Molecular Magnetic Resonance Imaging Allows the Detection of Activated Platelets in a New Mouse Model of Coronary Artery Thrombosis
Objective: The final event leading to myocardial infarction is adhesion and activation of platelets after rupture of an atherosclerotic plaque, ending in thrombotic occlusion of the coronary artery. Imaging of imminent vessel occlusion may improve patient care. The feasibility of molecular magnetic resonance imaging (MRI) for the detection of coronary artery thrombosis in mice was examined. Materials and Methods: The left anterior descending coronary artery was exposed by lateral thoracotomy and incubated with ferric chloride to induce nonocclusive thrombosis in C57Bl/6 mice. A single chain antibody targeting ligand-induced binding sites (LIBS) of the activated glycoprotein IIb/IIIa or control antibody was conjugated to 1 μm-sized microparticles of iron oxide (MPIOs), resulting in LIBS-MPIO or control-MPIO MRI contrast agent, and injected intravenously. Hearts were subjected to histology and ex vivo MRI at 9.4 Tesla. Results: Thrombus size was comparable in mice injected with control-MPIO and LIBS-MPIO in histology. Significant binding of MPIOs to thrombi was observed in LIBS-MPIO-injected animals while no binding was observed in control animals (P < 0.05). In MRI, LIBS-MPIO binding to thrombi of the left anterior descending coronary artery resulted in significant MPIO-induced signal void compared with controls (P < 0.05). MRI signal void and the amount of bound contrast agent particles in histology showed a significant positive linear correlation (r = 0.939, P < 0.001). Conclusions: We established a new mouse model of nonocclusive coronary artery thrombosis. LIBS-MPIO contrast agent binds to activated platelets in this model, allowing molecular MRI of coronary thrombosis. This could have important implications on the timely noninvasive detection of arterial thrombosis, helping to initiate early therapeutic interventions.