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Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:1311-1317
Published online before print May 8, 2008, doi: 10.1161/ATVBAHA.108.166173
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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:1311.)
© 2008 American Heart Association, Inc.


Integrative Physiology/Experimental Medicine

Detection of Neovessels in Atherosclerotic Plaques of Rabbits Using Dynamic Contrast Enhanced MRI and 18F-FDG PET

Claudia Calcagno; Jean-Christophe Cornily; Fabien Hyafil; James H.F. Rudd; Karen C. Briley-Saebo; Venkatesh Mani; Gregg Goldschlager; Josef Machac; Valentin Fuster; Zahi A. Fayad

From the Translational and Molecular Imaging Institute (C.C., J.-C.C., F.H., J.H.F.R., K.C.B.-S., V.M., J.M., Z.A.F.), the Department of Radiology (C.C., K.C.B.-S., V.M., Z.A.F.), the Center for Comparative Medicine and Surgery (G.G.), and the Zena and Michael A. Wiener Cardiovascular Institute and Marie-Josée and Henry R. Kravis Cardiovascular Health Center (J.-C.C., F.H., J.H.F.R., K.C.B.-S., V.M., V.F., Z.A.F.), Mount Sinai School of Medicine, New York.

Correspondence to Zahi A. Fayad, PhD, FAHA, FACC, Translational and Molecular Imaging Institute, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1234, New York, NY 10029. E-mail zahi.fayad{at}mssm.edu

Abstract

Objective— The association of inflammatory cells and neovessels in atherosclerosis is considered a histological hallmark of high-risk active lesions. Therefore, the development and validation of noninvasive imaging techniques that allow for the detection of inflammation and neoangiogenesis in atherosclerosis would be of major clinical interest. Our aim was to test 2 techniques, black blood dynamic contrast enhanced MRI (DCE-MRI) and 18-fluorine-fluorodeoxyglucose (18F-FDG) PET, to quantify inflammation expressed as plaque neovessels content in a rabbit model of atherosclerosis.

Methods and Results— Atherosclerotic plaques were induced in the aorta of 10 rabbits by a combination of 2 endothelial abrasions and 4 months hyperlipidemic diet. Six rabbits underwent MRI during the injection of Gd-DTPA, whereas 4 rabbits were imaged after injection of 18F-FDG with PET. We found a positive correlation between neovessels count in atherosclerotic plaques and (1) Gd-DTPA uptake parameters evaluated by DCE-MRI (r=0.89, P=0.016) and (2) 18F-FDG uptake evaluated by PET (r=0.5, P=0.103 after clustered robust, Huber-White, standard errors analysis).

Conclusion— DCE-MRI and 18F-FDG PET may allow for the evaluation of inflammation in atherosclerotic plaques of rabbits. These noninvasive imaging modalities could be proposed as clinical tools in the evaluation of lesion prognosis and monitoring of anti–angiogenic therapies.

Neovessels are hallmarks of high-risk inflamed atherosclerotic plaques. In this study we used DCE-MRI and 18F-FDG PET to detect inflammation in atherosclerosis expressed as plaque neovessels count evaluated by histology. We found a positive correlation between neovessels count, DCE-MRI parameters, and 18F-FDG uptake. We propose that these noninvasive modalities could be used in the future to evaluate plaque-associated risk in the clinics.


Key Words: atherosclerosis • inflammation • neovessels • MRI • PET