Cardiac magnetic resonance imaging of rapid VCAM-1 up-regulation in myocardial ischemia-reperfusion injury

Inflammatory response plays an important role in myocardial ischaemia-reperfusion (IR) injury. Up-regulation of vascular cell adhesion molecule-1 (VCAM) contributes to this. We examined the feasibility of using intravenously administered VCAM-MPIO (microparticle iron oxide) to characterize VCAM expression patterns in myocardial IR injury. Myocardial ischemia was simulated by 30 min of transient ligation of the left coronary vessel in rats. Purified, monoclonal, rat-specific, mouse VCAM antibody coupled to MPIO was administered through the tail vein at 3 h post reperfusion and the rats were sacrificed 1 h later. High resolution 3D ex vivo MRI images were acquired at 9.4 Tesla. Extensive foci of signal voids were observed on T2*-weighted gradient-echo sequences, which corresponded to focal deposits of MPIOs observed in histological sections. The spatial density of the signal voids (expressed as a percentage of pixels below a threshold value) was increased in the peri-infarct zone compared with non-infarct zone (32.5 +/- A 4 % vs. 13.9 +/- A 5 %; n = 6; p < 0.05) and was substantially greater than the signal loss due to non-specific binding seen in rats administered IgG control MPIO (2.0 +/- A 1 %; n = 6; p < 0.05). The VCAM-specific MPIO signal was also seen in myocardium and pericardium in segments remote from the IR injury, but not in rats undergoing a sham operation. In conclusion, molecular imaging in a model of myocardial IR injury is possible using high field MRI and VCAM-MPIOs and may provide novel insights beyond those achieved by standard histological and molecular analysis.