Modeling concentration distribution and deformation during convection-enhanced drug delivery into brain tissue

Abstract

Convection-enhanced drug delivery is a technique where a therapeutic agent is infused under positive pressure directly into the brain tissue. For predicting the final concentration distribution and optimizing infusion rate and catheter placement, numerical models can be of great help. However, despite advances in modeling this process, often the infused agent does not reach the targeted region prescribed in the modeling phase. In this study, patient-specific brain structure and parameters, obtained from diffusion tensor imaging (DTI), are implemented in a numerical model which describes the flow and transport in an elastic deformable matrix. To our knowledge, this is the first time that information from DTI is used in a numerical model which includes both transport of a therapeutic agent and tissue deformation. Fractional anisotropy (FA) is used to distinguish between gray and white matter and tortuosity to differentiate between inside and outside the brain tissue. One voxel in the DT-image is represented by one element of the numerical grid. The DT-images were in addition used to determine the orientation of the white matter fiber tracts and calibrate permeability and diffusion coefficients found in the literature. Values chosen for the porosity and Lamé parameters are also based on those found in the literature. Given realistic literature values, the calibration of the permeability and diffusion tensors are shown to be successful. Our result shows that preferential flow occur in direction of the white matter fiber tracts. The current model assumes linear deformation, corresponding to small porosity changes. But, because large porosity changes occur that may adversely affect drug transport, non-linear deformations should be included in the future