In vivo T2∗ weighted MRI visualizes cardiac lesions in murine models of acute and chronic viral myocarditis

Helluy X., Sauter M., Ye Y., Lykowsky G., Kreutner J., Yilmaz A., Jahns R., Boivin V., Kandolf R., Jakob P., Hiller K., Klingel K.

Research article (journal) | Peer reviewed

Abstract

Objective Acute and chronic forms of myocarditis are mainly induced by virus infections. As a consequence of myocardial damage and inflammation dilated cardiomyopathy and chronic heart failure may develop. The gold standard for the diagnosis of myocarditis is endomyocardial biopsies which are required to determine the etiopathogenesis of cardiac inflammatory processes. However, new non-invasive MRI techniques hold great potential in visualizing cardiac non-ischemic inflammatory lesions at high spatial resolution, which could improve the investigation of the pathophysiology of viral myocarditis. Results Here we present the discovery of a novel endogenous T2∗ MRI contrast of myocardial lesions in murine models of acute and chronic CVB3 myocarditis. The evaluation of infected hearts ex vivo and in vivo by 3D T2w and T2∗w MRI allowed direct localization of virusinduced myocardial lesions without any MRI tracer or contrast agent. T2∗w weighted MRI is able to detect both small cardiac lesions of acute myocarditis and larger necrotic areas at later stages of chronic myocarditis, which was confirmed by spatial correlation of MRI hypointensity in myocardium with myocardial lesions histologically. Additional in vivo and ex vivo MRI analysis proved that the contrast mechanism was due to a strong paramagnetic tissue alteration in the vicinity of myocardial lesions, effectively pointing towards iron deposits as the primary contributor of contrast. The evaluation of the biological origin of the MR contrast by specific histological staining and transmission electron microscopy revealed that impaired iron metabolism primarily in mitochondria caused iron deposits within necrotic myocytes, which induces strong magnetic susceptibility in myocardial lesions and results in strong T2∗ contrast. Conclusion This T2∗w MRI technique provides a fast and sensitive diagnostic tool to determine the patterns and the severity of acute and chronic enteroviral myocarditis and the precise localization of tissue damage free of MR contrast agents.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Details about the publication

JournalPloS one (PLoS One)
Volume12
Issue3
StatusPublished
Release year2017
Language in which the publication is writtenEnglish
DOI10.1371/journal.pone.0172084
Link to the full texthttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85014585249&origin=inward

Authors from the University of Münster

Yilmaz, Ali
Department for Cardiovascular Medicine