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0.09. 0.08. 0.07. 0.06. 0.05. 0.04. 0.03. 0.02. 0.01. 0. Clinical concentration field of L-dopa. Computational grid. Optimal result,. Transport & Kinetic Inversion. Motivation. Novel Imaging Techniques. Methodology.

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Clinical concentration field of L-dopa

Computational grid

Optimal result,

Transport & Kinetic Inversion

Motivation

Novel Imaging Techniques

Methodology

  • 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

fMRI –Used to

visualize brain

functions

(E.g. Blood Flow

to pathological

organs)

CT- Shows the

structure of the

brain and NOT

its functions

MR Imaging

Brain Geometry, CSF flow field

Direct Experimental

Measurements

Reconstruction tools

ImageJ, Insight SNAP, Mimics

PET- detects

radioactive material

that is injected

or inhaled to produce

an image of the brain

2D and 3D geometry

of the Ventricles and

Subarachnoid space

MRI-provides an

anatomical view

of the brain

Geometry

Grid Generation

Gambit

Live Patient MRI

Cine MRI –

Flow velocities and

Cannot predict

intracranial

pressure and

tissue deformation

  • 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.

DTI-Used to

demonstrate the

structural properties

of anatomical

substructures

Computational Mesh

PET image of F-dopa-derived radioactivity, merged with magnetic resonance image, computational grid and optimal result

Computational Fluid Dynamics

Continuity and Navier-Stokes Equations

for CSF Motion

  • 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.

Hydrocephalic Brain

Quantitative analysis

Velocity field and CSF dynamics

Prediction of Intracranial pressure (ICP)

Analysis of flow

And pressure

patterns

CSF flow and ICP measurements from fluid mechanics

Schematic of BBB in the brain

4th week

3rd week

1st week

2nd week

Regions of interest in targeted drug delivery

Present Case Study

Drug: NGF

Target: Caudate Nucleus

Injection Location: 1. Thalamus

Computer Assisted Design of Transport Processes in the Human BrainLaboratory for Product and Process Design, Director A. A. LINNINGERCollege of Engineering, University of Illinois,Chicago, IL, 60607, U.S.A. Grant Support: NSF, Medtronic, Susman and Asher Foundation.

Patient Specific Quantification of Intracranial Dynamics

Quantification of CSF flow field

CSF Flow Field during one cardiac cycle – Normal brain

Intracranial Pressure Pulsatility during one cardiac cycle – Normal brain

Quantification of Intracranial Pressure

CSF Flow Field during one cardiac cycle – Hydrocephalic brain

Intracranial Pressure Pulsatility during one cardiac cycle – Hydrocephalic brain

Tissue Properties

t= 60 %

t= 90 %

t= 0 %

t= 30 %

  • CSF Pulsatility increases 2.3 times than normal in hydrocephalic case
  • ICP increases by a factor of four in hydrocephalic case

Quantitative Prediction of Drug Distribution

Boundary Conditions

Prediction of treatment volume in a 2D coronal cut of a human brain using NGF as drug

Estimation of Penetration Depth

Site-specific drug delivery

  • 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 0.107 cc

Conclusions

Acknowledgements

  • Dr. Richard Penn, University of Chicago
  • BRIC, University of Chicago
  • Fluent Inc, Lebanon, NH
  • Materialise Inc, Ann Arbor, MI
  • ImageJ, NIH, MD.
  • 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.
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