Published Online
on August 17, 2009

A more recent version of this article appeared on September 1, 2009

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Original Article

Increased Neovascularization in Advanced Lipid-Rich Atherosclerotic Lesions Detected by Gadofluorine-M Enhanced Magnetic Resonance Imaging (MRI): Implications for Plaque Vulnerability

Marc Sirol^1,5; Pedro Moreno²; K-Raman Purushothaman²; Esad Vucic²; Vardan Amirbekian²; Hanns-Joachim Weinmann³; Paul Munter²; Valentin Fuster⁴ and Zahi Fayad²

¹ Lariboisière University Hospital, Paris, France; Mount Sinai School of Medicine, New York, NY;
² Mount Sinai School of Medicine, New York, NY;
³ Schering AG, Berlin, Germany;
⁴ Mount Sinai School of Med., New York, NY; CNIC, Madrid, Spain

^* Corresponding author; email: marc.sirol{at}lrb.aphp.fr

Background—Inflammation and neovascularization may play a significant role in atherosclerotic plaque progression and rupture. We evaluated Gadofluorine-M enhanced magnetic resonance imaging (MRI) for detection of plaque inflammation and neovascularization in an animal model of atherosclerosis.

Methods and Results—Sixteen rabbits with aortic plaque and 6 normal controls underwent Gadofluorine-M enhanced MRI. Eight rabbits had advanced atherosclerotic lesions whereas the remaining 8 had early lesions. MR atherosclerotic plaque enhancement was meticulously compared to plaque inflammation and neovessel density as assessed by histopathology. Advanced plaques and early atheroma were enhanced after Gadofluorine-M injection. Control animals displayed no enhancement. After accounting for the within-animal correlation of observations, mean contrast-to-noise ratio (CNR) was significantly higher in advanced plaques than compared to early atheroma (4.29±0.21 vs 3.00±0.32; P=0.004). Macrophage density was higher in advanced plaques in comparison to early atheroma (geometric mean = 0.43 [95% CI = 0.29-0.64] vs. 0.21 [0.12-0.37]; P=0.05). Furthermore, higher neovessel density was observed in advanced plaques (1.83 [95% CI: 1.51–2.21] vs 1.29 [0.99–1.69]; P=0.050). The plaque accumulation of Gadofluorine-M correlated with increased neovessel density as shown by linear regression analysis (r = 0.67; P < 0.001). Confocal and fluorescence microscopy revealed co-localization of Gadofluorine-M with plaque areas containing a high density of neovessels.

Conclusion—Gadofluorine-M enhanced MRI is effective for in vivo detection of atherosclerotic plaque inflammation and neovascularization in an animal model of atherosclerosis. These findings suggest that Gadofluorine-M enhancement reflects the presence of high-risk plaque features believed to be associated with plaque rupture. Gadofluorine-M plaque enhancement may therefore provide functional assessment of atherosclerotic plaque, in vivo.

Key Words: atherosclerosis • imaging • magnetic resonance imaging • plaque