Effect of Transvascular Fluid Exchange for Nonlinear, Biphasic Analyses of Flow-Controlled Infusion in Brain

Convection-enhanced delivery (CED) is a means to deliver therapeutic agents directly into brain tissue. Since CED often results in a rather significant interstitial fluid pressure, it is possible that infusions could result in a loss of fluid to the vasculature. While previous studies have included the effects of transvascular fluid exchange, they did so under the assumption of rigidity of the tissue [1, 2] or without considering its effect on the transport of the infused agent [3]. Recently, we proposed a spherical, biphasic model for constant flow-rate infusions that considers nonlinear stress-strain curves under finite deformation and nonlinear variation of hydraulic conductivity with deformation [4]. We have incorporated the effect of transvascular fluid exchange into this model and have studied the implications of variations in the vascular permeability, which may be of interest for improving drug delivery by CED.