In vivo imaging of inflammation with 19F-MRI in the subacute healing phase after myocardial infarction

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The present proposal aims to non-invasively image the subacute healing phase after myocardial infarction with 19F-magnet resonance tomography (19F-MRI) based on 19F-nanoparticles in a translational animal model. Inflammation after myocardial infarction is a major determinant of myocardial healing and subsequent myocardial remodeling. In this healing process, macrophages play an important role, while they modulate inflammatory processes and organize the assembly of connective tissue. The healing process and the involved inflammatory cells are a possible target of therapeutic intervention. Thus, it is highly desirable to image and to characterize inflammation and especially macrophages as key players in the myocardial healing process after myocardial infarction.19F-MRI is a MR-technique which has already been validated in experimental inflammatory mice models in the setting of high-field MRI at 9.4 Tesla. The major advantage of this approach in comparison to other MR-contrast agents is its capability of being directly quantifiable and its high specificity due to the lack of any fluorine background in the body. Besides that, monocytes/macrophages are selectively targeted due to their phagocytic capacity. Recently, we could demonstrate the feasibility of 19F-MRI using a clinical scanner (3 Tesla) in a preclinical model of myocardial infarction in explanted pig hearts.Therefore, the present proposal has the following specific aims:1. Validation of an in vivo MRI-imaging approach, characterizing the subacute healing phase after myocardial infarction in pigs in a multiparametric manner with 19F-MRI2. Characterization of 19F-Nanoparticle uptake in monocytes of pig and man, as well as the uptake in organs of the reticulo endothelial system (RES) and in the pig heart and 3. Visualization of inflammatory cells in the subacute healing phase after reperfused and non-reperfused myocardial infarctions with MRI and validation with histology.