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. (Circulation. 2014;130:676-687.)

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Purpose 19F‐MRI is gaining widespread interest for cell tracking and quantification of immune and inflammatory cells in vivo. Different fluorinated compounds can be discriminated based on their characteristic MR spectra, allowing in vivo imaging of multiple 19F compounds simultaneously, so‐called multicolor 19F‐MRI. We introduce a method for multicolor 19F‐MRI using an iterative sparse deconvolution method to separate different 19F compounds and remove chemical shift artifacts arising from multiple resonances. Methods The method employs cycling of the readout gradient direction to alternate the spatial orientation of the off‐resonance chemical shift artifacts, which are subsequently removed by iterative sparse deconvolution. Noise robustness and separation was investigated by numerical simulations. Mixtures of fluorinated oils (PFCE and PFOB) were measured on a 7T MR scanner to identify the relation between 19F signal intensity and compound concentration. The method was validated in a mouse model after intramuscular injection of fluorine probes, as well as after intravascular injection. Results Numerical simulations show efficient separation of 19F compounds, even at low signal‐to‐noise ratio. Reliable chemical shift artifact removal and separation of PFCE and PFOB signals was achieved in phantoms and in vivo. Signal intensities correlated excellently to the relative 19F compound concentrations (r−2 = 0.966/0.990 for PFOB/PFCE). Conclusions The method requires minimal sequence adaptation and is therefore easily implemented on different MRI systems. Simulations, phantom experiments, and in‐vivo measurements in mice showed effective separation and removal of chemical shift artifacts below noise level. We foresee applicability for simultaneous in‐vivo imaging of 19F‐containing fluorine probes or for detection of 19F‐labeled cell populations.