saisr guide to small animal imaging...small animal imaging senior staff associate saisr guide to...

SAISR Guide to Small Animal

Imaging Modalities and

Applications

Columbia University

Small Animal Imaging

Shared Resource

(SAISR))

Kenneth P. Olive, Ph.D. Director

Steven A. Sastra Manager

Christopher B. Damoci Senior Staff Associate Imaging Scientist

Andrew Kung, M.D., Ph.D. MR Director

Yanping Sun, Ph.D. Associate Research Scientist MR Physicist Room 2-200ST2 1130 Saint Nicholas Avenue New York NY, 10032 Phone: 212-851-4901 Fax: 212-851-4678 Mobile: 732-713-9911

Email: [email protected] IMAGING THE FUTURE OF CANCER RESEARCH

All Images and information are the copyright of the Columbia University Medical Center Small Animal Imaging Shared Resource and specific

approval must be given prior to reproduction or use.

Table of Contents

Page #

1. Contact information………………………………………………………………………………. 2

2. Locations……………………………………………………………………………………………….. 3

3. Getting Started…………………………………………………………………………………………………. 4

4. Infection Control ……………………………………………………………………………………………… 4

5. Rules and Procedures………………………………………………………………………………….……. 4

6. iLabs Scheduler………………………………………………………………………………………………… 5

7. Overview of instrumentation……………………………………………………………………………. 6

8. Perkin-Elmer IVIS Spectrum Optical Imaging System...……………………………………... 7

9. IVIS: Specification and Pricing……………………………………………………………………..……. 8

10. IVIS: Bioluminescent Imaging……………………………………………………………………………. 9

11. IVIS: Fluorescent Imaging…………………………………………………………………………………. 10

12. IVIS: Image Analysis………………………………………………………………………………………..... 11

13. VisualSonics VEVO 2100 High-Frequency Ultrasound.…………….……….………………. 12

14. VEVO 2100: Specification and Pricing...……………………………………………………………. 13

15. VEVO 2100: B-Mode Imaging..…………………………………………………………………………. 14

16. VEVO 2100: M-Mode……………………………………………….………………………………………. 15

17. VEVO 2100: Color Doppler……………………………………….………………………………………. 16

18. VEVO 2100: Pulse-Wave and Power Doppler……………………………………………………. 17

19. VEVO 2100: Non-Linear Contrast Imaging…………………………………………………………. 18

20. VEVO 2100: 3D-Volume Imaging Technology.……………………………………………………. 19

21. VEVO 2100: Ultrasound-Guided Imaging……………………………………………………………. 20

22. Perkin-Elmer Quantum FX micro-CT...……………………………………………..……………..…. 21

23. Quantum FX: Specification and Pricing……………………………………….………………………. 22

24. Quantum FX: Anatomical Imaging………………………………………………..……………………. 23

25. Quantum FX: Contrast Imaging...………………………………………………………………………. 24

26. Quantum FX: Bone Microarchitecture Imaging and Analysis……………..………………. 26

27. Quantum FX: Lung Volumes ……………………..………………………………………………………. 27

28. Quantum FX: Fat Mass and Muscle Mass Imaging……………………………………..………. 28

29. Quantum FX: Coregistration with IVIS ………………………………………………………………. 29

30. Quantum FX: Liver Steatosis.………………………………………………………….…………………. 30

31. Bruker BioSpec 9.4 Tesla High-Field Magnetic Resonance Imager.….…………………. 31

32. Bruker MRI: Specifications and Pricing………………………………………………………………. 32

33. Bruker MRI: Anatomical Imaging……………………………………………………….………………. 33

34. Bruker MRI: Cardiac Imaging………………………………………………………………..……………. 34

35. Bruker MRI: Angiography………………………………………………………………………..…………. 35

36. Bruker MRI: Perfusion/Diffusion Weighted Imaging…………..………………………………. 36

37. Bruker MRI: DTI Imaging………………………………………………………………………………….…. 37

38. Bruker MRI: MR Spectroscopy…….……………………………………………………………………….

39. Bruker MRI: fMRI Imaging………..……………………………………………………………….

Version date: October 13, 2015



Contact Information

Director

Kenneth P. Olive, Ph.D.

Email: [email protected]

Manager

Steve Sastra


Senior Staff Officer / Imaging Scientist

Christopher B. Damoci


Tel: 212-851-4901

Fax: 212-851-4678

Cellphone: 732-713-9911

MR Advisor

Andrew L. Kung, M, PhD


MR Physicist

Yanping Sun




Locations

The SAISR is located within the Irving Cancer Research Center (ICRC) Building on the campus of

Columbia University Medical Center.

