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Abstract
MRI sensitivity for diagnosis and localization of early myocarditis is limited, although it is of central clinical interest. The aim of this project was to test a contrast agent targeting activated platelets consisting of microparticles of iron oxide (MPIO) conjugated to a single-chain antibody directed against ligand-induced binding sites (LIBS) of activated glycoprotein IIb/IIIa (= LIBS-MPIO). Myocarditis was induced by subcutaneous injection of an emulsion of porcine cardiac myosin and complete Freund’s adjuvant in mice. 3D 7 T in-vivo MRI showed focal signal effects in LIBS-MPIO injected mice 2 days after induction of myocarditis, whereas in control-MPIO injected mice no signal was detectable. Histology confirmed CD41-positive staining, indicating platelet involvement in myocarditis in mice as well as in human specimens with significantly higher LIBS-MPIO binding compared to control-MPIO in both species. Quantification of the myocardial MRI signal confirmed a signal decrease after LIBS-MPIO injection and significant less signal in comparison to control-MPIO injection. These data show, that platelets are involved in inflammation during the course of myocarditis in mice and humans. They can be imaged non-invasively with LIBS-MPIO by molecular MRI at an early time point of the inflammation in mice, which is a valuable approach for preclinical models and of interest for both diagnostic and prognostic purposes.
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Details
1 University of Freiburg, Department of Cardiology and Angiology I, Heart Center Freiburg University, Faculty of Medicine, Freiburg, Germany (GRID:grid.5963.9)
2 University of Freiburg, Department of Radiology, Medical Physics, Medical Center - University of Freiburg, Faculty of Medicine, Freiburg, Germany (GRID:grid.5963.9)
3 Baker Heart & Diabetes Institute, Melbourne, Australia (GRID:grid.1051.5) (ISNI:0000 0000 9760 5620)
4 University Hospital Tuebingen, Cardiopathology, Institute for Pathology and Neuropathology, Tuebingen, Germany (GRID:grid.411544.1) (ISNI:0000 0001 0196 8249)