title: Histological Validation of measurement of diffuse interstitial myocardial fibrosis by myocardial extravascular volume fraction from Modified Look-Locker imaging (MOLLI) T1 mapping at 3 T.
abstract: BACKGROUND
  Gadolinium (Gd) Extracellular volume fraction (ECV) by Cardiovascular Magnetic Resonance (CMR) has been proposed as a non-invasive method for assessment of diffuse myocardial fibrosis. Yet only few studies used 3 T CMR to measure ECV, and the accuracy of ECV measurements at 3 T has not been established. Therefore the aims of the present study were to validate measurement of ECV by MOLLI T1 mapping by 3 T CMR against fibrosis measured by histopathology. We also evaluated the recently proposed hypothesis that native-T1 mapping without contrast injection would be sufficient to detect fibrosis.
  
  
  METHODS
  31 patients (age = 58 ± 17 years, 77% men) with either severe aortic stenosis (n = 12) severe aortic regurgitation (n = 9) or severe mitral regurgitation (n = 10), all free of coronary artery disease, underwent 3 T-CMR with late gadolinium enhancement (LGE) and pre- and post-contrast MOLLI T1 mapping and ECV computation, prior to valve surgery. LV biopsies were performed at the time of surgery, a median 13 [1-30] days later, and stained with picrosirius red. Pre-, and post-contrast T1 values, ECV, and amount of LGE were compared against magnitude of fibrosis by histopathology by Pearson correlation coefficients.
  
  
  RESULTS
  The average amount of interstitial fibrosis by picrosirius red staining in biopsy samples was 6.1 ± 4.3%. ECV computed from pre-post contrast MOLLI T1 time changes was 28.9 ± 5.5%, and correlated (r = 0.78, p < 0.001) strongly with the magnitude of histological fibrosis. By opposition, neither amount of LGE (r = 0.17, p = 0.36) nor native pre-contrast myocardial T1 time (r = -0.18, p = 0.32) correlated with fibrosis by histopathology.
  
