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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:2384.)
© 2004 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Quantification and 3D Reconstruction of Atherosclerotic Plaque Components in Apolipoprotein E Knockout Mice Using Ex Vivo High-Resolution MRI

Martina A. McAteer; Jürgen E. Schneider; Kieran Clarke; Stefan Neubauer; Keith M. Channon; Robin P. Choudhury

From the Department of Cardiovascular Medicine (M.A.M., J.E.S., S.N., K.M.C., R.P.C.) and University Laboratory of Physiology (K.C.), University of Oxford, United Kingdom.

Correspondence to Dr Robin Choudhury, Department of Cardiovascular Medicine, John Radcliffe Hospital, Oxford OX3 9DU. E-mail robin.choudhury{at}cardiov.ox.ac.uk

Objective— To investigate the ability of high-resolution MRI to determine composition and microanatomy of atherosclerosis in mouse aortic root and brachiocephalic artery.

Methods and Results— Aortic root and brachiocephalic arteries of apolipoprotein E knockout (apoE–/–) mice fed Western diet for 10, 20, or 30 weeks were imaged ex vivo (11.7 T; 3D multiecho sequence; resolution 47x47x62.5 µm). Using semiautomated histogram-based methods, MRI accurately quantified lipid-rich/necrotic areas in the aortic root (r²=0.84; P<0.001) and brachiocephalic artery (r²=0.90; P<0.001) compared with histology. Similarly, cell-rich caps in aortic roots, quantified by MRI and histology, correlated closely (r²=0.74; P<0.001). Reconstruction of segmented brachiocephalic arteries in 3D provided unique insights into plaque microanatomy and enabled volumetric quantification of plaque and lipid-rich/necrotic core. Between 10 and 30 weeks, 3D measurement identified an 11.6-fold increase in plaque volume (versus 4.1-fold for 2D) and a 21.3-fold increase in plaque lipid-rich/necrotic core volume (versus 6.4-fold for 2D), indicating superior power of 3D quantification.

Conclusions— Ex-vivo high-resolution 3D MRI accurately quantified lipid-rich/necrotic core and cell-rich cap areas in atherosclerotic lesions in apoE–/– mice. Reconstruction and volumetric quantification of segmented brachiocephalic arteries demonstrated greater sensitivity in detecting changes in plaque size and lipid composition over time than 2D analysis.

We tested the ability of high-resolution MRI to quantify mouse atherosclerotic plaque components ex vivo. MRI accurately quantified lipid-rich/necrotic core and cell-rich cap components, as confirmed by histopathology. Three-dimensional reconstruction of brachiocephalic arteries enabled more sensitive volumetric quantification of differences in plaque and lipid-rich/necrotic cores than 2D analysis.

Key Words: atherosclerosis • brachiocephalic artery • apoE–/– mice • MRI • lipid-rich/necrotic core

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