these data and could be used to uncover biological insights that can be revealed only through the analysis of multiple data sets from different sources Furthermore SBTs do not require prior knowledge about sequences of interest making it possible to identify for example the expression of unknown isoforms or long noncoding RNAs This algorithm makes it practical to search large sequencing repositories and may open up new uses for these rich collections of data This work was reported in Solomon Brad and Carl Kingsford Fast search of thousands of short-read sequencing experiments Nature biotechnology (2016)



Elaine Soohoo Lewis K Waldman Dennis R Trumble Carnegie Mellon University Department of Biomedical Engineering Purpose Our goal is to develop a torsion-based ventricular assist device (tVAD) as an alternative to traditional ventricular assist devices (VADs) currently available on the market The tVAD attaches to the apex of the heart and will rotate in synchrony with the heartbeat with the intention of reducing wall stress and increasing the ventriclesrsquo ability to empty more completely Methods The tVAD prototype was designed using a commercial CAD software package (Solidworks 2015 Dassault Systegravemes Solidworks Corp Waltham MA) The overall design approach was guided by computational simulations of applied apical torsion of the heart and results from in vivo pig experiments wherein a first generation tVAD rotated a hypokinetic heart a quarter turn during the systolic phase of the cardiac cycle Parametric computational simulations were performed using ContinuityPro software (Insilicomed Inc La Jolla CA) and used to determine design parameters for a second-generation tVAD prototype These simulations utilized beating heart models attached to a closed-loop circulatory system Ventricular size shape and dimensions were based on anatomic measurements taken from both adult porcine hearts and human heart failure patients while biomechanic and circulatory model parameters were taken from literature values Results We have recently created a working second-generation tVAD prototype design and surgical delivery scheme suitable for clinical use Model details will be fine-tuned prior to device manufacturing based on performance parameters derived from further computational simulations Initial results from a parametric study looking at the effects of increasing rotation on the ventricles demonstrated that when compared to a clinical heart failure model with increasing applied apical rotation (up to 75deg) there is an increase in both the ejection fraction (352) and stroke work (472) Conclusion Based on results from preliminary computational simulations and experiments on live porcine hearts applied apical torsion shows promise as an alternative method to traditional cardiac assist devices currently used to treat congestive heart failure


100 Pointwise Mutual Information Quantifies Intra-Tumor Heterogeneity in Tissue Sections Labeled with Multiple Fluorescent Biomarkers

DM Spagnolo R Gyanchandani Y Al-Kofahi AM Stern et al University of Pittsurgh Spatial intra-tumor heterogeneity measures are potentially important diagnostic biomarkers for cancer progression proliferation and response to therapy Spatial relationships among cells including cancer and stromal cells in the tumor microenvironment (TME) are key contributors to heterogeneity We demonstrate how to quantify spatial heterogeneity from immunofluorescence pathology samples using a set of breast cancer biomarkers We learn a set of dominant biomarker intensity patterns and map the spatial distribution of the biomarker patterns with a network We then describe the pairwise association statistics for each pattern within the network using pointwise mutual information (PMI) and visually represent heterogeneity with a two-dimensional map PMI is generalizable to highly multiplexed immunofluorescence images as well as spatial data from complementary in situ methods including FISSEQ and CyTOF sampling many different components within the TME [1 2] We hypothesize that PMI will uncover key spatial interactions in the TME that contribute to disease proliferation and progression 1 Lee JH et al Fluorescent in situ sequencing (FISSEQ) of RNA for gene expression profiling in intact cells and tissues Nat Protoc 2015 10(3) p 442-58 2 Giesen C et al Highly multiplexed imaging of tumor tissues with subcellular resolution by mass cytometry Nat Methods 2014 11(4) p 417-22


101 Imaging approaches to detect amp monitor changes in joint architecture amp brain networks

in TMJ pain

Megan M Sperry Sonia Kartha Ya-Hsin Yu Eric J Granquist et al University of Pennsylvania PURPOSE Temporomandibular joint (TMJ) osteoarthritis is a common low-grade inflammatory condition that has a multifactorial etiology including pain In most patients pain resolves without needing further clinical action However for a subset of patients chronic TMJ disorder develops with long-lasting symptoms Sustained neuronal hyperexcitability throughout the central nervous system is a major contributor to the development of chronic pain and can lead to changes in brain circuitry This study investigates alterations in the TMJ and brain using quantitative in vivo imaging techniques to compare different pain states METHODS All procedures were IACUC-approved Repeated mouth-opening was imposed daily for one week in female Holtzman rats under isoflurane anesthesia to induce either resolving or persistent pain (n=7group) Orofacial pain was assessed by measuring mechanical hyperalgesia CT images of the TMJ were acquired before loading (baseline) and at day 14 to quantify joint structure Image stacks were registered between days automatically segmented and reconstructed in 3D Changes in joint architecture were evaluated using image subtraction between registered images In addition FDG-PET images of the brain were acquired at baseline and day 7 to evaluate metabolic activity when the pain responses diverge Images were registered to Schwarzrsquos rat brain template Networks were created by representing each brain region as a node edges connecting nodes were defined by the Pearson correlation coefficient between FDG uptake in two regions for all rats Meso-scale structure of the network was evaluated by the Louvain algorithm RESULTS Orofacial sensitivity is established during the loading period for both groups (plt0001) but only remains at day 14 in the persistent pain group (plt0001) Flattening of the TMJ condylar head is evident at day 14 only in the persistent painful group this change in bone shape is not evident in the other group Image subtraction reveals image intensity changes between day 14 and baseline that are larger in the painful group (1785plusmn621) compared to the group (1232plusmn542) with no pain at that time In combining both groups the modularity of the brain networks significantly decreases (plt00001) at day 7 when pain is present However a change in community structure emerges in the sustained pain group at day 7 that is not evident in the resolving pain group CONCLUSIONS Both peripheral tissue and brain are altered when TMJ pain persists These findings suggest that these andor other imaging approaches may have predictive value in diagnosing disease (ie pain) progression in TMJ osteoarthritis



Elizabeth C Stahl Bryan N Brown University of Pittsburgh Purpose The immune system and in particular macrophages are implicated in wound healing pathogen clearance and cancer progression Studies show that tissue-resident macrophages become dysfunctional with aging likely contributing to mortality in the elderly population The liver contains approximately 80 of the total tissue-resident macrophages known as Kupffer cells Kupffer cells can be divided into two F480+ macrophage subsets embryonic derived CD68+ and bone marrow derived CD11b+ cells with different phenotypes and functions Currently it is unclear how these macrophage subsets are affected by aging and the implications for human health We expect that advanced age will promote the accumulation of CD11b+ ldquobone marrow derivedrdquo Kupffer cells in the liver that exhibit cellular dysfunction which may have implications for the overall health of aged hosts Methods We characterized differences in Kupffer cells from young (2-4 month) and aged (18-24 month) C57Bl6 wild-type mice using immunofluorescent histological staining as well as flow cytometry for the macrophage markers F480 CD11b CD32 and CD68 In addition we examined macrophage function by polarizing cells to classically or alternatively activated phenotypes (M1 amp M2) and measuring phagocytosis of ecoli particles in vitro Results Histological analyses showed the number of F480+ and CD68+ cells significantly increased with aging demonstrating an overall increase in the number of macrophages residing in the liver In addition the area of CD32+ staining which marks both macrophage progenitor and endothelial cells remained consistent with age Flow cytometry analysis confirmed differences in the macrophage subsets between young and aged murine livers with a significant increase in CD11b+ macrophages suggesting an increase in bone marrow origin of the tissue resident macrophages Finally functional analyses showed that aged Kupffer cells did not significantly polarize to an M1 or M2 phenotype but were more phagocytically active than young Kupffer cells at baseline Conclusions The overall increase in macrophages in the aged liver and increased phagocytic activity suggests Kupffer cells may be affected by inflammatory systemic cues characteristic of aging and this may disrupt normal liver homeostasis The significant increase in CD11b+ macrophages in the liver supports the hypothesized progressive replacement of embryonic macrophages with bone marrow derived macrophages in advanced age Further characterizing the functional and phenotypical differences in the subsets of Kupffer cells during aging will increase our understanding of the host response to infection and cancer and aid in better design of therapies that will extend the healthspan of the population


103 Optimizing unanesthetized cerebral oxygen consumption measures comparison of

MRI and near-infrared spectroscopy (NIRS) approaches in neonates with congenital heart

disease

Jeffrey N Stout Silvina L Ferradal Lilla Zollei Divya S Bolar et al Massachusetts Institute of Technology HST Purpose Moderate to severe congenital heart disease (CHD) affects 61000 live births with severe CHD resulting in adverse neurodevelopmental outcomes in over 50 The etiology of neurodevelopmental disorders is unknown but evaluation of the hemodynamic state of CHD infants pre- and post-surgically has become a focus with the cerebral metabolic rate of oxygen consumption (CMRO2) identified as a key parameter for clinical evaluation We present MRI and NIRS measures of cerebral hemodynamics in nine stable neonates with CHD MRI measures were performed without anesthesia and NIRS measures were performed at the bedside within one day of MRI without anesthesia MRI and NIRS measures are compared to literature values Methods MRI and NIRS studies were performed at Boston Childrenrsquos Hospital with IRB approval and parental consent Both studies (N=9 age=48plusmn25 days 8 male 1 female) took place in the pre-operative period within 12 hours of each other The MRI protocol Structural imaging (volume navigated MPRAGE and time of flight angiogram) was used to position velocity encoded phase contrast imaging to permit cerebral blood flow (CBF) calculation (TETR=4671665ms resolution=05x05x40mm velocity encoding=100cms Tacq=119) and T2-relaxation under spin tagging (TRUST) measurements of oxygen saturation in the superior sagittal sinus (TETR=155000ms resolution=23x23x5mm inversion time=1025ms tagging width=50mm tagging gap=15mm Tacq=119) The NIRS protocol Frequency-domain near-infrared spectroscopy (FD-NIRS) and diffuse correlation spectroscopy (DCS) FD-NIRS provided regional measurements of oxygenated and deoxygenated hemoglobin used to compute cerebral oxygen saturation DCS provided a measure of microvascular blood flow Results MRI results are reported as mean plusmn standard error and NIRS results as median (interquartile range) to permit comparison with previous literature Venous oxygen saturation (SvO2) was 554 plusmn 105 and 576 (51-599) CBF was 136 plusmn 23 ml100gmin and 205 (153-228) cm^2s CMRO2 was 396 plusmn 95 umol O2100gmin and 222 (192-242) ml O2cm^2dls Discussion Compared to other studies (P Liu et al NMR in Bio 2014 V Jain and E M Buckley JCBFM 2014 M Dehaes et al Bio Opt Exp 2015) our results show expected decreased mean CMRO2 compared to healthy neonates and slightly higher CMRO2 than in anesthetized subjects SvO2 measurements correlate across modalities (P = 0003 R^2 = 074) suggesting that SvO2 measures capture similar information andor are relatively stable in this cohort However there was no significant correlation between CBF and CMRO2 Conclusion MRI and NIRS provide complementary methods for quantification of cerebral hemodynamics that if cross-validated would increase our confidence in both


modalities and lead to more comprehensive clinical monitoring However before data between these two modalities can be compared or combined additional studies are needed to better understand the relationship between large vessel bulk flow and microvascular red blood cell flow SvO2 measurements in our study are significantly correlated between modalities but CBF and therefore CMRO2 are not in good agreement either due to differences in physiology or biases in these measurements Acknowledgements This publication was made possible by NIBIB-NIH grants 5T32EB1680 R01EB017337 U01HD087211 and by NIH-NICHD grants R21HD072505 NIH R01HD076258

104 A Parallel Approach to Energy Minimization of Protein-Ligand Interaction

Jocelyn Sunseri David Ryan Koes Carnegie Mellon University - University of Pittsburgh Computational Biology Fundamental physical limitations associated with processor design have reduced the single-threaded efficiency gains in software performance that were previously achieved by innovations in hardware This has led to increased reliance on parallel execution as a means of accelerating program performance catalyzing the rapid development of hardware capable of executing single program multiple data (SPMD) instruction streams efficiently In particular graphics processing units (GPUs) previously developed primarily for graphics rendering have found diverse applications in scientific computing Knowledge of underlying hardware and modifications of sequential algorithms to make them amenable to parallelization are required to yield significant gains from this approach We report our algorithm for performing energy minimization of a protein-ligand molecule pair on a GPU as well as relevant details of its implementation We report a XX speedup over a CPU implementation of our algorithm This type of energy minimization is useful for protein-ligand pose prediction (including docking) as well as binding free energy estimation which is applicable to scoring putative hits in a virtual screen Our implementation increases molecule screening throughput and is of particular value in performing real-time minimization requests made via our webserver pharmit



Stefanie A Sydlik Meng Deng Cato T Laurencin Robert S Langer Carnegie Mellon University Purpose Synthetic materials hold the promise of biocompatibility reduced foreign body response and elimination of compliance mismatch in the field of tissue regeneration Despite these promises major limitations still exist in the materials used today especially in cartilage repair In this proposal we present a new type of synthetic cartilage that mimics the chemical structure namely type-II collagen and glycosaminoglycans and ordered morphology of cartilage to reproduce the extraordinary material properties Methods A collagen mimetic peptide (CMP) based on repeating trimmers of GOP and capped with K residues was developed This peptide self-will be verified by circular dichoism (CD) Further the free amines are used to crosslink with aldehydes in modified hyalyronic acid (HA) or NHS-esters in chondroitin sulfate (CS) Maintenance of this collagen-mimetic morphology when crosslinked with HA or CS in the hydrogel was confirmed by SEM and mechanical properties of the material were monitored over time using rheology Human mesenchymal stem cells (hMSCs) were cultured on or crosslinked within the gel to study their differentiation Results CD and SEM confirms the maintenance of the collagen-like triple helix conformation of the peptide SEM shows nanofibular morphology in the crosslinked gel with fibers on the order of nanometers self assembling into larger micron sized domains of the copolymer Rheological study showed that the mechanical properties of the gel can be tuned to 50- 200 kPa which is on the order of native cartilage Enzymatic degradation was found with collagenase chondroitinase and hyaluronidase Human mesenchymal stem cells (hMSCs) were cultured on or crosslinked within the gel and show good morophology and suggest chondrogenic differentiation An ex vivo implant model showed good integration and adherence to native cartilage Conclusion A thermoset block copolymer has been developed that mimics the major chemical motifs in cartilage namely type II collagen and glycosaminoglycans through the use of a collagen mimetic peptide (CMP) and hyaluronic acid (HA) or chondroitin sulfate (CS) Self-assembly of nanofibers and nanophase separation of the blocks give a predictable morphology mimicking the ordered morphology found in native cartilage The shear mechanical properties of the hydrogel approach can be tuned to match those of cartilage and remain stable through in vitro experiments as cells as break down the material at the same rate new extracellular matrix is built While we have achieved very promising in vitro results we have yet to prove this system in vivo


106 A semiautomatic noninvasive technique for quantitative assessment of collateral

circulation

Elizabeth Tong MD Max Wintermark MD University of California San Francisco Purpose Collateral circulation plays a pivotal role in the pathophysiology of acute ischemic stroke treatment outcome and clinical outcome Collateral status is increasingly recognized as a promising biomarker for predicting the outcome of stroke However there is no single established grading system The goal of our study is to propose a noninvasive technique for quantitative assessment of collateral circulation and investigate the prognostic value of our proposed collateral-score Methods An original collateral-assessment software based on Perfusion CT was developed to semi-automatically (1) map out the collateral vessels (2) determine the vascular origin of the collaterals and (3) calculate the contribution from each vascular territory A collateral score reflecting the contribution from each vascular territory (MCA ACA and PCA) is computed Patients from a stroke registry with anterior-circulation occlusion were retrospectively identified and their collateral scores were assessed The correlation between collateral score with clinical outcome (as measured by 90-day modified Rankin Scale) and radiologic outcome (as measured by volume of infarct core) was investigated Results A total of 100 patients mean age 68 years with M1 andor M2 occlusion were included Mean collateral score is significantly different between the stroke hemisphere and the normal (contralateral) hemisphere The variance in the collateral score increases with age Good collateral score is associated with smaller infarct core volume and lower 90-day modified Rankin Scale Poor collateral score is associated with larger infarct core volume and higher 90-day modified Rankin Scale Conclusion Good collateral status is associated with lower modified Rankin Scale at 90-day and smaller final infarct volume Therefore evaluation of collaterals is important in stroke management Our new collateral-assessment software allows non-invasive objective and quantitative assessment of collaterals


107 Transurethral MR-guided high-intensity ultrasound system for focal ablation of

prostate cancer

Trivedi Hari Partanen Ari Wood Bradford Choyke Peter et al UCSF MR-guided transurethral ablation of prostatic tissue may be more accurate and safe than transrectal approaches The objective of this study was to develop and validate a transurethral ultrasound system for focal ablation of regions within the prostate while limiting damage to urethral or peri-prostatic tissue The MR-guided ultrasound system consists of an axially rotating applicator under robotic control with eight 05cm elements (f=3Mhz max Pac=4W) Each element can be modulated as the applicator is rotated to contour the ablation zone Degassed water is circulated to cool the applicator and adjacent urethral tissue Ablation zone is controlled through real-time feedback using PRF-based temperature monitoring Preliminary testing using all eight elements at 50 power (0 60 and 90 degree sweeps) was conducted in tissue- mimicking phantom Ablation zones (defined as 240 CEM43) were achieved to a depth of 4cm while sparing a 05cm zone around the applicator Sweeps resulted in ablation zones 5-10 degrees larger on either side than the programmed arc An ablation zone of 08x10cm was achieved in 60 seconds without rotation Transurethral MR-guided high-intensity ultrasound therapy can accurately ablate targeted volumes while limiting thermal exposure in the near and far field Pre-clinical trials have been completed and clinical trials are underway


108 Extracellular Matrix Hydrogel Promotes Tissue Remodeling Arteriogenesis and

Perfusion in a Rat Hindlimb Ischemia Model

Jessica L Ungerleider Todd D Johnson Melissa J Hernandez Dean I Elhag et al University of California San Diego Purpose The prevalence of peripheral artery disease (PAD) is increasing and can lead to critical limb ischemia (CLI) ultimately increasing the risk of potential limb amputation Currently there are no therapies for PAD to effectively treat all of the underlying pathologies including reduced tissue perfusion and muscle atrophy This study aimed to examine acellular extracellular matrix based hydrogels as potential therapies for treating PAD We tested the efficacy of using a tissue-specific injectable hydrogel derived from decellularized porcine skeletal muscle (SKM) compared to a new human umbilical cord derived matrix (hUC) hydrogel The latter could have greater potential for tissue regeneration due to its young tissue source age Methods In a rodent hindlimb ischemia model both hydrogels were injected 1-week post-surgery and perfusion was regularly monitored with laser speckle contrast analysis (LASCA) for 35 days post-injection Immunohistochemistry and histology were used to assess neovascularization and muscle remodeling Results Quantitative proteomic analysis showed that both SKM and hUC contained complex tissue-specific compositions Significant improvements in hindlimb tissue perfusion and perfusion kinetics were observed with both biomaterials End point histology indicated this was a result of arteriogenesis rather than angiogenesis and verified the materials were biocompatible Furthermore muscle fiber analysis showed the tissue specific matrix (SKM)-injected animals had muscle fiber area and circularity most closely resembling healthy contralateral muscle Conclusion These results show the efficacy of an injectable ECM hydrogel alone as a potential therapy for treating patients with PAD They also suggest that non-tissue specific responses such as vascularization can be stimulated with a non-tissue specific ECM hydrogel but a tissue specific ECM hydrogel may better influence muscle regeneration and remodeling


109 Phantom feasibility study for utilization of crawling wave elastography to improve

diagnosis of neonatal intracranial hemorrhage

Alexander M Vezeridis Kenneth Hoyt Clark Z Wu Robert F Mattrey UC San Diego Purpose Neonatal cranial ultrasound (US) is an imaging test commonly performed to diagnose intracranial hemorrhage (ICH) in newborns While an excellent test for detection of severe ICH cranial US has very poor sensitivity and interobserver agreement for grade I and grade II ICH The aim of our work is to improve detection neonatal ICH through the use of ultrasound elastography specifically crawling wave elastography by measuring stiffness of clot compared to surrounding brain parenchyma and cerebrospinal fluid (CSF) Methods Agarose phantoms were crafted to hold clotting blood Citrate-anticoagulated rabbit blood was introduced into the phantom and a blood clot was formed by the addition of calcium chloride solution and thrombin enzyme Before and the process of clotting crawling wave elastography was employed to dynamically assess the shear modulus of the blood or forming clot at time points 5 10 20 30 50 90 120 minutes Imaging of the crawling wave was performed using two different methods (1) a Philips iU22 ultrasound machine using power Doppler magnitude estimation and (2) a Verasonics ultrasound system using power Doppler variance estimation which was hypothesized to be more sensitive to the low shear wave velocities anticipated in blood clots according to prior studies Results Using power Doppler magnitude estimation crawling waves were not observed within clotting blood Using power Doppler variance estimation low crawling wave signal was observed in the clotting blood within 5 minutes of starting clotting but not in unclotted blood By the variance estimation method crawling wave signal was observed to increase over time and plateau at maximum levels at 50 minutes after beginning clotting Conclusions Crawling wave elastography with variance estimation methods demonstrates the sensitivity required to assess blood clot stiffness during clotting as evidenced by increased crawling wave signal over time during clotting With further study such methods may prove useful in distinguishing clotted blood from CSF (which does not propagate crawling waves) and normal brain parenchyma



Tim Wall Carl Kingsford Carnegie Mellon University The massive influx of next-generation sequencing (NGS) data over the past several years has given rise to two key problems in the field of NGS analysis read mapping or determining where on a template transcript a read could have originated and variant calling in which read alignments are used to determine potential genomic differences between a template transcript and the transcript from which the short reads are sequenced Numerous approaches have been developed for both concepts read mappers like Bowtie and BWA among others provide fast and accurate read alignments while variant calling tools from SAMtools and GATK are effective at accurately calling variants However current read mappers are prone to template bias as deviations from the template are edited in the process of mapping so true variants are not taken into account when editing the read which can cause a deviation from true mappings We propose a new mapper NIRMAL which combines a lightweight mapping algorithm augmented with a skip list data structure that allows potential variants to be efficiently stored and queried during mappings By tracking potential variants during the mapping process true variants can be determined and queried online allowing for potentially more accurate mappings This method could potentially prove highly useful in applications such as cancer genome variant detection and determining potential variants among closely related species


111 On-Axis Acoustic-Radiation-Force-based Quantitative Stiffness Estimation in Phantoms

Kristy Walsh Mark Palmeri Brett Byram Vanderbilt University Purpose In shear wave elasticity imaging (SWEI) stiffness can be estimated by measuring shear wave velocity at locations away from the acoustic radiation force (ARF) axis [1] Instead this research estimates stiffness by measuring the time-to-peak displacement directly along the ARF axis which reduces hardware and sequencing complexity We have shown previously in simulation results that an advanced displacement estimator reduces variability in the final stiffness estimate [2] Here we test the on-axis approach in 15 phantoms Methods We assume the phantoms are homogeneous isotropic and linearly elastic thus time-to-peak displacement is directly proportional to shear wave speed Since shear wave speed is directly related to shear stiffness we create a stiffness look-up table of the time-to-peak displacement as a function of depth We generated look-up tables using a 3D FEM model coupled to Field II simulations and the selected displacement estimation method We simulated time-to-peak look-up tables for shear moduli from 1-15 kPa and attenuation of 07 dBcm-MHz We used a CH4-1 probe with excitation focal depth of 49 cm transmit F2 and transmit frequency of 308 MHz Both normalized cross correlation (NCC) and Bayesian displacement estimators were evaluated We applied a quadratic motion filter to the data To evaluate the error of the on-axis method as compared to traditional shear wave methods we computed a robust lateral time-of-flight shear wave speed using a Radon sum transformation (LATSUM) and converted to a shear modulus for each phantom [3] Results and Conclusions The 15 phantoms had a mean shear modulus of 207 kPa and standard deviation of 012 kPa We took the root mean square error of the shear modulus estimated using either the Bayesian displacement estimator or the NCC-derived estimator In the depth of field the median RMSE of shear modulus for the Bayesian estimator was 046 kPa and 093 kPa for NCC The Bayes results show more agreement with the LATSUM results than NCC These phantom results show that on-axis methods coupled with a Bayesian displacement estimator produce stiffness estimates comparable to laterally offset shear wave methods [1] Sarvazyan A P et al Shear wave elasticity imaging a new ultrasonic technology of medical diagnostics UMB 249 1419-1435 (1998) [2] Walsh K et al ldquoOn-axis radiation-force-based quantitative stiffness estimation with a Bayesian displacement estimatorrdquo IEEE IUS 1-4 (2015) [3] Palmeri M L et al Quantifying Hepatic Shear Modulus In Vivo Using Acoustic Radiation Force UMB 344 546-558 (2008)



