P869Noninvasive multi-target imaging of vascular inflammation and progression of atherosclerosis in a mouse model using MRI

Introduction: Atherosclerosis is the leading cause for morbidity and mortality in our society. Traditionally, the emphasis of cardiovascular imaging to detect this disease entity was put on morphological changes of the vasculature. The interest to molecular markers as potential imaging targets increased, especially since the degree of stenosis is not the only and most important characteristic to determine the clinical destiny of atherosclerotic plaques. However, noninvasive characterization of atherosclerotic plaque inflammation and progression is still a major challenge. Elevated expression of vascular cell adhesion molecule 1 (VCAM-1) and lectin-like ox-LDL receptor (LOX-1) on the luminal surface of vulnerable, rupture-prone plaques in ApoE-/- mice and humans has been previously described using fluorescence imaging. Materials and methods: Antibodies against VCAM-1 and LOX-1 were conjugated to microparticles of iron oxide (MPIO), a hypo intense contrast agent for magnetic resonance imaging (MRI). We investigate ApoE-/- mice as a well-established animal model for atherosclerosis. At the age of 10 weeks, mice were fed a western-type high fat diet (HFD) for 3 months to increase plaque inflammation and progression. Therefore, it was possible to perform imaging at different stages of plaque development at three time points: 4, 8 and 12 weeks after initiation of the HFD. For exact quantification of the contrast agent-induced effect, it was essential to perform imaging before and after application of contrast agents. As controls, we used MPIOs conjugated to non-specific IgG antibodies. After imaging, histology was performed for each aortic arch to prove if plaque stages correlate with the MRI findings of the contrast agents.