J. Lipid Res.
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Originally published In Press as doi:10.1194/jlr.M500431-JLR200 on November 29, 2005

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Journal of Lipid Research, Vol. 47, 310-317, February 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology

Identification of cholesteryl esters in human carotid atherosclerosis by ex vivo image-guided proton MRS

Frederick L. Ruberg*, Jason Viereck{dagger},§, Alkystis Phinikaridou{dagger}, Ye Qiao{dagger}, Joseph Loscalzo* and James A. Hamilton1,{dagger}

* Whitaker Cardiovascular Institute, Evans Department of Medicine and Section of Cardiology, Boston University School of Medicine, Boston, MA
{dagger} Department of Physiology and Biophysics, Boston University School of Medicine, Boston, MA
§ Department of Neurology, Boston University School of Medicine, Boston, MA

Published, JLR Papers in Press, November 29, 2005.

1 To whom correspondence should be addressed. e-mail: jhamilt{at}bu.edu

Vulnerable atherosclerotic plaques may be identified by their large lipid component, particularly liquid cholesteryl ester (CE), covered by a fibrous cap. We hypothesized that image-guided 1H proton magnetic resonance spectroscopy (MRS) would identify mobile CE in discrete, preselected regions of atherosclerotic plaque. Human carotid endarterectomy specimens (n = 10) were imaged ex vivo by magnetic resonance imaging (MRI) at high field (11.7 T) utilizing standard T1- and T2-weighted spin echo protocols. MRS spectra were acquired from 1 mm3 voxels, localized to plaque regions that we judged by MRI to be lipid rich or lipid poor. The spectra revealed methyl and methylene resonances of fatty acyl chains with relative intensities and linewidths characteristic of pure CE, by comparison with lipid standards. Regions judged to be lipid rich by MRI showed much more intense CE resonances than did lipid-poor regions. The integrated intensities of lipid peaks were 5.5 ± 2.0% (lipid-rich regions) versus 0.9 ± 0.6% (lipid-poor regions) of the unsuppressed water peak (P < 0.0001). Lipid distribution by histology, MRS, and MRI showed strong correlation. Image-guided proton MRS accurately identified CE in selected regions of atherosclerotic plaque as small as 1 mm3 in an ex vivo setting. This procedure may permit the noninvasive detection and quantification of CE in atherosclerotic plaque in vivo.

Abbreviations: CE, cholesteryl ester; CSI, chemical shift imaging; FOV, field of view; IVUS, intravascular ultrasound; MRS, magnetic resonance spectroscopy; OCT, optical coherence tomography; T1W, T1-weighted; TG, triacylglycerol; TR, repetition time

Supplementary key words magnetic resonance spectroscopy • stroke • vulnerable plaque • plaque lipids


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