Prof. Dr. Timo Heidt (Freiburg / DE), Dr. Simon Reiss (Freiburg / DE), Julien Thielmann (Freiburg / DE), Christian Weber (Freiburg / DE), Timon Bühler (Freiburg / DE), Diana Chiang-Jurado (Freiburg / DE), Thomas Lottner (Freiburg / DE), Carolin Wadle (Freiburg / DE), Alexander Maier (Freiburg / DE), Dirk Westermann (Freiburg / DE), Prof. Dr. Michael Bock (Freiburg / DE), Prof. Dr. Constantin von zur Mühlen (Freiburg / DE)
Abstract-Text (inkl. Referenzen und Bildunterschriften)
Introduction: Post-ischemic myocardial injury is driven by inflammation. Expression of the cell adhesion molecule P-selectin by platelets and activated endothelial cells fosters recruitment of immune cells to the site of tissue injury. Due to its superior soft tissue contrast, magnetic resonance imaging (MRI) is ideal for myocardial tissue characterization. Molecular imaging further allows for functional assessment using target-specific contrast agents.
Aim: Assessment of ischemic cardiac lesions within the first hours after ischemia and reperfusion (I/R) in a porcine model using standard as well as advanced MRI techniques and molecular imaging targeting P-selectin.
Methods: Monoclonal P-selectin antibody was functionalized with microparticles of iron oxide (MPIO) and specific binding to the epitope of interest was confirmed by in vitro flow chamber experiments using activated platelets or endothelial cells. In vivo, a closed-chest model of balloon-occlusion of the circumflex artery served to induced I/R in juvenile farm pigs. 3T MRI was performed 2 – 4 hours after reperfusion and lesions were characterized using injury sensitive (T1 mapping), edema sensitive (T2 mapping) or iron sensitive (T2* mapping) sequences.
Results: Within the first hours after 40 min of ischemia, we detected increased inflammation in the blood by means of elevated numbers of innate immune cells. T1 mapping was most sensitive to tissue injury, yet no changes were detectable in edema sensitive T2 mapping at this time point. Intriguingly, P-selectin MPIO contrast agent selectively enhanced the ischemic area in iron sensitive T2* maps 4 hours after I/R which was confirmed by immunofluorescence staining from histology ex vivo.
Conclusion: Molecular MRI using P-selectin MPIO allows for sensitive detection of early myocardial inflammation following I/R beyond the capabilities of traditional inflammation sensitive imaging.