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Program in Cardiovascular Magnetic Resonance
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MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging

1H MAS Spectroscopy of Atherosclerotic Plaque


 

Directly resolving the proton NMR spectrum of macromolecules in excised tissue is possible through the use of 1H magic angle spinning (MAS). Spinning the samples oriented at the “magic angle” with respect to the main magnetic field improves spectral resolution by averaging local variations in the isotropic magnetic susceptibility and local dipolar interactions.  Typical spinning rates in the range of 3-6 kHz can be achieved with tissue samples which provides sufficient resolution to perform measures of inter- and intramolecular magnetic relaxation rates and transport properties.

 

Atherosclerotic plaque cholesterol esters exist in both solid and liquid crystalline phases and the analysis of the macromolecular composition by MR spectroscopy in situ rather than by traditional chemical analysis is therefore important for preservation of lipid phase behavior. In the figure below, we present high resolution 1H MAS spectra obtained on an 11.7 Tesla Bruker Avance NMR spectrometer. Tissue sections were micro-dissected from visibly distinct plaque regions within a carotid endarterectomy specimen. The 1H MAS spectra obtained with water presaturation are shown from three regions in the specimen: (1) calcified region above bifurcation and extending into the internal carotid, (2) fibroatheroma (white in appearance), and (3) thickened intima. Distinctions can be made among the spectra of micro-dissected sections of this heterogeneous advanced plaque.  The amounts of water, lipid (composition and concentration) and the associated spectral line widths vary in each section and are consistent with a variable distribution of atheromatous plaque lipids. The major lipid components of plaque include cholesterol esters where the methyl, methylene, and allylic chemical signatures dominate the 1H spectrum in the region of 0 - 3.0 ppm and have varying intensity ratios in these tissue sections. The lowest spectral amplitudes in the 0 - 3.0 ppm region were observed in the tissue section of thickened intima. It is noted for tissue in general that the hydrocarbon proton resonances for phospholipid membranes (1.0 and 1.5 ppm) are also observed. The calcified and fibroatheroma sections showed an increase in spectral amplitudes as well as additional lipid peaks in the 0 – 3.0 ppm region compared to the intima section.

Figure 1: 1H MAS 11.7 Tesla spectra of micro-dissected carotid plaque components from an endarterectomy specimen, showing the complexity and heterogeneity of regions  The major lipid components of plaque include cholesterol esters where the methyl, methylene, and allylic chemical signatures dominate the 1H spectrum in the region of 0 - 3.0 ppm.