Abstract 10425: A Platelet-specific Magnetic Resonance Imaging Contrast Agent Allows Detection of Thrombosis in a New Mouse Model of Coronary Artery Thrombosis
Introduction: The final event leading to myocardial infarction is adhesion and activation of platelets after rupture of an atherosclerotic plaque. Platelets then aggregate, culminating in thrombotic occlusion of the coronary artery. Imaging of imminent vessel occlusion may improve patient care. Here, we examined the feasibility of molecular magnetic resonance imaging (MRI) for the detection of coronary artery thrombosis in mice.
Methods: The left anterior descending coronary artery (LAD) was exposed by lateral thoracotomy and incubated with ferric chloride to induce non-occlusive thrombosis in intubated male C57Bl/6 mice. A single chain antibody targeting ligand-induced binding sites (LIBS) of activated glycoprotein IIb/IIIa or control antibody was conjugated to 1um-sized microparticles of iron oxide (MPIOs), Resultsing in LIBS-MPIO or control-MPIO contrast agent, and injected intravenously. Hearts were either harvested and stained for platetets in histology or subjected to magnetic resonance imaging (MRI) at 9.4 T.
Results: Incubation of the LAD with ferric chloride resulted in comparable sizes of arterial thrombosis in mice injected with control-MPIO and LIBS-MPIO (12.3±5.2% vs. 12.4±7.4%; n=8). In sham-operated animals, only negligible platelet adhesion was observed. Sham-operated mice and animals with control-MPIO-injection showed no binding of MPIOs on thrombus surface, whereas in LIBS-MPIO-injected animals significant binding of MPIOs was observed (2.8±1.8 *103mm-2; p<0.05). LIBS-MPIO binding to LAD thrombi resulted in a hypo-intense signal in MRI.
Conclusion: In this study, we established a new mouse model of coronary artery thrombosis. LIBS-MPIO binds to activated platelets in this model, allowing molecular MRI of coronary thrombosis in mice. This could have important implications on the timely detection of arterial thrombosis, helping to initiate early therapeutic interventions.
- © 2010 by American Heart Association, Inc.