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

Abstract

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.