Christopher Walter Samila Nasrollahi Amit Pathak Biomedical Engineering The ability of cells to communicate with their extracellular matrix (ECM) is important in many biological processes including wound healing development immune response and tumor metastasis The mechanical properties that define the ECM such as stiffness porosity and geometry can all play major roles in controlling cell differentiation shape and migration It has been shown that cell spreading depends on stiffness of the ECM away from the immediate microenvironment However this ability to sense distant ECM stiffness has been shown to be cell type dependent Here we cultured MCF10A human mammary epithelial cells on layered substrates with a collagen layer of varying concentration and thickness attached on top of a polyacrylamide gel of defined stiffness We tracked cell migration and performed morphological analysis of cells in contact with the collagen layer We found that both the thickness and the concentration of collagen gels altered cellular response to polyacrylamide stiffness We also found that focal adhesions and actomyosin contractility critically influence the ability of cells to sense both the micro-scale (collagen) and the macro-scale (polyacrylamide) ECM properties




Ziyi Wang Scott H Robertson Jennifer Wang Mu He et al Duke University ABSTRACT Background Idiopathic Pulmonary Fibrosis (IPF) is an interstitial lung disease in which progressive tissue fibrosis and inflammation impairs alveolar-capillary gas transfer There is a pressing need to rapidly detect worsening function or therapy response of existing and new coming drugs Here we demonstrate novel methods to visualize and quantify 129Xe uptake in barrier and RBCs to identify new biomarkers of gas exchange Methods The dissolved-phase images were decomposed into RBC and barrier images which were then divided on a voxel-by-voxel basis by the gas- phase image to generate a gas transfer ratio map These maps were denoised and displayed using linear binning (6 bins for RBCgas map and 8 for barriergas map) with thresholds derived from 10 young healthy subjects (age 27~31) This mapping was then applied to 12 IPF patients 7 of whom had follow-up scans to assess progression Results Compared to healthy subjects IPF patients show regions of diminished RBCgas and dramatically higher barriergas In IPF patients significantly more voxels fell in the lowest two RBCgas bins (plt0001 plt0001) while considerably more voxels fell in the 3 highest barriergas bins (plt0001 plt0001 plt0001) Preliminary evaluation of ratio map and histogram analysis shows the ability to detect disease progression and possible therapy response Conclusions Quantitative analysis method using binning maps with thresholds derived from a reference population reveals the key features of IPF IPF is characterized by significantly enhanced barriergas intensity throughout the lung whereas RBCgas remains normal over much of the lung This quantitative binning maps of 129Xe gas exchange are likely to be useful for assessing numerous other disorders


114 Imaging Bacterial Infection with 6-[18F]-Fluoromaltotriose and Positron Emission

Tomography

Mirwais Wardak Gayatri Gowrishankar Evgenios Neofytou Mohammad Namavari et al Stanford University Purpose Bacterial infections continue to represent a significant cause of morbidity and mortality worldwide especially with the emergence of several strains of resistant pathogenic bacteria (eg methicillin-resistant Staphylococcus aureus [MRSA] multidrug-resistant Streptococcus pneumonia etc) The current gold standard for the diagnosis of bacterial infections is based on the examination and culture of bacteria recovered from suspected sites However this method is invasive time-consuming and unable to determine the spread of infection Moreover it is important to find a method that can distinguish bacterial infection from non-bacterial inflammation Recently we developed a novel positron emission tomography (PET) tracer called 6-[18F]fluoromaltotriose which is transported via the maltose transporter a transport system that is exclusive to bacteria and not expressed on mammalian cells The purpose of this study was to investigate 6-[18F]fluoromaltotriose PET imaging for the detection quantification and therapeutic monitoring of bacterial infections in-vivo Methods Three nude rats which contracted a visceral staph infection post-cardiac surgery had dynamic microPET scans performed on them with the tracer 6-[18F]fluoromaltotriose before and after 1-month of therapy with Cefazolin (an antibiotic) List-mode PET data were acquired for 40 min (28 frames total) on a small-animal Inveon microPETCT scanner immediately after tracer injection via a tail vein catheter A healthy immunocompetent rat with an intact immune system served as our control The longitudinal PET images were visually and quantitatively assessed Results At baseline before the start of antibiotic treatment the 6-[18F]fluoromaltotriose PET images showed high tracer uptake at likely sites of bacterial infection near the heart The tracer did not accumulate in inflamed tissue and had a good clearance profile In addition the microflora in the gut is seen with the tracer On post-therapy PET images the original sites of bacterial infection were significantly decreased in their tracer uptake indicating therapeutic response The PET image of the control rat did not show any significant signal in the myocardial region as expected Conclusions 6-[18F]Fluoromaltotriose can be used to image and monitor bacterial infections in-vivo with high sensitivity and specificity We believe that this class of imaging probes will have a significant impact on the clinical management of patients suspected of having bacterial infections Based on these preliminary results plans are being made to do more animal studies and then bring this radiotracer to human trials


115 Multimodal Neuroimaging Evalution of the Default Mode Network in Chronic

Traumatic Brain Injury

Jeffrey Ware University of Pennsylvania Department of Radiology Purpose Traumatic brain injury (TBI) is a leading cause of cognitive morbidity around the world for which functional outcomes have improved little over time Difficulties in developing more effective rehabilitation strategies stem in part from incomplete understanding of the neurobiological substrates of cognitive disability following TBI While existing evidence suggests that structural functional and metabolic alterations within the brainrsquos default mode network (DMN) may underlie specific cognitive sequela of TBI few studies to date have employed multimodal approaches to concurrently investigate these relationships In this study a multimodal approach is used to characterize functional perfusional and structural abnormalities of the DMN in relation to posttraumatic cognitive deficits Methods This study includes 43 subjects who sustained TBI of at least moderate severity and 35 demographically-matched healthy controls Neuropsychological and neuroimaging evaluation was performed at 3 months following injury in the TBI group Imaging consisted of a magnetization-prepared recalled-gradient echo (MPRAGE) T1-weighted sequence 2D pseudo-continuous arterial spin-labelling (pCASL) brain perfusion and a 10-minute resting state fMRI acquisition T1-weighted images were used for manual segmentation of macrostructural lesions and assessment of atrophy using a tensor-based morphometry (TBM) approach ASL data were used to derive whole-brain maps of CBF Resting state data were used to derive measures of static and dynamic resting state functional connectivity (FNC) within the DMN Initially whole-brain CBF and measures of structural atrophy were compared in between TBI and control groups Subsequent analysis focused specifically on the relationship between neuropsychological measures and DMN-specific CBF functional connectivity and atrophy Results Compared to healthy controls subjects with TBI demonstrated several regions of significantly reduced resting perfusion in both cortical and subcortical locations (plt001) Reduced frontal and temporal cortical perfusion demonstrated spatial correspondence with encephalomalacia Reduced CBF was also present in locations without corresponding macrostructural lesions such as the thalamus and sub-regions of the DMN which also demonstrated evidence of atrophy Relative to controls subjects with TBI had elevated static FNC and reduced dynamic FNC within the DMN Among the TBI subject group DMN CBF correlated directly with attentional function (r=037 p=001) and inversely with dynamic connectivity (r=-035 p=002) Conclusions Chronic TBI is associated with persistent and inter-related alterations in structural integrity CBF and functional connectivity of the DMN Our findings suggest that DMN abnormalities are closely related to posttraumatic attentional dysfunction and demonstrate the advantages of using multimodal neuroimaging approaches to characterize and better undestand the neurobiological sequela of TBI



Marta Wells Yan Xu Pei Tang University of Pittsburgh Purpose ndash Glycine receptors (GlyRs) are inhibitory chloride-selective pentameric ligand-gated ion channels found primarily in the brainstem and spinal cord Δ9-tetrahydrocannabinol (THC) potentiates GlyR-α1 and GlyR-α3 subtypes through allosteric interactions with residue S296 in the transmembrane domain of the receptor This positive modulation directly contributes to cannabis-induced analgesia and is independent of the other psychoactive effects of THC Here we perform virtual screening at the S296 cannabinoid-binding site on an ensemble of GlyR-α3 structures in vitro functional validation of top ranked compounds and subsequent molecular dynamics simulations to characterize novel modulators of GlyR-α3 Methods ndash The transmembrane domain of the antagonist-bound GlyR-α3 crystal structure (PDB ID 5CFB) and a homology model of the open state GlyR-α1 NMR structure (PDB ID 2M6I) were used as independent starting points for molecular dynamics simulations to obtain a diverse ensemble of GlyR-α3 structures Over 2 million compounds from the ZINC database of drug-like molecules were screened at the S296 cannabinoid-binding site on each receptor structure Screened compounds were pre-filtered by physiochemical features selected for their ability to penetrate the blood-brain barrier and affect the central nervous system Drugs were ranked based on their predicted binding affinities across GlyR-α3 structures in the closed and open states Results ndash Leading compounds were selected for experimental validation in Xenopus laevis oocytes expressing human GlyR-α3 Several top ranked compounds were found to exhibit dose-dependent potentiation while others inhibited glycinergic currents The two most potent novel potentiators and inhibitors respectively were selected for further characterization in molecular dynamics simulations All four compounds were shown to be stable at the S296 cannabinoid binding site and simulations revealed specific interactions involved in the binding of potentiators and inhibitors and in their mechanisms of allosteric modulation Conclusions ndash We provide compelling evidence that these novel potentiators may be as effective as THC in relieving pain by modulating GlyR-α3 The identified compounds are strong candidates for further evaluation of their therapeutic potential in in vivo experiments In addition we have shown that interactions at the S296 cannabinoid-binding site on GlyR-α3 can produce both positive and negative allosteric effects demonstrating the complexity of the molecular mechanisms of drug modulation in glycine receptors



Moses Q Wilks Marc D Normandin Hushan Yuan Charalambos Kaittanis et al Massachusetts General Hospital Purpose Immune system response specifically monocyte and macrophage infiltration is an important component in a wide range of diseases with many ongoing investigations and clinical trials to measure this response Here we aim to develop an method to monitor monocytemacrophage trafficking with increased sensitivity by loading cells both in and ex vivo with a radio-labeled nanoparticle for PET imaging Methods Monocytes and macrophages were labeled using a modified form of the FDA approved drug Feraheme (FH) a treatment for iron anemia and a strong MRI contrast agent This compound was modified with the addition of 89Zr for PET imaging andor fluorochrome (Cy55) for microscopy and cytometry In Vitro Whole blood and isolated white blood cell fractions were taken from multiple species (mice non-human primate and pig) and were incubated with fluorescent and radioactive versions of the imaging agent at multiple drug concentrations and incubation temperatures for variable times Cellular uptake of nanoparticle was measured by relaxometry gamma counting and flow cytometry In Vivo Mice were given one IV injection of ~250 uCi of 89Zr-FH and imaged serially by microPETCT for up to two weeks Additionally Cy55-FH was administered IV to non-human primates Blood samples were taken from these animals up to 5 days after administration and cell labeling was measured by flow cytometry Results In vitro incubation across modalities showed time and concentration dependent labeling of the white blood cell fraction with labeling blocked when incubated at 4oC Flow cytometry showed that monocytes and macrophages were specifically labeled by Cy55-FH while all other cell types remained unlabeled PET results showed high 89Zr-FH uptake in the liver and spleen with standardized uptake values (SUV) in these organs of ~10 There were also high levels of 89Zr-FH in the lymphatic system with SUVs in excess of 20-30 in some lymph nodes Blood clearance half-life of the compound was ~1h but the uptake processes into the lymph nodes had half-lives ranging between 12-24 hours suggesting a slow cell trafficking process This was confirmed by FACS analysis of primate blood taken after administration of Cy55-FH Peak monocyte labeling occurred approximately 3 hours after injection but slow cell trafficking of these cells out of the blood pool was observed with labeled circulating monocytes present up to 5 days after administration Conclusion We showed a method to specifically label monocytes with a radio-labeled nanoparticle allowing for sensitive and quantitative measurement of monocyte trafficking in vivo


118 Localized Gradient-reversed Ultrafast Z-spectroscopy in vivo at 7T

Neil Wilson Kevin DAquilla Catherine Debrosse Hari Hariharan et al University of Pennsylvania Purpose Chemical exchange saturation transfer is a highly sensitive MR technique for observing metabolite content where labile protons are selectively saturated and allowed to exchange with water protons A z-spectrum is plot of the saturation as a function of offset frequency Here we developed a technique to collect ultrafast z-spectra in vivo that is relatively robust to voxel inhomogeneity Theory Saturating in the presence of a gradient encodes the frequency offset spatially across a voxel This encoding can be resolved by applying a similar gradient during readout Acquiring additional scans with the gradient polarity reversed effectively mirrors the spatial locations of the frequency offsets so that the same physical location of a positive offset in the original scan will contribute a negative offset in the gradient-reversed scan Methods Gradient-reversed ultrafast z-spectroscopy (GRUFZS) was implemented and tested in a modified localized PRESS sequence at 7T Lysine phantoms were scanned at various concentrations and compared with coventionally-acquired z-spectra Scans were acquired in vivo in human brain in homogeneous and inhomogeneous voxels with the ultrafast direction cycled between r p and s Results were compared to those from a similar conventional z-spectroscopy PRESS-based sequence Results Asymmetry spectra from GRUFZS are more consistent and reliable than those without gradient reversal and are comparable to those from conventional z-spectroscopy GRUFZS offers significant acceleration in data acquisition compared to traditional CEST methods with high spectral resolution and showed higher relative SNR effficiency Conclusion GRUFZS offers a method of collecting ultrafast z-spectra in voxels with the inhomogeneity often found in vivo


119 Functional Connectivity Structure of Cortical Calcium Dynamics in Anesthetized and

Awake Mice

Patrick W Wright Adam Q Bauer Grant Baxter Matt D Reisman et al Department of Biomedical Engineering Washington University in St Louis St Louis MO 63130 Purpose Hemodynamic-based markers of cortical activity (eg fMRI optical intrinsic signal imaging) driven by electrical and metabolic activity through neurovascular coupling are an indirect and slow report of brain function and are limited in their utility to deduce underlying brain network dynamics Here we extend functional connectivity (FC) analysis a method for mapping functional relationships using spontaneous brain activity from hemodynamic to Ca2+-dynamic imaging Methods Transgenic mice (n=7) expressing a fluorescent calcium indicator (GCAMP6) driven by the Thy1 promoter in cortical glutamatergic neurons were imaged transcranially in both ketamine-anesthetized and awake states Sequential LED illumination (λ=470 530 590 625nm) enabled concurrent imaging of both GCAMP6 fluorescence emission (corrected for hemoglobin absorption) and hemodynamic activity Somatosensory responses were evoked using a 05mA electrical hindpaw block paradigm Correlative FC network maps were generated for low (0009-008Hz) and high (04-4Hz) frequency bands Cross-correlation anaylsis was used to calculate time delays between GCAMP6 and HbO2 evoked responses as well as to construct pixelwise delay maps between the time series of spontaneous activity at each pixel relative to the whole-brain signal Results Following hindpaw stimulation GCAMP6 provided a response time course sensitive to individual high frequency (2Hz) pulse presentations and preceded the stereotypical hemodynamic response function by ~065s Homotopic HBO2 and GCAMP6 FC maps have similar topographies at low frequencies At higher frequencies GCAMP6 is sensitive to delta band (0-4Hz) activity associated with slow-wave sleep This phenomenon provides a striking effect on the correlation structure of the FC maps from anesthetized mice that is diminished upon wakefulness This state-dependent contrast is driven by an anterior-posterior delay topology associated with delta band activity Conclusions In summary functional neuroimaging of Ca2+ dynamics in mice provides evidence that spatiotemporal coherence in cortical activity is not exclusive to hemodynamics Concurrent Ca2+ and hemodynamic-based imaging will enable the dissociation of changes in ionic networks hemodynamic networks and neurovascular coupling and provide a framework for subsequent studies of neurological disease such as stroke



Iman K Yazdi Afsoon Fallahi Huseyin Avci Ali Tamayol et al Harvard Medical School Brigham and Womens Hospital Introduction Designing constructs that can mimic native skeletal muscle and induce 3D cellular alignment and elongated myotube formation remains an ongoing challenge for skeletal muscle tissue engineering Textile platform have opened a new area in the field Precise control over the distribution of different cell types and microarchitecture of fabricated constructs are considered as key advantages of this technology Insufficient mechanical properties of cell-carrying hydrogel fibers have limited their use Thus the concept of composite cell-laden fibers that can tolerate textile processing and support long-term cell survival and functionality has been recently explored to address these challenges In this work we present corendashshell composite fibers comprising a biodegradable core and UV crosslinkable hydrogel shell Alginate (ALG) and methacrylated gelatin (GelMA) were blended together to prepare composite hydrogel shell While ALG offers a good mechanical support and a template to control cellular alignment GelMA mimics the extracellular matrix and support cellular proliferation and differentiation desired cell functions and interactions Materials and Methods Composite cell-laden fibers were fabricated by coating a hydrogel blend mixed with cells on a biodegradable collagen based suture from ALG-GelMA with concentrations of 1-2 and 10 wv respectively A cell-laden hydrogel fiber was prepared by passing a thread through a hollow channel filled with ALG-GelMA solution mixed with C2C12 cells and then crosslinked with 2 (wv) CaCl2 to strengthen ALG network and then GelMA was further crosslinked through UV irradiation (365 nm 850 mW) We performed physical and mechanical characterization of composite fibers including compressive and elastic modulus In addition we assessed viability and metabolic activity of encapsulated cells using livedead and PrestoBlue assays Cellular morphology and alignment were also assessed through microscopy using α-actin and nuclei immunostaining Results and Discussion Fabricated composite cell-laden fibers containing C2C12 has a thickness of 700 to 1200μm by adjusting the diameter of hollow channel Encapsulated cells in 1 and 15 ALG concentration in ALG-GelMA composites appeared to have higher survival and bioactivity compared to 2 According to these findings at lower ALG concentration higher cell viability and adhesion were seen over 7 days of culture In addition immunostaining data demonstrated that at higher ALG concentration lower cell elongation behavior was seen Furthermore the cell alignment behavior appeared to be directly in correlation with cell density and the diameter of fiber Conclusions We developed a simple technique to fabricate composite cell-laden hydrogel fibers composed of a biodegradable core and a photocurable hydrogel shell for mimicking the native skeletal muscle tissue Encapsulation of C2C12 myoblasts in these fibers demonstrated high viability and ability to induce cellular alignment and elongation These results suggest that by encapsulating cells into composite hydrogel fiber structure guides cellular alignment and elongated myotube formation and provides a suitable 3D environment for nutrition exchange and mechanical support which can potentially be used for skeletal muscle regeneration applications



Rebecca Zaunbrecher Shiv Bhandari Andrea Leonard Kevin Beussman et al University of Washington The giant protein titin has numerous important roles in the cardiomyocyte including providing passive tension and facilitating sarcomere formation Recently an internal promoter was identified in the titin gene (TTN) indicating the presence of a previously unstudied isoform Cronos Although the function of Cronos titin is unknown the majority of disease-causing mutations in TTN are found downstream of this internal promoter suggesting an important role in health and disease To create a cell line to study the role of Cronos titin we have introduced homozygous frameshift mutations in exon 2 of the TTN gene in human induced pluripotent stem cells (Ex2 KO hiPSCs) using the CRISPRCas9 system to prevent translation of full-length titin while leaving the Cronos isoform intact Directed differentiation of Ex2 KO hiPSCs into cardiomyocytes (Ex2 KO hiPSC-CMs) yields contracting cells and immunofluorescence studies indicate the formation of short dispersed myofibrils in Ex2 KO hiPSC-CMs compared to isogenic wildtype controls Additionally staining Ex2 KO hiPSC-CMs with antibodies specific to the MIR and M8-M10 regions of titin downstream of the Cronos internal promoter demonstrates incorporation of these domains into the sarcomere Staining of Ex2 KO hiPSC-CMs with antibodies specific to the Z1Z2 and PEVK regions of titin upstream of the internal Cronos promoter suggests these domains are not present in the sarcomeres We conclude that the Ex2 KO hiPSC-CMs present a system in which to study Cronos titin and could provide important insights into the role of this isoform in sarcomere formation and function



Roy N Zhao JJ Emerson University of California Irvine The Drosophila Genome Nexus (DGN) dataset represents an extremely versatile resource for population genetic and genomic research in D melanogaster comprising a collection of hundreds of genome sequences generated under a consistent and rigorous protocol When performing genetic analyses it is useful to consider the population structure that exists within a dataset as it can confound conclusions about topics of interest such as nucleotide diversity natural selection and allele frequency distributions Population structure within the DGN genomes was investigated using the software structure and a parallel-processing framework for structure was developed to efficiently explore large datasets concurrently Analyses performed on the DPGP3 subset comprising 197 genomes from a single sub-Saharan ancestral range population reflect potential internal demographies within the sample Population structure inferences for the DPGP3 data indicated groupings that were not reported in the initial publication of the DGN with several of the genomes being reliably assigned to common clusters over multiple runs The preliminary results suggest the potential to detect fine-scale population structure within single ancestral range D melanogaster populations which are free from out-of-Africa bottleneck effects and mostly unaffected by cosmopolitan admixture Applying thorough population structure analyses to large diverse and methodologically consistent datasets like the DGN can facilitate the discovery of population genetic insights with high resolution less bias and higher power Additionally the parallelized version of structure is a broadly useful tool expanding the softwarersquos usefulness for analyzing large genomic datasets and enabling its flexible deployment on high-performance computing systems


Grant Writing Review Break-out Session

Group Leader Assignments and Locations

Room Discussion Group Leader Area of Interest

A Philip Bayly Mechanobiology Interdisciplinary research

A Joseph Bonventre

Physician scientist stem cells organoids CRISPR MD-PhD Tissue engineering kidney biomarkers injury and repair

C1C2 Georges El Fakhri

Imaging including Chemistry Nanoparticles Medical Physics and Medical Aspects For MD PhD MD-PhDs

C1C2 James Gee Career Development Grants Mentorship

E1E2 Thomas Link Physician scientist Imaging Musculoskeletal

E1E2 Mia Markey

E1E2 Andrew McCulloch

Professor of Bioengineering Cardiovascular Bioengineering Computational Biology

E1E2 Michael McNittGray

Medical Imaging Scientist Department of Radiology

E1E2 Satdarshan Pal Singh Monga

Physician Scientist Liver Research Regeneration Cancer and Fibrosis

E1E2 Robert Murphy Computational Biology and Automated Science

G1G2 Kathy Nightingale

G1G2 Kim Butts Pauly

MRI Devices Surgical Devices and Guidance Therapeutic Ultrasound

H Shuichi Takayama MicroNanotechnology Entrepreneurship

J Felix Wherli Career Development Awards


Map of Natcher Center


2016 TRAINING GRANTEES MEETING CONTACT LIST

Dr Mariam Aboian University of California San Francisco 25 Amherst Ct Menlo Park California 94025 Phone 650‐285‐7577 E‐mail mariamaboianucsfedu

Dr Alexander AdamHamilton Brook Smith Reynolds 155 Seaport Blvd Boston Massachusetts 2210 Phone 6176075900 E‐mail AlexanderAdamhbsrcom

Dr Olaguoke Akinwande Johns Hopkins School of Medicine 9524 Branchleigh rd Randallstown Maryland 21133 Phone 4104991078 E‐mail gokeakingmailcom

Mr Eric AliottaUCLA 11707 Goshen Ave Apt 7 Los Angeles California 90049 Phone 718‐619‐6877 E‐mail ealiottamednetuclaedu

Mr Gregory Jonathan AnthonyUniversity of Chicago 5461 S Ingleside Ave 1W Chicago Illinois 60615 Phone 815‐531‐9371 E‐mail gjanthonyuchicagoedu

Ms Natasha Antropova University of Chicago 1031 E Hyde Park Blvd apt 3 Chicago Illinois 60615 Phone 4144290135 E‐mail antropovauchicagoedu

Dr Sam Armato The University of Chicago 5841 S Maryland Ave MC 2026 Chicago Illinois 60637 Phone 773‐834‐3044 E‐mail s‐armatouchicagoedu

Dr Anthony AtalaWake Forest University School of Medicine Medical Center Blvd Winston‐Salem North Carolina 27157 Phone 336‐716‐5876 E‐mail aatalawakehealthedu



Dr Baharak Bahmani Harvard Medical School 221 Longwood Ave Boston Massachusetts 2115 Phone 951‐313‐4856 E‐mail bbahmanipartnersorg

Dr Richard BairdNIH NIBIB 6707 Democracy Blvd Bethesda Maryland 20817 Phone (301) 496‐7671 E‐mail bairdrimailnihgov

Dr Pelbreton C Balfour University of Virginia Health System 1215 Lee Street Charlottesville Virginia 22908 Phone 2403389694 E‐mail pcb2hvirginiaedu

Mr John BarrettUniversity of Chicago 510 W Briar Place Apt 407 Chicago Illinois 60657 Phone 7165171462 E‐mail jcb13outlookcom

Dr Robert L Barry Harvard Medical School 45 First Ave 209 Boston Massachusetts 2129 Phone 615‐801‐0795 E‐mail robertbarryvanderbiltedu

Mr Vikram BaruahUniversity of Texas at Austin 1300 Crossing Place Apartment 3321C Austin Texas 78741 Phone 7328957280 E‐mail vikbaruahgmailcom

Dr Walt Baxter Medtronic Neuromodulation 1851 east deere avenue santa ana California 92705 Phone 949‐399‐1677 E‐mail waltbaxtermedtroniccom

