Atherosclerotic plaque composition: analysis with multicolor CT and targeted gold nanoparticles.
OBJECTIVE
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.


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.


CONCLUSIONS
Spectral CT used with carefully chosen contrast agents may yield valuable information about atherosclerotic plaque composition.
Cormode
David P
DP
Translational and Molecular Imaging Institute, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA.
Roessl
Ewald
E
Thran
Axel
A
Skajaa
Torjus
T
Gordon
Ronald E
RE
Schlomka
Jens-Peter
JP
Fuster
Valentin
V
Fisher
Edward A
EA
Mulder
Willem J M
WJ
Proksa
Roland
R
Fayad
Zahi A
ZA
D000818:Animals; D001018:Aortic Diseases / Q000000981:diagnostic imaging* / Q000473:pathology; D050197:Atherosclerosis / Q000000981:diagnostic imaging* / Q000473:pathology; D003116:Color; D003287:Contrast Media; D006046:Gold; D007455:Iodine; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D053758:Nanoparticles; D019047:Phantoms, Imaging; D014057:Tomography, X-Ray Computed / Q000379:methods*
D003287:Contrast Media; D006046:Gold; D007455:Iodine