Transcript Only for AB_Linninge.. - University of Illinois at Chicago

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.
Novel Imaging Techniques
Motivation
• Millions of people are affected by diseases
of the Central Nervous System (CNS)
CT- Shows the
structure of the
brain and NOT
its functions
• 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
MRI- provides an
anatomical view
of the brain
Schematic of BBB in the brain
• About seventy thousand people in U.S
are affected by hydrocephalus.
Live Patient MRI
• Understanding pulsatile CSF dynamics or
intracranial dynamics is absolutely
necessary to predict and treat
hydrocephalus
• A quantitative first principles model is
presented that can accurately predict
patient-specific intracranial dynamics.
fMRI – Used to
visualize brain
functions
(E.g. Blood Flow
to pathological
organs)
PET- detects
radioactive material
that is injected
or inhaled to produce
an image of the brain
DTI- Used to
Cine MRI –
demonstrate the
structural properties
of anatomical
substructures
Flow velocities and
Cannot predict
intracranial
pressure and
tissue deformation
•These advanced imaging techniques provide only
qualitative information.
Hydrocephalic Brain
Methodology
•Quantitative information such as drug diffusivity,
metabolic reaction constant, binding coefficient are
not directly available from these images.
• Targeted Drug delivery to
specific substructures of
the human brain.
Key Achievements
• Geometric reconstruction of
patient-specific brain
dimensions based on MRI
data
TKIP
in Parkinson's
Disease
• Patient-specific dynamic
analysis of CSF flow in the
human brain
Proprietary and
Mimics Image
reconstruction tools
Advancement - Innovation
Quantitative first principle analysis
PET image of F-dopa-derived radioactivity, merged with magnetic
resonance image, computational grid and optimal result
Grid Generation
Proprietary
Solvers
(LPPD solvers)
Intracranial Pressure
Normal brain
Quantification of Intracranial Pressure
CSF Flow Field
Hydrocephalic brain
Tissue Properties
Intracranial Pressure
Hydrocephalic brain
• Prediction of drug distribution
Future Goals
Prediction of Drug Distribution
Regions of interest in targeted drug delivery
Estimation of Penetration Depth
• Higher Treatment Volumes were
realized for high flow Infusion at the
thalamus
Present Case Study
• The total treatment volume at the end
of 4 weeks was found to be 0.107 cc
Drug: NGF
Target: Caudate Nucleus
Injection Location: 1. Thalamus
Prediction of treatment volume in a 2D coronal cut of a human brain using NGF as drug
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Quantitative
analysis
• Coupling of the brain
parenchyma, vascular and
ventricular system in the
human brain.
Quantification of CSF flow field
• ICP increases by a factor of four in hydrocephalic case
Current state-of-the-art
approach
Commercial
Solvers
(Fluent)
• Prediction of large
deformations of the brain
parenchyma based on
Fluid-Structure Interaction
modeling.
CSF Flow Field
Normal brain
• CSF Pulsatility increases 2.3 times than normal in hydrocephalic case
Transport & Kinetic Inversion
MR Imaging
Intracranial Dynamics
Problem Statement
Deliverables
• ICP variation due to injection
• Prediction of the flow field
• Drug concentration
• Quantification of the metabolic
uptake
• Prediction of cell deformation,
tissue strain& stress
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• Optimal Drug Delivery to the
Human Brain.
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Clinical concentration field of Ldopa
Computational grid
Optimal result,
M eD
• Feedback control systems to
better treat Hydrocephalus.
1st week
2nd week
3rd week
4th week