Voxelized 3D Computational Transport Model of Infusions Into the Ventral Hippocampus: Comparison With Experimental Studies

Convection enhanced delivery (CED) is a promising local delivery technique for overcoming the blood brain barrier (BBB) and treating diseases of the central nervous system (CNS). For CED, infusate is infused directly into brain tissue and the drug agent is spread through the extracellular space, which is considered highly tortuous porous media. Previous studies have indicated that the infusion of therapeutic agents into the hippocampus is a potential treatment method for epilepsy [1]. In this study, a 3D interstitial transport modeling approach is presented in which tissue properties and anatomical boundaries are assigned on a voxel-by-voxel basis using tissue alignment data from magnetic resonance (MR) diffusion tensor imaging (DTI). The developed model was used to predict CED transport in the ventral hippocampus and predicted tracer distributions were compared with experimental studies. In rat CED experiments, T1-weighted contrast-enhanced MR images were acquired to measure Gd-DTPA albumin tracer distributions after infusion into the ventral hippocampus. Similar infusate distribution patterns were obtained demonstrating the reliability and repeatability of this modeling scheme. Qualitative comparisons between predicted and measured distribution patterns, volumes and shapes were also conducted to determine the model’s proficiency.