Magnetic resonance imaging of experimental atherosclerotic plaque: Comparison of two ultrasmall superparamagnetic particles of iron oxide

Abstract

To evaluate a new ultrasmall superparamagnetic particles of iron oxide (USPIO) compound, ferumoxytol, as a marker of macrophage activity in atherosclerotic plaques and to compare it to ferumoxtran-10. Ten mature heritable hyperlipidemic (WHHL) female Watanabe rabbits served as the animal model for atherosclerosis, four coeval female New Zealand White (NZW) rabbits were the control group. Five WHHL and two NZW received a single intravenous injection (250 micromol/kg) of either ferumoxtran-10 or ferumoxytol and were subjected to daily MR examinations on a 1.5T whole body scanner for the next five days. Development of signal intensity changes and susceptibility effects was assessed. Statistical analysis was based on a nonparametric Wilcoxon-Mann-Whitney-U test by using a P value at the 0.05 significance level. On day 5, the rabbits were sacrificed and the aorta was referred to histopathology, distribution of iron particles in the vessel wall was analyzed. MRI was feasible in all animals. Three days after injection of ferumoxytol the highest luminal signal intensity measurements were observed in the ferumoxytol group; the highest measurements were five days after injection in the ferumoxtran-10 group (P < 0.05). In the WHHL, susceptibility effects presented as homogeneous dark lines parallel to the aortic wall after ferumoxytol and spotted areas void of signal after ferumoxtran-10. None of these findings were observed in the NZW control groups. Ferumoxtran-10 and ferumoxytol at a respective dose of 250 mumol/kg appear well suited for atherosclerotic plaque detection with MRI in experimental atherosclerosis. Ferumoxytol warrants further analysis in humans.