title: Prediction of convection-enhanced drug delivery to the human brain.
abstract: The treatment for many neurodegenerative diseases of the central nervous system (CNS) involves the delivery of large molecular weight drugs to the brain. The blood brain barrier, however, prevents many therapeutic molecules from entering the CNS. Despite much effort in studying drug dispersion with animal models, accurate drug targeting in humans remains a challenge. This article proposes an engineering approach for the systematic design of targeted drug delivery into the human brain. The proposed method predicts achievable volumes of distribution for therapeutic agents based on first principles transport and chemical kinetics models as well as accurate reconstruction of the brain geometry from patient-specific diffusion tensor magnetic resonance imaging. The predictive capabilities of the methodology will be demonstrated for invasive intraparenchymal drug administration. A systematic procedure to determine the optimal infusion and catheter design parameters to maximize penetration depth and volumes of distribution in the target area will be discussed. The computational results are validated with agarose gel phantom experiments. The methodology integrates interdisciplinary expertise from medical imaging and engineering. This approach will allow physicians and scientists to design and optimize drug administration in a systematic fashion.
authors.affiliation: Laboratory for Product and Process Design, Department of Chemical and Bioengineering, University of Illinois, 851 S. Morgan St. 218 SEO, Chicago, IL 60607, USA. linninge@uic.edu <linninge@uic.edu>
authors.forename: Andreas A
authors.initials: AA
authors.lastname: Linninger
authors.forename: Mahadevabharath R
authors.initials: MR
authors.lastname: Somayaji
authors.forename: Megan
authors.initials: M
authors.lastname: Mekarski
authors.forename: Libin
authors.initials: L
authors.lastname: Zhang
mesh_terms: D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism*; D001931:Brain Mapping / Q000379:methods; D004396:Coloring Agents / Q000493:pharmacokinetics; D018481:Convection; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods; D016503:Drug Delivery Systems / Q000295:instrumentation / Q000379:methods*; D004867:Equipment Design; D006801:Humans; D007263:Infusions, Parenteral / Q000295:instrumentation; D008959:Models, Neurological; D016062:Porosity; D012212:Rheology; D014343:Trypan Blue / Q000493:pharmacokinetics
chemical_list: D004396:Coloring Agents; D014343:Trypan Blue