Dr Philip BaylyWashington University in St Loouis Campus Box 1185 1 Brookings Drive Saint Louis Missouri 63130 Phone 314‐935‐6081 E‐mail lbarkerwustledu



Hillary Walker Bedell Case Western Reserve 3649 Silsby Rd University Heights Ohio 44118 Phone 3308196202 E‐mail hillarybedell1gmailcom

Mr Michael BellaviaThe Georgia Institute of Technology 925 Canterbury Rd NE Apt 221 Atlanta Georgia 30324 Phone 3158827357 E‐mail mbellavia3gatechedu

Fabrice Christopher Bernard Georgia Institute of Technology 470 16th Street NW APT 1019 Atlanta Georgia 30363 Phone 5162860238 E‐mail fbernard6gatechedu

Mr Adam Scott Bernstein University of Arizona 3940 E Timrod St 267 Tucson Arizona 85711 Phone 9285810482 E‐mail asb2emailarizonaedu

Dr Rohit Bhargava University of Illinois at Urbana‐Champaign 405 N Mathews Ave Urbana Illinois 61801 Phone 2172656596 E‐mail rxbillinoisedu

Emmeline BlanchardGeorgia Institute of Technology 1031 State St NW Apt 201 Atlanta Georgia 30318 Phone 4843402085 E‐mail eblanchard6gatechedu

Mr Kory Blose University of Pittsburgh 13 Hawthorne Rd Pittsburgh Pennsylvania 15221 Phone 8149529934 E‐mail kjb71pittedu

Dr Joseph V Bonventre Brigham and Womens HospitalHarvard Medical School 101 Boston Post Road Wayland Massachusetts 1778 Phone 6174292146 E‐mail joseph_bonventrehmsharvardedu



Mr Nathaniel Braman Case Western Reserve University 11477 mayfield road Cleveland Ohio 44106 Phone 4126512081 E‐mail nmb60caseedu

Ms Macauley Smith Breault Johns Hopkins University 104 West University Pkwy Apt F5 Balitmore Maryland 21210 Phone 908‐963‐2301 E‐mail mbreaul1jhuedu

Dr Colin Brenan HiFiBiO Inc 800 Main Street Cambridge Massachusetts 2139 Phone 781‐248‐9318 E‐mail colinjbrenanieeeorg

Mr Gabriel BronkBrandeis University 91 High St Apartment 3 Waltham Massachusetts 2453 Phone 6179906136 E‐mail gbronkbrandeisedu

Mr Matthew Brovold Wake Forest Institute for Regenerative Medicine 1604 Colonial Ave Greensboro North Carolina 27408 Phone 651‐329‐8999 E‐mail mbrovoldwakehealthedu

Dr Pedro BrugarolasThe University of Chicago 727 East 60th Street Apt 1607 Chicago Illinois 60637 Phone 7735266885 E‐mail brugarolasuchicagoedu

Mr Evan Gregory Buettmann Washington University in St Louis 9158 North Swan Cir Brentwood Missouri 63144 Phone 6362365676 E‐mail buettmannevwudosiswustledu

Alex BuiNA 11696 Montana Ave 302 Los Angeles California 90049 Phone 310‐820‐2186 E‐mail buiamiiuclaedu



Mrs Michelle Bukowski Vanderbilt Institute in Surgery and Engineering 2301 Vanderbilt Place Nashville Tennessee 37235 Phone 6153435447 E‐mail michellebukowskivanderbiltedu

Susie ChaBoston University 44 Cummington St Boston Massachusetts 2215 Phone 14047343952 E‐mail susiechabuedu

Julie Champion Georgia Institute of Technology 950 Atlantic Dr NW Atlanta Georgia 0 Phone 404‐894‐2874 E‐mail juliechampionchbegatechedu

Vandiver ChaplinVanderbilt University 745 East Argyle Ave Nashville Tennessee 37203 Phone 6153105650 E‐mail vlchaplingmailcom

Mr Alvin Chen Rutgers University 599 Taylor Road Piscataway New Jersey 8854 Phone 9083095603 E‐mail alv6688gmailcom

Weilin ChenUniversity of California San Francisco 525 Nelson Rising Lane Apt 717B San Francisco California 94158 Phone 17812289642 E‐mail Inachenucsfedu

Dr Ian Chen Stanford University PO Box 60297 Palo Alto California 94306 Phone 7148564047 E‐mail iychenstanfordedu

Ms Breanne ChristieCase Western Reserve University 2733 Hampshire Rd Apt 405 Cleveland Hts Ohio 44106 Phone 2484598605 E‐mail bpc31caseedu



Dr Fergus Coakley OHSU 3181 SW Sam Jackson Park Road Portland Oregon 97211 Phone 5034944511 E‐mail coakleyfohsuedu

Emily ConlanNIH NIBIB 6707 Democracy Blvd Suite 200 Bethesda Maryland 20892 Phone 301‐451‐2613 E‐mail emilyconlannihgov

Dr Richard Conroy NIBIB 6707 Democracy Blvd Bethesda Maryland 20892 Phone 3014021486 E‐mail conroyrimailnihgov

Crystal CoolbaughVanderbilt University 1161 21st Avenue South Medical Center North AA‐1105 Nashville Tennessee 37232 Phone 615‐936‐0988 E‐mail crystalcoolbaughvanderbiltedu

Brian Thomas Crouch Duke University 3321 Lassiter St Durham North Carolina 27707 Phone 4806784065 E‐mail briancrouchdukeedu

Ms Ivana CuberovicCase Western Reserve University 2741 Euclid Heights Blvd Apt 10 Cleveland Ohio 44106 Phone 214‐437‐2668 E‐mail ixc86caseedu

Dr Joseph P Culver Washington University in St Louis 4515 McKinley Ave St Louis Missouri 63110 Phone 314‐614‐0618 E‐mail culverjwustledu

Kyle S DeckerDuke University 147 Stratford Lakes Drive Durham North Carolina 27713 Phone 716‐863‐2662 E‐mail ksd15dukeedu



Mr Kofi Mawuli Deh Weill Cornell Medical College 445 E 69th St 820 New York New York 10021 Phone 16467190314 E‐mail kod2002medcornelledu

Elizabeth Nyambura DeLassus Washington University St Louis 3849 Virginia Ave St Louis Missouri 63118 Phone 314‐810‐6897 E‐mail delassuslwustledu

Mr Michael Dempsey CIMIT Harvard University 125 Nashua Street Boston Massachusetts 2114 Phone 617‐643‐3844 E‐mail MDEMPSEY1mghharvardedu

Dr Jamal Derakhshan University of Pennsylvania 3400 Spruce St 1 Silverstein Philadelphia Pennsylvania 19104 Phone 215‐964‐5775 E‐mail jamalderakhshanuphsupennedu

Mr Mahesh Devarasetty Wake Forest Institute for Regenerative Medicine 50 W 4th Street Apartment 305 Winston‐Salem North Carolina 27101 Phone 6169013397 E‐mail mdevarasgmailcom

Hendrik DewaldDepartment of Biomedical Engineering Case Western Reserve University 2593 Hampshire Road Apt 15 Cleveland Heights Ohio 44106 Phone (630)550‐6246 E‐mail hendrikdewaldcaseedu

Chelsey Dunham Washington University in St Louis 4910 West Pine Blvd Apt 417 St Louis Missouri 63108 Phone 7034757342 E‐mail chelseydunhamwustledu

Dr Georges El FakhriGordon Center for Medical Imaging Massachusetts General Hospital Harvard Medical School White 427 Radiology Massachusetts General Hospital 55 Fruit Street Boston Massachusetts 2114 Phone 617‐726‐9640 E‐mail elfakhripetmghharvardedu



Ms Alexandriya M X EmondsJohns Hopkins University 1010 Saint Paul Street Apartment 5F Baltimore Maryland 21202 Phone 9894158346 E‐mail aemonds2jhmiedu

Dr Zeynep ErimNIHNIBIB 6707 Democracy Blvd Suite 200 Bethesda Maryland 20892 Phone 301‐451‐4797 E‐mail erimzmailnihgov

Dr Chikezie Eseonu Johns Hopkins Univeristy 1800 Orleans Street Sheikh Zayed Tower Room 6007 Baltimore Maryland 21287 Phone 8049204833 E‐mail ceseonu1jhmiedu

Dr Omid FarokhzadBrigham and Womenrsquos Hospital Harvard Medical School 75 Francis Street Boston Massachusetts 2115 Phone 617‐732‐6093 E‐mail ofarokhzadbwhharvardedu

Mr Greg R Fedewa UCSF 999 Bush St Apt 302 San Francisco California 94109 Phone 5178623648 E‐mail fedewaggmailcom

Mr Stephen Ferguson University of Michigan 930 N University Ave Ann Arbor Michigan 48109 Phone 8437291585 E‐mail safergusumichedu

Mr Dimitrios J Floros UCSD 9500 Gilman Dr Skaggs School of Pharmacy and Pharm Sciences La Jolla California 92093 Phone 8144416784 E‐mail dflorosucsdedu

Daniel FoustWashington University 4394 W Pine Blvd Apt 312 St Louis Missouri 63108 Phone 5093668167 E‐mail dfoustwustledu



Dr Peter T Fox University of Texas Health Science Center at San Antonio Research Imaging Institute UTHSCSA 8403 Floyd Curl Drive San Antonio Texas 78229 Phone 210‐567‐8150 E‐mail foxuthscsaedu

Dr James Solomon Fraser UCSF 600 16th St GH S472E MC 2240 San Francisco California 94107 Phone 4155021863 E‐mail jfraserfraserlabcom

Kara Ellspermann Garcia Washington University in Saint Louis 530 Union Blvd Apt 306 Saint Louis Missouri 63108 Phone 8127069777 E‐mail karaellspermannwustledu

James GeeUniversity of Pennsylvania Penn Image Computing and Science Laboratory Department of Radiology Richards Medical Research Laboratories 3700 Hamilton Walk 6th Floor Philadelphia Pennsylvania 19104 Phone 215 746 6295 E‐mail GEEMAILMEDUPENNEDU

Dr Jeff Gelles Brandeis University Dept of Biochemistry MS009 PO Box 549110 Waltham Massachusetts 2454 Phone 7817362377 E‐mail gellesbrandeisedu

Eric GibbsDuke University 17 Sangre de Cristo Durham North Carolina 27705 Phone 503‐670‐4407 E‐mail edg15dukeedu

Dr Arthur F Gmitro University of Arizona Department of Biomedical Engineering PO Box 245067 University of Arizona Tucson Arizona 0 Phone 520 626‐4720 E‐mail gmitroemailarizonaedu

Dr Randy Lyanne Gollub Massachusetts General Hospital Building 120 2nd Ave Suite 101D MGH Psychiatric Neuroimaging Charlestown Massachusetts 2120 Phone 339‐368‐1689 E‐mail rgollubpartnersorg



Dr John C Gore Vanderbilt University Institute of Imaging Science 1161 21st Ave South Nashville Tennessee 37232 Phone 6153228359 E‐mail johngorevanderbiltedu

Dr Mark GrinstaffBoston University 590 Commonwealth Avenue Department of Chemistry Rm 299 Boston Massachusetts 2215 Phone 617‐358‐3429 E‐mail mgrinbuedu

Mr Simon X Han UCLA 924 Westwood Blvd Suite 420 Los Angeles California 90024 Phone (310) 794‐3539 E‐mail simonxhanuclaedu

Dr Bin HeUniversity of Minnesota 312 Church Street SE Minneapolis Minnesota 55455 Phone 6126261115 E‐mail binheumnedu

Mr Graham Heimberg UC San Francisco Nelson Rising Lane 4th street San Francisco California 94158 Phone 8056989652 E‐mail gheimberggmailcom

Dr William HsuUniversity of California Los Angeles 924 Westwood Blvd Ste 420 Los Angeles California 90024 Phone 310‐794‐3536 E‐mail whsumednetuclaedu

Dr Rosemarie Hunziker NIH NIBIB 6707 Democracy Blvd Bethesda Maryland 20817 Phone 301‐451‐1609 E‐mail hunzikerrmailnihgov

Dr Alan JasanoffMassachusetts Institute of Technology 77 Massachusetts Ave Rm 16‐561 Cambridge Massachusetts 2478 Phone 617‐452‐2538 E‐mail jasanoffmitedu



Mrs Stacy Jones NIH NIBIB 6707 Democracy Blvd Bethesda Maryland 20817 Phone 301‐451‐4780 E‐mail stacyjones‐straehlenihgov

Dr Hilton M KaplanRutgers University 145 Bevier Rd LSB‐101 Piscataway New Jersey 8854 Phone 805‐242‐2050 E‐mail hiltonkaplanrutgersedu

Elizabeth Kay Case Western Reserve University 2096 Surrey Road Apt 6 Cleveland Heights Ohio 44106 Phone 7405013364 E‐mail ekd25caseedu

Dr Christine KelleyNIH NIBIB 6707 Democracy Blvd Bethesda Maryland 20817 Phone 301‐451‐4778 E‐mail kelleycmailnihgov

Amritha Kidiyoor Wake Forest Institute for Regenerative Medicine 391 Technology Way Winston Salem North Carolina 27101 Phone 336‐716‐8672 E‐mail akidiyoowakehealthedu

Dr Lynn Mertens King NIDCR 6701 Democracy Blvd Bethesda Maryland 20892 Phone 301‐594‐5006 E‐mail lynnkiingnihgov

Mr Nathaniel Owen King Washington University in St Louis Juniata St 2W Saint Louis Missouri 63116 Phone 4104040978 E‐mail nkingwustledu

Dr Joachim KohnNew Jersey Center for Biomaterials at Rutgers University 145 Bevier Road Piscataway New Jersey 8854 Phone 848‐445‐3888 E‐mail kohndlsrutgersedu



Surya Kotha University of Washington 850 Republican Street Brotman 419 Seattle Washington 98109 Phone 4259858671 E‐mail suryakuwedu

Christopher M Kramer University of Virginia Health System Box 800170 1215 Lee St Charlottesville Virginia 22908 Phone 4342430736 E‐mail ckramervirginiaedu

Dr Anderson KuoUniversity of Texas Health Science Center at San Antonio 8012 Eagle Peak Helotes Texas 78023 Phone 4048229573 E‐mail kuoauthscsaedu

Dr Robert LabadieVanderbilt University Medical Center 10269 Medical Center North South Tower 1215 21st Avenue South Nashville Tennessee 37232 Phone 615‐936‐2493 E‐mail robertlabadievanderbiltedu

Dr Todd Lawrence Landsman Shape Memory Medical Inc 6078 Ostenberg Dr San Jose California 95120 Phone 8058447229 E‐mail toddshapememcom

Dr Tiffani Bailey LashNIH NIBIB 6707 Democracy Blvd Bethesda Maryland 20817 Phone 3014514778 E‐mail baileytimailnihgov

Ms Karin L Lee Case Western Reserve University 2753 Euclid Heights Blvd Apt 201 Cleveland Heights Ohio 44106 Phone (585)298‐6849 E‐mail kxl313caseedu

Mr Jin Woo LeeUniversity of Michigan 1875 Lake Lila Ln Apt A5 Ann Arbor Michigan 48105 Phone 845‐300‐8829 E‐mail leejinwumichedu



Ms Lily Li University of California Irvine University of California Irvine ‐ CCBS 2620 Biological Sciences 3 Irvine California 0 Phone 949‐293‐8481 E‐mail lillyl1uciedu

Mr Adam LiJohns Hopkins University 108 West 39th Street Apt WC13 Baltimore Maryland 21210 Phone 8058075898 E‐mail ali39jhuedu

Li Li Brigham and Womens Hospital 427 Washington Street Unit 5 Brookline Massachusetts 2446 Phone 801‐550‐5529 E‐mail lli29partnersorg

Jessica Shinwei LinGeorgia Institute of Technology 821 Durant Pl Apt 1 Atlanta Georgia 30308 Phone 6786652493 E‐mail jessicalingatechedu

Mr Eric Lin University of Michigan 911 Oakland Ave Apt 2 Ann Arbor Michigan 48104 Phone 4152728646 E‐mail gogodidiumichedu

Dr Thomas Marc LinkUCSF 400 Parnassus Ave A‐367 Box 0628 San Francisco California 94143 Phone 415‐353‐2450 E‐mail thomaslinkucsfedu

Allen Liu Georgia Institute of Technology 361 17th St NW Unit 2101 Atlanta Georgia 30363 Phone 4044062260 E‐mail aliu30gatechedu

Ms Eulanca Yuka LiuUC San Diego 10710 Wallingford Rd San Diego California 92126 Phone 6269935233 E‐mail eyl015ucsdedu



Willie Jie Long Duke University 1000 N Duke St Apt 24 Durham North Carolina 27701 Phone 3036535358 E‐mail willielongdukeedu

Mr Andrew Joseph Loza Washington University in St Louis School of Medicine 4943 Laclede Ave Apt 1W St Louis Missouri 63108 Phone 614‐204‐2964 E‐mail lozaawustledu

Mr Christopher Mahoney University of Pittsburgh 1019 N Negley Avenue Pittsburgh Pennsylvania 15206 Phone 8046905307 E‐mail cmm237pittedu

Dr Andrew Maidment University of Pennsylvania 3400 Spruce St Radiology Philadelphia Pennsylvania 19104 Phone 2157468763 E‐mail AndrewMaidmentuphsupennedu

Dr Mia K Markey The University of Texas at Austin 107 W Dean Keeton C0800 BME 3314 Austin Texas 78712 Phone 5124711711 E‐mail miamarkeyutexasedu

Mr Nicholas John Matiasz UCLA 924 WESTWOOD BLVD STE 420 LOS ANGELES California 90024 Phone 8608787958 E‐mail matiaszuclaedu

Jonquil R Mau University of Pittsburgh 405 Center for Biotechnology and Bioengineering 300 Technology Drive Pittsburgh Pennsylvania 15213 Phone 678‐768‐2773 E‐mail jrf71pittedu

Mr Aaron Thomas Mayer Stanford University Munger Bldg 3 433C 610 Bowdoin Ln Stanford California 94305 Phone 3214278901 E‐mail amayer9stanfordedu



Margaret McCue MIT 254 Sylvia St Arlington Massachusetts 2476 Phone 8589478747 E‐mail mgmccuemitedu

Dr Andrew D McCulloch UC San Diego Departments of Bioengineering and Medicine 0412 9500 Gilman Drive La Jolla California 0 Phone 858‐534‐5796 E‐mail amccullochucsdedu

Dr Michael Alexander McDonaldJohns Hopkins Medical Institutions Divisions of Nuclear Medicine and Medical Imaging Physics Department of Radiology and Radiological Science 601 N Caroline Street Baltimore Maryland 21287 Phone 3012211819 E‐mail mmcdon21jhmiedu

Dr Michael McNitt‐Gray David Geffen School of Medicine at UCLA Thoracic Imaging Research Group Suite 650 924 Westwood Blvd Los Angeles California 90024 Phone 310‐894‐8979 E‐mail mmcnittgraymednetuclaedu

Dr Christopher Medberry Johnson and Johnson 1301 Goshen Parkway West Chester Pennsylvania 19380 Phone 508‐212‐5171 E‐mail christophermedberrygmailcom

Dr Esther MenaJohns Hopkins 601 North Caroline Str Baltimore Maryland 21287 Phone 4436769893 E‐mail emenago1jhmiedu

Ms Kayla Rae Mendel University of Chicago 5020 S Lake Shore Drive Apt N0309 Chicago Illinois 60615 Phone 4253726064 E‐mail kaylamendelgmailcom

Mr Todd MerchakNIH NIBIB 6707 Democracy Blvd Bethesda Maryland 20817 Phone 301‐496‐8592 E‐mail merchaktmailnihgov



Dr Michael Ian Miga Vanderbilt University VU Station B 351631 Nashville Tennessee 37235 Phone 6153438336 E‐mail michaelmigavanderbiltedu

Dr Satdarshan Monga University of Pittsburgh S422 Biomedical Science Tower University of Pittsburgh 200 Lothrop Street Pittsburgh Pennsylvania 15261 Phone 412‐648‐9966 E‐mail smongapittedu

Mr Manuel Antonio Morales Harvard‐MIT Health Sciences amp Technology 235 Albany street Cambridge Florida 2139 Phone 8476680931 E‐mail moralesqmitedu

Ms Lynn MorinNational Institute on Alcohol Abuse and Alcoholism 5635 Fishers Lane Rockville Maryland 20852 Phone 3014020176 E‐mail lynnmorinnihgov

Michael Mullen University of Minnesota 7514 Ahles Road Saint Cloud Minnesota 56301 Phone 3208282817 E‐mail mulle399umnedu

Dr Robert F MurphyCarnegie Mellon University Computational Biology Department 5000 Forbes Avenue Pittsburgh Pennsylvania 15213 Phone 4122683480 E‐mail murphycmuedu

Dr Kazim H Narsinh UC San Diego 200 West Arbor Drive 8756 San Diego California 92103 Phone 6195436222 E‐mail knarsinhucsdedu

Dan NguyenUCLA Physics and Biology in Medicine Graduate Program 11707 Goshen Avenue Apt 7 Los Angeles California 90049 Phone (832)758‐7108 E‐mail DanNguyenmednetuclaedu



Dr Qing Nie University of California Irvine University of California Irvine ‐ CCBS 540F Rowland Hall Irvine California 0 Phone 949‐824‐5530 E‐mail qnieuciedu

Dr Kathy Nightingale Department of Biomedical Engineering Duke University PO Box 90281 Durham North Carolina 27708 Phone 9196605175 E‐mail kathynightingaledukeedu

Dr Kristin OGrady Vanderbilt University Institute of Imaging Science 1161 21st Avenue South Medical Center North AA‐1105 Nashville Tennessee 0 Phone 512‐791‐3871 E‐mail kristinpogradyvanderbiltedu

Ms Abiola OlatundeMassachusetts General Hospital 149 13th Street Charlestown Massachusetts 2129 Phone 3476784986 E‐mail aolatundemghharvardedu

Dr Laura Ortiz‐Teraacuten Massachusetts General Hospital 149 13th Street Charlestown Massachusetts 2129 Phone 617‐945‐3384 E‐mail lauraortizterangmailcom

Ms Jenna Kirk Osborn Duke University 3208 McQueen Dr Durham North Carolina 27705 Phone 9196193699 E‐mail jennaosborndukeedu

Dr Austin Ryan Pantel Hospital of the University of Pennsylvania 301 South 19th Street Apartment 7C Philadelphia Pennsylvania 19103 Phone 914‐799‐4922 E‐mail austinpanteluphsupennedu

Ramya Parameswaran Biophysical Sciences University of Chicago 5454 South Shore Drive Apt 311 Chicago Illinois 60615 Phone 9253303116 E‐mail ramyapuchicagoedu



Dr Kim Butts Pauly Stanford University Lucas Center 1201 Welch Rd Stanford California 94305 Phone (650)725‐8551 E‐mail kbpaulystanfordedu

John Mark PaulyStanford University 358 Packard Electrical Engineering 350 Serra Mall Stanford California 94305 Phone 650‐723‐4569 E‐mail paulystanfordedu

Mrs Rose Schmitt Perea Physics and Astronomy at Vanderbilt University 600 Rothwood Ave Apt B9 Madison Tennessee 37115 Phone 575‐621‐1126 E‐mail rosespereavanderbiltedu

Ms Steffi Liu PerkinsStanford University 47 Olmsted Road Apt 310 Stanford California 94305 Phone 720‐334‐4161 E‐mail slp979stanfordedu

Dr William J Polacheck Harvard University Center for Life Sciences Boston 2nd Floor 3 Blackfan Circle Boston Massachusetts 2115 Phone 617‐353‐2805 E‐mail polachecbuedu

Dr Joao Prola NettoOregon Health and Science University 3181 SW Sam Jackson Park Rd L603 Portland Oregon 97239 Phone 5034945626 E‐mail prolanetohsuedu

Dr Cyrus A Raji UCSF Department of Radiology 10751 Wilshire Blvd Apt 608 Los Angeles California 90024 Phone 7155137186 E‐mail cyrusrajigmailcom

Dr David RampullaNIH NIBIB 6707 Democracy Blvd Bethesda Maryland 20817 Phone 301‐451‐4774 E‐mail davidrampullanihgov



Ms Anisha Rastogi Case Western Reserve University Department of Biomedical Engineering 2101 Murray Hill Road Apartment 2 Cleveland Ohio 44106 Phone 2196291590 E‐mail axr474caseedu

Dr Michael RegnierUniversity of Washington 1705 NE Pacific St Foege Hall N310F Seattle Washington 98006 Phone 206‐616‐4325 E‐mail mregnieruwedu

Vicki Rein NIH 6707 Democracy Blvd Suite 200 Bethesda Massachusetts 20892 Phone 301‐496‐8126 E‐mail reinvmailnihgov

Ms Stephanie Nicole Reynolds Georgia Institute of Technology 1760 Northside Drive NW Apt 136 Atlanta Georgia 30318 Phone 8507666035 E‐mail sreynolds8gatechedu

Daniel S ReynoldsBoston University 5 Davis Avenue Apt 4 Brookline Massachusetts 2445 Phone 6073721816 E‐mail drey35buedu

