In vivo MRI detection of atherosclerosis in ApoE-deficient mice by using tenascin-C-targeted USPIO

Background: Atherosclerosis is the main cause of cardiovascular and cerebrovascular diseases. Non-invasive molecular imaging to detect and characterize the plaques is essential for reducing life-threatening cardiovascular events. Purpose: To investigate the possibility of the anti-tenascin-C-USPIO specific probe as a molecular marker of atherosclerotic plaques detected by 7.0-T magnetic resonance imaging (MRI). Material and Methods: Twenty ApoE(-/-) mice fed with a high fat diet were used for detecting the aorta arch atherosclerotic plaques by 7.0-T MRI at 16 and 24 weeks. Ten mice in the targeted group were injected with anti-tenascin-C-USPIO and another ten in the control group were injected with pure USPIO (n = 5 each time point in each group). Histopathologic examination was used to evaluate the plaques and immunohistochemistry analysis was used to compare tenascin-C expression. Results: The relative signal intensity (rSI) changes of the targeted group decreased more than those of the control group (16 weeks: -15.65 +/- 0.78% vs. -3.43 +/- 2.57%; 24 weeks: -26.38 +/- 1.54% vs. -11.12 +/- 1.60%, respectively; P < 0.05). Histopathological analyses demonstrated visible atherosclerotic plaques formation and development over time from 16 weeks to 24 weeks. Tenascin-C expression of the plaques at 24 weeks was higher than that at 16 weeks (0.22 +/- 0.04 vs. 0.13 +/- 0.02, P < 0.05). The MR images correlated well with the progression of atherosclerotic plaques. Conclusion: Tenascin-C expression increased with the progression of atherosclerosis. Anti-tenascin-C-USPIO could provide a useful molecular imaging tool for detecting and monitoring atherosclerotic plaques by MRI.