Distribution of Intravascular and Extravascular Extracellular Volume Fractions by Total Area under Curve for Neovascularization Assessment by Dynamic Contrast-Enhanced Magnetic Resonance Imaging

In this paper, we propose and investigate distribution of intravascular and extravascular extracellular volume fractions (DIEEF) as a noninvasive biomarker for neovascularization assessment by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). A generalized two-compartment exchange model (G2CXM) that uniformly includes the Patlak model, Tofts model, extended Tofts model, and recent two-compartment exchange model as special instances is first presented. Based on the total area under curve of the G2CXM a method of DIEEF estimation without knowing the artery input function is proposed. The mean square error of DIEEF estimate in the presence of noise and with incomplete DCE-MRI data is analyzed. Simulation results demonstrate that DIEEF estimate is accurate when signal to noise ratio is only 5 dB in both cases of tracer infusion and bolus injection, and slightly favors the bolus injection. Tested on a model of atherosclerotic rabbits, the DIEEF of aorta plaques is positively correlated with the histological neovessel count with correlation coefficient of 0.940 and P = 0.017, and outperforms six semiquantitative parameters in the literature. DIEEF might be useful as a biomarker for noninvasive neovascularization assessment by DCE-MRI.