Dual-Contrast Molecular Imaging Allows Noninvasive Characterization of Myocardial Ischemia/Reperfusion Injury After Coronary Vessel Occlusion in Mice by Magnetic Resonance Imaging
Dual-Contrast Molecular Imaging Allows Noninvasive Characterization of Myocardial Ischemia/Reperfusion Injury After Coronary Vessel Occlusion in Mice by Magnetic Resonance Imaging
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DOI：
10.1161/circulationaha.113.008157
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发表时间：
2014-08-01
期刊：
影响因子：
37.8
通讯作者：
von zur Muhlen, Constantin
中科院分区：
文献类型：
--
作者：
von Elverfeldt, Dominik;Maier, Alexander;von zur Muhlen, Constantin
背景：炎症和心肌坏死在冠状动脉闭塞再通后缺血/再灌注损伤中起重要作用。检测炎症活动和心肌坏死程度本身具有重要的临床和预后意义。我们开发了一种双重、无创的成像方法，使用分子磁共振成像在体内小鼠心肌缺血和再灌注模型中进行成像。方法与结果：采用冠状动脉左前降支暂时结扎法，对10周龄C57BL/6N小鼠进行缺血再灌注损伤。活化的血小板被一种造影剂靶向，造影剂由氧化铁微粒（MPIOs）偶联单链抗体组成，该单链抗体针对活化的糖蛋白IIb/IIIa （LIBS-MPIOs）上的配体诱导结合位点（LIBS）。注射后，LIBS-MPIOs成像，晚期钆增强显示心肌坏死；这些影像学实验也在P2Y(12)（-/-）小鼠中进行。所有影像学结果均与免疫组织化学结果相关。再灌注2小时后，磁共振成像通过左冠状动脉前降支闭塞区LIBS-MPIOs引起的显著信号效应检测到活化血小板。同时，晚期钆增强可识别心肌坏死的程度。免疫组化证实，LIBS-MPIOs与再灌注心肌的微血栓结合显著。仅在P2Y(12)（-/-）小鼠中发现背景结合。结论：心肌缺血/再灌注损伤的双分子成像可以通过LIBS-MPIOs表征血小板驱动的炎症，通过晚期钆增强表征心肌坏死。这种无创成像策略在诊断和预后方面具有临床意义，并突出了分子磁共振成像在表征缺血/再灌注损伤方面的潜力。
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.