Ultrasmall superparamagnetic iron oxides for enhanced magnetic resonance imaging to detect atherosclerotic plaques of abdominal aorta in rabbits

BACKGROUND: Macrophages invasiveness is considered as an important marker in atherosclerotic plaques instability, along with the development and application of ultrasmall superparamagnetic iron oxides (USPIOs), its function of targeting macrophages made the imaging of atherosclerosis possible.OBJECTIVE: To investigate whether USPIOs can be phagocytosed by macrophages in rabbit abdominal aortic atherosclerotic plaques induced by high-cholesterol diet, if phagocytosed, and whether magnetic susceptibility artifacts generated by USPIOs particles in atherosclerotic plaques can be detectable and quantifiable by MRI. DESIGN, TIME AND SETTING: A randomized controlled animal experiment was performed from March 2006 to March 2007 in Image Center of The First Affiliated Hospital of Soochow University.MATERALS: Twenty rabbit models were randomly divided into experiment group (n=15) and normal group (n=5). Experiment group was adopted to make the model of rabbit's abdominal aortic atheroma by means of balloon injury and man-made high-cholesterol diet. Four months later, 15 rabbit models were assigned into USPIOs enhanced scanning group (n=10) and model control group (n=5). In addition, 5 normal rabbits were fed with a normal way.METHODS: MR scanning was performed before injection into each group. Superparamagnetic iron oxide SHU 555 C (200 mol/kg) was injected into rabbits of experiment group, while physiological saline into rabbits of model control group. Immediately after injection and at 1, 3, 5 days after injection, 4 times of MRI scanning were performed at each timing respectively in USPIOs enhanced scanning group; at 5 days after model control group was injected with physiological saline, MR scanning was administrated; at 5 days after normal group was injected with same dose of SHU 555, MR scanning was administrated. Three-dimensional time of flight gradient recall echo magnetic resonance angiography sequence was applied for MRI scanning. Scanning range included abdominal aorta celiac trunk crotch and iliac artery crotch. MAIN OUTCOME MEASURES: The signal-to-noise ratio (SNR) of aortic walls was measured at different time points. The numerical value and reduction percentage in transversal area were compared before and after injection. Aortic specimens were stained with hematoxylin-eosin and Prussian blue for histological observations.RESULTS: In USPIOs enhanced scanning group, the walls began to exhibit visible irregularity after the administration of SHU555 C. These manifestations appeared as wall's signal voids and local luminal stenosis, which became more pronounced on 5 days after injection. Although there was no significant difference in wall's SNR values between precontrast and 5 days postcontrast image sets obtained in model control group and normal group (P > 0.05), a vast difference was evident in USPIOs enhanced scanning group (P < 0.05). The numerical value and reduction percentage in transversal area had a statistical significance among 3 groups (P < 0.05). Both the numerical value and reduction percentage in transversal area were significantly higher in USPIOs enhanced scanning group compared with model control group and normal group (P < 0.01). No significant difference was found between the two later groups (P > 0.05). On histopathological sections with Prussian blue staining of aorta, we observed thickening of intima with marked staining of Fe particles (blue spots and patches) embedded in atherosclerotic plaque.CONCLUSION: USPIOs are phagocytosed by macrophages in rabbit abdominal aortic atherosclerosis induced by high-cholesterol diet in a quantity sufficient to cause magnetic susceptibility artifacts detectable by MRI. The numerical value and reduction percentage in transversal area can be used to quantify unstable atherosclerotic plaques, as well as a surrogate of magnetic susceptibility artifact size.