Late-phase detection of recent myocardial ischaemia using ultrasound molecular imaging targeted to intercellular adhesion molecule-1

Aims In this study, we attempted to detect a recent myocardial ischaemic event using ultrasound molecular imaging (UMI) with microbubbles (MB) targeted to intercellular adhesion molecule-1 (ICAM-1) in the late phase of reperfusion. Methods and results We created a myocardial ischaemia-reperfusion model in 60 C57/BL male mice to simulate an angina attack (ischaemia for 15 min, reperfusion for 1-24 h). The degree of myocardial inflammation and levels of ICAM-1 protein were determined by histological and immunohistochemical analyses. UMI with MB targeted to endothelial ICAM-1, as well as routine non-invasive methods including electrocardiography, echocardiography, and plasma troponin I levels, were utilized to evaluate ischaemia over the time course of reperfusion. Levels of ICAM-1 in the vascular endothelium were significantly increased over the time course of reperfusion (8-24 h) of the ischaemic myocardium. The video intensity of ICAM-1 molecular images of the ischaemic anterior wall was almost three times greater than that in the non-ischaemic posterior wall during the late phase (8-24 h) of reperfusion. In contrast, routine methods yielded only weak evidence of ischaemia. Conclusion UMI with MB targeted to endothelial ICAM-1 provides reliable evidence of a recent myocardial ischaemic event in the late phase of reperfusion.