Murine atherosclerotic plaque imaging with the USPIO Ferumoxtran-10

Front Biosci (Landmark Ed). 2009 Jan 1;14:2546-52. doi: 10.2741/3396.

Abstract

In this study we intended to image plaque inflammation in a murine model of atherosclerosis with MRI and Ferumoxtran-10 (Sinerem, Guerbet, France). 8 apoE-/- mice were injected 500 micromol Fe/kg or 1000 micromol Fe/kg Ferumoxtran-10. 2 apoE-/- mice were injected NaCl. After a post-contrast time of 24 to 336 hours the mice were scarificed and the aortas were imaged ex vivo. All measurements were performed on a 17.6 Tesla Bruker AVANCE 750WB MR scanner (Bruker, Germany). Spin-echo sequences and gradient-echo sequences with variable TE were performed and T2* maps were generated. Prussian-blue and hematoxilin-eosin histology were obtained afterwards and iron-uptake was quantified by counting iron positive areas. 2 apoE-/- mice were imaged in vivo before and 48 hours after 1000 micromol Fe/kg. Atheroma iron uptake was not elevated after 24 hours compared to controls. 48 hours after 1000 micromol Fe/kg but not 500 micromol Fe/kg histology revealed a 1.3- fold increase in plaque iron content compared to NaCl injected mice. Normalized T2*-times decreased from 0.86+/-0.02 in controls to 0.66+/-0.15 after a dose of 500 micromol Fe/ml and 0.59+/-0.14 in mice injected with 1000 micromol Fe/Kg (p=0.038). These results translated into a mean of 122% increase in CNR, as measured by in vivo MRI. We have demonstrated that Ferumoxtran-10 is taken up by atherosclerotic plaques in untreated apoE-/- mice and this alters plaque signal properties.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apolipoproteins E / genetics
  • Atherosclerosis / diagnosis
  • Atherosclerosis / pathology*
  • Dextrans
  • Ferrosoferric Oxide
  • Iron*
  • Magnetic Resonance Imaging
  • Magnetite Nanoparticles
  • Mice
  • Mice, Knockout
  • Oxides*

Substances

  • Apolipoproteins E
  • Dextrans
  • Magnetite Nanoparticles
  • Oxides
  • ferumoxtran-10
  • Iron
  • Ferrosoferric Oxide