Introduction: Inflammation is a hallmark of post-ischemic myocardial injury. Expression of P-selectin by platelets and activated endothelial cells drives recruitment of immune cells to the deprived area and may serve as an early indicator of tissue injury. Due to its pristine soft tissue contrast, magnetic resonance imaging (MRI) is used for myocardial tissue characterization. Molecular imaging further allows for functional assessment using target-specific contrast agents. In this study, we non-invasively assessed ischemic cardiac lesions within the first hours after ischemia/reperfusion (I/R) in a porcine model using standard and advanced MRI techniques as well as molecular imaging targeting the cell adhesion molecule P-selectin.

Methods: For molecular imaging, monoclonal P-selectin antibody was functionalized with microparticles of iron oxide (MPIO). Specific binding of the contrast agent to the epitope of interest was confirmed by FACS and in vitro flow chamber using activated platelets. In vivo, we used a closed-chest model of I/R of the circumflex artery in juvenile farm pigs by balloon-occlusion for 40 minutes. 3T MRI was performed 2 – 4 hours after reperfusion and lesions were characterized using injury (T1 mapping), edema (T2 mapping) and iron (T2* mapping) sensitive sequences. 

Results:  Within the first hours after I/R, we detected increased inflammatory activity by means of higher numbers of innate immune cells in the blood. We found T1 mapping to be most sensitive for tissue injury, while no changes were detectable in edema sensitive T2 mapping this early. Intriguingly, P-selectin MPIO contrast agent selectively enhanced the ischemic area in iron sensitive T2* mapping 4 hours after I/R which was confirmed ex vivo by histology.   

Conclusion: Molecular MRI using P-selectin MPIO allows for sensitive detection of early myocardial inflammation after I/R beyond the capabilities of traditional edema sensitive imaging.