Role of convection and diffusion on DCE-MRI parameters in low leakiness KHT sarcomas

Abstract

The solid tumor is an abnormal environment that is resistant to systemically delivered drugs. Increased plasma leakiness and extracellular matrix density along with poor lymphatic function can result in interstitial flow that attenuates the effectiveness of therapeutics. This study expands upon a previously presented magnetic resonance (MR) imaging-based porous media model by investigating low permeability tumors, where interstitial flow may have increased effect on systemically delivered solutes. The solute transport of the porous media model is compared to that of experiment and the two-compartment model. Small non-necrotic tumors (n=3) were MR-imaged, serially, for 90min after a bolus injection of Gd-based contrast agent (CA). These data provided for the calculation of experimental CA concentration over 90min, while only early time points (15min) were used to create vascular permeability, Ktrans, maps for the porous media model. A Ktrans scale factor (range=1.3–2.5) in the porous media model was found to account for the reduction of permeability (measured by two-compartment model) due to interstitial flow. The optimized porous media simulations showed: 1) better dynamic CA behavior agreement with the experimental data than the two-compartment model (>33% reduction of RMS error); 2) similar spatial CA distribution trends across tumor with increased uptake at the tumor boundary.