Incorporating contrast agent diffusion into the analysis of DCE-MRI data.

Standard two-compartment pharmacokinetic models that describe the dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) time course of gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) concentration in a tissue do not account for the passive diffusion of contrast agent (CA) from a well-perfused to a less vascularized region. Even when the arterial input function (AIF) is perfectly known, the standard Tofts model returns inaccurate values of K(trans) (mean absolute relative difference [ARD] of 43%) from realistic simulated data where a well-defined delineation exists between a well-perfused and a poorly vascularized region. This contribution proposes a diffusion-perfusion (DP) model in which diffusion of a low molecular weight CA is incorporated in the standard two-compartment Tofts model. The proposed DP model reliably retrieved the values of K(trans) and v(e) (mean ARD of 16% and 17%, respectively) from simulated data. On mouse adenocarcinoma xenograft data showing evidence of CA diffusion, the standard model returned unphysical values of v(e) in the tumor core whereas the proposed DP model found values that were in the physical range (0 < v(e) < 1) throughout the tissue. In addition, K(trans) distributions from the DP model more closely corresponded to the observed sharp delineation between highly and poorly perfused areas observed in the mouse tumors.