Dr Pavel RodriguezThe University of Texas Health Science Center at San Antonio Department of Radiology The University of Texas Health Science Center at San Antonio 7703 Floyd Curl Drive San Antonio Texas 78229 Phone 210‐618‐2015 E‐mail rodriguezp3uthscsaedu

Erica Rosemond NCATS 6701 Demoncracy Blvd Bethesda Maryland 20892 Phone 301‐594‐8927 E‐mail rosemondemailnihgov

Dr Bruce Robert Rosen Massachusetts General Hospital Bldg 149 13th Street Room 2301D Charlestown Massachusetts 2129 Phone 617‐726‐3197 E‐mail brucenmrmghharvardedu



Ms Jacquelyn Olivia Russell University of Pittsburgh 245 Melwood Avenue Apt 804 Pittsburgh Pennsylvania 15213 Phone 609‐202‐7785 E‐mail jor76pittedu

Dr Henry Grady Rylander The University of Texas at Austin 2500 Spanish Oak Trail Round Rock Texas 78681 Phone 512‐259‐1960 E‐mail rylandermailutexasedu

Ms Lindsey T Saldin University of Pittsburgh 450 Technology Drive Suite 300 Pittsburgh Pennsylvania 15219 Phone 412‐624‐5253 E‐mail saldinltupmcedu

Ms Daniela Yvonne Santiesteban UT 220 26th St NW Apmt 3004 Atlanta Georgia 30309 Phone 2252882942 E‐mail dsantigatechedu

Andrew Sawyer Brandeis University 415 South St Waltham Massachusetts 2453 Phone 8164050277 E‐mail asawyerbrandeisedu

Dr Mitchell SchnallUniversity of Pennsylvania Department of Radiology 3400 Spruce St Philadelphia Pennsylvania 19104 Phone 2156623030 E‐mail mitchellschnalluphsupennedu

Dr Seila Selimovic NIHNIBIB 6707 Democracy Blvd Bethesda Maryland 20892 Phone 3014514577 E‐mail seilaselimovicnihgov

Preya ShahUniversity of Pennsylvania 4141 Spruce Street Apt 305 Philadelphia Pennsylvania 19104 Phone 631‐371‐6339 E‐mail preyaashahgmailcom



Mr Adhvait Shah Massachusetts Institute of Technology 4 Hope St Burlington Massachusetts 1803 Phone 7816357918 E‐mail amshahmitedu

Caitlin Anne ShortUniversity of Wisconsin Madison 1618 Fordem Ave Apt 209 Madison Wisconsin 53704 Phone 574‐238‐6170 E‐mail cshort2wiscedu

Mr Adam Robert Sibley University of Chicago 5330 S Kimbark Ave Apt 2 Chicago Illinois 60615 Phone 312‐647‐0018 E‐mail janisper116gmailcom

Dr Claude B SirlinUniversity of California San Diego MR3T Clinical Research Lab‐Liver Imaging Group 408 Dickinson St MC 8226 San Diego California 0 Phone 858249‐9465 E‐mail byddertempucsdedu

Nova F Smedley University of California Los Angeles 924 Westwood Blvd Los Angeles California 90024 Phone 4253308150 E‐mail novasmedleyuclaedu

Brad SolomonCarnegie Mellon 919 Greenfield Ave Pittsburgh Pennsylvania 15217 Phone 314‐440‐4108 E‐mail bradsolgmailcom

Ms Elaine Soohoo Carnegie Mellon University Department of Biomedical Engineering 23A S 25th St Pittsburgh Pennsylvania 15203 Phone 9162303631 E‐mail esoohooandrewcmuedu

Dr Tobin SosnickUniversity of Chicago 929 E 57th St GCIS W101C Chicago Illinois 60637 Phone 773‐218‐5950 E‐mail trsosnicuchicagoedu



Daniel Spagnolo University of Pittsurgh 4355 Murray Ave 2nd Floor Pittsburgh Pennsylvania 15217 Phone 6317415782 E‐mail dspagnolo09gmailcom

Megan Marie SperryUniversity of Pennsylvania 240 Skirkanich Hall 210 S 33rd St Philadelphia Pennsylvania 19104 Phone 9783873763 E‐mail sperrymseasupennedu

Ms Elizabeth Stahl University of Pittsburgh 5507 Margaretta Street Apt 2 Pittsburgh Pennsylvania 15206 Phone 570‐850‐3784 E‐mail ecs40pittedu

Marianne Stark13 1684 Waldeck Street Frisco Minnesota 75034 Phone 817‐397‐0873 E‐mail gagglevolatilestfbigmountainpeacledxyz

Dr Nicole F Steinmetz Case Western Reserve University 10990 Euclid Avenue Cleveland Ohio 44106 Phone 8583568515 E‐mail nicolesteinmetzcaseedu

Mr Jeffrey StoutMassachusetts Institute of Technology HST945 Memorial Dr 411 Dunster House Cambridge Massachusetts 2138 Phone 8579191422 E‐mail jstoutmitedu

Dr Michael Summers Howard Hughes Medical Institute at the University of Maryland Baltimore County 1000 Hilltop Circle Baltimore Maryland 21250 Phone 410‐455‐2527 E‐mail summershhmiumbcedu

Jocelyn SunseriCarnegie Mellon University ‐ University of Pittsburgh Computational Biology 4566 Friendship Avenue Floor 2 Pittsburgh Pennsylvania 15224 Phone 8142320649 E‐mail jss97pittedu



Dr Stefanie Arlene Sydlik Carnegie Mellon University 2323 Sherbrook St Pittsburgh Pennsylvania 15217 Phone 6104425617 E‐mail ssydlikandrewcmuedu

Dr Shuichi Takayama University of Michigan 2800 Plymouth Rd Ann Arbor Michigan 48109 Phone 7346155539 E‐mail takayamaumichedu

Elizabeth Tong University of California San Francisco 2560 Geary Blvd Apt 303 Apartment san francisco California 94115 Phone 4088398985 E‐mail liztonggmailcom

Hari TrivediUCSF 22 Terra Vista Ave Apt A7 San Francisco California 94115 Phone 6787702741 E‐mail haritrivedigmailcom

Ms Jessica Leigh Ungerleider University of California San Diego 9388 Redwood Drive Apt F La Jolla California 92037 Phone 7039658536 E‐mail jlungerlengucsdedu

Dr Hannah Valantine NIH 9000 Rockville Pike Building 1 Rm 316 Bethesda Maryland 20892 Phone 301‐451‐4296 E‐mail HannahValantinenihgov

Dr Alexander Vezeridis UC San Diego 3162 via Alicante Unit H La Jolla California 92037 Phone 4013744275 E‐mail Avezeridisucsdedu

Dr William R WagnerMcGowan Institute for Regenerative Medicine 450 Technology Drive Bridgeside Point II Suite 300 Pittsburgh Pennsylvania 15219 Phone (412) 624‐5327 E‐mail wagnerwrupmcedu



Timothy Adams Wall Carnegie Mellon University 5 Bayard Road Apartment 105 Pittsburgh Pennsylvania 15213 Phone 2158704460 E‐mail twallandrewcmuedu

Kristy WalshVanderbilt University 2517 Fairfax Ave Nashville Tennessee 37212 Phone 440‐525‐4618 E‐mail kristymwalshvanderbiltedu

Christopher Walter Biomedical Engineering 916 Bishops Gate Ln Apt A St Louis Missouri 63122 Phone 3146035823 E‐mail christophermwalterwustledu

Mr Ziyi WangDuke University 2748 Campus Walk Ave 20G Durham North Carolina 27705 Phone 9198086264 E‐mail zw73dukeedu

Dr Xiaoqin Wang Johns Hopkins University 720 Rutland Avenue Traylor 410 Baltimore Maryland 21205 Phone 410‐614‐4547 E‐mail xiaoqinwangjhuedu

Dr Yi WangCornell University 515 East 71st Street Suite 102 New York New York 10021 Phone 6469622621 E‐mail yiwangmedcornelledu

Dr Mirwais Wardak Stanford University The James H Clark Center at Stanford University 318 Campus Drive East Wing First Floor Room E150 Stanford California 94305 Phone 949‐870‐9515 E‐mail mwardakstanfordedu

Dr Jeffrey WareUniversity of Pennsylvania Department of Radiology 1420 Locust Street Apartment 15Q Philadelphia Pennsylvania 19102 Phone 347‐414‐1439 E‐mail jeffreyware2uphsupennedu



Dr Felix W Wehrli University of Pennsylvania Perelman School of Medicine Radiology 1 Founders Building MRI Education Center 3400 Spruce Street Philadelphia Pennsylvania 19104 Phone 215‐662‐7951 E‐mail wehrlimailmedupennedu

Marta WellsUniversity of Pittsburgh 5519 Wilkins Ave Pittsburgh Pennsylvania 15217 Phone 636‐322‐9976 E‐mail mmw88pittedu

Dr Moses Quinn Wilks Massachusetts General Hospital 4 Park Vale Ave Apt 6 Allston Massachusetts 2134 Phone 6075926496 E‐mail MWilksmghharvardedu

Dr David L WilsonCase Western Reserve University 2829 North Park blvd Cleveland Heights Ohio 44118 Phone 2163100302 E‐mail davidwilsoncaseedu

Neil Wilson University of Pennsylvania B1 Stellar‐Chance Laboratories 422 Curie Boulevard Philadelphia Pennsylvania 19104 Phone 8626860480 E‐mail newilsonmailmedupennedu

Mr Michael WolfsonNIH NIBIB 6707 Democracy Blvd Bethesda Maryland 20817 Phone 301‐451‐4778 E‐mail michaelwolfsonnihgov

Dr Dean F Wong Johns Hopkins University School of Medicine Johns Hopkins Outpatient Center 601 N Caroline Street Rm 3245 Baltimore Maryland 21287 Phone 410‐955‐8433 E‐mail dfwongjhmiedu

Dr Savio L‐Y WooUniversity of Pittsburgh 405 Center for Bioengineering 300 Technology Drive Pittsburgh Pennsylvania 15219 Phone 412‐648‐2000 E‐mail ddecenzopittedu



Mr Patrick William Wright Department of Biomedical Engineering Washington University in St Louis St Louis MO 63130 4476 Chouteau Avenue Unit B Saint Louis Missouri 63110 Phone 2566039864 E‐mail pwwrightwustledu

Dr Iman YazdiHarvard Medical School Brigham and Womens Hospital 77 Ave Louis Pasteur HIM 550 Boston Massachusetts 2115 Phone 5127515876 E‐mail iyazdibwhharvardedu

Dr John‐Paul Yu University of Wisconsin School of Medicine and Public Health 4118 Birch Ave Madison Wisconsin 53711 Phone 4159941037 E‐mail jpyuuwhealthorg

Dr Xin YuCase Western Reserve University 10900 Euclid Ave Wickenden 430 Cleveland Ohio 44124 Phone 2163683918 E‐mail xinyucaseedu

Rebecca Zaunbrecher University of Washington 1515 NW 58th St Apt 203 Seattle Washington 98107 Phone 9785051610 E‐mail bzaunuwedu

Mr Roy Nan ZhaoUniversity of California Irvine University of California Irvine ‐ CCBS 2620 Biological Sciences 3 Irvine California 0 Phone 630‐506‐1978 E‐mail royzhaouciedu

Phone E‐mail

Phone E‐mail

DIVISION OF INTERDISCIPLINARY TRAINING

December 2015 wwwnibibnihgovNIHTurning Discovery Into Health

Introduction

Undergraduate Training

Career Development Awards Pre and Post Doctoral Training

NIBIB ContactRichard Baird PhDDirectorDivision of Interdisciplinary TrainingMain 301-451-4792bairdrimailnihgov

wwwnibibnihgov

The mission of the National Institute of Biomedical Imaging and Bioengineering (NIBIB) is to improve human health by leading the development and accelerating the application of biomedical technologies The Institute is committed to integrating the physical and engineering sciences with the life sciences to advance basic research and medical care

To attract and train bright and talented researchers the NIBIB provides support in a broad range of training programs These include disciplinary programs to support and bridge areas of NIBIB relevance multidisciplinary programs to promote the clinical translation of emerging technology and interdisci-plinary programs to train a new cadre of researchers working at the intersection of the biological and physical sciences These programs are designed to support researchers throughout the career con-tinuum increase the number of clinician-scientists and enhance the participation of underrepresented populations in biomedical imaging and bioengineering research

bull Biomedical Engineering Summer Internship Program (BESIP) provides undergraduate biomedical engineering students the opportunity to participate in cutting-edge biomedical research projects at NIH intramural laboratories bull Team-Based Design in Biomedical Engineering (R25) Awards provide support for new or existing design courses in which undergraduate students work in teams on open- ended biomedical design projectsbull DEsign by Biomedical Undergraduate Teams (DEBUT) Challenge awards $45000 in prizes to teams of undergraduate students workingonprojectsofferinginnovative solutions to unmet clinical and health problemsbull Expanding Diversity in Engineering and the Physical Sciences Program supports mentoring research and professional development activities that attract and retain underrepresented undergraduates in STEM fields

Ruth L Kirschstein National Research Service Awards support predoctoral students working toward research degrees and postdoctoral fellows pursuing research in mentorsrsquo laboratories

bull T32 ndash Institutional Research Training Awards support focused predoctoral and postdoctoral research training programs in biomedical engineering for graduate students postdoctoral fellows and radiology residents as well as broad based multidisciplinary and interdisciplinary research training integrating engineering with the biological computational and physical sciences

bull T35 ndash Short-Term Institutional Research Training Awards support short-term clinical or translational research experiences for biomedical engineering graduate studentsbull F30 ndash Individual Predoctoral MDPhD or Other Dual-Doctoral Degree Fellowships provide support for the integrated research and clinical training of promising predoctoral students who are matriculated in a dual-doctoral degree training programbull F31 ndash Individual Predoctoral Fellowships offersupporttooutstandingdoctoralcandidates undertaking training in bioengineering and biomedical imagingbull F31 ndash Individual Predoctoral Fellowships to Promote Diversity in Health-Related Researchofferuptotwoyearsofdoctoral training support to individuals from underrepresented racial and ethnic groups persons with disabilities and those from disadvantaged backgroundsbull F32 ndash Individual Postdoctoral Fellowships provide postdoctoral training support for qualifiedindividualswhohavereceivedthe PhD (or equivalent) degree

Career development awards provide salary and laboratory support for postdoctoral fellows transitioning to faculty positions and junior faculty whoarechangingresearchfieldsorneedprotectedresearch time during critical periods of their careers Transitional Career Developmentbull Pathway to Independence (K99R00) Awards offerfundingforbothmentored training (K99) and independent research (R00) shortening the time between postdoctoral training and research independence

National Institute of Biomedical Imaging and Bioengineering National Institutes of Health


wwwnibibnihgovNIHTurning Discovery Into Health

NIH Blueprint for Neuroscience

NIH Common Fund (Roadmap)

ConferenceMeeting Awards (R13)

Academic Research Enhancement Awards (AREA ndash R15)

Research Education Programs (R25)

Research Supplements

Big Data to Knowledge (BD2K)BD2K is a trans-NIH initiative established to enable biomedical research as a digital research enterprise to facilitate discovery and support new knowledge and to maximize community engagement Thefollowingfundingopportunitiesareofferedinsupportof4 major aims 1) to facilitate broad use of biomedical digital assets by making them discoverable accessible and citable 2) to conduct research and develop the methods software and tools needed to analyze biomedical Big Data 3) to enhance training in the development and use of methods and tools necessary for biomedical Big Data science and 4) to support a data ecosystem that accelerates discovery as part of a digital enterprise

bull Predoctoral Training in Biomedical Big Data Science (T32)bull Mentored Career Development Award in Biomedical Big Data Science for Clinicians and Doctorally Prepared Scientists (K01) bull Revisions to Add Biomedical Big Data Training to Active Institutional Training Grants (T32) bull Courses for Skills Development in Biomedical Big Data Science (R25) bull Open Educational Resources for Biomedical Big Data (R25) Additional information at httpbd2knihgov

December 2015

Basic Career Developmentbull K01 ndash Mentored Research Scientist Development Awards provide basic researchers who wish to obtain experience in an areadifferentfromtheirdoctoralorpostdoctoral research focus up to four years of mentored research support as they transition to research independence bull K25 ndash Mentored Quantitative Research Career Development Awards provide up to four years of mentored research support to individuals with quantitative backgrounds but little experience in biology or medicine who wish to refocus their research on biomedical research

Clinical Career Developmentbull K08 ndash Mentored Clinical Scientist Development Awardsofferclinician-scientistsuptofouryearsofmentored research support as they transition to research independence bull K23 ndash Mentored Patient-Oriented Research Career Development Awards provide clinically trained professionals with up to four years of mentored patient-oriented research support as they transition to research independence

R13 Awards help support national conferences and meetings thatsignificantlyimpactthescientificfieldsrelevanttotheNIBIBmission Priority is given to applications that encourage the participation of students fellows and junior faculty especially members of underrepresented groups

AREA Awards provide up to three years of support for biomedical research conducted by faculty and students at academic institutions that have not been major recipients of NIH research awardsInstitutionaleligibilitycanbeverifiedat httpgrantsnihgovgrantsfundingareahtm

bull Team-Based Design in Biomedical Engineering ndash see Undergraduate Training NIBIB Summer Research Experience Program supports summer research experiences that enhance the communication and research skills of high school science teachers and community college STEM facultybull NIBIB Research Education Programs for Residents and Clinical Fellows provide one or two years of salary and laboratory support for residents from radiology and other NIBIB-relevant residency programs

bull Research Supplements to Promote Diversity in Health-Related Research Awards support individuals from underrepresented racial and ethnic groups persons with disabilities and those from disadvantaged backgrounds bull Research Supplements for Career Reentry Awards enable talented fellows and early-career faculty with high research potential to reenter an active research career after a qualifying interruption for family or other responsibilities

Enhancing Neuroscience Diversity through Undergraduate Research Education (ENDURE) funds collaborative neuroscience research partnerships between undergraduate institutions and graduate neuroscience research training programs Additional information at httpneuroscienceblueprintnihgov

NIH Directorrsquos Early Independence Awards allow exceptional early-career researchers to omit postdoctoral training and establish independent research programs NIH Directorrsquos New Innovator Awards support innovative proposals from early-career researchers with the potential for high impact on biomedical research Additional information at httpcommonfundnihgov

NIBIB ContactsPleasecontactthefollowingprogramstaffwithquestionsaboutthe above programs We welcome the opportunity to speak with potential applicants about our training programsMore information at httpwwwnibibnihgovTrainingRichard Baird PhD Director Division of Interdisciplinary Training (DIDT)301-496-7671 bairdrimailnihgov

Zeynep Erim PhD Program Director DIDT 301-451-4797 erimzmailnihgov


October 2014 wwwnibibnihgovNIHTurning Discovery Into Health

Introduction


Pre and Post Doctoral Training

NIBIB ContactRichard Baird PhDDirectorDivision of Interdisciplinary TrainingMain 301-451-4792bairdrimailnihgovwwwnibibnihgov


To attract and train bright and talented researchers the NIBIB provides support in a broad range of training programs These include disciplinary programs to support and bridge areas of NIBIB relevance multidisciplinary programs to promote the clinical translation of emerging technology and interdisci-plinary programs to train a new cadre of researchers working at the intersection of the biological and physical sciences These programs are designed to support researchers throughout the career contin-uum increase the number of clinician-scientists and enhance the participation of underrepresented populations in biomedical imaging and bioengineering research

bull Biomedical Engineering Summer Internship Program (BESIP) provides undergraduate biomedical engineering students the opportunity to participate in cutting-edge biomedical research projects at NIH intramural laboratories

bull Team-Based Design in Biomedical Engineering (R25) Awards provide support for new or existing design courses in which undergraduate students work in teams on open- ended biomedical design projects

bull DEsign by Biomedical Undergraduate Teams (DEBUT) Challenge awards $45000 in prizes to teams of undergraduate students working on projects offering innovative solutions to unmet clinical and health problems

bull Expanding Diversity in Engineering and the Physical Sciences Program supports mentoring research and professional development activities that attract and retain underrepresented undergraduates in STEM fields

Ruth L Kirschstein National Research Service Awards support predoctoral students working toward research degrees and postdoctoral fellows pursuing research in mentorsrsquo laboratories Institutional Awards

bull T32 ndash Institutional Research Training Awards support focused predoctoral and postdoctoral research training programs in biomedical engineering for graduate students postdoctoral fellows and radiology residents as well as broad based multidisciplinary and

interdisciplinary research training integrating engineering with the biological computational and physical sciences

bull T35 ndash Short-Term Institutional Research Training Awards support short-term clinical or translational research experiences for biomedical engineering graduate students Individual Awards

bull F30 ndash Individual Predoctoral MDPhD or Other Dual-Doctoral Degree Fellowships provide support for the integrated research and clinical training of promising predoctoral students who are matriculated in a dual-doctoral degree training program

bull F31 ndash Individual Predoctoral Fellowships offer support to outstanding doctoral candidates undertaking training in bioengineering and biomedical imaging

bull F31 ndash Individual Predoctoral Fellowships to Promote Diversity in Health-Related Research offer up to two years of doctoral training support to individuals from underrepresented racial and ethnic groups persons with disabilities and those from disadvantaged backgrounds

bull F32 ndash Individual Postdoctoral Fellowships provide postdoctoral training support for qualifiedindividualswhohavereceivedthe PhD (or equivalent) degree


Training Programs







October 2014

Career development awards provide salary and laboratory support for postdoctoral fellows transitioning to faculty positions and juniorfacultywhoarechangingresearchfieldsorneedprotectedresearch time during critical periods of their careers Transitional Career Development

bull Pathway to Independence (K99R00) Awards offer funding for both mentored training (K99) and independent research (R00) shortening the time between postdoctoral training and research independence

Basic Career Development

bull K01 ndash Mentored Research Scientist Development Awards provide basic researchers who wish to obtain experience in an area different from their doctoral or postdoctoral research focus up to four years of mentored research support as they transition to research independence

bull K25 ndash Mentored Quantitative Research Career Development Awards provide up to four years of mentored research support to individuals with quantitative backgrounds but little experience in biology or medicine who wish to refocus their research on biomedical research

Clinical Career Development

bull K08 ndash Mentored Clinical Scientist Development Awards offer clinician-scientists up to four years of mentored research support as they transition to research independence

bull K23 ndash Mentored Patient-Oriented Research Career Development Awards provide clinically trained professionals with up to four years of mentored patient-oriented research support as they transition to research independence



bull Team-Based Design in Biomedical Engineering ndash see Undergraduate Training

bull NIBIB Summer Research Experience Program supports summer research experiences that enhance the communication and research skills of high school science teachers and community college STEM faculty

bull NIBIB Research Education Programs for Residents and Clinical Fellows provide one or two years of salary and laboratory support for residents from radiology and other NIBIB-relevant residency programs

bull Research Supplements to Promote Diversity in Health-Related Research Awards support individuals from underrepresented racial and ethnic groups persons with disabilities and those from disadvantaged backgrounds

bull Research Supplements for Career Reentry Awards enable talented fellows and early-career faculty with high research potential to reenter an active research career after a qualifying interruption for family or other responsibilities

NIBIB ContactsPlease contact the following program staff with questions about the above programs We welcome the opportunity to speak with potential applicants about our training programsMore information at httpwwwnibibnihgovTrainingRichard Baird PhD Director Division of Interdisciplinary Training (DIDT)301-496-7671 bairdrimailnihgov


Career Development Awards

Trans-nIH Programs



IntroductionNIBIB ContactsRichard Baird PhDDirectorDivision of Interdisciplinary TrainingMain 301-451-4792bairdrimailnihgov

wwwnibibnihgov

Lorem ipsum dolor sit amet consectetur adipiscing elit sed do eiusmod tempor incididunt ut labore et dolore magna aliqua Ut enim ad minim veniam quis nostrud exercitation ullamco laboris nisi ut aliquip ex ea com-modo consequat Duis aute irure dolor in reprehenderit in voluptate velit esse cillum dolore eu fugiat nulla pariatur


