Dual-contrast molecular MRI using LIBS-MPIOs and late gadolinium enhancement successfully detected activated platelets and myocardial necrosis 2 hours after reperfusion in a mouse model.
Does dual-contrast molecular MRI using LIBS-MPIOs and late gadolinium enhancement allow noninvasive characterization of platelet-driven inflammation and myocardial necrosis in a mouse model of ischemia/reperfusion injury?
Dual-contrast molecular MRI using LIBS-MPIOs and late gadolinium enhancement successfully characterizes platelet-driven inflammation and myocardial necrosis in a preclinical model of ischemia/reperfusion injury.
Background— Inflammation and myocardial necrosis play important roles in ischemia/reperfusion injury after coronary artery occlusion and recanalization. The detection of inflammatory activity and the extent of myocardial necrosis itself are of great clinical and prognostic interest. We developed a dual, noninvasive imaging approach using molecular magnetic resonance imaging in an in vivo mouse model of myocardial ischemia and reperfusion. Methods and Results— Ischemia/reperfusion injury was induced in 10-week-old C57BL/6N mice by temporary ligation of the left anterior descending coronary artery. Activated platelets were targeted with a contrast agent consisting of microparticles of iron oxide (MPIOs) conjugated to a single-chain antibody directed against a ligand-induced binding site (LIBS) on activated glycoprotein IIb/IIIa (LIBS-MPIOs). After injection and imaging of LIBS-MPIOs, late gadolinium enhancement was used to depict myocardial necrosis; these imaging experiments were also performed in P2Y 12 −/− mice. All imaging results were correlated to immunohistochemistry findings. Activated platelets were detectable by magnetic resonance imaging via a significant signal effect caused by LIBS-MPIOs in the area of left anterior descending coronary artery occlusion 2 hours after reperfusion. In parallel, late gadolinium enhancement identified the extent of myocardial necrosis. Immunohistochemistry confirmed that LIBS-MPIOs bound significantly to microthrombi in reperfused myocardium. Only background binding was found in P2Y 12 −/− mice. Conclusions— Dual molecular imaging of myocardial ischemia/reperfusion injury allows characterization of platelet-driven inflammation by LIBS-MPIOs and myocardial necrosis by late gadolinium enhancement. This noninvasive imaging strategy is of clinical interest for both diagnostic and prognostic purposes and highlights the potential of molecular magnetic resonance imaging for characterizing ischemia/reperfusion injury.
Elverfeldt et al. (Sat,) conducted a other in Myocardial ischemia/reperfusion injury. Dual-contrast molecular MRI (LIBS-MPIOs and late gadolinium enhancement) vs. P2Y12 -/- mice (for specificity) was evaluated on Detection of activated platelets and myocardial necrosis via MRI signal effect. Dual-contrast molecular MRI using LIBS-MPIOs and late gadolinium enhancement successfully detected activated platelets and myocardial necrosis 2 hours after reperfusion in a mouse model.