Irving Cancer Research Center

1130 Saint Nicholas Avenue

New York NY, 10032

Administrative offices of the SAISR are located in Room 200ST2, on the second floor of the ICRC

Building. Upon exiting the elevator, make a left down the corridor. The offices for the SAISR

are just around the corner at the end of the hallway on the right had side.

The Main Imaging Suite is located within the 11th Floor animal barrier facility of the ICRC

Building in Rooms 1104 AB, AC, and AD.

The MRI Imaging Suite is located within the 10th Floor animal barrier facility of the ICRC

Building on Room 1015.

Hiccc.columbia.edu



Getting Started

The Columbia University Small Animal Imaging Shared Resource is here to assist our research

community with advanced in vivo imaging technologies and applications. There are a few steps that

users must take ahead of time to enable use of the SAISR instrumentation:

1) All research performed on animals at Columbia University Medical Center must receive prior

approval by the Institutional Animal Care and Uses Committee (IACUC). If there is interest in using

an imaging instrument for experiments that do NOT involve animals, please speak to Chris Damoci

about steps for access.

2) First time users of any instrumentation must schedule a training session within the iLabs scheduling

system in order to understand the methodology and processes of the technology, and the specific

procedure required by our facility. Please follow up with the SAISR to schedule this in advance of

your first experimental imaging session.

3) All usage of the SAISR instrumentation and analysis suites must be logged into the iLabs system prior

to use. If this is not done, it will be back-billed at full assisted usage price.

4) All decisions pertaining to mouse transfers from one barrier facility to another are made solely at

the discretion of the Columbia University Institute of Comparative Medicine (ICM).

5) Access to the barrier facility is only allowed to those that are previously authorized by the ICM or

those escorted by an authorized user at all times. This is for the safety of the animals and research

being done throughout the HICCC animal facility.

Infection Control

1. By its nature, any imaging facility presents a MAJOR POINT OF SUSCEPTIBILITY for the transmission

of pathogens within an animal colony, because animals are removed from their cages and come into

prolonged contact with a single set of equipment.

2. We have developed an extensive set of procedures designed to mitigate this risk. If fully adhered to,

these procedures will be highly effective in preventing the transmission of pathogens within the

SAISR.

3. It is the responsibility of EVERY USER to adhere to these procedures and promote a pathogen-free

environment. The science and research of the entire HICCC depends on everybody’s cooperation.

Rules and Procedures

1. Anyone scheduled for a specific time on an system has priority. Please be courteous to your fellow

researchers.

2. No researcher is allowed to use the facility without supervision unless they are previously trained in

the use of the instruments of the Small Animal Imaging Shared Resource.

3. Please be sure to turn off the oxygen on the wall upon completion of research. The oxygen supply

will be depleted if left on, and users will be subject to a surcharge for lost oxygen supplies.



iLabs Scheduling System

Columbia University Medical Center utilizes the iLabs core facility management system to

schedule and track all usage of the Columbia University Small Animal Imaging Shared Resource. This

system allows users to schedule their times and makes payments quickly and efficiently. Log on to

https://cumc.corefacilities.org with your UNI and Password to get started!

iLabs allows you to choose from any of our instrumentation and

analysis options and schedule the time you need to utilize the

equipment with ease.

iLabs allows easy login via your

Columbia UNI and Password.

Cumc.corefacilities.org

Cumc.corefacilities.org



Overview of Instrumentation

The SAISR is currently host to four imaging instruments as well as anesthesia instruments and

tools for the acquisition of physiological data. Each imaging modality is capable of being used for

multiple experimental applications, and this manual is designed to highlight these applications

and their capabilities. For any additional information, please speak to Chris Damoci, Steve Sastra,

or Ken Olive.

IVIS Spectrum Optical Imager (Perkin Elmer)

This instrument is used to perform bioluminescent or fluorescent imaging in vivo. Spectral

imaging capabilities enable acquisition of 3D datasets that can be co-registered with other

modalities (particularly micro CT). Kinetic imaging enables the study of signal intensity over time.

Vevo 2100 High Resolution Ultrasound (VisualSonics)

This instrument uses ultrasound in the 25-55MHz range to image tissues. his instrument is useful

for anatomical imaging of all abdominal organs, the heart, and the soft tissues of the extremeties.

Multiple applications are enabled including 3D tomography, Doppler imaging, Cardiac imaging,

contrast imaging, RF output. The facility also has a coaxial image-guided injection mount to

facility the injection or withdrawal of fluids at specific anatomical locations.

IVIS Quantum FX Micro CT (Perkin Elmer)

This high sensitivity CT instrument is designed to facilitate low-dose longitudinal imaging studies

while also enabling extremely high resolution scans. It has exceptional utility for bone, lung, and

CNS imaging, and may be used for contrast imaging of soft tissues as well as body composition

analysis. Integrated software enable simple co-registration of optical images acquired on the IVIS

Spectrum instrument.

