Use of Contrast Enhancement and High-Resolution 3D Black-Blood MRI to Identify Inflammation in Atherosclerosis

Abstract

We investigated the contributing factors for plaque enhancement and examined the relationships between regional contrast enhancement and the inflammatory activity of atherosclerotic plaques in an experimental rabbit model using contrast-enhanced high-resolution 3-dimensional (3D) black-blood magnetic resonance imaging (MRI) in comparison with histopathologic analysis. Inflammation plays a critical role in plaque initiation, progression, and disruption. As such, inflammation represents an emerging target for the treatment of atherosclerosis. MRI findings suggest that contrast agent-induced signal enhancement is associated with the degree of macrophage infiltration and neovessels that can be detected in plaque. Ten atherosclerotic rabbits and 3 normal control rabbits underwent high-resolution 3D contrast-enhanced black-blood MRI. Magnetic resonance images and the corresponding histopathologic sections were divided into 4 quadrants. Plaque composition was analyzed for each quadrant according to histopathologic criteria (percent of lipid-rich, fibrous, macrophage area and microvessel density) and imaging criteria (enhancement ratio [ER], ER = signal intensity(post)/signal intensity(pre)). Multiple linear regression analysis was performed to determine independent factors for plaque enhancement. A total of 62 noncalcified plaques (n = 248; 156 lipid-rich quadrants and 92 fibrous quadrants) were identified based on histopathologic analysis. Mean ER values were significantly higher in atherosclerotic vessel walls than in normal vessel walls (2.03 ± 0.25 vs. 1.58 ± 0.15; p = 0.017). The mean ER values were significantly higher in lipid-rich quadrants compared with the fibrous quadrants (2.14 ± 0.31 vs. 1.84 ± 0.21; p = 0.001). Mean ER values were significantly higher in macrophage-rich plaques compared with the macrophage-poor plaques (2.21 ± 0.28 vs. 1.81 ± 0.22; p = 0.001). Using multiple regression analysis, macrophage area and microvessel density were associated independently with ER values that reflected plaque enhancement (p < 0.001). Contrast-enhanced high-resolution 3D black-blood MRI may be an efficient method to detect plaque inflammation.