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Atherosclerotic Plaque Composition: Analysis With Multicolor CT And Targeted Gold Nanoparticles.
D. Cormode, E. Roessl, A. Thran, T. Skajaa, R. Gordon, J. Schlomka, V. Fuster, E. Fisher, W. Mulder, R. Proksa, Z. Fayad
Published 2010 · Medicine
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PURPOSE To investigate the potential of spectral computed tomography (CT) (popularly referred to as multicolor CT), used in combination with a gold high-density lipoprotein nanoparticle contrast agent (Au-HDL), for characterization of macrophage burden, calcification, and stenosis of atherosclerotic plaques. MATERIALS AND METHODS The local animal care committee approved all animal experiments. A preclinical spectral CT system in which incident x-rays are divided into six different energy bins was used for multicolor imaging. Au-HDL, an iodine-based contrast agent, and calcium phosphate were imaged in a variety of phantoms. Apolipoprotein E knockout (apo E-KO) mice were used as the model for atherosclerosis. Gold nanoparticles targeted to atherosclerosis (Au-HDL) were intravenously injected at a dose of 500 mg per kilogram of body weight. Iodine-based contrast material was injected 24 hours later, after which the mice were imaged. Wild-type mice were used as controls. Macrophage targeting by Au-HDL was further evaluated by using transmission electron microscopy and confocal microscopy of aorta sections. RESULTS Multicolor CT enabled differentiation of Au-HDL, iodine-based contrast material, and calcium phosphate in the phantoms. Accumulations of Au-HDL were detected in the aortas of the apo E-KO mice, while the iodine-based contrast agent and the calcium-rich tissue could also be detected and thus facilitated visualization of the vasculature and bones (skeleton), respectively, during a single scanning examination. Microscopy revealed Au-HDL to be primarily localized in the macrophages on the aorta sections; hence, the multicolor CT images provided information about the macrophage burden. CONCLUSION Spectral CT used with carefully chosen contrast agents may yield valuable information about atherosclerotic plaque composition.
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