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Comparison of Gadofluorine-M and Gd-DTPA for Noninvasive Staging of Atherosclerotic Plaque Stability Using MRI

From the Robarts Research Institute (J.A.R., Y.C., R.A.H., B.K.R.), the Department of Medical Biophysics (J.A.R.), the Department of Anatomy and Cell Biology (A.J.-L.B., A.M.H., K.A.R.), and the Department of Medical Imaging (B.K.R.), University of Western Ontario, London, Ontario, Canada; Bayer Schering Pharma AG (B.M.), Research Laboratories, Berlin, Germany; and the Department of Radiology (B.K.R.), Stanford University, Palo Alto, Calif.

Correspondence to Dr John A. Ronald, Robarts Research Institute, Department of Medical Biophysics, University of Western Ontario, 100 Perth Drive, London, ON, Canada N6A 5K8. E-mail jronald{at}imaging.robarts.ca

Received October 7, 2008; accepted March 23, 2009.

Background— Inflammation and neovascularization play critical roles in the stability of atherosclerotic plaques. Whole-body quantitative assessment of these plaque features may improve patient risk-stratification for life-threatening thromboembolic events and direct appropriate intervention. In this report, we determined the utility of the MR contrast agent gadofluorine-M (GdF) for staging plaque stability and compared this to the conventional agent Gd-DTPA.

Methods and Results— Five control and 7 atherosclerotic rabbits were sequentially imaged after administration of Gd-DTPA (0.2 mmol/kg) and GdF (0.1 mmol/kg) using a T₁-weighted pulse sequence on a 3-T MRI scanner. Diseased aortic wall could be distinguished from normal wall based on wall-to-muscle contrast-to-noise values after GdF administration. RAM-11 (macrophages) and CD-31 (endothelial cells) immunostaining of MR-matched histological sections revealed that GdF accumulation was related to the degree of inflammation at the surface of plaques and the extent of core neovascularization. Importantly, an MR measure of GdF accumulation at both 1 and 24 hours after injection but not Gd-DTPA at peak enhancement was shown to correlate with a quantitative histological morphology index related to these 2 plaque features.

Conclusions— GdF-enhanced MRI of atherosclerotic plaques allows noninvasive quantitative information about plaque composition to be acquired at multiple time points after injection (within 1 and up to 24 hours after injection). This dramatically widens the imaging window for assessing plaque stability that is currently attainable with clinically approved MR agents, therefore opening the possibility of whole-body (including coronary) detection of unstable plaques in the future and potentially improved mitigation of cataclysmic cardiovascular events.

Key Words: MRI • atherosclerosis • inflammation • angiogenesis • contrast media

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