title: Atherosclerotic plaque composition: analysis with multicolor CT and targeted gold nanoparticles.
abstract: 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.
authors.affiliation: Translational and Molecular Imaging Institute, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA.
authors.forename: David P
authors.initials: DP
authors.lastname: Cormode
authors.forename: Ewald
authors.initials: E
authors.lastname: Roessl
authors.forename: Axel
authors.initials: A
authors.lastname: Thran
authors.forename: Torjus
authors.initials: T
authors.lastname: Skajaa
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Gordon
authors.forename: Jens-Peter
authors.initials: JP
authors.lastname: Schlomka
authors.forename: Valentin
authors.initials: V
authors.lastname: Fuster
authors.forename: Edward A
authors.initials: EA
authors.lastname: Fisher
authors.forename: Willem J M
authors.initials: WJ
authors.lastname: Mulder
authors.forename: Roland
authors.initials: R
authors.lastname: Proksa
authors.forename: Zahi A
authors.initials: ZA
authors.lastname: Fayad
mesh_terms: 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*
chemical_list: D003287:Contrast Media; D006046:Gold; D007455:Iodine