Big Data to Knowledge (BD2K)BD2K is a trans-NIH initiative established to enable biomedical research as a digital research enterprise to facilitate discovery and support new knowledge and to maximize community engagement The following funding opportunities are offered in support of 4 major aims 1) to facilitate broad use of biomedical digital assets by making them discoverable accessible and citable 2) to conduct research and develop the methods software and tools needed to analyze biomedical Big Data 3) to enhance training in the development and use of methods and tools necessary for biomedical Big Data science and 4) to support a data ecosystem that accelerates discovery as part of a digital enterprise

bull NIH Big Data to Knowledge (BD2K) Initiative Research Education Massive Open Online Course (MOOC) on Data Management for Biomedical Big Data (R25) This funding announcement seeks applications for the development of a Massive Open Online Course (MOOC) that covers a comprehensive set of topics related to the management of biomedical Big Data httpgrantsnihgovgrantsguiderfa-filesRFA-LM-15-001html

bull NIH Big Data to Knowledge (BD2K) Initiative Research Education Open Educational Resources for SharingAnnotatingandCuratingBiomedicalBigData(R25) This funding announcement seeks applications for the development of curriculum modules that can be used by librarians and other information specialists to prepare researchers graduate students and research staff to be full participants in the global community that maintains and accesses digitally-stored biomedical Big Data httpgrantsnihgovgrantsguiderfa-filesRFA-LM-15-002html

bull Predoctoral Training in Biomedical Big Data Science (T32) This funding announcement seeks applications for graduate training programs in Big Data Science for the expressed purpose of training the next generation of scientists who will develop computational and quantitative approaches and tools needed by the biomedical research community to work with biomedical Big Data in the biomedical sciences httpgrantsnihgovgrantsguiderfa-filesRFA-HG-14-004html

bull RevisionstoAddBiomedicalBigDataTrainingtoActiveInstitutionalTrainingGrants(T32) This funding announcement seeks to allow revisions (competitive supplements) to add a Big Data Science track to active T32 institutional training grants for the expressed purpose of training the next generation of scientists who will develop computational and quantitative approaches and tools needed by the biomedical research community httpgrantsnihgovgrantsguiderfa-filesRFA-HG-14-005html

bull RevisionstoAddBiomedicalBigDataTrainingtoActiveNLMInstitutionalTrainingGrantsin Biomedical Informatics (T15) This funding announcement seeks to solicit revisions (competitive supplements) to add a Big Data Science track to active T15 institutional training grants for the expressed purpose of training the next generation of scientists who will develop computational and quantitative approaches and tools needed by the biomedical research community httpgrantsnihgovgrantsguiderfa-filesRFA-HG-14-006html

bull MentoredCareerDevelopmentAwardinBiomedicalBigDataScienceforCliniciansandDoctorally PreparedScientists(K01) The objective of this NIH Mentored Research Scientist Development Award (K01) is to provide salary and research support for a sustained period of ldquoprotected timerdquo (3-5 years) for intensive research career development under the guidance of an experienced mentor or sponsor in biomedical Big Data Science httpgrantsnihgovgrantsguiderfa-filesRFA-HG-14-007html

bull Courses for Skills Development in Biomedical Big Data Science (R25) This funding announcement encourages the development of creative educational activities with a primary focus on Courses for Skills Development httpgrantsnihgovgrantsguiderfa-filesRFA-HG-14-008html



wwwnibibnihgovNIHTurning Discovery Into HealthOctober 2014

NIH Common Fund (Roadmap)NIH Directorrsquos Early Independence Awards allow exceptional early-career researchers to omit postdoctoral training and establish independent research programs httpcommonfundnihgovearlyindependenceindex

NIH Directorrsquos New Innovator Awards support innovative proposals from early-career researchers with the potential for high impact on biomedical researchhttpcommonfundnihgovnewinnovatorindex

NIH Directorrsquos Pioneer Awards complement NIHrsquos traditional investigator-initiated grant programs by supporting individual scientists of exceptional creativity who propose pioneering ndash and possibly transforming approaches ndash to major challenges in biomedical and behavioral researchhttpcommonfundnihgovpioneerindex

NIH Directorrsquos Transformative Research Awards are created specificallytosupportexceptionallyinnovativeandorunconventionalresearch projects that have the potential to create or overturn fundamental paradigmshttpcommonfundnihgovTRA

Additionalinformationathttpcommonfundnihgov

NIH Blueprint for NeuroscienceEnhancing Neuroscience Diversity through Undergraduate Research Education (ENDURE) funds collaborative neuroscience research partnerships between undergraduate institutions and graduate neuroscience research training programs Additionalinformationathttpneuroscienceblueprintnihgov

bull Open Educational Resources for Biomedical Big Data (R25) This funding opportunity announcement encourages the development of creative educational activities with a primary focus on Curriculum or Methods Development httpgrantsnihgovgrantsguiderfa-filesRFA-HG-14-009html

bull Additionalinformationathttpbd2knihgov

BRAIN InitiativeLorem ipsum dolor sit amet consectetur adipiscing elit sed do eiusmod tempor incididunt ut labore et dolore magna aliqua Ut enim ad minim veniam quis nostrud exercitation ullamco laboris nisi ut aliquip ex ea commodo consequat Duis aute irure dolor in reprehenderit in voluptate velitessecillumdoloreeufugiatnullapariaturExcepteursintoccaecatcupidatatnonproidentsuntinculpaquiofficiadeseruntmollitanimidest laborum

Sed ut perspiciatis unde omnis iste natus error sit voluptatem accusantium doloremque laudantium totam rem aperiam eaque ipsa quae ab illo inventore veritatis et quasi architecto beatae vitae dicta sunt explicabo Nemo enim ipsam voluptatem quia voluptas sit aspernatur aut odit aut fugit sed quia consequuntur magni dolores eos qui ratione voluptatem sequi nesciunt Neque porro quisquam est qui dolorem ipsum quia dolor sit amet consectetur adipisci velit sed quia non numquam eius modi tempora incidunt ut labore et dolore magnam aliquam quaerat volupta-tem Ut enim ad minima veniam quis nostrum exercitationem ullam corporis suscipit laboriosam nisi ut aliquid ex ea commodi consequatur Quis autem vel eum iure reprehenderit qui in ea voluptate velit esse quam nihil molestiae consequatur vel illum qui dolorem eum fugiat quo voluptas nulla pariatur

NIBIB Scientific Program

Presentations

Brief Program OverviewAdvanced Biomaterials (AB)

Design synthesis characterization processing and manufacturing of novel materials

and their development and use in medical therapies (particularly for implantable

devices tissue engineering imaging agents biosensors and actuators)

Current Award Distribution

(by mechanism)


(by topic)

Active Awards (FY15)

Total = $7007630 N = 23

Success rates

FY13 = 4

FY14 = 8

FY15 = 15

Devices (7)

Scaffolds (8)

Growth

Factors (5)

Imaging (1)

Cell

Interactions (2)

Rosemarie Hunziker

Chart1

0
0
1
0
5
0
1
13
3
0
0
0
0
0

Data

Data

Criteria

Formats

Chart1

8
7
1
2
5

Data

Data

Criteria

Formats

Brief Program Overview

Tissue EngineeringRegenerative Medicine (TE)Enabling technologies for engineered constructs (in vitro and in vivo)

Scaffolds that mimic extracellular matrix in composition and structure to support

multiple cell types in defined spatial orientation

Biomaterials for scaffolds that guide cell growth differentiation and migration

Real-time non-invasive monitoring of function and cell-environment interactions

Predictive computational models and rational design of engineered 3D tissues

High throughput assays and instruments that reduce cost time complexity

Novel bioreactors and systems for large scale production of cells and tissues

Preservation sterilization packaging and transporting living tissue-products

Rosemarie Hunziker

Success rates

FY13 = 13

FY14 = 14

FY15 = 18


Total = $37278793 N = 91

Award Distribution (by mechanism)

Chart1

0
3
3
3
34
4
10
29
1
1
2
1
0
0

Data

Data

Criteria

Formats


Tissue EngineeringRegenerative Medicine (TE) - 2

Award Distribution(by target tissue)

Award Distribution(by technology thrust)

Scaffolds (38)

Bioreactors (6) Cells (5)Devices (6)

Electrical Signaling (5)

Growth Factors (3)

Tissue Chips (13)

Imaging (6)

Mechanics

(14)Preservation

(3)

Blood (8)

Bone cartilage (7)

Cardio-vascular (21)

Neural (9)Liver (6)

Stem Cells

(13)

Other (30)

Other includes gut immune kidney lung

cancer reproductive skinconnective sensory Rosemarie Hunziker

Chart1

6
5
6
5
3
13
6
14
4
38

Data

Data

Criteria

Formats

Chart1

8
7
21
9
6
13
30

Data

Data

Criteria

Formats

Rosemarie Hunziker PhD


Micro-Biomechanics (BM)

Listed on the web site but not populated

This research falls under ldquoBiomaterialsrdquo or sometimes

ldquoTissue Engineeringrdquo One grant here and link to EB is

weak There is a SPARC grant here for tracking purposes

but it is really a Tissue Engineering project

Tiffani Bailey Lash PhD

SensorsMicro- and Nano Systems Platform Technologies

Telehealth

7

Biosensors

bull Includes novel signal transduction approaches materials for molecular recognition biocompatibility signal processing fabrication technologies actuators and power sources

Micro- and Nano Systems Platform Technologies

bull Includes the development of BioMEMS microfluidics and nanoscale technologies including micro-total analysis systems arrays and biochips for detection and quantitation of clinically relevant analytes in complex matrices

Telehealth

bull Supports technology development that incorporates telemetry and remote access in the acquisition analysis and monitoring of biomedical data

The NETWORK

The National Institute of Biomedical Imaging and Bioengineering (NIBIB) proposed a nationwide initiative to create a research network that would build multidisciplinary partnerships and expertise in the development of integrated systems that address unmet clinical needs at the point-of-care

The CENTERS

Collaborate with scientists and engineers on exploratory technology projects Provide training dissemination and mentoring resources to the POC

technologies community Engage clinicians and POCT developers to facilitate clinical adoption Promote collaborations and partnerships with multiple stakeholders including

academia industry non-profit investors and government

8

bull Goal Develop a non-invasive health monitoring system for pediatric asthma epidemiological research

bull Components

Pediatric Research using Integrated Sensor Monitoring Systems (PRISMS) Program

Sensorsbull Sensor development bull Environment and physiological measurements

Informatics

bull Environmental data acquisition capabilities bull Secure data transmission processing

integration

DataCoordination

bull Consistent annotation of data and tools

bull Integrate and link data for access and analysis

10

bull NSF NIH Smart and Connected Health (R01)bull NCI Academic Industry Partnerships (R01)bull Cancer Detection Diagnosis and Treatment

Technologies for Global Health (UH2UH3)bull Development of Translation of Medical

Technologies to Reduce Health Disparities (SBIR)

David RampullaProgram DirectorDelivery Systems for Drugs and Biologics

Synthetic Biology for Technology Development

NIBIBNIH

301-451-4774 davidrampullanihgov

Programs

Gene and Drug Delivery

Synthetic Biology

Technologies

Gene and Drug Delivery Areas of Interest

bull What we want to deliverhellipndash Drugs nucleic acids peptides proteins vaccines genes small

molecules and theranostics

bull Getting it therehellipndash Liposomes micelles nanoparticles dendrimers microneedles

and other biomaterials avoiding immune uptake delivery mechanisms

bull Triggering deliveryhellipndash Receptor-ligand binding ultrasound electroporation and

implantable pumps

bull The scopehellipndash Engineering delivery vehicle or device proof-of-concept testing

from in vitro to in vivo studies

About getting the cargo to disease sitehellip intact with as few side effects

as possible with maximum efficacy

Bioengineering Brain Cancer Therapy Targeted Gene Therapy Using Nanoparticles

Limitations of brain cancer

treatment and deliverybull Median survival with glioblastoma

lt2 years

bull Current treatment surgery

chemotherapy and radiation

therapy

bull Viral methods currently used for

gene therapy in humans have poor

safety profiles

Alternative Nanoparticle gene therapy that works in vivo

Drug + NPsSuicide gene expressed

Tumor killing

An inactive ldquoprodrugrdquo administered systemically gets ldquoturned onrdquo only in proliferating (ie cancer) cells by a suicide gene in optimized nanoparticles (NPs) to shrink tumors

httppubsacsorgdoipdf101021nn504905q

ACS NANO

Nanoparticle Gene Delivery Works1

Identified top NP

formulations

which lead to

nearly 100 killing

of cancer cells in

vitro

hellipthat distribute

widely throughout

tumor

2

Suicide geneControl

Prodrug Concentration (microgml)

Cell KillingRat Glioma

C

ell D

eath

hellipand lead to enhanced

survival in rat model

3

Control

Prodrug

DNA + Prodrug

Control NPs + ProdrugSuicide Gene NPs + Prodrug

Synthetic Biology Areas of Interest

bull Synthetic Biology ishellipndash The design and wholesale construction of new biological parts and systems and

the re-design of existing natural biological systems for tailored purposes

bull Applications inhellipndash Biomaterials drug and gene delivery systems and devices mathematical

modeling simulation and analysis medical implants sensors and tissue engineering

bull Synthetic biology approaches forhellipndash Development of signal-sensing biomaterials genetic switches for the control of

gene delivery synthetically engineered viruses and bacteriophages as therapies synthetic circuits for gene therapy synthetic control of biosensors through environmentally responsive promoters and synthetic control systems for the production of biomaterials

bull The scopehellipndash Engineering control strategies to enable cell-based systems for health

About creating the tools for new or improved biological function from the

bottom-up

Areas of Growthbull Engineered immune cells programmed

to adapt and kill (cancer)

bull Engineered bacteria to sense and

release anti-inflammatory molecules

(Crohnrsquos disease)

bull Engineered bacteria to digest sugars

and signal to an engineered human cell

to trigger a satiety response (metabolic

syndrome)

MA Fischbach et al 179 Sci Transl Med

Cell-based therapeutics

Engineering and delivery

David Rampulla PhD

Program Director Delivery Systems for Drugs and Biologics Synthetic Biology for Technology Development

National Institute of Biomedical Imaging and Bioengineering (NIBIB)

National Institutes of Health (NIH)

301-451-4774davidrampullanihgovwwwnibibnihgov

hellip improving health by leading the development and accelerating the application of biomedical technologies

Precise neural control of end-organ system function to treat diseases and conditions

Opportunity Neuromodulation of end-organ function holds promise in treating many diseasesconditions

Challenge The mechanisms of action for neuromodulation therapies remain poorly understood

The SPARC program will uncover the underlying mechanisms of neuromodulation therapies and spur development of more advanced safe and effective therapies

Anatomical and Functional Mapping Neural circuit maps for multiple major organs Electrodes surgical procedures and stimulation protocols

Next Generation Tools and Technologies Technologies to define PNS control of organ function Next generation neuromodulation therapies

Market-Approved Technology for New Market Indications New indications for existing approved devices New therapeutic opportunities and methodologies

Data Coordination Mapping and Modeling Center Public data resource containing all SPARC data Neural Circuit Maps

Technology

BiologyTherapy

Grace CY Peng PhDNIBIBgracepengnihgovhttpswwwimagwikinibibnihgov

Environment

Organism

Organ Systems

Organs

Tissues

Cells organelles

Pathways

Protein

RNA

DNA

ldquohellipunderstanding physiological systems in health and disease can only be achieved through quantitative modeling and cannot be understood using lsquomental modelsrsquo rdquo

- Winslow et al 2012

George Em Karniadakis

Division of Applied Science amp Technology

The focus of the division is to support the development of innovative biomedical imaging technologies that are low cost and accessible transform

our understanding of biological and disease processes and enable patient centered healthcare

httpswwwnibibnihgovresearch-fundingdivision-applied-science-technology-dast

The primary focus of this program is the improvement of technologies for diagnostic interventional and therapeutic uses of ultrasound The diagnostic ultrasound program includes but is not limited to the design development and construction of transducers transducer arrays and transducer materials innovative image acquisition and display methods innovative signal processing methods and devices and optoacoustic and thermoacoustic technology It also includes the development of image-enhancement devices and methods such as contrast agents image and data presentation and mapping methods such as functional imaging and image fusion

The interventional ultrasound program includes the use of ultrasound for therapeutic use or as an adjunct for enhancement of non-ultrasound therapy applications Examples include but are not limited to high-intensity focused ultrasound (HIFU) as a non-invasive or minimally invasive interventional surgical or therapy tool and as an adjunct interventional tool It also includes the use of ultrasound contrast agents for therapy and for targeted drug delivery and the use of ultrasound for image-guided surgery biopsy and other interventions

Ultrasound Diagnostic and Interventional

Richard Conroy PhD

bull Ultrasound Imaging of Breast by Use of a Hemispheric Array and Inverse Scattering

bull Gap Feedback Linearization of CMUTs for Harmonic Imaging and HIFUbull Acoustic Holography as a Metrological Tool in Ultrasound Therapy bull Rapid Multiscale Sensing Using Acoustic Detection Mechanisms bull Blood-based biomarker amplification using high intensity focused ultrasound

(HIFU)bull Clutter Suppression in Echocardiography Using Short-Lag Spatial Coherence

Imaging bull Acoustic Imaging of Sentinel Node Matastasis using Plasmonic Nanosensorsbull Dual-frequency intravascular arrays for functional imaging of atherosclerosisbull Brain Ultrasound Computed Tomography Through the Intact Skull bull Biogenic Gas Nanostructures As Molecular Imaging Reporters For Ultrasound bull Acoustic Radiation Force Based Hepatic Elasticity Quantification and Imagingbull Metrology and Nonlinear Acoustics Bioeffects of High Intensity Focused

Ultrasound

Ultrasound Diagnostic and InterventionalCurrently Funded Technologies

Molecular Imaging

This program supports development optimization and application of targeting imaging agents imaging methods and related softwarehardware for the detection of normal biological and pathophysiological processes in living subjects at the cellular and molecular levels Imaging agents may include surface modified molecular targeting or bioreactive nanoparticles radionucleate-labeled agents theranostic agents and high sensitivityspecificity molecular imaging approaches etc The goal of this program is to generate robust molecular imaging agents and platforms applicable to basic preclinical and clinical research across all disease areas for better understanding of disease progression and therapeutic developments

Richard Conroy PhD

bull Nanophotosensitizers for Regenerative Phototherapy of Tumorsbull Study of Advanced Eu(II)-Based Contrast Agents for Ultra-High Field

Magnetic Resonancebull Hybrid nanomaterials for dynamic intracellular radioisotope detectionbull Developing Biosensors for Signaling Lipidsbull Tracking cardiac engraftment and viability of MiPSC by MRIbull Advanced Manufacturing Process for High Performance MRI Contrast Agentbull Microscopic Imaging of Tissue Oxygen Delivery Altered by Microvascular

Changebull Nanoparticle CT Contrast Agents for Reduced Radiation Dose and New

Imaging Applicationsbull Multi-Layered Valency A Novel Design of Peptidic Imaging Agents for αvβbull Designing group specific PET ligands for mGluR2 bull Targeted fluorescent indicators for endothelial physiology Ca(II) ROS NObull Developing MRI sensors for monitoring Zn2+ using iCEST

Molecular ImagingCurrently Funded Technologies

Optical Imaging and Spectroscopy

The development and application of optical imaging microscopy and spectroscopy techniques and the application of optical imaging contrasts and probes Supported research areas include fluorescence bioluminescence OCT SHG IR imaging diffuse optical tomography optical microscopy and spectroscopy confocal and multiphoton microscopy flow cytometry and the development of innovative light sources and fiber optic imaging devices

Behrouz Shabestari PhD

bull Adaptive Miniature Microscopy Platform for High Throughput Biological Imaging

bull In Vivo Optical Detection of Dysplasia in Esophagus

bull Desorption Electrospray Ionization Mass Spectrometry Imaging in Clinical Diagnostics

bull Partnership for Primary Care Imaging

bull Technology development for in vivo deep tissue imaging

bull Cost-effective MHz rate Optical Coherence Tomography for biomedical applications

bull Nondestructive High Resolution Imaging Platform For Tissue Regeneration Research

bull Fluorescence lifetime tomography of tumor physiology in small animals

bull Development of preclinical HTS for discovery of drugs modulating apoptosis

bull In vivo Handheld Coherent Raman Scattering (CRS) Microscopy for Glioma Imaging

bull Axial Slice Light Sheet Microscopy

bull Super-resolution imaging via programmable autonomous blinking

bull Optical small animal imaging unit for quantification of bacterial infections

Optical Imaging and SpectroscopyCurrently Funded Technologies

P41 Centers with Optical Imaging and Spectroscopy Components

The Center for Biomedical OCT Research and Translation (CBORT)

Advanced Structural Imaging

Functional and Compositional Contrast

Multimodal OCT Imaging

httpoctresearchorg

httplbrcmitedu

integrative photonic solutions to complex problems in biological research pharmaceutical development and medical diagnosis

P41 Centers withOptical Imaging and Spectroscopy Components

httplammpbliuciedu

X-Ray CT and Ion Beam

Peer-Reviewed research grants (R01 R21 R03) Bioengineering Research Partnerships (BRP) Cooperative Agreements (U01) and SBIRsSTTRs

Areas of interest include but not limited to computed tomography and radiography digital fluoroscopy development of novel improved detector systems CT reconstruction algorithms photon-counting detectors spectral CT approaches to radiation dose reduction CT contrast agents novel applications such as scattered radiation phase contrast imaging proton and other ion beam imaging and associated technologies (eg improved Bragg peak localization)


Initiative Dose Reduction in CT amp X-Ray Imaging

In response to public concerns NIBIB launched the ldquoAchieving Sub-mSvStudiesrdquo initiative which calls for development of new technologies to lower patient exposures without compromising diagnostic image quality performanceA combination of approaches can yield ~10x reduction in dose


In the three years of the FOA five complementary grants have been funded encompassing hardware algorithmic and observer-based studies to accomplish the overall goal

bull U01 EB017185 (PI McCollough - Mayo Clinic 2013) Model observers that correlate with human performance photon-counting detectors software for patient- and task-optimized scanning parameters (Platform Siemens)

bull U01 EB018758 (PI Stayman - Johns Hopkins U 2014) Task-driven diagnostic CT scanner with task-based mathematical observer for patient-specific acquisition-dependent beam modulation (Platform Phillips)


bull U01 EB017140 (MPIs Pelc Wang Edic - Stanford U Rensselaer GE 2014) Photon-counting detectors dynamic adaptive X-ray source low-dose spectral reconstruction compress sensing and statistical reconstruction (Platform GE)

bull U01 EB018753 (PI Fessler - U of Michigan 2014) Advanced statistical image reconstruction methods for all tasks (Applicable to All platforms)

bull U01 EB018760 (MPIs Otazo Sodickson - New York U 2015) SparseCT Order-of-magnitude dose reduction with interrupted-beam acquisition (Platform Siemens)

Image-Guided Interventions

Research on use of images for guidance navigation and orientation in minimally invasive procedures to reach specified targets

Examples include image-guided interventions for minimally invasive therapies such as surgery and radiation treatment for biopsies and for the delivery of drugs genes and therapeutic devices

httpswwwnibibnihgovresearch-fundingimage-guided-interventions

Steven Krosnick MD

Image-Guided Interventions Currently Funded Technologies

bull Multifunction Robotic Tools for Natural Orifice and Single Incision Surgerybull Endovascular Magnetic Catheter for Interventional MRIbull Reducing morbidity in surgical resections Third-harmonic generation microscopybull Computer Modeled Multiportal Approaches to the Skull Basebull Multi-lumen steerable needles for transoral access to lung nodulesbull A Low-Cost Portable Guidance System for Needle Biopsybull Intrabiliary MRRF-enhanced chemotherapy of malignant biliary obstructionsbull A Novel Optical Spectral Imaging System for Rapid Imaging of Breast Tumor

Marginsbull Enhanced Navigation for Endoscopic Sinus Surgery Through Video Analysisbull MRI-Photoacoustic-Raman Nanostars for Pre- and Intraoperative Multimodal

Imagingbull Testing Fluorescently Labeled Probes for Nerve Imaging during Surgerybull NRI Small Magnetic Resonance Imaging Guided Co-Robotic Active Catheter

System

Magnetic Biomagnetic and Bioelectric Devices

Peer-Reviewed research grants (R01 R21 R03) and SBIRsSTTRsThe program supports technological development of magnetic biomagnetic and bioelectric devices such as those required for electroencephalography (EEG) magnetoencephalography (MEG) eletricalimpedance spectroscopy (EIS) etcAreas of interest include but not limited to novel detectors increased sensitivity and spatial resolution improved reconstruction algorithms multiplexing with other imaging techniques

Antonio Sastre PhD

bull Magnetic Resonance Electrical Properties Tomographybull EIT a non-radiating functional imaging method for cystic fibrosisbull Functional proton-electron double-resonance imaging development and

applicationbull A Cryogen-Free Low-Cost Atomic Magnetometer Array for

Magnetoencephalographybull Modeling of the Magnetic Particle Imaging Signal Due to Magnetic

Nanoparticlesbull Catheter guided endovascular electric field ablation for thrombosis therapybull Conformal pediatric whole-head MEG system with optically-pumped

magnetometersbull Liquid-helium-free persistent-mode HTS magnets for NMR and MRI

applicationsbull Multifunctional in Vivo EPR Imaging of Tumor Microenvironmentbull Miniature EPR sensor for on-site oximetrybull Commercialization of a preclinical Magnetic Particle Imaging system with

sub-millimeter resolution nano-molar sensitivity and integrated CT

Magnetic Biomagnetic and Bioelectric DevicesCurrently Funded Technologies

Nuclear Medicine

This program supports the research and development of technologies and techniques that create images out of the gamma-ray or positron (and resulting photon) emissions from radioactive agents that are injected inhaled or ingested into the body and then concentrate in specific biological

Antonio Sastre PhD

Areas of interest include but not limited to Synthesis and study of targeted radio-labeled molecular imaging probes

bull Particular interest in multimodal environmentally-sensitive and switchable agents

bull Development of new cameras scintillators and collimatorsI

bull mproved reconstruction algorithms and the development of new cameras and detectors new approaches to increasing sensitivity and trackinglowering radiation dose

bull Wedding of positron emission tomography (PET) and single photon emission computed tomography (SPECT) to CT andor to MRI

bull Design of higher spatial and temporal resolution systems including the compensation of artifacts lower cost and portable systems and kits

bull Multimodal microPET and microMRI Imaging Instrumentationbull Energy-Independent Single Photon Molecular Imaging Technologybull Optical Barriers to Improve Performance of a Continuous Detector for

