Laboratory for Product and Process Design Computer Assisted Design of Transport Processes in the Human Brain Laboratory for Product and Process Design, Director A. A. LINNINGER College of Engineering, University of Illinois, Chicago, IL, 60607, U.S.A. Grant Support: NSF, Medtronic, Susman and Asher Foundation. Neurodegenerative disease DrugInfusion SiteAnimal / Human Reference Parkinsons Disease GDNF IP: PutamenRhesus MonkeyGash et al, 2003 IP: Substantia Nigra Rhesus Monkey Gash et al, 2003 IP: Putamen Human Trials Gill S.S et al, 2003 Ventricles & and Central part of the Putamen Rhesus Monkeys Grondin R et al, 2002 GDNF/ r- metHUGDNF ICV Monkeys/Human Trials Nutt J.G et al, 2003 Quantitative Prediction of Drug Distribution Conclusions Acknowledgements Dr. Richard Penn, University of Chicago BRIC, University of Chicago Fluent Inc, Lebanon, NH Materialise Inc, Ann Arbor, MI ImageJ, NIH, MD. Tissue properties ParameterValue porosity GM WM k permeability GM WM m -2 X: m -2 Y : m -2 inertia resist. GM WM 8.32*10 9 m -1 X: 5*10 8 m -1 Y: 2*10 8 m -1 Tortuosity GM WM Prediction of treatment volume in a 2D coronal cut of a human brain using NGF as drug Boundary Conditions Site-specific drug delivery Accurately reconstruction of the human brain geometry to quantify transport processes. A novel method for extracting transport and reaction constants from experimental data was presented based on TKIP Prediction of treatment volumes based on site-specific drug delivery for NGF was presented. Accurate quantification of CSF flow and Intracranial pressure fields. Validation of CFD simulations with Cine Phase MRI measurements at select regions of the ventricular system. Estimation of Penetration Depth Methodology Computational Fluid Dynamics Continuity and Navier-Stokes Equations for CSF Motion MR Imaging Brain Geometry, CSF flow field Reconstruction tools ImageJ, Insight SNAP, Mimics Grid Generation Gambit Quantitative analysis Velocity field and CSF dynamics Prediction of Intracranial pressure (ICP) Direct Experimental Measurements 2D and 3D geometry of the Ventricles and Subarachnoid space Analysis of flow And pressure patterns Geometry Computational Mesh CSF flow and ICP measurements from fluid mechanics Patient Specific Quantification of Intracranial Dynamics Intracranial Pressure Pulsatility during one cardiac cycle Normal brain CSF Flow Field during one cardiac cycle Hydrocephalic brain Tissue Properties CSF Pulsatility increases 2.3 times than normal in hydrocephalic case ICP increases by a factor of four in hydrocephalic case t= 0 %t= 30 % t= 60 % t= 90 % Motivation Millions of people are affected by diseases of the Central Nervous System (CNS) Systematic design of drug infusion policies based on Transport and Kinetic Inversion Problem (TKIP) Qualitative & Quantitative prediction of treatment volume of site-specific drug delivery from fluid mechanics Provide decision support to medical community by specifying the parameters for invasive drug delivery Schematic of BBB in the brain About seventy thousand people in U.S are affected by hydrocephalus. Understanding pulsatile CSF dynamics or intracranial dynamics is absolutely necessary to predict and treat hydrocephalus Non-invasive in-vivo MR measurements cannot fully capture all of the events of intracranial dynamics A quantitative first principles model is presented that can accurately predict patient-specific intracranial dynamics. Hydrocephalic Brain Live Patient MRI 4 th week 3 rd week 1 st week 2 nd week Regions of interest in targeted drug delivery Present Case Study Drug: NGF Target: Caudate Nucleus Injection Location: 1. Thalamus Higher Treatment Volumes were realized for high flow Infusion at the thalamus The total treatment volume at the end of 4 weeks was found to be cc Transport & Kinetic Inversion Clinical concentration field of L-dopa Computational grid Optimal result, PET image of F-dopa-derived radioactivity, merged with magnetic resonance image, computational grid and optimal result Novel Imaging Techniques CT- Shows the structure of the brain and NOT its functions fMRI Used to visualize brain functions (E.g. Blood Flow to pathological organs) MRI- provides an anatomical view of the brain PET- detects radioactive material that is injected or inhaled to produce an image of the brain Cine MRI Flow velocities and Cannot predict intracranial pressure and tissue deformation DTI- Used to demonstrate the structural properties of anatomical substructures These advanced imaging techniques provide only qualitative information. Quantitative information such as drug diffusivity, metabolic reaction constant, binding coefficient are not directly available from these images. Knowledge about these parameters is important in systematic design of drug delivery policies. CSF Flow Field during one cardiac cycle Normal brain Intracranial Pressure Pulsatility during one cardiac cycle Hydrocephalic brain Quantification of CSF flow field Quantification of Intracranial Pressure