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

Sci Rep. 2020 Aug 6;10(1):13211. doi: 10.1038/s41598-020-70043-9.

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.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Blood Platelets*
  • Cardiomyopathies / diagnostic imaging
  • Contrast Media / administration & dosage
  • Disease Models, Animal
  • Early Diagnosis
  • Humans
  • Integrin beta3 / metabolism
  • Magnetic Resonance Imaging*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Myocarditis / diagnostic imaging*
  • Platelet Activation
  • Platelet Membrane Glycoprotein IIb / metabolism

Substances

  • Contrast Media
  • Integrin beta3
  • Platelet Membrane Glycoprotein IIb