BioSpec 94/20 9.4T MRI (Bruker)

This high-field research MRI is operated through the SAISR in collaboration with Dr. Andrew

Kung. This powerful instrument is capable of extremely high resolution anatomical imaging as

well as advanced functional imaging applications such as contrast MRI, diffusion weighted

imaging, and spectral imaging. The SAISR aids with the development of new imaging sequences

in collaboration with MRI physicist Dr. Yanping Sun.



Perkin-Elmer IVIS Spectrum Optical Imaging System

Luminescence Fluorescence

IVIS Optical Bioluminescent and Fluorescent enable the visualization of

genetically targeted alleles in cells or tissues of mice. Appropriately designed

alleles can provide anatomical location data, an indirect measure of tumor

volume, or functional information on gene expression.

SAISR Core




Specifications and Pricing

• High-sensitivity in vivo imaging of fluorescence and bioluminescence

• High throughput (5 mice) with 23 cm field of view

• High resolution (to 20 microns) with 3.9 cm field of view

• Twenty eight high efficiency filters spanning 430 – 850 nm

• Supports spectral unmixing applications (enhanced fluorescent imaging ability)

• Ideal for distinguishing multiple bioluminescent and fluorescent reporters

• Optical switch in the fluorescence illumination path allows reflection-mode or transmission-mode

illumination

• 3D diffuse tomographic reconstruction for both fluorescence and bioluminescence

• Ability import and automatically co-register CT or MRI images yielding a functional and anatomical

context for your scientific data.

• NIST traceable absolute calibrations

Pricing: Assisted Use / Training : Cancer Center Member—$71.00/hr

Internal—Columbia—$75.00.hr

Unassisted Use: Cancer Center Member—$48.00/hr

Internal—Columbia—$50.00/hr




Application: Bioluminescent Imaging

Bioluminescence imaging measures light emission resulting from an enzymatic reaction catalyzed by one

of several different luciferase enzymes. The luciferase gene may be incorporated into cells that are

implanted in mice, or directly into mouse tissues through genetic engineering or viral transduction.

Expression may be driven from general promoters as an indirect measure of tumor volume, or from gene-

specific promoters to functionally visualize pathway activity.

Three luciferase systems are in wide use:

Firefly luciferase requires D-luciferin to be injected into the subject prior to imaging. The peak emission

wavelength is about 560 nm. Due to the attenuation of blue-green light in tissues, the red-shift of this

emission makes detection of firefly luciferase much more sensitive in vivo (compared to the other

systems).

Renilla luciferase requires its substrate, coelenterazine, to be injected. As opposed to luciferin,

coelenterazine has a lower bioavailability. Additionally, the peak emission wavelength is about 480 nm, a

wavelength at which tissue attenuation is greater.

Bacterial luciferase has an advantage in that the lux operon used to express it also encodes the enzymes

required for substrate biosynthesis. Although originally believed to be functional only in prokaryotic

organisms, where it is widely used for developing bioluminescent pathogens, it has been genetically

engineered to work in mammalian expression systems as well. This luciferase reaction has a peak

wavelength of about 490 nm.

While the total amount of light emitted from bioluminescence is comparatively low (not detectable by

the human eye), the fact that there is no background light emission makes it extremely specific. The ultra-

sensitive CCD camera within the IVIS Spectrum can image bioluminescence with great sensitivity.

Common applications of BLI include in vivo studies of infection (with bioluminescent pathogens), cancer

progression (using a bioluminescent cancer cell line), and reconstitution kinetics (using bioluminescent

stem cells).

Perkin-Elmer SAISR Core




Application: Fluorescent Imaging

The IVIS Spectrum can image and quantify all commonly used fluorophores, including fluorescent

proteins, dyes and conjugates. Our IVIS Spectrum achieves superior spectral unmixing through a wide

range of high resolution, short cut-off filters and advanced spectral unmixing algorithms.

Spectral unmixing not only allows detection and separation of multiple reporters, but greatly reduces

the effects of tissue auto-fluorescence. The IVIS Spectrum is the most sensitive system to visualize these

fluorescent agents in various in vivo research needs for Principal Investigators here at Columbia

University Medical Center

The IVIS Spectrum optical imaging system:

• Uncompromised sensitivity and flexibility

• Transmission and epi-illumination imaging

• Emitted light from the excitation filter wheel feeds through a fiber optic bundle to illuminate the

specimen from either the top, in epi-illumination (reflectance) mode, or from underneath the

stage, by means of an automated bundle switch. Trans illuminating the subject from below at

precise x, y-locations allows for transmission imaging, enabling more sensitive detection and

accurate quantification of deep sources. Transmission fluorescence imaging also reduces the

effects of auto fluorescence.