  
  CONCLUSIONS
  ECV determined by 3 T CMR T1 MOLLI images closely correlates with histologically determined diffuse interstitial fibrosis, providing a non-invasive estimation for quantification of interstitial fibrosis in patients with valve diseases. By opposition, neither non-contrast T1 times nor the amount of LGE were indicative of the magnitude of diffuse interstitial fibrosis measured by histopathology.
authors.affiliation: Division of Cardiology, Department of Cardiovascular Diseases, Cliniques Universitaires St. Luc UCL, Av Hippocrate 10 / 2806, B-1200, Woluwe St. Lambert, Belgium. christophe.demeester@uclouvain.be.|Pôle de Recherche Cardiovasculaire (CARD), Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain, Brussels, Belgium. christophe.demeester@uclouvain.be.
authors.forename: Christophe
authors.initials: C
authors.lastname: de Meester de Ravenstein
authors.affiliation: Division of Cardiology, Department of Cardiovascular Diseases, Cliniques Universitaires St. Luc UCL, Av Hippocrate 10 / 2806, B-1200, Woluwe St. Lambert, Belgium. caroline.bouzin@uclouvain.be.|Pôle de Recherche Cardiovasculaire (CARD), Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain, Brussels, Belgium. caroline.bouzin@uclouvain.be.
authors.forename: Caroline
authors.initials: C
authors.lastname: Bouzin
authors.affiliation: Division of Cardiology, Department of Cardiovascular Diseases, Cliniques Universitaires St. Luc UCL, Av Hippocrate 10 / 2806, B-1200, Woluwe St. Lambert, Belgium. siham.lazam@uclouvain.be.|Pôle de Recherche Cardiovasculaire (CARD), Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain, Brussels, Belgium. siham.lazam@uclouvain.be.
authors.forename: Siham
authors.initials: S
authors.lastname: Lazam
authors.affiliation: Division of Cardiology, Department of Cardiovascular Diseases, Cliniques Universitaires St. Luc UCL, Av Hippocrate 10 / 2806, B-1200, Woluwe St. Lambert, Belgium. jamila.boulif@uclouvain.be.|Pôle de Recherche Cardiovasculaire (CARD), Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain, Brussels, Belgium. jamila.boulif@uclouvain.be.
authors.forename: Jamila
authors.initials: J
authors.lastname: Boulif
authors.affiliation: Division of Cardiology, Department of Cardiovascular Diseases, Cliniques Universitaires St. Luc UCL, Av Hippocrate 10 / 2806, B-1200, Woluwe St. Lambert, Belgium. amzulescum@yahoo.com.|Pôle de Recherche Cardiovasculaire (CARD), Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain, Brussels, Belgium. amzulescum@yahoo.com.
authors.forename: Mihaela
authors.initials: M
authors.lastname: Amzulescu
authors.affiliation: Division of Cardiology, Department of Cardiovascular Diseases, Cliniques Universitaires St. Luc UCL, Av Hippocrate 10 / 2806, B-1200, Woluwe St. Lambert, Belgium. julie.melchior@gmail.com.|Pôle de Recherche Cardiovasculaire (CARD), Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain, Brussels, Belgium. julie.melchior@gmail.com.
authors.forename: Julie
authors.initials: J
authors.lastname: Melchior
authors.affiliation: Division of Cardiology, Department of Cardiovascular Diseases, Cliniques Universitaires St. Luc UCL, Av Hippocrate 10 / 2806, B-1200, Woluwe St. Lambert, Belgium. agnes.pasquet@uclouvain.be.|Pôle de Recherche Cardiovasculaire (CARD), Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain, Brussels, Belgium. agnes.pasquet@uclouvain.be.
authors.forename: Agnès
authors.initials: A
authors.lastname: Pasquet
authors.affiliation: Division of Cardiology, Department of Cardiovascular Diseases, Cliniques Universitaires St. Luc UCL, Av Hippocrate 10 / 2806, B-1200, Woluwe St. Lambert, Belgium. david.vancraeynest@uclouvain.be.|Pôle de Recherche Cardiovasculaire (CARD), Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain, Brussels, Belgium. david.vancraeynest@uclouvain.be.
authors.forename: David
authors.initials: D
authors.lastname: Vancraeynest
authors.affiliation: Division of Cardiology, Department of Cardiovascular Diseases, Cliniques Universitaires St. Luc UCL, Av Hippocrate 10 / 2806, B-1200, Woluwe St. Lambert, Belgium. anne-catherine.pouleur@uclouvain.be.|Pôle de Recherche Cardiovasculaire (CARD), Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain, Brussels, Belgium. anne-catherine.pouleur@uclouvain.be.
authors.forename: Anne-Catherine
authors.initials: AC
authors.lastname: Pouleur
authors.affiliation: Division of Cardiology, Department of Cardiovascular Diseases, Cliniques Universitaires St. Luc UCL, Av Hippocrate 10 / 2806, B-1200, Woluwe St. Lambert, Belgium. jean-louis.vanoverschelde@uclouvain.be.|Pôle de Recherche Cardiovasculaire (CARD), Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain, Brussels, Belgium. jean-louis.vanoverschelde@uclouvain.be.
authors.forename: Jean-Louis J
authors.initials: JL
authors.lastname: Vanoverschelde
authors.affiliation: Division of Cardiology, Department of Cardiovascular Diseases, Cliniques Universitaires St. Luc UCL, Av Hippocrate 10 / 2806, B-1200, Woluwe St. Lambert, Belgium. Bernhard.gerber@uclouvain.be.|Pôle de Recherche Cardiovasculaire (CARD), Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain, Brussels, Belgium. Bernhard.gerber@uclouvain.be.
authors.forename: Bernhard L
authors.initials: BL
authors.lastname: Gerber
mesh_terms: D000328:Adult; D000368:Aged; D001022:Aortic Valve Insufficiency / Q000473:pathology* / Q000503:physiopathology; D001024:Aortic Valve Stenosis / Q000473:pathology* / Q000503:physiopathology; D001706:Biopsy; D003287:Contrast Media; D005355:Fibrosis; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D008944:Mitral Valve Insufficiency / Q000473:pathology* / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology*; D009942:Organometallic Compounds; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D012720:Severity of Illness Index
chemical_list: D003287:Contrast Media; D009942:Organometallic Compounds; C090600:gadobutrol