Submitted on September 29, 2005
Revised on November 8, 2005
Accepted on November 28, 2005
Identification of cholesteryl esters in human carotid atherosclerosis by ex vivo image-guided proton magnetic resonance spectroscopy
Frederick L. Ruberg, Jason Viereck, Alkystis Phinikaridou, Ye Qiao, Joseph Loscalzo, and James A. Hamilton
Department of Physiology and Biophysics, Boston Univeristy Medical Campus, Boston, MA 02118
Corresponding Author: 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, pre-selected 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. Magnetic resonance spectroscopy (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 lipid-poor regions. The integrated intensities of lipid peaks were 5.5%±2.0% (lipid-rich regions) vs. 0.9%±0.6% (lipid-poor regions) of the unsuppressed water peak (p<0.0001). Lipid distribution by histology, MR spectroscopy, and MR imaging 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 non-invasive detection and quantification of CE in atherosclerotic plaque in vivo.