Quantifying and modeling convection-enhanced delivery

Virginia Commonwealth University, Richmond VA

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Abstract

DESCRIPTION (provided by applicant): Convection-enhanced delivery (CED) is an investigational technique in which a cannula is implanted directly into brain tissue and a medication is infused with pressure gradients into and through the extracellular space of the brain. For CED to be safe and effective in many disease states, including ischemic stroke and traumatic brain injury, it must be controllable and predictable when the extracellular space of the brain is altered by vasogenic or cytotoxic edema. To test if medication transport is altered in these pathological states, infusion distributions in rat models of edema will be non-invasively quantified in three dimensions. A mathematical model will provide a framework for relating the edematous changes to observed differences in infusion distributions. Using commercial software, a nodal-point integration scheme will be used to solve a porous media convection-diffusion transport equation over the complex geometry of the three-dimensional rat brain. The model will incorporate tissue convective and diffusive anisotropies, measured in each edema state non-invasively. For each state, the model will be optimized by adjusting assumptions and parameters to most closely match the experimental data. Successful completion of these specific aims will result in (1) a method to non-invasively and accurately characterize CED distributions, valuable for clinical use of surrogate tracers; (2) an experimentally verified model of CED that can predict three-dimensional medication distributions in normal and edematous rat brain; and (3) more accurate understanding of the relationship between the diffusivity tensor and the hydraulic conductivity tensor, in normal brain and in edema states. These results will be the first step towards a clinically valuable predictive model of CED.