• Software designed to simplify advanced and complex biological models by intuitively guiding the

user through experiential setup and analysis. The imaging wizard with the newly added probe

library will help design imaging settings and select the right filter pair for fluorescence studies.

The software also offers a step by step guide for spectrally unmixing multiple fluorescent signals

from the same animal. Advanced spectral-unmixing algorithms and a broad range of high

spectral resolution filter sets minimize auto fluorescence and provides the opportunity to image

a wide variety of targeted and activatable fluorescent probes and reporters.

Spectral Unmixing of 4

fluorophores (SAISR Core)

Perkin-Elmer

Fluorescent Imaging Techniques with the IVIS Spectrum allow

for a wide range of interrogation techniques for all Columbia

University Principal Investigators. Contact us to see how we

can help your research going forward in this area!




Image Analysis

Living Image® software brings the IVIS imaging technology to life by facilitating an intuitive workflow for

in vivo optical, X-ray and microCT image acquisition, analysis and data organization. Co-register DICOM

and VOX files acquired through the Quantum FX microCT and 3rd party imaging platforms through the

Living Image Multimodality Module. The DyCE imaging module enables temporal separation for real

time analysis of bio distribution and clearance events.

Living Image Software

Allows for ease of use of

the IVIS Imaging

Platform. Quantification

of your data and

investigating regions of

interest are made push-

button simple.

Living Image Analysis (SAISR Core)



Visualsonics VEVO 2100 High-Frequency Ultrasound

Contrast Ultrasound Image (Olive lab)

Spleen

Splenic artery

Pancreatic tumor Pancreas Stomach



VisualSonics VEVO 2100 High-Frequency Ultrasound


Ultrasound imaging is based on the reflection of high frequency sound by tissues. Sound pulses

are emitted from a transducer held against the subject and the reflected signal is detected and used to

construct an image. The ultrasound can distinguish different tissues because each has its own properties

of reflecting greater or lesser proportions of the emitted signal. In general, fluid-filled tissues transmit

more sound than air-filled tissues, and therefore the relative water content of tissues impacts the

resulting image. For most soft tissues, as the sound passes through each point in the tissues, a fraction is

reflected back to the tumor, while the rest continues on. As a result, tissues far away from the

transducer (i.e. at the bottom of the screen for a linear array transducer) will appear darker or black.

Ultrasonography is a powerful imaging modality that enables non-invasive, real time

visualization of abdominal organs and tissues. This technology has been adapted for use in mice through

the utilization of higher frequency transducers, allowing for extremely high resolution imaging. This

technique is particularly well-suited to small animal imaging due to the ultrasonographic properties of

the normal mouse tissue, easily accessible imaging planes of mouse tissue, and the comparative

difficulty in imaging the mouse tissue with other technologies. A suite of measurements tools is

available to characterize the normal and diseased states of tissues. Easily screened organs include all

peritoneal organs (liver, stomach, intestines, kidney, pancreas, spleen, bladder, prostate, ovaries),

subcutaneous ectopic xerographs, mammary tissue, melanomas, etc.

The VEVO 2100 system expands the functionality, flexibility and image quality of small animal

ultrasound, operating at frequencies never before achieved with solid-state array transducers.

MicroScan transducers provide increased frame rates, superb contrast, unrivaled resolution and a wider

field of view. The system is easy to use, non-invasive and fast, providing extremely high throughput

when needed.

- 30 micron resolution

- Frame rates in 2D up to 740 fps (for a 4x4 mm field of view)

- 3D-Mode Imaging for anatomical and vascular visualization, when combined with either B-Mode,

Power Doppler Mode or Nonlinear Contrast Imaging; allows for quantification of volume and vascularity

within a defined anatomical structure

Pricing: Assisted Use / Training : Cancer Center Member—$95.00/hr







Application: B-Mode Imaging

B-Mode is a two-dimensional ultrasound image. The brightness of each pixel is determined by

the amplitude of the returned echo signal from that location. These images allow for visualization and

quantification of anatomical structures, as well as for the visualization of diagnostic and therapeutic

procedures. Lesions such as tumors and atherosclerotic plaques can be identified and the extent of

disease burden can be quantified.

In addition, B-Mode can be used for image guided injections by enabling real-time imaging of needle

placement of an injection or aspiration procedure. Example procedures include injection of chemicals,

DNA or other biochemical compounds/materials into tissue regions that can be clearly seen within the

image area; extraction of fluids and/or cells under image guidance for biopsy, bio-assays and analysis is

also possible.

B-Mode Ultrasound Imaging (Olive Lab)




Application: M-Mode Cardiac Imaging

M-Mode imaging provides very high temporal resolution (1000 fps) of tissue motion along a

single ultrasound beam, and is generally used in cardiovascular research to study the movement of the

myocardium and valves, quantify cavity dimensions or to study the movement of vessel walls.