Clinical PETbull New PET near IR-fluorescence tools for multimodal imaging in oncologybull Quantitative Methods for Clinical Whole Body Dynamic PETbull Cerenkov-emission based nanosensors to detect biologic activities in vivobull Dose Reduction in Pediatric Molecular Imagingbull Quantitative Evaluation of Cerenkov Luminescence for Imaging and Therapybull SPECT Imaging and Parallel Computingbull Functional PET Imaging of Oxidative Stressbull Superhigh Sensitivity SPECT Imaging with Dense Camera Arraysbull Photodynamic Therapy Mediated by Cerenkov Light Emitted from

Radiopharmaceuticalsbull Preclinical Optical Imaging System Scintillator and Pinhole Insertbull A cost-effective high-performance ceramic garnet scintillator for PET

Nuclear MedicineCurrently Funded Technologies

Guoying Liu PhD

Magnetic Resonance Imaging and Spectroscopy

Supports a very large and active research field Broad spectrum of diverse cutting-edge technology development projectsMany novel methods have already ended up in the clinicsMore support is needed

bull faster higher resolution more robust better quality and more quantitative

bull accessible to more people around the world

bull More robust for special populations (eg young children)

MRI Number of Grants by Subcategories

High Field MRI Technical Development (ParallelTransmit RF Pulse Design Safety andShimming)13

Novel Acquisition Strategies and New TissueContrasts11

MRSI Technical Development (includingHyperpolarized C-13)13

Functional Neuroimaging23

Cardiovascular MRI 8

Musculoskeletal MRI 4

FetalNeonatalPediatric MRI4

Lung MRI3

Cancer MRI3

High Field Technical Development 15

Novel Acquisition Strategies and New Tissue Contrasts 11

Functional Neuroimaging 23

MR Spectroscopic Imaging Technical Development 15


THE BRAIN INITIATIVEreg

Next Generation Human Brain ImagingThe Brain Research through Advancing Innovative Neurotechnologiesreg (BRAIN) Initiative is part of a new Presidential focus aimed at revolutionizing our understanding of the human brain By accelerating the

development and application of innovative technologies researchers will be able to produce a revolutionary new dynamic picture of the brain that for the first time shows how individual cells and complex neural circuits interact in both time and space Long desired by researchers seeking new ways

to treat cure and even prevent brain disorders this picture will fill major gaps in our current knowledge and provide unprecedented opportunities for exploring exactly how the brain enables the

human body to record process utilize store and retrieve vast quantities of information all at the speed of thought


Currently SupportingNext Generation Human Brain Imaging

Three-year R24 planning grants 15 awardsbull New portable technologies MRI amp PET scannersbull New methods magnetic particle imaging neurotransmitter

modulation imaging direct imaging of neuroelectric activities combinations of EEG MRI ampor ultrasound latency mapping non-invasive neuromodulation

bull New approaches to current imaging modalities functional molecular imaging with vasoactive probes vascular interface for brain imaging and stimulation amp microscale cortical imaging


NIBIB ndash Home for Two New BRAIN RFAs

1 Development of Next Generation Human Brain Imaging Tools and Technologies Phase 2

bull Full-scale development of breakthrough imaging tools and technologies bull Budget appropriate for full phase 2 developmentbull Open to all applicants

2 Proof of Concept Development of Early Stage Next Generation Human Brain Imaging

bull Small scale proof of concept development of exceptionally innovative concepts

bull Capture emergent ideas not ready for full scale development

bull Greater emphasis on development than with planning grants

bull Dr Petra-Wilder Smith University of California Irvine

bull Grantee in the Indo-US Program on Affordable Medical Devices (R03)

bull Indian Collaborator Dr Moni Kuriakose Mazumdar-Shaw Cancer Center

bull In a pilot group of 79 subjects a simple diagnostic algorithmic approach using reflectivity and thickness ratios of superficial anatomical structures provided excellent PPV (92) NPV (90) kappa (92) diagnostic sensitivity (86) and specificity (gt84)

Vinay Pai PhD

Initiative Indo-US Collaborative Program on Affordable Medical Devices

Fourth Clinical testing with triage guidance algorithm in 79 subjects with leukoplakia and erythroplakia

In 3 subjects (below) tissues appear similar and differential diagnosis is not possible based on clinical appearance

SG

SD

1mm

SG

1mm

TRIAGE CODE

NO ACTION

E

BM

BV

SGM

1mm

Health

y

Potentially

premalignant

(dysplasia)

Malignant

(Sq Cell Ca no BM)

TRIAGE CODE

RE-CHECK IN

3 MONTHS

TRIAGE CODE

SEND TO

SPECIALIST

IMMEDIATELY

E

E

BM (Basement

membrane)

BM

National Institute of Biomedical Imaging amp Bioengineering

Division of Health Information Technology (DHIT)

Health Informaticsbull Mobile Platforms bull Clinical Decision Support bull Medical Reporting bull Tele-health telemedicine

Center of Excellence for Mobile Sensor Data-to-Knowledge (MD2K)

Santosh Kumar PI


PI K Gilchrist

Developing a mobile seizure alert device

using non-invasive physiological measures

Developed detection algorithm from

clinical data

Systems Engineeringbull Workflow issues bull Human-computer interfacebull Clinical interoperability bull Cyber-physical systems

Systems Engineeringbull Workflow issues bull Human-computer interface bull Learning healthcare systemsbull Clinical interoperability bull Cyber-physical systems

Quantum Medical Device Interoperability (QMDI) projectbull 5 year project (2010)bull wwwmdpnporgbull Multiple institutions

bull MGH UPenn KSU UIUCbull Anakena DocBox Moberg

Researchbull FDA VAbull Funded by NIBIB NSF DoD

Image Processing Visual Perception amp Display

bull Design amp development of algorithms for post-

acquisition image processing amp analysis

bull Development of theoretical models amp analysis tools to

evaluate amp improve the perception of medical images

bull Research in the optimization of image display for

improved detection

DIVISIONAL FOCUSbull Imaging Informatics

bull Image processing segmentation and registrationbull Computer-aided decision-makingbull Biomedical big-data processing

[Credit Jack van Horn and his colleagues LONI USC]

DHIT involvement in FOAsbull Smart amp Connected Health ndash NIH PA-13-543 - NSF 13-543bull Cyber-physical Systemsndash NIH PA-13-543 - NSF 13-543bull Joint NSFNIH Initiative on Quantitative Approaches to Biomedical Big Data (QuBBD)bull Design and Development of Novel Technologies for Healthy Independent Living (R01R21)

bull PAR-11-0118 amp -0119bull mHealth Tools for Individuals with Chronic Conditions to Promote Effective Patient-Provider

Communication Adherence to Treatment and Self-management (R01R21)bull PA-14-180 amp -181

bull Mobile Health Technology and Outcomes in Low and Middle Income Countries (R21)bull PAR-14-028

bull Translational Research to Help Older Adults Maintain their Health and Independence in the Community (R01R21) ndash PA-14-159 amp PA-14-161

bull Bioengineering Research Exploratory Grants (PA-12-284) Grants (PAR-13-137) Partnerships (PAR-10-234)

bull Training Opportunities Postdoctoral Junior Investigator Clinician-Scientist Diversity

bull Also Investigator Initiated R01 R21 R03 P41 P30 T32 F303132 K25 K99R00 SBIRSTTRrsquoshellip

httpwwwnibibnihgovfundingfunding-opportunities

Contact infoRichard Conroy PhD Steven Krosnick MDconroyrimailnihgov krosnicsmailnihgov

Tiffani Lash PhD Vinay Pai PhDbaileytimailnihgov Acting DHIT Director

paivmailnihgov

Edward RamosPhD Mary Rodgers PhD EdRamosnihgov rodgersmmmailnihgov

Seila Selimovic PhDseilaselimovicnihgov

TGM 2016 Final Agenda

TGM Agenda Monday

TGM Agenda Tuesday

TGM TPD Session agenda

Speaker Bios

Poster List with Abstract Titles

Abstract Booklet

Break out session leaders and rooms

Contact List

DIDT Fact Sheet December 2015

DIDT Fact Sheet Training Programs 2014

DIDT Fact Sheet TransNIH 2014

Scientific Program Presentations

NIBIB Scientific Program Presentations

Slide Number 2

Slide Number 3

Slide Number 4

Slide Number 5

SensorsMicro- and Nano Systems Platform TechnologiesTelehealth

Slide Number 7

Slide Number 8


Slide Number 10

Slide Number 11

Slide Number 12


Nanoparticle Gene Delivery Works

Slide Number 15

Slide Number 16

Slide Number 17

Implantable and Assistive Medical Devices

Non-hypothesis driven research

Neuromodulation

SPARC ndash Stimulating Peripheral Activity to Relieve Conditions


Brain Research through Advancing Innovative Neurotechnologies

Interagency Modeling and Analysis Group (IMAG)

Life extends across scales

Simulation of platelet aggregation


Slide Number 28

Slide Number 29

Slide Number 30

Slide Number 31

Slide Number 32

Slide Number 33

Slide Number 34

Slide Number 35





Slide Number 40

Slide Number 41


Slide Number 43

Nuclear Medicine

Slide Number 45

Slide Number 46


Slide Number 48

Slide Number 49

Slide Number 50


Fourth Clinical testing with triage guidance algorithm in 79 subjects with leukoplakia and erythroplakiaIn 3 subjects (below) tissues appear similar and differential diagnosis is not possible based on clinical appearance


Slide Number 54

Slide Number 55

Slide Number 56

Slide Number 57

Slide Number 58

Slide Number 59

DHIT involvement in FOAs

Contact info

headerstyle 3333 1000 1000 $1000 100000 Charsm CharMed wwwmsncom 20100105 20100105 120000 AM 1510

HDR PCT INT COMINT CURR COMDEC TEXTSTD TEXTBIG HYPER DATESTD DATETM DATEMDY

QVR Custom Download

Query Criteria Project Number Contains EB ICs = EB Primary and Dual Projects All Active Grants which were active TODAY Program Class Code Contains ___W____ Extramural Grants

Sort Criteria PCCActivityPI Name(s) All

Download Cols TypeActvProject PI Name(s) AllTitlePCCObl $ Tot (IMPAC)

User HUNZIKERR

DateampTime Run ts 2015-11-10 120616

Type Actv Project PI Name(s) All Title PCC Obl $ Tot (IMPAC) Technology Code Target Tissue

5 R01 EB006745-08 PRUITT BETH L (contact) GOODMAN MIRIAM B Force Clamp Systems for Evaluation of Mechanotransduction ABMW $453696 TM ay

$453696

5 P41 EB001046-13 KOHN JOACHIM B Integrated Technologies for Polymeric Biomaterials RESBIO DABW $1186035 TS TB (TC TM) ax DP1 0

5 R01 EB009701-07 COLLIER JOEL H Immunomodulatory Biomaterials via Peptide and Protein Self-Assembly DABW $348390 TF ai DP2 0

5 R01 EB014283-04 KAPLAN DAVID L Multifunctional Tropoelastin-Silk Biomaterial Systems DABW $289871 TS (TM ) ax (az an) P41 1

1 R01 EB020690-01 REGE KAUSHAL Photothermal Nanocomposites for Tissue Repair DABW $381636 TD (TS) ad R00 0

5 R01 EB014315-04 ROY SHUVO Biocompatibility of Implantable Renal Replacement Devices DABW $650323 TS ak R01 5

5 R01 EB014404-04 STENKEN JULIE A Modulating and Monitoring the Foreign Body Response to Implants DABW $332830 TD (TC) at R01 (BRP) 0

5 R01 EB005772-07 SZLEIFER IGAL G (contact) MESSERSMITH PHILLIP B Antifouling Peptide Mimetic Polymers DABW $334082 TF TS ao R03 1

5 R01 EB012575-05 YANG JIAN Creating Safe Biodegradable Photoluminescent Implant Polymers DABW $309018 TI TF ag R21 13

5 R03 EB018422-02 KAAR JOEL Enzyme-containing Anti-biofilm Coatings for Urological Catheters DABW $69106 TD (TS) ak R4 3

1 R21 EB019166-01A1 BABENSEE JULIA E Multifunctional Biomaterial for Amelioration of MS in Murine EAE Model DABW $210157 TC (TF) ai (an) U01 0

1 R21 EB019118-01A1 DRELICH JAROSLAW W Improved Biocompatibility and Biodegradation of Zn-based Stent Materials through Surface Nano-Engineering DABW $203996 TD (TS) ac UH23 0

5 R21 EB019068-02 GUZZETTA NINA (contact) BARKER THOMAS HARRISON Augmentation of Hemostasis in Pediatric Cardiopulmonary Bypass DABW $198311 TC (TF) ac U18 0

1 R21 EB020860-01 MAUNEY JOSHUA ROBERT (contact) ESTRADA CARLOS R Development of Silk Fibroin Grafts for Reconstruction of Pathological Bladders DABW $220938 TS ak Other 0

1 R21 EB021026-01 MCGRATH JAMES L Small Animal Hemodialysis with Ultrathin Silicon Nanomembranes DABW $191875 TS ak Contract 0

5 R21 EB017377-02 MELLER AMIT (contact) GRINSTAFF MARK W Tunable Nanofiber Mesh Coatings for Improved Nanopores Sensing DABW $198486 TD ag 23

5 R21 EB013721-02 NAZARIAN ARA (contact) GRINSTAFF MARK W RODRIGUEZ EDWARD A Portable Wound Hemostasis System Using a Hydrogel Polymeric Foam DABW $224130 TS at

5 R21 EB018617-02 PLAXCO KEVIN W A new tool for measuring surface-biomolecule interactions DABW $223252 TD ag TS 8

5 R21 EB018637-02 PUN SUZIE H (contact) WHITE NATHAN J Synthetic hemostats for trauma treatment DABW $231750 TS TC ac aa TD 7

5 R21 EB016838-02 REYNOLDS MELISSA M (contact) FINKE RICHARD G Catalytic Nitric Oxide Release Coating for Prolonged Anti-Clotting Catheters DABW7 $181788 TF TS ac TI 1

5 R21 EB016737-02 ROY-CHAUDHURY PRABIR (contact) MEYERHOFF MARK E Reducing Tunneled Dialysis Catheter Dysfunction through Nitric Oxide Release DABW $194987 TF TS ac TC 2

5 R21 EB016662-02 SOKOLOFF ALAN (contact) GHOVANLOO MAYSAM Optimization Biocompatibility and Safety Assessment of Tongue Implants DABW $181798 TD TS ay TF 5

5 R21 EB015612-02 STACHELEK STANLEY JOSEPH (contact) FISHBEIN ILIA Increasing biocompatibility of stents through CD47 functionalization DABW $243713 TF TS ac ai 0

1 R43 EB022016-01A1 LANDSMAN TODD Shape Memory Polymer Foam Vascular Occlusion Device for the Treatment of Chronic Venous Insufficiency DABW $199591 TS ac 23

3 R43 EB022016-01A1S1 LANDSMAN TODD Shape Memory Polymer Foam Vascular Occlusion Device for the Treatment of Chronic Venous Insufficiency DABW $25000

1 R43 EB019225-01A1 RADZIEMSKI LEON Enhancing longevity of implanted medical devices DMDW $153567 $7007630 TE ag

1 DP2 EB022358-01 LIPOMI DARREN J Stretchable Biodegradable and Self-Healing Semiconductors for Wearable and Implantable Sensors DTEW $2193330 TE (TI) ag DP1 0

7 DP2 EB020537-02 MCALPINE MICHAEL 3D Printed Nano-Bionic Organs DTEW $0 TS (TE) ay DP2 3

1 DP2 EB020549-01 ZHANG LIJIE GRACE A Novel 3D Bioprinted Smart Vascularized Nano Tissue DTEW $2287500 TS TF ac P41 3

3 P41 EB002520-12S1 KAPLAN DAVID L Tissue Engineering Resource Center DTEW $64351 R00 3

5 P41 EB002520-12 KAPLAN DAVID L Tissue Engineering Resource Center DTEW $1243616 TS TB (TC TH) ab ac R01 34

2 P41 EB002025-31A1 SUPERFINE RICHARD Computer Integrated Systems for Microscopy and Manipulation (CISMM) DOIW $1401412 TI TM al R01 (BRP) 4

5 P41 EB002503-12 TONER MEHMET Bio-MicroElectroMechanical Systems (BioMEMS) Resource Center DTEW $1252826 TD TH (TC) ao av R03 10

5 R00 EB013630-05 BELLAN LEON MARCEL 3D Microvascular Networks in Hydrogels Fabricated with Sacrificial Structures DTEWZ $229853 TS (TC) ac az R21 29

5 R00 EB013446-05 GODULA KAMIL NeoProteoglycans as synthetic materials for regenerative medicine and bioimaging DTEWZ $237934 TS (TH) at (ax) R4 1

4 R00 EB017723-02 QUINN KYLE PATRICK Non-invasive label-free quantitative imaging for chronic wound characterization DTEWZ $249000 TI TS as U01 1

5 R01 EB017129-03 AMEER GUILLERMO ANTONIO (contact) KIBBE MELINA RAE Preclinical Investigation of a Bioengineered Vascular Graft DTEW $418612 TC TS ac UH23 2

5 R01 EB010039-04 BEEBE DAVID J (contact) HUTTENLOCHER ANNA Understanding cell migration through microscale in vitro models DTEW $464661 TH (TF) ai (al) U18 1

5 R01 EB011516-06 BIRLA RAVI KUMAR Fabrication of 3D Cardiac Patches for Myocardial Recovery DTEW $288690 TM (TB TC) ac Other 0

5 R01 EB008722-06 BURDICK JASON A (contact) MAUCK ROBERT L Engineering Developmental Microenvironments Cartilage Formation and Maturation DTEW $426990 TS (TM ) ab Contract 0

5 R01 EB020367-02 CAPLAN ARNOLD I CWRU Center for Multimodal Evaluation of Engineered Cartilage DTEW $387902 TI TS (TC) ab 91

2 R01 EB000262-16A1 CHEN CHRISTOPHER S Local Regulation of Angiogenesis by Microenvironment DTEW $368325 TS (TF TM) av (ac)

2 R01 EB008396-05A1 CHEN CHRISTOPHER S (contact) BHATIA SANGEETA N Engineering Multicellular Tissue Structure Function and Vascularization DTEW $788491 TM (TS TC0 ac TB 6

5 R01 EB013297-04 COSGRIFF-HERNANDEZ ELIZABETH MARIE (contact) HAHN MARIAH S MULTILAYER VASCULAR GRAFTS BASED ON COLLAGEN-MIMETIC HYDROGELS DTEW $307176 TS (TC) ac TC 5

5 R01 EB015776-05 DEMIRCI UTKAN Minimizing the role of cryoprotectant toxicity for cryopreservation TTEW $389438 TP ax TD 6

5 R01 EB002425-10 ELLIOTT DAWN M (contact) MAUCK ROBERT L Multi-scale biomechanics of engineered and native fibrous load-bearing tissue DTEW $441366 TM (TS) at TE 5

5 R01 EB013011-04 FREEMAN THERESA Non-Thermal Plasma in Biomedicine A New Paradigm for Redox Cell Activation DTEW $336605 TE (TC) az (ab) TF 3

5 R01 EB011879-04 GRAINGER DAVID W Foreign Body Response as a Performance Metric for Implanted Scaffolds DTEW $243100 TS (TF) az TH 13

5 R01 EB012108-05 HE XIAOMING Microencapsulation of oocytes for low-CPA (cryoprotectant) vitrification DTEW $329975 TP ar TI 6

5 R01 EB016629-02 HIRSCHI KAREN K Neurovascualar Regeneration DTEW $938623 TS TC (TI TD) an TM 14

5 R01 EB018210-02 HOCKING DENISE (contact) DALECKI DIANE Ultrasound standing wave fields for vascular tissue engineering DTEW $457941 TS TI ac TP 4

1 R01 EB020004-01 INGBER DONALD E Mechanotransduction analysis in a microengineered lung-on-a-chip DTEW $619351 TH (TF) al TS 38

5 R01 EB016041-04 KAPLAN DAVID L In vitro bioreactor sys for platelet formation DTEW $334072 TB (TS TC) aa total 100

5 R01 EB009429-04 LAMBERT STEPHEN Functional Invitro CNS and PNS Myelination Model DTEW $395027 TH an

5 R01 EB006834-08 LEE FRANCIS YOUNG-IN Mechanobiological Mechanism for Inflammaory Bone Loss ATEW $352800 TS ab aa 8

5 R01 EB014869-04 LELE TANMAY P Substrate Rigidity and Gene Expression Role of Nuclear Tension DTEW $413937 TM ag ab 7

5 R01 EB013674-04 MAYNARD HEATHER D Stable and Active bFGF-Polymer Conjugates for Wound Healing DTEW $333747 TF TS as ac 21

5 R01 EB014703-04 MOONEY DAVID J (contact) SCADDEN DAVID T WEITZ DAVID A WESTERVELT ROBERT M Building the Hematopoietic Stem Cell Niche DTEW $779887 TS (TC) aa ad 4

5 R01 EB016458-03 OHTA AARON NRI Paraellel Independent Control of Microrobots for Microassembly of Tissues DTEW $88062 TD TI ax ag 2

5 R01 EB007534-08 PALECEK SEAN P Regulating human pluripotent stem cell differentiation by colony confinement DTEW $357125 TB (TC) az ac ai 4

5 R01 EB012521-05 PAREKKADAN BIJU Artificial Humanized Stem Cell Niches DTEW $668221 TS (TI) aa ao ak 2

5 R01 EB013212-04 RUBENSTEIN DAVID A Development of a BioMIMETIC Composite Scaffold to promote vascular network growth DTEW $222174 TS TC ac al 3

5 R01 EB014351-03 RUBIN CLINTON T (contact) JUDEX STEFAN RUBIN JANET E Harnessing mechanical signals to control mesenchymal stem cell fate DTEW $337722 TE TF TC az an 9

2 R01 EB005678-09 SHEA LONNIE D (contact) ANDERSON AILEEN J Controlled Release Scaffolds for Nerve Regeneration DTEW $593118 TS (TC) an ao 4

2 R01 EB009910-06A1 SHEA LONNIE D (contact) LUO XUNRONG Protein-Releasing Microporous Scaffolds for Cell Replacement Therapy DTEW $558726 TS TC ai ap ar 2

5 R01 EB003806-10 STUPP SAMUEL I Bioactive Scaffolds for Regeneration in Spinal Cord Injury DTEW $663372 TS an as 2

5 R01 EB015007-04 SUGGS LAURA J Nanotracer Development to Track Stem Cell Therapy DTEW $436314 TS TI ac az at 4

5 R01 EB013281-04 THOMPSON DEANNA M APPLICATION OF ELECTRICAL STIMULATION FOR RAPID AND DIRECTED RE-GROWTH VIA ELECTR DTEW $344344 TE TS an av 6

5 R01 EB014986-04 TUSZYNSKI MARK H (contact) SAKAMOTO JEFFREY Bioengineered Scaffolds for Spinal Cord Injury DTEW $462221 TS an ax 2

1 R01 EB019430-01A1 TUAN ROCKY S Cholesterol Sensitivity and Mechanisms of MSC Responses to 3D Substrate Rigidity DTEW7 $324358 TS az ab ay 1

5 R01 EB017753-02 WELLS REBECCA G (contact) JANMEY PAUL A SHENOY VIVEK Pathological consequences of altered tissue mechanics in fibrosis DTEW $424155 TS TM av az 13

1 R01 EB020050-01 XIA YOUNAN (contact) BOULIS NICHOLAS M Nanofiber Conduits with a Honeycomb Structure for Repairing Large Defects in Thick Nerves DTEW $321210 TS an 94

5 R01 EB003060-09 YASZEMSKI MICHAEL J (contact) LU LICHUN Injectable and Preformed Osteoinductive Biodegradable Composites DTEW $459871 TS ab

1 R01 EB019411-01A1 ZHAO RUOGANG Fibrotic microtissue chips for screening of anti-fibrotic therapies DTEW $352982 TH TM al blood 8

1 R03 EB019552-01A1 CONVERSE GABRIEL L Recellularization mechanisms in mononuclear cell seeded tissue engineered valves DTEW $75000 TC (TB) ac bone cart 7

1 R03 EB018889-01A1 DEARTH CHRISTOPHER L NSAIDs and the Role of COX2 in Biologic Scaffold-Mediated Tissue Reconstruction DTEW $77878 TS (TC) ai (at) cardio-vasc 21

1 R03 EB018430-01A1 GRAYSON WARREN L Tunable Oxygen Delivery to Cells using Novel Microtank Technology DTEW $81000 TD (TC) az neuro 9

5 R03 EB017344-02 JUN HO-WOOK A hybrid nanosack for the enhanced islet engraftment in the omentum DTEW $71295 TS ad liver 6

7 R03 EB019184-03 KHETANI SALMAN R Engineering zonal human liver functions in vitro using microfluidics DTEW7 $90743 TH av stem cells 13

1 R03 EB020910-01 MA MINGLIN Organogenesis in microcapsules developing an efficient and scalable organoid culture platform DTEW $72118 TS (TH) ad (az) all other 30

