Implications of transvascular fluid exchange in nonlinear, biphasic analyses of flow-controlled infusion in brain

A nonlinear, coupled biphasic-mass transport model that includes transvascular fluid exchange is proposed for flow-controlled infusions in brain tissue. The model accounts for geometric and material nonlinearities, a hydraulic conductivity dependent on deformation, and transvascular fluid exchange according to Starling's law. The governing equations were implemented in a custom-written code assuming spherical symmetry and using an updated Lagrangian finite-element algorithm. Results of the model indicate that, using normal physiological values of vascular permeability, transvascular fluid exchange has negligible effects on tissue deformation, fluid pressure, and transport of the infused agent. As vascular permeability may be increased artificially through methods such as administering nitric oxide, a parametric study was conducted to determine how increased vascular permeability affects flow-controlled infusion. Increased vascular permeability reduced both tissue deformation and fluid pressure, possibly reducing damage to tissue adjacent to the infusion catheter. Furthermore, the loss of fluid to the vasculature resulted in a significantly increased interstitial fluid concentration but a modestly increased tissue concentration. From a clinical point of view, this increase in concentration could be beneficial if limited to levels below which toxicity would not occur. However, the modestly increased tissue concentration may make the increase in interstitial fluid concentration difficult to assess in vivo using co-infused radiolabeled agents.