Software analysis tools allow for quantification of key cardiac function parameters including

ejection fraction, fractional shortening and cardiac output while M-Mode for visualization and

quantification of wall motion in cardiovascular research, single line acquisition allows for the very high-

temporal (1000 fps) resolution necessary for analysis of LV function. It is widely used by many

researchers here at Columbia University Medical Center for assessing mouse cardiac structure and

function.

M-Mode Ultrasound Imaging (SAISR Core)




Application: Color Doppler Imaging

Color Doppler Mode provides a visual overview of flow within the vessel or cardiac structure of interest.

Flow direction and velocity can be delineated by red and blue color spectrums and is used for guidance

when placing pulsed wave velocity sample volumes. This technique provides rapid identification of

vessels, valves of interest and their corresponding flow rates. The ability to quantify flow direction and

velocity greatly improves user confidence in vessel identification. Color flow sensitivity can be

automatically pre-set by the user for various flow rates such as heart, carotid, kidney or small vessels

such as femoral and arcuate arteries.

Example Color Doppler Imaging (Olive Lab)

Color Doppler Imaging is a

powerful tool for

visualizing the blood flow

and vascular health of

certain tissues. It is also

vitally important when

surgical techniques involve

areas of high vascular

density.




Application: Pulse Wave and Power Doppler Imaging

Pulsed-Wave (PW) Doppler Mode is used primarily for the hemodynamic assessment of blood

flow through the arteries and veins; it provides quantifiable information about the direction and velocity

of blood through the specified vessel. PW Doppler can measure both direction and velocity of blood flow;

abnormal flow is represented by an increase or decrease in velocity, a change in direction or flow, or the

presence of turbulent flow. PW Doppler also provides information on the relationship between velocities

in a cycle. For example, the ratio of systolic peak velocity to end-diastolic velocity in the renal artery relates

to the health of the kidney vasculature in diabetic conditions.

Power Doppler Mode can provide a visual overview and general quantification of flow velocity

and spatial vascular profile. This is a particularly useful tool in the assessment of vascularity. Measurement

tools in the Power Doppler Mode can calculate percent vascularity which is an index of relative vascular

density. Small changes in organ vascularity can be detected with Power Doppler imaging and monitored

with progression and regression of pathology or as a response to therapy. Power Doppler imaging can be

done in conjunction with 3D-Mode to provide volumetric information.

Example Pulse-Wave Doppler and Power Doppler Imaging (SAISR Core)

The CUMC SAISR can help you asses the

blood flow of tissues of interest.

Investigators interested in hemodynamic

research would find this technique

extremely valuable to any preclinical

research.




Application: Nonlinear Contrast Imaging

Contrast Agents allow untargeted and targeted contrast to be used with the VEVO 2100 high-

resolution in vivo micro-imaging systems. The contrast agents and protocols have been optimized

specifically for high-frequency micro-ultrasound and for preclinical applications.

Ultrasound-based contrast agents are typically small micron sized micro-bubbles that may be air

or gas filled. Tissue typically reacts linearly to ultrasound energy while micro-bubbles react in a non-

linear fashion to the same energy. Using proprietary filtering the VEVO system removes virtually all the

linear response of tissue signal from the quantification process, allowing researchers to quantify only

the micro-bubble response. As these microbubbles are intravascular, they are easily introduced

intravenously and pass through the vascular stream mimicking red blood cell movement.

Untargeted VEVO MicroMarker Contrast Agents provide image enhancement of the blood pool

such as imaging and quantification of tumor and organ perfusion (including myocardial perfusion). The

study and quantification of relative perfusion in vivo is an important metric for both cardiovascular

studies (i.e. myocardial perfusion) as well as cancer research and tumorigenesis study (i.e. tumor

perfusion) and general organ perfusion. Vascular architecture and structures can be visualized in tumor

models and relative tumor perfusion can be quantified. For cardiovascular studies, imaging myocardial

perfusion is possible along with the VEVO system's capabilities to perform complete cardiovascular

assessments.

Contrast Imaging Example (Olive Lab)

Contrast Imaging is a specialty here at the Columbia

University SAISR. Our Experts can help you with

valuable vascular studies for your investigations.



Visualsonics VEVO 2100 High-Frequency Ultrasound

Application: 3D-Volume Imaging Technology

3D-Mode combined with B-Mode, Power Doppler Mode and Contrast and Photoacoustic Imaging

Functionality allow for advanced data acquisition and analysis in various application areas. Semi-

automated 3-dimensional imaging can be performed rapidly and reproducibly. Following 3D acquisition,

the VEVO software constructs the scans into a 3D image.

