Molecular imaging of atherosclerosis in mice with MRI and near-infrared fluorescence imaging

Objective To explore the feasibility of detecting atherosclerotic plaques with 7.0 T MRI and near-infrared fluorescence imaging(NIRF) using molecular imaging probes.Methods Atherosclerotic plaques were established in male atherosclerotic apolipoprotein E knockout(ApoE-/-) mice fed with high-cholesterol diet for 20 weeks.Wild-type C57BL/6 mice were used as negative controls.7.0 T MRI was performed before and 36 h after intravenously administration of ultrasmall superparamagnetic partical of iron oxide (USPIO).NIR 797 was conjugated with anti-mouse-oxidized modified low density lipoprotein (oxLDL) antibodies to construct an anti-oxLDL-Ab-NIR 797 probe while non-specific IgG-NIR 797 and PBS used as controls.NIRF was performed 24 h after tail vein injection of the probe.Independent sample ttest and one-way analysis of variance were used to analyze the data by SPSS 17.O.Results In APOE-/-mice,in vivo 36 h post-USPIO T2WI images revealed strong focal signal loss in the abdominal aorta than that of pre-USPIO,with relative signal intensity 0.70 ± 0.04 and 1.28 ± 0.06,respectively ( t =3.376,P ＜0.05 ).The percent of signal reduced was ( - 56.58 ± 4.25 ) ％.The Prussian blue staining confirmed the depositions of iron particles in the plaque lesions.Significant fluorochrome accumulation in atherosclerotic plaques was demonstrated in aortic root,aortic arch and the starting of descending aorta 24 h after injection of the anti-oxLDL-Ab-NIR 797 probe.Minimal antibody uptake was observed in normal vessels from wildtype mice receiving the anti-oxLDL-Ab-NIR 797 (SNR:2.29 ± 1.11 ) and in atherosclerotic vessels from ApoE-/- mice receiving the non-specific IgG-NIR 797 ( 19.58 ±3.06) or PBS (4.19 ±0.82),which was significantly different from the uptake of anti-oxLDL-Ab-NIR 797 group (42.51 ±5.24,F =25.104,P ＜ 0.05 ).Comparison between oil red O staining and NIRF 24 h after injection of NIR 797 labeled oxLDL-antibody revealed a significant correlation ( r =0.738,P ＜ 0.05,n =8 ).The positive areas in imaging were (41.69 ± 5.29) ％ and (39.45 ± 5.35 ) ％,respectively.Immunofluorescence staining demonstrated that the expression of oxLDL was closely associated to macrophage infiltrates.Conclusion This study demonstrates that atherosclerotic plaque MRI and NIRF imaging are feasible by using novel molecular imaging probes and may help to identify high-risk plaques,providing a foundation for multimodality imaging of atherosclerosis. Key words: Atherosclerosis;  Magnetic resonance imaging;  Near-infrared fluoroscence imaging; Animals, laboratory