Magnetic Resonance In Vivo Imaging Studies Targeting Tenascin-C Expression In Atherosclerotic Plaques

Part 1 MR Imaging of the Atherosclerosis and the expression of Tenascin-C and CD68 in ApoE^-/-mouse modelObjective To explore the feasibility of 7.0T MR scanner in mouse aorta atherosclerosis models.Visualising the TN-C in atherosclerotic plaque by immunohistochemistry and its correlation with CD68 to provide experimental basis for the feasibility of TN-C in targeted MRI.Methods ApoE^-/-mice and wild type C57 mice were fed on High fat diet to establish aorta atery atherosclerosis model?n=10?,the aorta were observed by MRI after 14 weeks.The aorta atery specimens were taken to stain with HE to observe the pathological changes.The plaque were stained with oil red O,anti-TNC and TN-C antibody respectively to observe the fat,CD68 and TN-C in plaque.Results 7.0 MRI showed the aorta wall of the experimental group was thicker and high signal on T1 WI and PDWI,low signal on T2 WI after 14 weeks.The histopathlogy examination showed the intima was thicker obviously,and the lumen was irregularly narrow.Both of CD68 and TN-C were highly expressed in plaque,the distribution of TN-C correlated with CD68.In the contrast group,no case showed hyper signal in the vessel wall of aorta or lumen narrow by MRI,and the histopathlogy showed no atherosclerotic plaque formation in the aorta artery.Conclusion Aorta artery atherosclerotic plaque can be established through high fat diet on ApoE^-/-mouse,and 7.0 MR can successfully detect it.TN-C is high expressed in AS plaque and the expression is correlated with CD68.They may collaborate with each other in the development of AS.Detecting TN-C could be useful for the further study of atherosclerotic plaque.Part 2 Research of targeted MR imaging of the expression of tenascin-C in atherosclerosis plaque in vivo.Objective To visualize TN-C in atherosclerotic plaque and to explore the feasibility of TN-C by targeted MRI in vivo.Methods High fat diet were fed on ApoE^-/-mice to establish aorta artery atherosclerosis models.The atherosclerotic plaque were observed by7.0T micro-MRI after 14 weeks.Specimens of the samples were obtained randomly and were taken to stain with H&E and oil red O to observe the pathological changes.The plaque were stained with anti-TNC antibody to testify the TN-C.Targeted probe?anti-TNC-SPIO?was synthesized through chemical coupling methods.The experimental group was injected by targeted probe through tail vein?dose 10 mg Fe/kg?,and USPIO was used as controls.MRI was processed 8h after administration;specimens were taken after scanning,and were stain by Perl's blue.Results MRI showed the aorta wall was thicker after 14 weeks;signal was higher on T1 WI and PDWI,but lower on T2 WI.The H&E stain showed the intima was significantly thicker then before.The plaque was confirmed by the oil red O staining.Immunoreaction showed TN-C was highly expressed in the plaque.MRI signal was lost on T2 WI in the atherosclerotic lesions after administration of anti-TNC-SPIO at 8h,with statistical significance?p<0.05?,and matched Perl's stained section showed blue particles deposition within the plaque.Signal variationof the contrast group did not occur,and little blue particles were observed.Conclusion This study shows that targeted MRI is feasible to detect TN-C in the plaque in vivo,which may provide experimental base of molecular imaging by MRI in atherosclerotic plaque.