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

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 dire...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7413393/
https://www.ncbi.nlm.nih.gov/pubmed/32764735
http://dx.doi.org/10.1038/s41598-020-70043-9
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author 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
author_facet 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
author_sort Maier, Alexander
collection PubMed
description 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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spelling pubmed-74133932020-08-10 Molecular magnetic resonance imaging of activated platelets allows noninvasive detection of early myocarditis in mice 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 Sci Rep Article 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. Nature Publishing Group UK 2020-08-06 /pmc/articles/PMC7413393/ /pubmed/32764735 http://dx.doi.org/10.1038/s41598-020-70043-9 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
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
Molecular magnetic resonance imaging of activated platelets allows noninvasive detection of early myocarditis in mice
title Molecular magnetic resonance imaging of activated platelets allows noninvasive detection of early myocarditis in mice
title_full Molecular magnetic resonance imaging of activated platelets allows noninvasive detection of early myocarditis in mice
title_fullStr Molecular magnetic resonance imaging of activated platelets allows noninvasive detection of early myocarditis in mice
title_full_unstemmed Molecular magnetic resonance imaging of activated platelets allows noninvasive detection of early myocarditis in mice
title_short Molecular magnetic resonance imaging of activated platelets allows noninvasive detection of early myocarditis in mice
title_sort molecular magnetic resonance imaging of activated platelets allows noninvasive detection of early myocarditis in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7413393/
https://www.ncbi.nlm.nih.gov/pubmed/32764735
http://dx.doi.org/10.1038/s41598-020-70043-9
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