The transfer constant K is commonly employed in dynamic contrast-enhanced MRI studies, but the utility and interpretation of K 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 K . 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 K and plasma flow F , vessel permeability PS and extraction rate EF under various transport conditions were assessed by correlation and regression analysis. Results show that the MP model provides an alternative two-tier interpretation of K based on the vascular transit time. K is primarily associated with F and EF respectively, in the slow and rapid vascular transit states, independent of the magnitude of PS. The relative magnitudes of PS and F only serve as secondary constraints for which K can be further associated with EF and PS in the slow and rapid transit states, respectively.
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