Interventional real-time molecular MRI allows diagnostic targeting of early myocardial injury in a pig model of ischemia and reperfusion

Abstract

Abstract 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 high 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 assessed ischemic cardiac lesions non-invasively 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, a monoclonal P-selectin antibody was functionalized with microparticles of iron oxide (MPIO). Specific binding to the target was confirmed by in vitro flow chamber using activated platelets as well as endothelial cells. 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, and real time MRI-guided coronary injection of MPIO-based contrast agents. 3T MRI was performed 2–4 hours after reperfusion, and lesions were characterized using injury (T1 mapping, LGE), edema (T2 mapping) and iron (T2* mapping) sensitive MRI. 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 histologically, while late gadolinium enhancement was always absent. Conclusion: By using real time MRI-guided coronary intervention, 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.