Superparamagnetic iron oxide-enhanced MRI of atherosclerotic plaques in Watanabe hereditable hyperlipidemic rabbits

RATIONALE AND OBJECTIVES. Inflammatory atherosclerotic plaques are characte rized by increased endothelial permeability and multiple macrophages, Blood -pool MRI contrast agents like superparamagnetic iron oxide (SPIO) have an affinity for the monocyte-macrophage system and thus, may label inflammator y plaques. The objective was to demonstrate SPIO uptake in plaques of ather osclerotic rabbits by MRI and histology, METHODS. Aortas of anesthetized Watanabe hereditable hyperlipidemic rabbits were studied with a moderately T2*-weighted gradient-echo sequence at 1.5 T, Four groups of five animals each were studied: (1) without ultrasmall SP IO (carboxydextran coating; particle size, 25 nm; estimated plasma half-lif e, 6 hours) or with imaging after intravenous injection of SPIO at a dose ( mu mol Fe/kg) and postcontrast time delay (hours) of 50/8 (2), 50/24 (3), o r 200/48 (4), In vivo MRI was compared with corresponding ex vivo histologi cal iron stains. RESULTS. Animals receiving 200 mu mol Fe/kg demonstrated areas of focal sig nal loss clearly confined to the aortic wall on a mean of 24 +/- 9 (31% +/- 11%) of 76 +/- 5 images compared with 0 +/- 0 of 76 +/- 5 images in contro ls (P = 0.009). The number of images with this finding in groups 2 and 3 wa s not significantly different compared with controls, By microscopy, SPIO-i ron was seen in the endothelial cells and subendothelial intimal macrophage s of atherosclerosis-prone aortic wall segments, Atherosclerotic lesions de monstrating iron uptake also showed a high macrophage content. CONCLUSIONS. SPIO accumulates In aortic plaques of atherosclerotic rabbits, producing a characteristic MRI finding. As SPIO accumulates in plaques wit h increased endothelial permeability and a high macrophage content, two est ablished features of plaque inflammation, it may have a potential for nonin vasive assessment of inflammatory atherosclerotic plaques.