Molecular magnetic resonance imaging of activated platelets allows noninvasive detection of early myocarditis in mice.

Alexander Maier; Moritz Braig; Katharina Jakob; Thomas Bienert; Michaela Schäper; Annette Merkle; Carolin Wadle; Marius Menza; Irene Neudorfer; István Bojti; Peter Stachon; Daniel Duerschmied; Ingo Hilgendorf; Timo Heidt; Christoph Bode; Karlheinz Peter; Karin Klingel; Dominik von Elverfeldt; Constantin von Zur Mühlen
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.
Journal SCIENTIFIC REPORTS
ISSN 2045-2322
Published 06 Aug 2020
Volume 10
Issue 1
Pages 13211
DOI 10.1038/s41598-020-70043-9
Type Journal Article
Sponsorship NHMRC: 1185314