Understanding Ktrans: a simulation study based on a multiple-pathway model

Abstract

The transfer constant Ktrans is commonly employed in dynamic contrast-enhanced MRI studies, but the utility and interpretation of Ktrans as a potential biomarker of tumor vasculature remains unclear. In this study, computer simulations based on a comprehensive tracer kinetic model with multiple pathways was used to provide clarification on the interpretation and application of Ktrans. Tissue concentration-time curves pertaining to a wide range of transport conditions were simulated using the multiple-pathway (MP) model and fitted using the generalized kinetic (GK) and extended GK models. Relationships between Ktrans and plasma flow Fp, vessel permeability PS and extraction rate EFp under various transport conditions were assessed by correlation and regression analysis. Results show that the MP model provides an alternative two-tier interpretation of Ktrans based on the vascular transit time. Ktrans is primarily associated with Fp and EFp respectively, in the slow and rapid vascular transit states, independent of the magnitude of PS. The relative magnitudes of PS and Fp only serve as secondary constraints for which Ktrans can be further associated with EFp and PS in the slow and rapid transit states, respectively.