Abstract 10322: Molecular Magnetic Resonance Imaging Allows in Vivo Evaluation of Ischemia-reperfusion Injury by Simultaneous Targeting of Activated Platelets and Myocardial Necrosis in Mice
Introduction: Inflammation and myocardial necrosis play important pathophysiological roles in ischemia-reperfusion injury after coronary artery occlusion. Detection of inflammatory activity by activated platelets and myocardial necrosis itself would be of clinical and prognostic interest. Therefore, we pursue in this project a simultaneous non-invasive evaluation of these two pathophysiological processes by molecular magnetic resonance imaging (MRI) in an in vivo mouse model.
Methods: Ischemia-reperfusion injury was induced in 10 week old C57BL/6N mice by a 50 minute temporary ligation of the ,,left anterior descending coronary artery“ (LAD). As a marker of inflammatory activity in reperfused myocardium, activated platelets were targeted with a contrast agent consisting of microparticles of iron oxide (MPIO) conjugated to a single chain antibody directed against ligand-induced binding sites (LIBS) on activated glycoprotein IIb/IIIa (=LIBS-MPIO). In comparison, we applied an unspecific control antibody linked to microparticles of iron oxide (control-MPIO). After injection of LIBS- or control-MPIO for the specific detection of activated platelets in the myocardium, late gadolinium enhancement was used to depict myocardial necrosis. Finally, presence of microthrombi in the ischemia-reperfusion area was evaluated by immunohistochemistry.
Results: We could specifically detect activated platelets via the signal effect of LIBS-MPIO in the area of LAD-occlusion two hours after reperfusion in magnetic resonance imaging, whereas there was no signal effect for control-MPIO. In parallel, imaging with gadolinium allowed detection of the extent of myocardial necrosis. Histology confirmed that LIBS-MPIO significantly bound to microthrombi in reperfused myocardium (p<0.01).
Conclusion: Using this approach of simultaneous molecular imaging for 1.) activated platelets in ischemia-reperfusion injury by LIBS-MPIO and 2.) myocardial necrosis by late gadolinium enhancement, we were able to characterize this important pathophysiology by in vivo MRI noninvasively. This strategy is of clinical interest for both diagnostic and prognostic purposes, and highlights the potential of molecular MRI for characterization of complex diseases.
- © 2013 by American Heart Association, Inc.