Computational methods for predicting drug transport in anisotropic and heterogeneous brain tissue

Abstract

Effective drug delivery for many neurodegenerative diseases or tumors of the central nervous system is challenging. Targeted invasive delivery of large macromolecules such as trophic factors to desired locations inside the brain is difficult due to anisotropy and heterogeneity of the brain tissue. Despite much experimental research, prediction of bio-transport phenomena inside the brain remains unreliable. This article proposes a rigorous computational approach for accurately predicting the fate of infused therapeutic agents inside the brain. Geometric and physiological properties of anisotropic and heterogeneous brain tissue affecting drug transport are accounted for by in-vivo diffusion tensor magnetic resonance imaging data. The three-dimensional brain anatomy is reconstructed accurately from subject-specific medical images. Tissue anisotropy and heterogeneity are quantified with the help of diffusion tensor imaging (DTI). Rigorous first principles physical transport phenomena are applied to predict the fate of a high molecular weight trophic factor infused into the midbrain. Computer prediction of drug distribution in humans accounting for heterogeneous and anisotropic brain tissue properties have not been adequately researched in open literature before.