Biphasic finite element model of solute transport for direct infusion into nervous tissue.

Abstract

Infusion-based techniques are promising drug delivery methods for treating diseases of the nervous system. Direct infusion into tissue parenchyma circumvents the blood-brain barrier, localizes delivery, and facilitates transport of macromolecular agents. Computational models that predict interstitial flow and solute transport may aid in protocol design and optimization. We have developed a biphasic finite element (FE) model that accounts for local, flow-induced tissue swelling around an infusion cavity. It solves for interstitial fluid flow, tissue deformation, and solute transport in surrounding isotropic gray matter. FE solutions for pressure-controlled infusion were validated by comparing with analytical solutions. The influence of deformation-dependent hydraulic permeability was considered. A transient, nonlinear relationship between infusion pressure and infusion rate was determined. The sensitivity of convection-dominated solute transport (i.e., albumin) over a range of nervous tissue properties was also simulated. Solute transport was found to be sensitive to pressure-induced swelling effects mainly in regions adjacent to the infusion cavity (r/a 0 <or= 5 where a 0 is the outer cannula radius) for short times infusion simulated (3 min). Overall, the biphasic approach predicted enhanced macromolecular transport for small volume infusions (e.g., 2 microL over 1 h). Solute transport was enhanced by decreasing Young's modulus and increasing hydraulic permeability of the tissue.