This powerful software enables investigators numerous functions, such as:

• Virtual sections in all directions, x-, y-, z- and any other plane variation

• 3D rendering to illustrate 3D depths

• Accurate volume measurement

3D imaging can be performed in B-Mode, Power Doppler Mode and Contrast Mode providing higher

throughput when compared to other imaging modalities.

Volume Surface Topographic Images (SAISR Core)




Application: Ultrasound-Guided Injection

B-Mode high-frequency ultrasound imaging can be used for guided injections by enabling real-

time imaging of needle placement of an injection or aspiration procedure. Example procedures include

injection of chemicals, DNA or other biochemical compounds/materials into tissue regions that can be

clearly seen within the image area; extraction of fluids and/or cells under image guidance for biopsy,

bio-assays and analysis is also possible.

This is a widely used technique here at the Irving Cancer Research Center for the orthotopic

implantation of tumor cells into organs of interest to better recreate the disease model compared to

subcutaneous tumor xenografts. It is also possible to carry out image-guided injections of embryos in

utero as early as mid-gestation.

Ultrasound Guided Needle Injection into a Tumor (SAISR Core)

www.mouseimaging.ca



Perkin-Elmer Quantum FX Micro-CT

Clockwise from Top Left: 1) Example of bone microarchitecture 2) CT lung imaging shown within

skeletal structure of the mouse 3) The Perkin-Elmer Quantum FX micro-CT 4) Example of nanoparticle

blood pool imaging of the vascular system of a mouse. (All performed at the SAISR Core)




Specification and Pricing

Computed Tomography (CT) is a widely used imaging modality in the clinical setting. A CT scan

makes use of computer-processed combinations of many X-ray images taken from different angles to

produce cross-sectional (tomographic) images of specific areas of a scanned object, allowing the user to

see inside the object without cutting.

Digital geometry processing is used to generate a three-dimensional image of the inside of the

object from a large series of two-dimensional radiographic images taken around a single axis of rotation.

Cross-sectional images are used for diagnostic and therapeutic purposes in various medical disciplines.

Many different investigators in multiple disciplines can benefit from the use of CT images.

The Columbia University Medical Center is proud to have the Perkin-Elmer Quantum FX micro-

CT imaging system for preclinical small animal imaging.

Fluoroscopy mode

Real-time imaging enables precise animal positioning

Enables fast, high throughput workflow

Purpose-built for small animal imaging

Integrated animal handling

Animal transfer bed for IVIS Spectrum`

Pricing: Assisted Use / Training: Cancer Center Member—$119.00/hr







Application: Anatomical Imaging

The Quantum FX is the first stand-alone micro-CT to deliver high quality images at an X-Ray

doses low enough to enable TRUE longitudinal micro-CT in preclinical studies. An investigator can

monitor and characterize disease progression throughout their complete study with ease. By

thresholding for different signal intensities, it is possible to visualize different types of tissues, and

create surface maps of various anatomical structures.

Example anatomical imaging (SAISR core and Perkin-Elmer)




Application: Contrast Imaging

The Columbia University SAISR is proud to provide detailed vascular and contrast imaging via

micro CT. Iodinated and nanoparticle contrast agents can provide detailed 3D representation of tissues

of interest as well as provide great clarity to the vascularity of any area of interest. Feel free to contact

us to see how these contrast agents can help the imaging of your research.

SAISR Core

IN THIS EXAMPLE, THE LACK OF VASCUALRITY WITHIN A PANCREATIC DUCTAL

ADENOCARCINOMA IN THE KPC MOUSE MODEL IS SHOWN VIA THE USAGE OF THE EXITRON

6000 NANOPARTICLE CONTRAST AGENT FROM MILTENYI BIOSCIENCE.




Application: Contrast Imaging (continued)

In addition to high contrast vascular imaging, Exitron 6000 nanoparticles by Miltenyi Biosciences

can be used to longitudinally show the growth of tumor metastases throughout the length of a study.

Please feel free to contact us to discuss how we can assist in the identification and size of liver

metastases in your research.

In this example, Exitron 6000 was injected into the blood pool of the animal and remains

within the healthy liver cells of the animal for up to four weeks. This Image was taken

Four weeks post injection showing the growth of a Liver tumor

Kadenhe-Chiweshe Lab




Application: Bone Microarchitecture Imaging & Analysis

SAISR has the ability to provide automatic and user-guided isolation of bone from non-bone

tissue by means of threshold-based segmentation and a novel segmentation algorithm that separately

identifies the cortical and trabecular bone in whole-bone specimens. Our analysis suite uses the

segmented regions to automatically drive the calculation of common bone morphometric indices that

provide researchers with a quantitative description of bone microarchitecture. The micro architectural

characteristics of the trabecular and cortical bone are listed below (table 1 and 2).