5 R03 EB017927-02 PRICE RICHARD J Application of Laser Speckle Flowmetry to Vascular Remodeling DTEW $76146 TI ac 94

5 R03 EB018575-02 SANT SHILPA Engineered Microenvironments to model effect of size in tumor progression DTEW $77000 TM (TB) ao

5 R03 EB018851-02 TIEN JOE Y In Vivo Microsurgical Anastomosis of Prevascularized Tissues DTEW7 $81850 TS TD ac

5 R03 EB015744-02 WANG HONGJUN Novel Strategies to Increase Insulin Independence after Islet Autotransplantation DTEW $72507 TF TS ap

5 R21 EB018505-02 ANSETH KRISTI S Protease Activity in 3D Matrices DTEW $222224 TS (TC) ao

5 R21 EB019230-02 BROWN JUSTIN L Migratory Morphology A Function of Fibrous Extracellular Matrix Geometry Sensing DTEW $179818 TM (TC) az

5 R21 EB017876-02 CHEN SHAOCHEN Biomimetic design of human induced pluripotent stem cells on a chip DTEW $225525 TH av (az)

1 R21 EB020978-01 COSGRIFF-HERNANDEZ ELIZABETH MARIE EFFECT OF IMPROVED GRAFT COMPLIANCE MATCHING ON INTIMAL HYPERPLASIA DTEW $208152 TM (TS) ac

5 R21 EB016393-02 COSGRIFF-HERNANDEZ ELIZABETH MARIE DEVELOPMENT OF PICKERING EMULSIONS AS INJECTABLE BONE GRAFTS DTEW $168503 TS (TC) ab

5 R21 EB017078-02 DENG CHERI X (contact) FU JIANPING Ultrasound-mediated Directed Osteogenic Differentiation of Mesenchymal Stem Cells DTEW7 $194375 TM ab

1 R21 EB018538-01A1 EROGLU ALI New Cell Desiccation Strategy Using Non-Isothermal Drying and Biophysical Models DTEW $256094 TP ar

1 R21 EB021005-01 HAN ARUM A High-Throughput Microfluidic in vitro CNS Myelination Model towards Drug Screening DTEW $179524 TH an

1 R21 EB018481-01A1 HARLEY BRENDAN A Label-free interrogation of heterogeneities in HSC fate decision signatures DTEW $193022 TI (TB) aa (az)

5 R21 EB016792-02 HATEFI ARASH Bioengineering a Safe and Efficient Vector Technology for Stem Cell Transfection DTEW $193750 TF (TC) az

1 R21 EB021003-01 HEALY KEVIN EDWARD iPSC Derived Cardiac Microchambers for Embryonic Drug Screening DTEW $235438 TM (TH) ac

1 R21 EB020235-01 HEILSHORN SARAH C (contact) HUANG NGAN F Injectable Hydrogels to Improve the Efficacy of iPSC-derived Therapies DTEW $243575 TM (TC) ac

5 R21 EB018407-02 HEILSHORN SARAH C Engineered Intestinal Microenvironments as Preclinical Drug Screening Platforms DTEW7 $193259 TH (TM ) ad

5 R21 EB016774-02 HUARD JOHNNY Biomimetic Coacervate Delivery of Muscle Stem Cell to Improve Cardiac Repair DTEW $233424 TS TC ac (az)

5 R21 EB016247-02 HUBEL ALLISON Technology platform for development of multi-component preservation solution DTEW $171838 TP az

5 R21 EB017184-02 ISENBERG JEFFREY S (contact) BADYLAK STEPHEN F Bioengineering Tracheas Through Targeting Activated CD47 DTEW $192500 TB TS (TC) at

5 R21 EB016359-02 KUMAR SANJAY Genetic strategies for the quantitative control of cell-matrix mechanobiology DTEW $189756 TM TC TM az

5 R21 EB017384-02 LAPOTKO DMITRI O (contact) SHPALL ELIZABETH J All-in-one purification and engineering of therapeutic cell systems DTEW $231384 TD (TC) aa

5 R21 EB017539-02 LEE LY JAMES (contact) OTERO JOSE JAVIER Large Scale Nanochannel Electroporation (NEP) for Cell Reprogramming DTEW $198383 TD (TC) az

1 R21 EB019508-01A1 MASTERS KRISTYN S Development of Complex Culture Systems to Study Valvular Dysfunction DTEW $182770 TS (TB) ac

5 R21 EB017868-02 REICHERT WILLIAM MONTGOMERY Aptamer-based affinity capture of circulating CAD EPCs DTEW $151487 TD (TC) aa

1 R21 EB019646-01 RYLANDER MARISSA NICHOLE (contact) VLACHOS PAVLOS P Nanoparticle Transport as a function of Physiologic and Hyperthermic Conditions in a 3D Vascularized Microfluidic Tumor Platform DTEW $233531 TB (TS TH) ao

1 R21 EB020282-01 SETHU PALANIAPPAN Functional Maturation of Induced Pluripotent Stem Cell Cardiomyocytes (IPS-CMs) via Targeted Mechanical Conditioning and Work DTEW7 $206165 TM TC ac

1 R21 EB020107-01 SHIRWAN HAVAL (contact) GARCIA ANDRES J Immuno-vasculogenic hydrogels for islet engraftment and localized tolerance DTEW $196683 TS TC ai ap

1 R21 EB020192-01A1 USTA OSMAN BERK Novel Microfluidic Platforms for Actively Controlled in-vitro Liver Zonation DTEW $261000 TH av

5 R21 EB019123-02 VERBRIDGE SCOTT S 3D micro-addressable tissue models to understand spatiotemporal heterogeneity in transcriptional regulation DTEW $220830 TH an ag

5 R21 EB015906-04 WANG QI Device to mechanically interrogate tissue and skin across research environments DTEW $167779 TM at

1 R21 EB019509-01A1 YOUNG PAMPEE P (contact) SUNG HAK-JOON Thermosensitive injectable polymer-based stem cell therapy for limb ischemia DTEW $235329 TS ac az

5 R21 EB015737-02 ZHAO MIN Guiding angiogenesis DTEW $186725 TE TF ac az

3 R43 EB021704-01S1 CROSSWELL HOWLAND E The 3D Platelet Bank A Clinical-grade Scalable 3D Microbioreactor Bone Marrow Mimetic for Platelet Production DTEW $29260

1 R43 EB021704-01 CROSSWELL HOWLAND E The 3D Platelet Bank A Clinical-grade Scalable 3D Microbioreactor Bone Marrow Mimetic for Platelet Production DTEW $225000 TS (TB) aa

1 U01 EB021214-01 ROY SHUVO (contact) FISSELL WILLIAM H Building an Implantable Artificial Kidney DTEW $1331543 TS TC TB ak

5 UH3 EB013647-05 HAMMER BRUCE E Gravitational Regulation of Osteoblast Genomics and Metabolism DTEW $423517 TC (TB) ab

5 UH3 EB017103-04 VUNJAK-NOVAKOVIC GORDANA Integrated heart-liver-vascular systems for drug testing in human health and dise DTEW $2092852 TH ac av

3 UH3 EB017103-04S2 VUNJAK-NOVAKOVIC GORDANA Integrated heart-liver-vascular systems for drug testing in human health and dise DTEW $200000



1 U18 EB021780-01 WELLS JAMES M (contact) HELMRATH MICHAEL A Establishment of in vitro and in vivo models of human gastrointestinal organoids with a functional ENS DBMW $287040 TH ad

$37278793

$44707119 $44740119

Technology Codes Target Tissue Codes

TB=Biorx aa=blood bone marrow

TC=cells ab=bone cartilage tendonligament

TD=devoces ac-cardio-vascular

TE=electronics power ad=digestive (gut intestine)

TF=factors ag=generalized

TH=tissue chips ai=immune ar=reproductive

TI=imaging ak=kidney urologic (bladder) as=skin

TM=mechanics al=lung at=connective

TP=preservation am=muscle av=liver

TS=scaffolds an=neuro ax=mixed

TX=mixed ao=oncology cancer ay=sensory (eye earnose)

ap=pancreas az=non-adherent stem cells

blood

bone cart

cardio-vasc

neuro

liver

stem cells

all other



QVR Custom Download




User HUNZIKERR




$453696






















































5 R01 EB006834-08 LEE FRANCIS YOUNG-IN Mechanobiological Mechanism for Inflammaory Bone Loss ATEW $352800 TS ab

5 R01 EB014869-04 LELE TANMAY P Substrate Rigidity and Gene Expression Role of Nuclear Tension DTEW $413937 TM ag

5 R01 EB013674-04 MAYNARD HEATHER D Stable and Active bFGF-Polymer Conjugates for Wound Healing DTEW $333747 TF TS as

5 R01 EB014703-04 MOONEY DAVID J (contact) SCADDEN DAVID T WEITZ DAVID A WESTERVELT ROBERT M Building the Hematopoietic Stem Cell Niche DTEW $779887 TS (TC) aa

5 R01 EB016458-03 OHTA AARON NRI Paraellel Independent Control of Microrobots for Microassembly of Tissues DTEW $88062 TD TI ax

5 R01 EB007534-08 PALECEK SEAN P Regulating human pluripotent stem cell differentiation by colony confinement DTEW $357125 TB (TC) az ac

5 R01 EB012521-05 PAREKKADAN BIJU Artificial Humanized Stem Cell Niches DTEW $668221 TS (TI) aa ao

5 R01 EB013212-04 RUBENSTEIN DAVID A Development of a BioMIMETIC Composite Scaffold to promote vascular network growth DTEW $222174 TS TC ac

5 R01 EB014351-03 RUBIN CLINTON T (contact) JUDEX STEFAN RUBIN JANET E Harnessing mechanical signals to control mesenchymal stem cell fate DTEW $337722 TE TF TC az

2 R01 EB005678-09 SHEA LONNIE D (contact) ANDERSON AILEEN J Controlled Release Scaffolds for Nerve Regeneration DTEW $593118 TS (TC) an

2 R01 EB009910-06A1 SHEA LONNIE D (contact) LUO XUNRONG Protein-Releasing Microporous Scaffolds for Cell Replacement Therapy DTEW $558726 TS TC ai ap

5 R01 EB003806-10 STUPP SAMUEL I Bioactive Scaffolds for Regeneration in Spinal Cord Injury DTEW $663372 TS an

5 R01 EB015007-04 SUGGS LAURA J Nanotracer Development to Track Stem Cell Therapy DTEW $436314 TS TI ac az

5 R01 EB013281-04 THOMPSON DEANNA M APPLICATION OF ELECTRICAL STIMULATION FOR RAPID AND DIRECTED RE-GROWTH VIA ELECTR DTEW $344344 TE TS an

5 R01 EB014986-04 TUSZYNSKI MARK H (contact) SAKAMOTO JEFFREY Bioengineered Scaffolds for Spinal Cord Injury DTEW $462221 TS an

1 R01 EB019430-01A1 TUAN ROCKY S Cholesterol Sensitivity and Mechanisms of MSC Responses to 3D Substrate Rigidity DTEW7 $324358 TS az ab

5 R01 EB017753-02 WELLS REBECCA G (contact) JANMEY PAUL A SHENOY VIVEK Pathological consequences of altered tissue mechanics in fibrosis DTEW $424155 TS TM av

1 R01 EB020050-01 XIA YOUNAN (contact) BOULIS NICHOLAS M Nanofiber Conduits with a Honeycomb Structure for Repairing Large Defects in Thick Nerves DTEW $321210 TS an


1 R01 EB019411-01A1 ZHAO RUOGANG Fibrotic microtissue chips for screening of anti-fibrotic therapies DTEW $352982 TH TM al

1 R03 EB019552-01A1 CONVERSE GABRIEL L Recellularization mechanisms in mononuclear cell seeded tissue engineered valves DTEW $75000 TC (TB) ac

1 R03 EB018889-01A1 DEARTH CHRISTOPHER L NSAIDs and the Role of COX2 in Biologic Scaffold-Mediated Tissue Reconstruction DTEW $77878 TS (TC) ai (at)

1 R03 EB018430-01A1 GRAYSON WARREN L Tunable Oxygen Delivery to Cells using Novel Microtank Technology DTEW $81000 TD (TC) az

5 R03 EB017344-02 JUN HO-WOOK A hybrid nanosack for the enhanced islet engraftment in the omentum DTEW $71295 TS ad

7 R03 EB019184-03 KHETANI SALMAN R Engineering zonal human liver functions in vitro using microfluidics DTEW7 $90743 TH av

1 R03 EB020910-01 MA MINGLIN Organogenesis in microcapsules developing an efficient and scalable organoid culture platform DTEW $72118 TS (TH) ad (az)

5 R03 EB017927-02 PRICE RICHARD J Application of Laser Speckle Flowmetry to Vascular Remodeling DTEW $76146 TI ac










































$37278793

$44707119 $44740119














TB

TC

TD

TE

TF

TH

TI

TM

TP

TS



QVR Custom Download




User HUNZIKERR


Type Actv Project PI Name(s) All Title PCC Obl $ Tot (IMPAC)

5 R01 EB006745-08 PRUITT BETH L (contact) GOODMAN MIRIAM B Force Clamp Systems for Evaluation of Mechanotransduction ABMW $453696

$453696

5 P41 EB001046-13 KOHN JOACHIM B Integrated Technologies for Polymeric Biomaterials RESBIO DABW $1186035 DP1 0

5 R01 EB009701-07 COLLIER JOEL H Immunomodulatory Biomaterials via Peptide and Protein Self-Assembly DABW $348390 DP2 0

5 R01 EB014283-04 KAPLAN DAVID L Multifunctional Tropoelastin-Silk Biomaterial Systems DABW $289871 P41 1

1 R01 EB020690-01 REGE KAUSHAL Photothermal Nanocomposites for Tissue Repair DABW $381636 R00 0

5 R01 EB014315-04 ROY SHUVO Biocompatibility of Implantable Renal Replacement Devices DABW $650323 R01 5

5 R01 EB014404-04 STENKEN JULIE A Modulating and Monitoring the Foreign Body Response to Implants DABW $332830 R01 (BRP) 0

5 R01 EB005772-07 SZLEIFER IGAL G (contact) MESSERSMITH PHILLIP B Antifouling Peptide Mimetic Polymers DABW $334082 R03 1

5 R01 EB012575-05 YANG JIAN Creating Safe Biodegradable Photoluminescent Implant Polymers DABW $309018 R21 13

5 R03 EB018422-02 KAAR JOEL Enzyme-containing Anti-biofilm Coatings for Urological Catheters DABW $69106 R4 3

1 R21 EB019166-01A1 BABENSEE JULIA E Multifunctional Biomaterial for Amelioration of MS in Murine EAE Model DABW $210157 U01 0

1 R21 EB019118-01A1 DRELICH JAROSLAW W Improved Biocompatibility and Biodegradation of Zn-based Stent Materials through Surface Nano-Engineering DABW $203996 UH23 0

5 R21 EB019068-02 GUZZETTA NINA (contact) BARKER THOMAS HARRISON Augmentation of Hemostasis in Pediatric Cardiopulmonary Bypass DABW $198311 U18 0

1 R21 EB020860-01 MAUNEY JOSHUA ROBERT (contact) ESTRADA CARLOS R Development of Silk Fibroin Grafts for Reconstruction of Pathological Bladders DABW $220938 Other 0

1 R21 EB021026-01 MCGRATH JAMES L Small Animal Hemodialysis with Ultrathin Silicon Nanomembranes DABW $191875 Contract 0

5 R21 EB017377-02 MELLER AMIT (contact) GRINSTAFF MARK W Tunable Nanofiber Mesh Coatings for Improved Nanopores Sensing DABW $198486 23

5 R21 EB013721-02 NAZARIAN ARA (contact) GRINSTAFF MARK W RODRIGUEZ EDWARD A Portable Wound Hemostasis System Using a Hydrogel Polymeric Foam DABW $224130

5 R21 EB018617-02 PLAXCO KEVIN W A new tool for measuring surface-biomolecule interactions DABW $223252

5 R21 EB018637-02 PUN SUZIE H (contact) WHITE NATHAN J Synthetic hemostats for trauma treatment DABW $231750

5 R21 EB016838-02 REYNOLDS MELISSA M (contact) FINKE RICHARD G Catalytic Nitric Oxide Release Coating for Prolonged Anti-Clotting Catheters DABW7 $181788

5 R21 EB016737-02 ROY-CHAUDHURY PRABIR (contact) MEYERHOFF MARK E Reducing Tunneled Dialysis Catheter Dysfunction through Nitric Oxide Release DABW $194987

5 R21 EB016662-02 SOKOLOFF ALAN (contact) GHOVANLOO MAYSAM Optimization Biocompatibility and Safety Assessment of Tongue Implants DABW $181798

5 R21 EB015612-02 STACHELEK STANLEY JOSEPH (contact) FISHBEIN ILIA Increasing biocompatibility of stents through CD47 functionalization DABW $243713

1 R43 EB022016-01A1 LANDSMAN TODD Shape Memory Polymer Foam Vascular Occlusion Device for the Treatment of Chronic Venous Insufficiency DABW $199591


1 R43 EB019225-01A1 RADZIEMSKI LEON Enhancing longevity of implanted medical devices DMDW $153567 $7007630

1 DP2 EB022358-01 LIPOMI DARREN J Stretchable Biodegradable and Self-Healing Semiconductors for Wearable and Implantable Sensors DTEW $2193330 DP1 0

7 DP2 EB020537-02 MCALPINE MICHAEL 3D Printed Nano-Bionic Organs DTEW $0 DP2 3

1 DP2 EB020549-01 ZHANG LIJIE GRACE A Novel 3D Bioprinted Smart Vascularized Nano Tissue DTEW $2287500 P41 3


5 P41 EB002520-12 KAPLAN DAVID L Tissue Engineering Resource Center DTEW $1243616 R01 34

2 P41 EB002025-31A1 SUPERFINE RICHARD Computer Integrated Systems for Microscopy and Manipulation (CISMM) DOIW $1401412 R01 (BRP) 4

5 P41 EB002503-12 TONER MEHMET Bio-MicroElectroMechanical Systems (BioMEMS) Resource Center DTEW $1252826 R03 10

5 R00 EB013630-05 BELLAN LEON MARCEL 3D Microvascular Networks in Hydrogels Fabricated with Sacrificial Structures DTEWZ $229853 R21 29

5 R00 EB013446-05 GODULA KAMIL NeoProteoglycans as synthetic materials for regenerative medicine and bioimaging DTEWZ $237934 R4 1

4 R00 EB017723-02 QUINN KYLE PATRICK Non-invasive label-free quantitative imaging for chronic wound characterization DTEWZ $249000 U01 1

5 R01 EB017129-03 AMEER GUILLERMO ANTONIO (contact) KIBBE MELINA RAE Preclinical Investigation of a Bioengineered Vascular Graft DTEW $418612 UH23 2

5 R01 EB010039-04 BEEBE DAVID J (contact) HUTTENLOCHER ANNA Understanding cell migration through microscale in vitro models DTEW $464661 U18 1

5 R01 EB011516-06 BIRLA RAVI KUMAR Fabrication of 3D Cardiac Patches for Myocardial Recovery DTEW $288690 Other 0

5 R01 EB008722-06 BURDICK JASON A (contact) MAUCK ROBERT L Engineering Developmental Microenvironments Cartilage Formation and Maturation DTEW $426990 Contract 0

5 R01 EB020367-02 CAPLAN ARNOLD I CWRU Center for Multimodal Evaluation of Engineered Cartilage DTEW $387902 91

2 R01 EB000262-16A1 CHEN CHRISTOPHER S Local Regulation of Angiogenesis by Microenvironment DTEW $368325

2 R01 EB008396-05A1 CHEN CHRISTOPHER S (contact) BHATIA SANGEETA N Engineering Multicellular Tissue Structure Function and Vascularization DTEW $788491

5 R01 EB013297-04 COSGRIFF-HERNANDEZ ELIZABETH MARIE (contact) HAHN MARIAH S MULTILAYER VASCULAR GRAFTS BASED ON COLLAGEN-MIMETIC HYDROGELS DTEW $307176

5 R01 EB015776-05 DEMIRCI UTKAN Minimizing the role of cryoprotectant toxicity for cryopreservation TTEW $389438

5 R01 EB002425-10 ELLIOTT DAWN M (contact) MAUCK ROBERT L Multi-scale biomechanics of engineered and native fibrous load-bearing tissue DTEW $441366

5 R01 EB013011-04 FREEMAN THERESA Non-Thermal Plasma in Biomedicine A New Paradigm for Redox Cell Activation DTEW $336605

5 R01 EB011879-04 GRAINGER DAVID W Foreign Body Response as a Performance Metric for Implanted Scaffolds DTEW $243100

5 R01 EB012108-05 HE XIAOMING Microencapsulation of oocytes for low-CPA (cryoprotectant) vitrification DTEW $329975

5 R01 EB016629-02 HIRSCHI KAREN K Neurovascualar Regeneration DTEW $938623

5 R01 EB018210-02 HOCKING DENISE (contact) DALECKI DIANE Ultrasound standing wave fields for vascular tissue engineering DTEW $457941

1 R01 EB020004-01 INGBER DONALD E Mechanotransduction analysis in a microengineered lung-on-a-chip DTEW $619351

5 R01 EB016041-04 KAPLAN DAVID L In vitro bioreactor sys for platelet formation DTEW $334072

5 R01 EB009429-04 LAMBERT STEPHEN Functional Invitro CNS and PNS Myelination Model DTEW $395027

5 R01 EB006834-08 LEE FRANCIS YOUNG-IN Mechanobiological Mechanism for Inflammaory Bone Loss ATEW $352800

5 R01 EB014869-04 LELE TANMAY P Substrate Rigidity and Gene Expression Role of Nuclear Tension DTEW $413937

5 R01 EB013674-04 MAYNARD HEATHER D Stable and Active bFGF-Polymer Conjugates for Wound Healing DTEW $333747

5 R01 EB014703-04 MOONEY DAVID J (contact) SCADDEN DAVID T WEITZ DAVID A WESTERVELT ROBERT M Building the Hematopoietic Stem Cell Niche DTEW $779887

5 R01 EB016458-03 OHTA AARON NRI Paraellel Independent Control of Microrobots for Microassembly of Tissues DTEW $88062

5 R01 EB007534-08 PALECEK SEAN P Regulating human pluripotent stem cell differentiation by colony confinement DTEW $357125

5 R01 EB012521-05 PAREKKADAN BIJU Artificial Humanized Stem Cell Niches DTEW $668221

5 R01 EB013212-04 RUBENSTEIN DAVID A Development of a BioMIMETIC Composite Scaffold to promote vascular network growth DTEW $222174

5 R01 EB014351-03 RUBIN CLINTON T (contact) JUDEX STEFAN RUBIN JANET E Harnessing mechanical signals to control mesenchymal stem cell fate DTEW $337722

2 R01 EB005678-09 SHEA LONNIE D (contact) ANDERSON AILEEN J Controlled Release Scaffolds for Nerve Regeneration DTEW $593118

2 R01 EB009910-06A1 SHEA LONNIE D (contact) LUO XUNRONG Protein-Releasing Microporous Scaffolds for Cell Replacement Therapy DTEW $558726

5 R01 EB003806-10 STUPP SAMUEL I Bioactive Scaffolds for Regeneration in Spinal Cord Injury DTEW $663372

5 R01 EB015007-04 SUGGS LAURA J Nanotracer Development to Track Stem Cell Therapy DTEW $436314

5 R01 EB013281-04 THOMPSON DEANNA M APPLICATION OF ELECTRICAL STIMULATION FOR RAPID AND DIRECTED RE-GROWTH VIA ELECTR DTEW $344344

5 R01 EB014986-04 TUSZYNSKI MARK H (contact) SAKAMOTO JEFFREY Bioengineered Scaffolds for Spinal Cord Injury DTEW $462221

1 R01 EB019430-01A1 TUAN ROCKY S Cholesterol Sensitivity and Mechanisms of MSC Responses to 3D Substrate Rigidity DTEW7 $324358

5 R01 EB017753-02 WELLS REBECCA G (contact) JANMEY PAUL A SHENOY VIVEK Pathological consequences of altered tissue mechanics in fibrosis DTEW $424155

1 R01 EB020050-01 XIA YOUNAN (contact) BOULIS NICHOLAS M Nanofiber Conduits with a Honeycomb Structure for Repairing Large Defects in Thick Nerves DTEW $321210

5 R01 EB003060-09 YASZEMSKI MICHAEL J (contact) LU LICHUN Injectable and Preformed Osteoinductive Biodegradable Composites DTEW $459871

1 R01 EB019411-01A1 ZHAO RUOGANG Fibrotic microtissue chips for screening of anti-fibrotic therapies DTEW $352982

1 R03 EB019552-01A1 CONVERSE GABRIEL L Recellularization mechanisms in mononuclear cell seeded tissue engineered valves DTEW $75000

1 R03 EB018889-01A1 DEARTH CHRISTOPHER L NSAIDs and the Role of COX2 in Biologic Scaffold-Mediated Tissue Reconstruction DTEW $77878

1 R03 EB018430-01A1 GRAYSON WARREN L Tunable Oxygen Delivery to Cells using Novel Microtank Technology DTEW $81000

5 R03 EB017344-02 JUN HO-WOOK A hybrid nanosack for the enhanced islet engraftment in the omentum DTEW $71295

7 R03 EB019184-03 KHETANI SALMAN R Engineering zonal human liver functions in vitro using microfluidics DTEW7 $90743

1 R03 EB020910-01 MA MINGLIN Organogenesis in microcapsules developing an efficient and scalable organoid culture platform DTEW $72118

