title: Noninvasive assessment of atherosclerotic plaque progression in ApoE-/- mice using susceptibility gradient mapping.
abstract: BACKGROUND
  Macrophages have been identified as a major contributor to plaque development and destabilization in atherosclerosis. The aim of this study was to noninvasively assess uptake of citrate coated very small iron oxide particles at different stages of plaque development in the brachiocephalic artery of apoE(-/-) mice. Susceptibility gradient mapping (SGM) was applied to generate positive contrast images and to quantify iron oxide uptake.
  
  
  RESULTS
  ApoE(-/-) mice were fed a high-fat diet for 4, 8, or 12 weeks; 300 μmol Fe/kg was injected 24 and 48 hours before final MRI. Increasing very small iron oxide particle uptake was observed over the course of atherosclerotic plaque development. Simultaneous administration of pravastatin led to a significant decrease in very small iron oxide particle uptake, assessed by mass spectroscopy and histology. SGM-MRI allowed the generation of positive contrast images, and magnitudes (mT/m) of contrast enhancement in SG parameter maps significantly correlated with the absolute iron oxide content (R(2)=0.70, P<0.05) and the macrophage density (R(2)=0.71, P<0.05).
  
  
  CONCLUSIONS
  This study shows an increase in iron oxide uptake (measured by in vivo SGM-MRI, histology, and mass spectroscopy) with the progression of plaque development in an apoE(-/-) mouse model of accelerated atherosclerosis. Positive contrast provided by SGM-MRI allowed for a clear visualization of intraplaque iron oxide depositions, and magnitudes (mT/m) of contrast enhancement in SG parameter maps allowed for the quantification of intraplaque iron oxide particles.
authors.affiliation: King's College London, Division of Imaging Sciences and Biomedical Engineering, London, United Kingdom. marcus.makowski@kcl.ac.uk
authors.forename: Marcus R
authors.initials: MR
authors.lastname: Makowski
authors.forename: Gopal
authors.initials: G
authors.lastname: Varma
authors.forename: Andrea J
authors.initials: AJ
authors.lastname: Wiethoff
authors.forename: Alberto
authors.initials: A
authors.lastname: Smith
authors.forename: Katherine
authors.initials: K
authors.lastname: Mattock
authors.forename: Christian H P
authors.initials: CH
authors.lastname: Jansen
authors.forename: Alice
authors.initials: A
authors.lastname: Warley
authors.forename: Matthias
authors.initials: M
authors.lastname: Taupitz
authors.forename: Tobias
authors.initials: T
authors.lastname: Schaeffter
authors.forename: Rene M
authors.initials: RM
authors.lastname: Botnar
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D015153:Blotting, Western; D016122:Brachiocephalic Trunk / Q000473:pathology; D003287:Contrast Media; D018450:Disease Progression; D005290:Ferric Compounds; D037502:Galectin 3; D007091:Image Processing, Computer-Assisted; D008264:Macrophages / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D018345:Mice, Knockout; D058226:Plaque, Atherosclerotic / Q000175:diagnosis / Q000473:pathology*
chemical_list: D001057:Apolipoproteins E; D003287:Contrast Media; D005290:Ferric Compounds; D037502:Galectin 3; C000499:ferric oxide