Detection of Vulnerable Atherosclerotic Plaques in Experimental Atherosclerosis with the USPIO-Enhanced MRI

Abstract

This study's goal was to assess the diagnostic value of the USPIO-(ultra-small superparamagnetic iron oxide) enhanced magnetic resonance imaging (MRI) in detection of vulnerable atherosclerotic plaques in abdominal aorta in experimental atherosclerosis. Thirty New Zealand rabbits were randomly divided into two groups, Group A and Group B. Each group comprised 15 animals which were fed with high cholesterol diet for 8 weeks and then subjected to balloon-induced endothelial injury of the abdominal aorta. After another 8 weeks, animals in Group B received adenovirus carrying p53 gene that was injected through a catheter into the aortic segments rich in plaques. Two weeks later, all rabbits were challenged with the injection of Chinese Russell's viper venom and histamine. Pre-contrast images and USPIO-enhanced MRI images were obtained after pharmacological triggering with injection of USPIO for 5 days. Blood specimens were taken for biochemical and serological tests at 0 and 18 weeks. Abdominal aorta was histologically studied. The levels of serum ICAM-1 and VCAM-1 were quantified by ELISA. Vulnerable plaques appeared as a local hypo-intense signal on the USPIO-enhanced MRI, especially on T2*-weighted sequences. The signal strength of plaques reached the peak at 96 h. Lipid levels were significantly (p < 0.05) higher in both Group A and B compared with the levels before the high cholesterol diet. The ICAM-1 and VCAM-1 levels were significantly (p < 0.05) higher in Group B compared with Group A. The USPIO-enhanced MRI efficiently identifies vulnerable plaques due to accumulation of USPIO within macrophages in abdominal aorta plaques.

Atheroprotective Effects and Mechanisms of Postmarketing Chinese Patent Formulas in Atherosclerosis Models: A Systematic Review

“…The major limitation of ApoE −/− mice is the rare occurrence of thrombosis and plaque rupture, which is common in humans [ 16 ]. Owing to the studies of vulnerable plaques, the rabbit model is successfully established through the overexpression of p53 in local plaques and triggered by RVV [ 83 ]. Rats and C57BL/6 mice are used in the included studies; these animals are naturally resistant to atherogenesis and lack plasma cholesteryl ester transfer protein (CETP) activity [ 79 , 84 ].…”

Iron Oxide Nanoparticles in Regenerative Medicine and Tissue Engineering

“…A large number of studies have reported the imaging of atherosclerotic plaques by labelling of macrophages with IONPs. In particular, the use of ultra-small IONPs or very-small IONPs particles for the detection of macrophages and pathological inflammation in atherosclerotic tissue is well established [ 135 , 136 , 137 , 138 , 139 , 140 , 141 ]. Especially, ferumoxytol (Feraheme ® ) and ferumoxtran-10 (Sinerem ® /Combidex ® ), which have an excellent safety profile and are selectively taken up by macrophages, has been widely reported [ 142 , 143 , 144 , 145 , 146 , 147 , 148 , 149 , 150 , 151 ].…”