5 R03 EB017927-02 PRICE RICHARD J Application of Laser Speckle Flowmetry to Vascular Remodeling DTEW $76146

5 R03 EB018575-02 SANT SHILPA Engineered Microenvironments to model effect of size in tumor progression DTEW $77000

5 R03 EB018851-02 TIEN JOE Y In Vivo Microsurgical Anastomosis of Prevascularized Tissues DTEW7 $81850

5 R03 EB015744-02 WANG HONGJUN Novel Strategies to Increase Insulin Independence after Islet Autotransplantation DTEW $72507

5 R21 EB018505-02 ANSETH KRISTI S Protease Activity in 3D Matrices DTEW $222224

5 R21 EB019230-02 BROWN JUSTIN L Migratory Morphology A Function of Fibrous Extracellular Matrix Geometry Sensing DTEW $179818

5 R21 EB017876-02 CHEN SHAOCHEN Biomimetic design of human induced pluripotent stem cells on a chip DTEW $225525

1 R21 EB020978-01 COSGRIFF-HERNANDEZ ELIZABETH MARIE EFFECT OF IMPROVED GRAFT COMPLIANCE MATCHING ON INTIMAL HYPERPLASIA DTEW $208152

5 R21 EB016393-02 COSGRIFF-HERNANDEZ ELIZABETH MARIE DEVELOPMENT OF PICKERING EMULSIONS AS INJECTABLE BONE GRAFTS DTEW $168503

5 R21 EB017078-02 DENG CHERI X (contact) FU JIANPING Ultrasound-mediated Directed Osteogenic Differentiation of Mesenchymal Stem Cells DTEW7 $194375

1 R21 EB018538-01A1 EROGLU ALI New Cell Desiccation Strategy Using Non-Isothermal Drying and Biophysical Models DTEW $256094

1 R21 EB021005-01 HAN ARUM A High-Throughput Microfluidic in vitro CNS Myelination Model towards Drug Screening DTEW $179524

1 R21 EB018481-01A1 HARLEY BRENDAN A Label-free interrogation of heterogeneities in HSC fate decision signatures DTEW $193022

5 R21 EB016792-02 HATEFI ARASH Bioengineering a Safe and Efficient Vector Technology for Stem Cell Transfection DTEW $193750

1 R21 EB021003-01 HEALY KEVIN EDWARD iPSC Derived Cardiac Microchambers for Embryonic Drug Screening DTEW $235438

1 R21 EB020235-01 HEILSHORN SARAH C (contact) HUANG NGAN F Injectable Hydrogels to Improve the Efficacy of iPSC-derived Therapies DTEW $243575

5 R21 EB018407-02 HEILSHORN SARAH C Engineered Intestinal Microenvironments as Preclinical Drug Screening Platforms DTEW7 $193259

5 R21 EB016774-02 HUARD JOHNNY Biomimetic Coacervate Delivery of Muscle Stem Cell to Improve Cardiac Repair DTEW $233424

5 R21 EB016247-02 HUBEL ALLISON Technology platform for development of multi-component preservation solution DTEW $171838

5 R21 EB017184-02 ISENBERG JEFFREY S (contact) BADYLAK STEPHEN F Bioengineering Tracheas Through Targeting Activated CD47 DTEW $192500

5 R21 EB016359-02 KUMAR SANJAY Genetic strategies for the quantitative control of cell-matrix mechanobiology DTEW $189756

5 R21 EB017384-02 LAPOTKO DMITRI O (contact) SHPALL ELIZABETH J All-in-one purification and engineering of therapeutic cell systems DTEW $231384

5 R21 EB017539-02 LEE LY JAMES (contact) OTERO JOSE JAVIER Large Scale Nanochannel Electroporation (NEP) for Cell Reprogramming DTEW $198383

1 R21 EB019508-01A1 MASTERS KRISTYN S Development of Complex Culture Systems to Study Valvular Dysfunction DTEW $182770

5 R21 EB017868-02 REICHERT WILLIAM MONTGOMERY Aptamer-based affinity capture of circulating CAD EPCs DTEW $151487

1 R21 EB019646-01 RYLANDER MARISSA NICHOLE (contact) VLACHOS PAVLOS P Nanoparticle Transport as a function of Physiologic and Hyperthermic Conditions in a 3D Vascularized Microfluidic Tumor Platform DTEW $233531

1 R21 EB020282-01 SETHU PALANIAPPAN Functional Maturation of Induced Pluripotent Stem Cell Cardiomyocytes (IPS-CMs) via Targeted Mechanical Conditioning and Work DTEW7 $206165

1 R21 EB020107-01 SHIRWAN HAVAL (contact) GARCIA ANDRES J Immuno-vasculogenic hydrogels for islet engraftment and localized tolerance DTEW $196683

1 R21 EB020192-01A1 USTA OSMAN BERK Novel Microfluidic Platforms for Actively Controlled in-vitro Liver Zonation DTEW $261000

5 R21 EB019123-02 VERBRIDGE SCOTT S 3D micro-addressable tissue models to understand spatiotemporal heterogeneity in transcriptional regulation DTEW $220830

5 R21 EB015906-04 WANG QI Device to mechanically interrogate tissue and skin across research environments DTEW $167779

1 R21 EB019509-01A1 YOUNG PAMPEE P (contact) SUNG HAK-JOON Thermosensitive injectable polymer-based stem cell therapy for limb ischemia DTEW $235329

5 R21 EB015737-02 ZHAO MIN Guiding angiogenesis DTEW $186725


1 R43 EB021704-01 CROSSWELL HOWLAND E The 3D Platelet Bank A Clinical-grade Scalable 3D Microbioreactor Bone Marrow Mimetic for Platelet Production DTEW $225000

1 U01 EB021214-01 ROY SHUVO (contact) FISSELL WILLIAM H Building an Implantable Artificial Kidney DTEW $1331543

5 UH3 EB013647-05 HAMMER BRUCE E Gravitational Regulation of Osteoblast Genomics and Metabolism DTEW $423517

5 UH3 EB017103-04 VUNJAK-NOVAKOVIC GORDANA Integrated heart-liver-vascular systems for drug testing in human health and dise DTEW $2092852




1 U18 EB021780-01 WELLS JAMES M (contact) HELMRATH MICHAEL A Establishment of in vitro and in vivo models of human gastrointestinal organoids with a functional ENS DBMW $287040

$37278793

$44707119 $44740119

DP1

DP2

P41

R00

R01

R01 (BRP)

R03

R21

R4

U01

UH23

U18

Other

Contract



QVR Custom Download




User HUNZIKERR




$453696


























































































































$37278793

$44707119 $44740119














TS

TD

TI

TC

TF

0



QVR Custom Download




User HUNZIKERR




$453696


























2 P41 EB002025-31A1 SUPERFINE RICHARD Computer Integrated Systems for Microscopy and Manipulation (CISMM) DOIW $1401412

1 DP2 EB022358-01 LIPOMI DARREN J Stretchable Biodegradable and Self-Healing Semiconductors for Wearable and Implantable Sensors DTEW $2193330

7 DP2 EB020537-02 MCALPINE MICHAEL 3D Printed Nano-Bionic Organs DTEW $0

1 DP2 EB020549-01 ZHANG LIJIE GRACE A Novel 3D Bioprinted Smart Vascularized Nano Tissue DTEW $2287500

3 P41 EB002520-12S1 KAPLAN DAVID L Tissue Engineering Resource Center DTEW $64351

5 P41 EB002520-12 KAPLAN DAVID L Tissue Engineering Resource Center DTEW $1243616

5 P41 EB002503-12 TONER MEHMET Bio-MicroElectroMechanical Systems (BioMEMS) Resource Center DTEW $1252826

5 R01 EB017129-03 AMEER GUILLERMO ANTONIO (contact) KIBBE MELINA RAE Preclinical Investigation of a Bioengineered Vascular Graft DTEW $418612

5 R01 EB010039-04 BEEBE DAVID J (contact) HUTTENLOCHER ANNA Understanding cell migration through microscale in vitro models DTEW $464661

5 R01 EB011516-06 BIRLA RAVI KUMAR Fabrication of 3D Cardiac Patches for Myocardial Recovery DTEW $288690

5 R01 EB008722-06 BURDICK JASON A (contact) MAUCK ROBERT L Engineering Developmental Microenvironments Cartilage Formation and Maturation DTEW $426990

5 R01 EB020367-02 CAPLAN ARNOLD I CWRU Center for Multimodal Evaluation of Engineered Cartilage DTEW $387902









































1 R13 EB020518-01 IRIMIA DANIEL Student Support for the ASME Conference in NanoEngineering for Medicine and Biology (NEMB 2015) DTEW $10000









































5 R00 EB013630-05 BELLAN LEON MARCEL 3D Microvascular Networks in Hydrogels Fabricated with Sacrificial Structures DTEWZ $229853

5 R00 EB013446-05 GODULA KAMIL NeoProteoglycans as synthetic materials for regenerative medicine and bioimaging DTEWZ $237934

4 R00 EB017723-02 QUINN KYLE PATRICK Non-invasive label-free quantitative imaging for chronic wound characterization DTEWZ $249000


$37278793

$44717119 $44740119

DP1

DP2

P41

R00

R01

R01 (BRP)

R03

R21

R4

U01

UH23

U18

Other

Contract

TUESDAY JULY 12 2016

800 AM REGISTRATION AND POSTER VIEWING

830 AM PLENARY SPEAKER ndash Main Auditorium

BREAKOUT SESSIONS

930 AM

Traineesrsquo Session - Main Auditorium

Rosemarie Hunziker PhD NIBIB

Understanding NIH

Training Program Directorsrsquo Session - Room D

NIBIB funding NIHNIBIB program and policy

changes

1030 AM BREAK and poster viewing BREAK and poster viewing

1045 AM

Michael Summers PhD Professor and HHMI Investigator

University of Maryland Baltimore County

Grant-writing from the PIs Point of view

Training Program Directorsrsquo session

hellip continued

1145 AM

Working Lunch Entrepreneurship Panel

Todd Merchak Program Specialist NIBIB

Todd Landsman Engineering Manager Shape Memory

Therapeutics Inc

Michael K Dempsey Entrepreneur in Residence

Accelerator Program Leader CIMIT Harvard University

(Pre-order your lunch at tgmnibibnihgovlogistics)

100 PM

Grant WritingReview Break-out Session - Rooms A C1C2

E1E2 G1G2 H J Small group discussions of grant

applications withTraining Program Directors other grantees

and NIH staff

Adjourn

200 PM

NETWORKING SESSION - Rooms A E1E2 G1G2

Meet and network with predoctoral trainees postdoctoral

fellows Training Program Directors other grantees and NIH

staff

250 PM Take down posters and adjourn

300 PM

Post-meeting Tours (Select one)

NIBIB Intramural Laboratories

NIH Clinical Center

430 PM Shuttle to hotel

Bruce Rosen MD PhD Professor in Radiology Harvard Medical School Director Athinoula A Martinos Center for

Biomedical Imaging

Lessons Learned



930 AM ndash 100 PM




































































Efficacy Data






UCLA
















Vaccination
























Rohit Bhargava



















Brandeis University





Pedro Brugarolas



Forelimb







Boston University







Stanford University





imaging


Rutgers University


Nerves




muscle contraction






Duke University





Kyle S Decker

Duke University










Studies




Cancer













UCSF





plants


UCSD








Eric Gibbs

Duke University




Mark W Grinstaff

Boston University



UCLA


system monitoring


UC San Francisco








Nathaniel O King

























vesicles






UC San Diego






Duke University










UCLA


Fixation





Stanford University



MIT


BREAST CANCER







carcinoma


Johns Hopkins


populations












UC San Diego









Cancer









Duke University















Stanford University




Harvard University





Cyrus A Raji MD PhD



tetraplegia







Spheroids


Boston University



et al







Hydrogels







UT



Brandeis University












nephritis




Patients





Carnegie Mellon









TMJ pain






















cancer


UCSF








UC San Diego















Duke University


Tomography


Stanford University


Injury

Jeffrey Ware












Mice














MEETING

ABSTRACT BOOK












































Model











Tissue














Correlates













Rabbit Forelimb










Induced Autophagy







ultrasound imaging




Peripheral Nerves








models
















MRI Studies




Colorectal Cancer

























strain analysis

















Glioma






























membrane vesicles


























Tissue Fixation




immunotherapies





































Prostate Cancer




Children












activity




Imaging

















tetraplegia







Spheroids












Hydrogels










model











lupus nephritis




Multiforme Patients













in TMJ pain








disease











circulation




prostate cancer

























Tomography

















Awake Mice
















A Joseph Bonventre






E1E2 Mia Markey

















































































































































































































































































Phone E‐mail

Phone E‐mail



Introduction




wwwnibibnihgov



















December 2015













Introduction



















Training Programs







October 2014



















Trans-nIH Programs




wwwnibibnihgov

























Presentations






(by mechanism)


(by topic)


Total = $7007630 N = 23

Success rates

FY13 = 4

FY14 = 8

FY15 = 15

Devices (7)

Scaffolds (8)

Growth

Factors (5)

Imaging (1)

Cell

Interactions (2)

Rosemarie Hunziker

Chart1

0
0
1
0
5
0
1
13
3
0
0
0
0
0

Data

Data

Criteria

Formats

Chart1

8
7
1
2
5

Data

Data

Criteria

Formats











Rosemarie Hunziker

Success rates

FY13 = 13

FY14 = 14

FY15 = 18


Total = $37278793 N = 91


Chart1

0
3
3
3
34
4
10
29
1
1
2
1
0
0

Data

Data

Criteria

Formats





Scaffolds (38)



Growth Factors (3)

Tissue Chips (13)

Imaging (6)

Mechanics

(14)Preservation

(3)

Blood (8)

Bone cartilage (7)


Neural (9)Liver (6)

Stem Cells

(13)

Other (30)



Chart1

6
5
6
5
3
13
6
14
4
38

Data

Data

Criteria

Formats

Chart1

8
7
21
9
6
13
30

Data

Data

Criteria

Formats











Telehealth

7

Biosensors




Telehealth


The NETWORK


The CENTERS




8


bull Components



Informatics


integration

DataCoordination



10






NIBIBNIH


Programs


Synthetic Biology

Technologies







implantable pumps








lt2 years



therapy



safety profiles



Tumor killing



ACS NANO


Identified top NP

formulations

which lead to

nearly 100 killing

of cancer cells in

vitro


widely throughout

tumor

2

Suicide geneControl



C

ell D

eath



3

Control

Prodrug

DNA + Prodrug











bottom-up









syndrome)




David Rampulla PhD














Technology

BiologyTherapy


Environment

Organism

Organ Systems

Organs

Tissues

Cells organelles

Pathways

Protein

RNA

DNA











Richard Conroy PhD





Ultrasound


Molecular Imaging


Richard Conroy PhD




























httpoctresearchorg

httplbrcmitedu



httplammpbliuciedu



















Steven Krosnick MD





System



Antonio Sastre PhD









Nuclear Medicine


Antonio Sastre PhD











Guoying Liu PhD














Lung MRI3

Cancer MRI3




























Vinay Pai PhD




SG

SD

1mm

SG

1mm

TRIAGE CODE

NO ACTION

E

BM

BV

SGM

1mm

Health

y

Potentially

premalignant

(dysplasia)

Malignant

(Sq Cell Ca no BM)

TRIAGE CODE

RE-CHECK IN

3 MONTHS

TRIAGE CODE

SEND TO

SPECIALIST

IMMEDIATELY

E

E

BM (Basement

membrane)

BM





Santosh Kumar PI


PI K Gilchrist




clinical data












improved detection















paivmailnihgov




TGM Agenda Monday

TGM Agenda Tuesday


Speaker Bios


Abstract Booklet


Contact List






Slide Number 2

Slide Number 3

Slide Number 4

Slide Number 5


Slide Number 7

Slide Number 8


Slide Number 10

Slide Number 11

Slide Number 12



Slide Number 15

Slide Number 16

Slide Number 17



Neuromodulation








Slide Number 28

Slide Number 29

Slide Number 30

Slide Number 31

Slide Number 32

Slide Number 33

Slide Number 34

Slide Number 35





Slide Number 40

Slide Number 41


Slide Number 43

Nuclear Medicine

Slide Number 45

Slide Number 46


Slide Number 48

Slide Number 49

Slide Number 50




Slide Number 54

Slide Number 55

Slide Number 56

Slide Number 57

Slide Number 58

Slide Number 59


Contact info



QVR Custom Download




User HUNZIKERR




$453696


























































































































$37278793

$44707119 $44740119














blood

bone cart

cardio-vasc

neuro

liver

stem cells

all other



QVR Custom Download




User HUNZIKERR




$453696


























































































































$37278793

$44707119 $44740119














TB

TC

TD

TE

TF

TH

TI

TM

TP

TS



QVR Custom Download




User HUNZIKERR




$453696


























































































































$37278793

$44707119 $44740119

DP1

DP2

P41

R00

R01

R01 (BRP)

R03

R21

R4

U01

UH23

U18

Other

Contract



QVR Custom Download




User HUNZIKERR




$453696


























































































































$37278793

$44707119 $44740119














TS

TD

TI

TC

TF

0



QVR Custom Download




User HUNZIKERR




$453696



























































































































$37278793

$44717119 $44740119

DP1

DP2

P41

R00

R01

R01 (BRP)

R03

R21

R4

U01

UH23

U18

Other

Contract



930 AM ndash 100 PM




































































Efficacy Data






UCLA
















Vaccination
























Rohit Bhargava



















Brandeis University





Pedro Brugarolas



Forelimb







Boston University







Stanford University





imaging


Rutgers University


Nerves




muscle contraction






Duke University





Kyle S Decker

Duke University










Studies




Cancer













UCSF





plants


UCSD








Eric Gibbs

Duke University




Mark W Grinstaff

Boston University



UCLA


system monitoring


UC San Francisco








Nathaniel O King

























vesicles






UC San Diego






Duke University










UCLA


Fixation





Stanford University



MIT


BREAST CANCER







carcinoma


Johns Hopkins


populations












UC San Diego









Cancer









Duke University















Stanford University




Harvard University





Cyrus A Raji MD PhD



tetraplegia







Spheroids


Boston University



et al







Hydrogels







UT



Brandeis University












nephritis




Patients





Carnegie Mellon









TMJ pain






















cancer


UCSF








UC San Diego















Duke University


Tomography


Stanford University


Injury

Jeffrey Ware












Mice














MEETING

ABSTRACT BOOK












































Model











Tissue














Correlates













Rabbit Forelimb










Induced Autophagy







ultrasound imaging




Peripheral Nerves








models
















MRI Studies




Colorectal Cancer

























strain analysis

















Glioma






























membrane vesicles


























Tissue Fixation




immunotherapies





































Prostate Cancer




Children












activity




Imaging

















tetraplegia







Spheroids












Hydrogels










model











lupus nephritis




Multiforme Patients













in TMJ pain








disease











circulation




prostate cancer

























Tomography

















Awake Mice
















A Joseph Bonventre






E1E2 Mia Markey

















































































































































































































































































Phone E‐mail

Phone E‐mail



Introduction




wwwnibibnihgov



















December 2015













Introduction



















Training Programs







October 2014



















Trans-nIH Programs




wwwnibibnihgov

























Presentations






(by mechanism)


(by topic)


Total = $7007630 N = 23

Success rates

FY13 = 4

FY14 = 8

FY15 = 15

Devices (7)

Scaffolds (8)

Growth

Factors (5)

Imaging (1)

Cell

Interactions (2)

Rosemarie Hunziker

Chart1

0
0
1
0
5
0
1
13
3
0
0
0
0
0

Data

Data

Criteria

Formats

Chart1

8
7
1
2
5

Data

Data

Criteria

Formats











Rosemarie Hunziker

Success rates

FY13 = 13

FY14 = 14

FY15 = 18


Total = $37278793 N = 91


Chart1

0
3
3
3
34
4
10
29
1
1
2
1
0
0

Data

Data

Criteria

Formats





Scaffolds (38)



Growth Factors (3)

Tissue Chips (13)

Imaging (6)

Mechanics

(14)Preservation

(3)

Blood (8)

Bone cartilage (7)


Neural (9)Liver (6)

Stem Cells

(13)

Other (30)



Chart1

6
5
6
5
3
13
6
14
4
38

Data

Data

Criteria

Formats

Chart1

8
7
21
9
6
13
30

Data

Data

Criteria

Formats











Telehealth

7

Biosensors




Telehealth


The NETWORK


The CENTERS




8


bull Components



Informatics


integration

DataCoordination



10






NIBIBNIH


Programs


Synthetic Biology

Technologies







implantable pumps








lt2 years



therapy



safety profiles



Tumor killing



ACS NANO


Identified top NP

formulations

which lead to

nearly 100 killing

of cancer cells in

vitro


widely throughout

tumor

2

Suicide geneControl



C

ell D

eath



3

Control

Prodrug

DNA + Prodrug











bottom-up









syndrome)




David Rampulla PhD














Technology

BiologyTherapy


Environment

Organism

Organ Systems

Organs

Tissues

Cells organelles

Pathways

Protein

RNA

DNA











Richard Conroy PhD





Ultrasound


Molecular Imaging


Richard Conroy PhD




























httpoctresearchorg

httplbrcmitedu



httplammpbliuciedu



















Steven Krosnick MD





System



Antonio Sastre PhD









Nuclear Medicine


Antonio Sastre PhD











Guoying Liu PhD














Lung MRI3

Cancer MRI3




























Vinay Pai PhD




SG

SD

1mm

SG

1mm

TRIAGE CODE

NO ACTION

E

BM

BV

SGM

1mm

Health

y

Potentially

premalignant

(dysplasia)

Malignant

(Sq Cell Ca no BM)

TRIAGE CODE

RE-CHECK IN

3 MONTHS

TRIAGE CODE

SEND TO

SPECIALIST

IMMEDIATELY

E

E

BM (Basement

membrane)

BM





Santosh Kumar PI


PI K Gilchrist




clinical data












improved detection















paivmailnihgov




TGM Agenda Monday

TGM Agenda Tuesday


Speaker Bios


Abstract Booklet


Contact List






Slide Number 2

Slide Number 3

Slide Number 4

Slide Number 5


Slide Number 7

Slide Number 8


Slide Number 10

Slide Number 11

Slide Number 12



Slide Number 15

Slide Number 16

Slide Number 17



Neuromodulation








Slide Number 28

Slide Number 29

Slide Number 30

Slide Number 31

Slide Number 32

Slide Number 33

Slide Number 34

Slide Number 35





Slide Number 40

Slide Number 41


Slide Number 43

Nuclear Medicine

Slide Number 45

Slide Number 46


Slide Number 48

Slide Number 49

Slide Number 50




Slide Number 54

Slide Number 55

Slide Number 56

Slide Number 57

Slide Number 58

Slide Number 59


Contact info



QVR Custom Download




User HUNZIKERR




$453696


























































































































$37278793

$44707119 $44740119














blood

bone cart

cardio-vasc

neuro

liver

stem cells

all other



QVR Custom Download




User HUNZIKERR




$453696


























































































































$37278793

$44707119 $44740119














TB

TC

TD

TE

TF

TH

TI

TM

TP

TS



QVR Custom Download




User HUNZIKERR




$453696


























































































































$37278793

$44707119 $44740119

DP1

DP2

P41

R00

R01

R01 (BRP)

R03

R21

R4

U01

UH23

U18

Other

Contract



QVR Custom Download




User HUNZIKERR




$453696


























































































































$37278793

$44707119 $44740119














TS

TD

TI

TC

TF

0



QVR Custom Download




User HUNZIKERR




$453696



























































































































$37278793

$44717119 $44740119

DP1

DP2

P41

R00

R01

R01 (BRP)

R03

R21

R4

U01

UH23

U18

Other

Contract



QVR Custom Download

Query Criteria		Project Number Contains EB ICs = EB Primary and Dual Projects All Active Grants which were active TODAY Program Class Code Contains ___W____ Extramural Grants

Sort Criteria		PCCActivityPI Name(s) All

Download Cols		TypeActvProject PI Name(s) AllTitlePCCObl $ Tot (IMPAC)

User		HUNZIKERR

DateampTime Run		ts 2015-11-10 120616

2016 nibib training grantees meeting 9:00 am … · scientific research, project management,...

Documents

Chart1

Data

Data

Criteria

Formats

Chart1

Data

Data

Criteria

Formats

Chart1

Data

Data

Criteria

Formats

Chart1

Data

Data

Criteria

Formats

Chart1

Data

Data

Criteria

Formats

Chart1

Data

Data

Criteria

Formats

Chart1

Data

Data

Criteria

Formats

Chart1

Data

Data

Criteria

Formats

Chart1

Data

Data

Criteria

Formats

Chart1

Data

Data

Criteria

Formats

Chart1

Data

Data

Criteria

Formats

Chart1

Data

Data

Criteria

Formats

Chart1

Data

Data

Criteria

Formats

Chart1

Data

Data

Criteria

Formats

Chart1

Data

Data

Criteria

Formats