SAISR Core




Application: Lung Volumes

The Quantum FX micro CT allows for the quantification and characterization of lung pneumonitis

and fibrosis, as well as lung capacity longitudinally using our custom built lung imaging platform to allow

for repeated accurate measurements of small animal lungs. Our analysis program allows for lung

volumes to be quantified throughout the course of a study.

THE ABILITY TO CALCULATE LUNG CAPACITY AND

CHARACTERIZE THE HEALTH OF THE TISSUE CAN

BE A VALUABLE ASSET TO YOUR RESERCH NEEDS!

All Images Courtesy of: Brenner Lab /

SAISR Core




Application: Fat Mass and Muscle Mass Imaging

Columbia University SAISR is also pleased to offer to its investigators research teams the

ability to perform longitudinal quantitative imaging of visceral and subcutaneous fat volumes as

well as the lean whole body muscle mass of small animals using our sensitive micro-CT imager.

Longitudinal studies in

the quantitative loss of

muscle tissue is

particularly useful with

cancer associated

cachexia disease states.

With this method a

researcher can follow

muscle wasting

throughout cancer

progression.

Analyze Direct Example Images from SAISR Core / Oberstein Lab




Application: Co-registration with Perkin-Elmer IVIS Optical Imaging System

The Living Image software system provides the ability to co-register images with both our

Quantum FX micro-CT and the IVIS Spectrum to allow for anatomical localization of optical image data.

Living Image Software

allows for volumetric

reconstruction, color-

opacity mapping, and

Gradient illumination

throughout the

registered CT and IVIS

image.

Images Courtesy of SAISR Core / Perkin-Elmer




Application: Liver Steatosis

The Quantum FX micro-CT can be used by investigators into liver function for steatohepatitis

and steatosis disease states. Fatty liver quantification can be done over numerous longitudinal imaging

sessions for any mouse model.

Quantitative Liver Fat Images (SAISR Core)

In this example, the above image

shows the fat content of a lobe of

a normal mouse liver in red. In

the below image, a genetically

engineered mouse model of liver

steatosis was used at endpoint to

show quantitatively the difference

in fat volume within a lobe of the

liver at endpoint. Longitudinal

imaging of treatment can be

shown in live animals throughout

the study.



Bruker BioSpec 94/20 9.4 Tesla MRI

Sagittal anatomical cross section of a mouse head (SAISR Core / Yanping Sun)




Please note that many of the applications described below have not yet been performed at

CUMC SAISR. Therefore, use of a specific technique may require development time and/or

collaborations with the imaging core and other scientists at CUMC.


The BioSpec series is designed for preclinical and molecular MR imaging and MRI research. State-of-the-

art MRI CryoProbe™ technology combined with ultra-high field USR magnets deliver high spatial

resolution in-vivo, enabling users to achieve the molecular and cellular level research they desire.

- Helium zero-boil-off and Nitrogen free magnet technology

- Scalable AVANCE III HD MRI RF architecture incorporating up to 16 receiver, 4 independent and 8

parallel transmitter channels

- Parallel imaging (GRAPPA) for almost all applications including EPI Multiple transmit imaging

applications

- High performance BGA-S gradients with highest amplitudes and slew rates, shim strengths and duty

cycles optimized for high field MRI

- AutoPac: motorized and software controlled animal positioning system for routine handling and

increased throughput

- IntraGate self-gated, steady-state cardiac imaging (no external sensor hardware and triggering devices

required)

- Phased-array RF coil technology for maximum sensitivity and minimum scan times

BioSpec 94/20 USR

• Field strength: 9.4 T

• Diameter of clear bore: 200 mm

• Stray-field (5 Gauss): +/- 3 m axial, +/- 2 m radial

Pricing:





Application: Anatomical Imaging

The BioSpec high-field magnetic resonance imager allows for images of your research of the

highest caliber possible. Extremely low voxel size and high detail allow for crystal clear imaging of the

organs of interest for your research needs. Whether it’s looking for sites of cancer growth in the

abdomen, to glioblastoma growth, the MRI allows for consequence free longitudinal imaging throughout

your studies. T1 and T2 weighted images allow for multiple methods of high quality morphological

imaging and contrast to help identify your regions of interest.

This is an example of a high resolution images that we have taken here at

the CUMC SAISR. Similar images can be taken of any organ of your

interest. Contact us to find out more!

T1-Weighted Coronal Image of a Mouse Brain (SAISR Core / Yanping Sun)




Application: Cardiac Imaging

Dedicated phased-array coils allow for high sensitivity for cardiac imaging of rodents.

Accelerated acquisition allows high temporal resolution applications such as first pass myocardial

perfusion. Self-gating methods or real-time physiological triggering enables free breathing functional

cardiac investigations on your research animals here at Columbia University.

