Computational Design of Drug Delivery Policies

Motivation: The development of systematic drug delivery for diseases of the central nervous system (CNS) is a formidable challenge and there is hardly any successful treatment protocol for many CNS diseases. Data published by National Institutes of Health suggest that CNS diseases such as Parkinson’s, Alzheimer’s and Huntington’s affect millions of people worldwide. Targeted delivery of large macromolecules to specific locations in the brain is a challenging task in CNS drug delivery owing to the presence of blood-brain barrier (BBB) [1]. In addition, the restriction offered by the white matter tracts hampers the transport and metabolism of drugs in target areas and pose difficulty to catheter design and placement [2]. Methodology: In this presentation, we propose three innovations embedded into a hierarchical design procedure. The systematic approach to designing drug targeting faces three challenges and we aim to address them in this presentation: 1. Accurate three-dimensional reconstruction of the patient-specific brain geometry 2. Quantification of achievable treatment volume subject to anisotropy 3. Optimal catheter design and placement The first challenge is to reconstruct the physiologically consistent three-dimensional patient-specific brain geometry and specific substructures of the midbrain considered as infusion sites. Fig.1a depicts an accurate geometric rendering of a normal human brain. Reconstruction step is imperative for quantification of transport processes. State of the art geometric image reconstruction tools are used to render and construct computational grids from novel imaging techniques such MRI and histological data [3], [4]. Fig.1b depicts the computational grid of lateral ventricles of a normal subject required for quantitative analysis. The second task is to calculate the achievable treatment volume in anisotropic regions of the brain using transport and kinetic inversion problem (TKIP). The TKIP approach extracts the unknown diffusion tensor of the drug in anisotropic regions of the brain. Specifically, the white matter tracts are aligned (a) Patient-Specific reconstruction of the cortex of a normal subject (b) Computational grid of the lateral ventricles Fig.1: Computer Assisted Brain Analysis