title: In vivo T2* weighted MRI visualizes cardiac lesions in murine models of acute and chronic viral myocarditis.
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 virus-induced 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Experimental Physics V, Institute of Physics, University of Wuerzburg, Wuerzburg, Germany.
authors.forename: Xavier
authors.initials: X
authors.lastname: Helluy
authors.affiliation: Department of Molecular Pathology, Institute for Pathology and Neuropathology, University Hospital Tuebingen, Tuebingen, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Sauter
authors.affiliation: Department of Experimental Physics V, Institute of Physics, University of Wuerzburg, Wuerzburg, Germany.|Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, United States of America.
authors.forename: Yu-Xiang
authors.initials: YX
authors.lastname: Ye
authors.affiliation: Research Center Magnetic-Resonance-Bavaria (MRB), Wuerzburg, Germany.
authors.forename: Gunthard
authors.initials: G
authors.lastname: Lykowsky
authors.affiliation: Research Center Magnetic-Resonance-Bavaria (MRB), Wuerzburg, Germany.
authors.forename: Jakob
authors.initials: J
authors.lastname: Kreutner
authors.affiliation: Department of Cardiology and Angiology, University Hospital Münster, Münster, Germany.
authors.forename: Ali
authors.initials: A
authors.lastname: Yilmaz
authors.affiliation: Comprehensive Heart Failure Centre (CHFC) and Interdisziplinary Bank of Biomaterials and Data (ibdw), University Hospital of Würzburg, Würzburg, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Jahns
authors.affiliation: Institute of Pharmacology and Toxicology, University of Würzburg, Würzburg, Germany.
authors.forename: Valerie
authors.initials: V
authors.lastname: Boivin
authors.affiliation: Department of Molecular Pathology, Institute for Pathology and Neuropathology, University Hospital Tuebingen, Tuebingen, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Kandolf
authors.affiliation: Research Center Magnetic-Resonance-Bavaria (MRB), Wuerzburg, Germany.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Jakob
authors.affiliation: Research Center Magnetic-Resonance-Bavaria (MRB), Wuerzburg, Germany.|Fraunhofer Institute for Integrated Circuits, Magnetic Resonance and X-Ray Imaging Department, Würzburg, Germany.
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Hiller
authors.affiliation: Department of Molecular Pathology, Institute for Pathology and Neuropathology, University Hospital Tuebingen, Tuebingen, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Klingel
mesh_terms: D000208:Acute Disease; D000818:Animals; D001706:Biopsy; D002908:Chronic Disease; D004195:Disease Models, Animal; D008279:Magnetic Resonance Imaging / Q000379:methods; D051379:Mice; D009205:Myocarditis / Q000000981:diagnostic imaging* / Q000473:pathology / Q000821:virology*; D009206:Myocardium / Q000473:pathology / Q000648:ultrastructure; D013997:Time Factors