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Noninvasive detection of macrophage-rich atherosclerotic plaque in hyperlipidemic rabbits using ``positive contrast'' magnetic resonance imaging

Korosoglou, Grigorios and Weiss, Robert G. and Kedziorek, Dorota A. and Walczak, Piotr and Gilson, Wesley D. and Schaer, Michael and Sosnovik, David E. and Kraitchman, Dara L. and Boston, Raymond C. and Bulte, Jeff W. M. and Weissleder, Ralph and Stuber, Matthias (2008) Noninvasive detection of macrophage-rich atherosclerotic plaque in hyperlipidemic rabbits using ``positive contrast'' magnetic resonance imaging. JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 52 (6). pp. 483-491. ISSN 0735-1097

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Objectives This study was designed to identify macrophage-rich atherosclerotic plaque noninvasively by imaging the tissue uptake of long-circulating superparamagnetic nanoparticles with a positive contrast off-resonance imaging sequence (inversion recovery with ON-resonant water suppression [IRON]). Background The sudden rupture of macrophage-rich atherosclerotic plaques can trigger the formation of an occlusive thrombus in coronary vessels, resulting in acute myocardial infarction. Therefore, a noninvasive technique that can identify macrophage-rich plaques and thereby assist with risk stratification of patients with atherosclerosis would be of great potential clinical utility. Methods Experiments were conducted on a clinical 3-T magnetic resonance imaging (MRI) scanner in 7 heritable hyperlipidemic and 4 control rabbits. Monocrystalline iron-oxide nanoparticles (MION)-47 were administrated intravenously (2 doses of 250 mu mol Fe/kg), and animals underwent serial IRON-MRI before injection of the nanoparticles and serially after 1, 3, and 6 days. Results After administration of MION-47, a striking signal enhancement was found in areas of plaque only in hyperlipidemic rabbits. The magnitude of enhancement on magnetic resonance images had a high correlation with the number of macrophages determined by histology (p < 0.001) and allowed for the detection of macrophage-rich plaque with high accuracy (area under the curve: 0.92, SE: 0.04, 95% confidence interval: 0.84 to 0.96, p < 0.001). No significant signal enhancement was measured in remote areas without plaque by histology and in control rabbits without atherosclerosis. Conclusions Using IRON-MRI in conjunction with superparamagnetic nanoparticles is a promising approach for the noninvasive evaluation of macrophage-rich, vulnerable plaques.

Item Type:Article
Uncontrolled Keywords:atherosclerosis; vulnerable plaque; superparamagnetic nanoparticles; molecular imaging; inversion recovery with ON-resonant water suppression (IRON) positive contrast; magnetic resonance imaging
Subjects:Biomedical Science > Nanomedicine
ID Code:583
Deposited By:M T V
Deposited On:11 Dec 2008 15:31
Last Modified:11 Dec 2008 15:31

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