title: Histological validation of cardiac magnetic resonance analysis of regional and diffuse interstitial myocardial fibrosis.
abstract: OBJECTIVE
  Myocardial fibrosis is fundamental in the pathogenesis of heart failure. Late gadolinium enhancement (LGE) with cardiac magnetic resonance (CMR) imaging is commonly assumed to represent myocardial fibrosis; however, comparative human histological data are limited, especially in non-ischaemic cardiac disease. Diffuse interstitial myocardial fibrosis is increasingly recognized as central in the pathogenesis of cardiomyopathy and can be quantified using newer CMR techniques such as T1 mapping. We evaluated the relationship of CMR assessment of regional and diffuse fibrosis with human histology.
  
  
  RESULTS
  Eleven patients on the waiting list for heart transplantation (43.5 ± 7.6 years, 64% male) and eight patients undergoing surgical myectomy for obstructive hypertrophic cardiomyopathy (57.1 ± 8.6 years, 63% male) were recruited and underwent CMR prior to cardiac transplantation or myectomy. Quantification of fibrosis in explanted hearts using digitally analysed Masson-trichrome-stained slides was validated against picrosirius red-stained slides analysed using Image J, with an excellent correlation (R = 0.95, P < 0.0001). Significant correlations were observed between LGE and histological fibrosis across a range of signal intensity thresholds in the explanted hearts (range: 2-10 standard deviations above reference myocardium), with maximal accuracy at a threshold of 6 SD (R = 0.91, P < 0.001). Assessment of interstitial myocardial fibrosis with post-contrast T1 times demonstrated a significant correlation on both segmental (R = -0.64, P = 0.002) and per-patient (R = -0.78, P = 0.003) analyses.
  
  
  CONCLUSIONS
  CMR provides accurate, non-invasive assessment of regional myocardial fibrosis using LGE, while diffuse interstitial myocardial fibrosis is accurately assessed with post-contrast T1 mapping.
authors.affiliation: Department of Cardiovascular Medicine, Alfred Hospital, Melbourne, Australia Baker IDI Heart and Diabetes Institute, Melbourne, Australia l.iles@alfred.org.au.
authors.forename: Leah M
authors.initials: LM
authors.lastname: Iles
authors.affiliation: Department of Cardiovascular Medicine, Alfred Hospital, Melbourne, Australia Baker IDI Heart and Diabetes Institute, Melbourne, Australia.
authors.forename: Andris H
authors.initials: AH
authors.lastname: Ellims
authors.affiliation: Department of Anatomical Pathology, Alfred Hospital, Melbourne, Australia.
authors.forename: Huw
authors.initials: H
authors.lastname: Llewellyn
authors.affiliation: Department of Cardiovascular Medicine, Alfred Hospital, Melbourne, Australia Baker IDI Heart and Diabetes Institute, Melbourne, Australia.
authors.forename: James L
authors.initials: JL
authors.lastname: Hare
authors.affiliation: Department of Cardiovascular Medicine, Alfred Hospital, Melbourne, Australia Baker IDI Heart and Diabetes Institute, Melbourne, Australia.
authors.forename: David M
authors.initials: DM
authors.lastname: Kaye
authors.affiliation: Department of Anatomical Pathology, Alfred Hospital, Melbourne, Australia.
authors.forename: Catriona A
authors.initials: CA
authors.lastname: McLean
authors.affiliation: Department of Cardiovascular Medicine, Alfred Hospital, Melbourne, Australia Baker IDI Heart and Diabetes Institute, Melbourne, Australia.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Taylor
mesh_terms: D000328:Adult; D001707:Biopsy, Needle; D006348:Cardiac Surgical Procedures / Q000379:methods; D002312:Cardiomyopathy, Hypertrophic / Q000175:diagnosis / Q000473:pathology* / Q000601:surgery*; D018450:Disease Progression; D004719:Endomyocardial Fibrosis / Q000175:diagnosis / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D019786:Gadolinium DTPA; D016027:Heart Transplantation / Q000379:methods; D006801:Humans; D007150:Immunohistochemistry; D019028:Magnetic Resonance Imaging, Cine / Q000379:methods / Q000592:standards*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011856:Radiographic Image Enhancement / Q000379:methods; D018570:Risk Assessment; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D014850:Waiting Lists
chemical_list: D019786:Gadolinium DTPA
keywords: Cardiomyopathy; Magnetic resonance imaging; Pathology; myocardial fibrosis