Abstract
Several treatment modalities for neurodegenerative diseases or tumors
of the central nervous system involve invasive delivery of large
molecular weight drugs to the brain. Despite the ample record of
experimental studies, accurate drug targeting for the human brain
remains a challenge. A promising approach to drug delivery without
chemical drug transformations includes invasive drug administration.
Invasive techniques insert a dilute drug solution into the cerebral
extracellular space via an infusion catheter, thus by-passing the
blood-brain barrier.
Convection-enhanced delivery (CED) has received attention because
larger distribution volumes can be achieved than by molecular
diffusion alone. In CED, volumes of drug distribution depend on (i)
infusion parameters like infusion pressure, flow rate and drug
concentration; (ii) molecular properties such as effective
diffusivity and hydraulic conductivity; (iii) catheter design and
position.
We developed novel methods of computer-assisted brain analysis
featuring the following innovations: (i) accurate reconstruction of
the brain geometry and tissue anisotropy, and (ii) prediction of
treatment volumes based on transport principles. The proposed
rigorous mathematical framework predicts achievable volumes in target
regions as a function of brain anatomy and infusion catheter
position. The two-dimensional brain anatomy is reconstructed
accurately using medical images; tissue anisotropy and heterogeneity
are quantified with the help of diffusion tensor imaging (DTI).
Infusion experiments are also conducted in agarose gel brain phantoms
for quantifying the distribution volume using image analysis of
digital images or MRI. Optical methods are also being applied to
investigate tissue deformation due to infusion.
The Speaker Madhu Iyer recently completed her M.S. in Bio-engineering from the University of Illinois at Chicago.
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