Molecular magnetic resonance imaging of activated platelets allows noninvasive detection of early myocarditis in mice Conference Paper uri icon

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.

authors

  • Maier, Alexander
  • Braig, Moritz
  • Jakob, Katharina
  • Bienert, Thomas
  • Schäper, Michaela
  • Merkle, Annette
  • Wadle, Carolin
  • Menza, Marius
  • Neudorfer, Irene
  • Bojti, István
  • Stachon, Peter
  • Duerschmied, Daniel
  • Hilgendorf, Ingo
  • Heidt, Timo
  • Bode, Christoph
  • Peter, Karlheinz
  • Klingel, Karin
  • von Elverfeldt, Dominik
  • von zur Mühlen, Constantin

publication date

  • December 2020