Objective-Ultrasmall superparamagnetic iron oxide (USPIO) contrast agents have been used for noninvasive MRI assessment of atherosclerotic plaque inflammation. The purpose of this study was to noninvasively evaluate USPIO uptake in aorta of apoE Ϫ/Ϫ mice and to determine the effects of Angiotensin II (Ang II) infusion and chronic antiinflammatory treatment with a p38 MAPK inhibitor on this uptake. Methods and Results-ApoEϪ/Ϫ mice were administered saline or Ang II (1.44 mg/kg/d) for 21 days. In vivo MRI assessment of USPIO uptake in the aortic arch was observed in all animals. However, although the Ang II group had significantly higher absolute iron content (1103%, PϽ0.001) in the aortic arch compared with the saline group, the p38 MAPK inhibitor (SB-239063, 150 mg/kg/d) treatment group did not (16%, NS). The in vivo MRI signal intensity was significantly correlated to the absolute iron content in the aortic arch. Histological evaluation of the aortic root lesion area showed colocalization of USPIO with macrophages and a reduction in USPIO but not macrophage content with SB-239063 treatment. Conclusion-The present study demonstrates that noninvasive assessment of USPIO uptake, as a marker for inflammation in murine atherosclerotic plaque, is feasible and that p38 MAPK inhibition attenuates the uptake of USPIO in aorta of Ang II-infused apoE Key Words: atherosclerosis Ⅲ inflammation Ⅲ magnetic resonance imaging Ⅲ USPIO Ⅲ apoE Ϫ/Ϫ Ⅲ p38 MAPK A lthough experimental evidence linking inflammatory processes to the fate of the atherosclerotic plaque development exists, it is difficult to examine these processes noninvasively and to provide convincing links between preclinical and clinical studies. In this regard, ultrasmall superparamagnetic iron oxide (USPIO) contrast agents, optimized for uptake by the mononuclear phagocytic system, 1-3 are of particular interest for translational cardiovascular research. These agents have been used for noninvasive MRI assessment of atherosclerotic plaque inflammation in humans 4 -6 as well as hypercholesterolemic balloon-injured NZW 7 and WHHL 8 -11 rabbits. However, descriptions of USPIO use in extensively-studied murine genetic models of atherosclerosis have been limited. Investigators have used other targeted 12,13 and nontargeted 14 approaches to noninvasively assess plaque burden or inflammation in atherosclerotic mouse models. Additionally, superparamagnetic iron oxide (SPIO) has been used to quantify monocyte recruitment histologically in atherosclerotic lesions of the apolipoprotein E-deficient (apoE Ϫ/Ϫ ) mouse. 15 In that study, acute administration of tumor necrosis factor (TNF), interleukin (IL)-1␤, and interferon (INF)-␥ was shown to stimulate SPIO uptake by 4-fold in plaque. Although this study supports the hypothesis that plaque targeting of the USPIO contrast agent in mouse is facilitated by monocyte recruitment or activation of macrophage phagocytosis, noninvasive assessment of USPIO uptake in mouse atherosclerotic lesions has not been reported. Recent evidence sugg...

Over time the dermatitis and eosinophilia resolved spontaneously. The animal is currently free of any lesions and maintains an eosinophil count within normal limits.

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