-Black and Bright Blood Imaging

-First Pass Myocardial Perfusion

-Intragate – Self Gating

All options for cardiac MR imaging here at the CUMC

SAISR

Anatomical Cardiac MR Images Courtesy of Bruker Corporation




Application: Angiography

The Bruker BioSpec 9.4 tesla MR has the ability to provide high-resolution images of the blood

system within the animals of your research. Magnetic Resonance Angiography (MRA) can find problems

within the vasculature of the animal that may be causing issues in blood flow and vessel wall condition.

Research into aneurysms, and stenosis of blood vessels are common uses for this imaging type.

Time of Flight (TOF) protocols are

used for clear images of vessels

were blood is flowing.

Phase Contrast Angiography (PCA)

protocols can be done for

quantitative analysis such as

velocity mapping and Fourier Flow.

Contact us for more info!

Vascular Images Courtesy of SAISR Core / Bruker Corporation




Application: Perfusion/Diffusion Weighted Imaging

The contrast in Diffusion Weighted Imaging (DWI) originates from the difference in amount of diffusion.

Regions that have pathologically disturbed diffusion, such as found when multiple sclerosis, epilepsy,

and schizophrenia, stroke, or tumors are present, are easily visible. Greatest sensitivity is achieved with

higher b values, which can only be realized with extremely strong gradients. The Bruker BioSpec 9.4

Tesla high-field magnet allows Columbia University Researchers to obtain critical information about:

• Tumor Infiltration

• Cardiac Infarction

• Connectivity

• Stroke

When you use Bruker’s pre-prepared DWI and DTI protocols, no

separate scanning is necessary to receive a non-diffused A0

image and to calculate trace images, Fractional Anisotropy (FA)

images, and Apparent Diffusion Coefficient (ADC) maps.

DWI Example Images Courtesy of Bruker Corporation



Bruker BioSpec 94/20 9.4-Tesla MRI

Application: DTI Imaging via Cryoprobe

Diffusion Tensor Imaging (DTI) surpasses other imaging methods in addressing many biological

questions. Since DTI visualizes the diffusion orientation, it is used to assess fiber connectivity in the

embryonic development of transgenic models. It is also the only method that can accurately visualize

the level of tumor infiltration into healthy tissue.

DTI Example Images Courtesy of Bruker Corporation

High-resolution (46 x 46 µm in-

plane) mouse spine imaging

using TurboRARE, acquired in

less than 7 minutes at 9.4 T.

Excellent differentiation of gray

and white matter and

visualization of fine anatomical

details, such as root ganglions,

vessels, and cerebrospinal fluid

Segmented echo planar diffusion tensor imaging of the

mouse spine. The fractional anisotropy (FA) exhibits very

high contrast between gray and white matter. The color

encoded directional components of the diffusion tensor

displays fibers in left-right direction in red, allowing for

identification of nerve fibers leaving the spinal cord (here

towards the front extremities left and right).




Application: MR Spectroscopy

• The brain, liver, and muscles contain more than just water, and MR spectroscopy makes non-

invasive studies of metabolic processes in these tissues possible.

• Identify metabolic disorders and observe long term changes in metabolic processes even in

millimolar concentrations.

• Higher sensitivity and spectral resolution make this the ideal instrument for spectroscopy and

spectroscopic imaging of species involving MR-visible nuclei such as 1H, 13C, 19F, 23Na, 31P and

others.

LEFT: Isoflurane collection in adipose tissue of

mouse abdomen gradient echo image with

overlayed Fluorine image taken after 2 hours

of isoflurane anesthesia. (Example image,

not from CUMC)

BELOW: Proton MRS of a normal mouse

brain, obtained in a 10 minute acquisition

(Example image, not from CUMC)

Isofluorane Spectroscopy and NMR

Courtesy of SAISR Core and Bruker

Corporation of Bruker Corporation




Application: fMRI

Functional MR Imaging requires very high magnet and gradient performance in combination with

maximum system stability. The Bruker BioSpec Gradient System allows researchers to collect whole

brain image data sets in a single take. Excellent shim performance delivers minimum geometrical Mouse

Abdomen distortions even when using echo planar imaging techniques. Unique frequency and phase

stability enables even segmented diffusion tensor imaging with EPI.

• Functional neuroimaging procedure

• Measures Brain Activity

• Shows active fibers of the brain, or what has been hindered

Functional magnetic resonance imaging (fMRI)

can help Columbia University Researchers

measure and map the brain activity of their

research animals in a noninvasive manner. It is

being used in many studies to better

understand how the brain works, and in a

growing number of studies it is being applied to

understand how that normal function is

disrupted in many different disease states.

Example images not from CUMC

fMRI Example Images Courtesy of Bruker Corporation

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