title: Histological validation of cardiovascular magnetic resonance T1 mapping markers of myocardial fibrosis in paediatric heart transplant recipients.
abstract: BACKGROUND
  Adverse fibrotic remodeling is detrimental to myocardial health and a reliable method for monitoring the development of fibrotic remodeling may be desirable during the follow-up of patients after heart transplantation (HTx). Quantification of diffuse myocardial fibrosis with cardiovascular magnetic resonance (CMR) has been increasingly applied and validated histologically in adult patients with heart disease. However, comparisons of CMR findings with histological fibrosis burden in children are lacking. This study aimed to compare native T1 times and extracellular volume fraction (ECV) derived from CMR with the degree of collagen on endomyocardial biopsy (EmBx), and to investigate the association between myocardial fibrosis and clinical as well as functional markers in children after HTx.
  
  
  METHODS
  EmBx and CMR were performed on the same day. All specimens were stained with picrosirius red. The collagen volume fraction (CVF) was calculated as ratio of stained collagen area to total myocardial area on EmBx. Native T1 values and ECV were measured by CMR on a mid-ventricular short axis slice, using a modified look-locker inversion recovery approach.
  
  
  RESULTS
  Twenty patients (9.9 ± 6.2 years of age; 9 girls) after HTx were prospectively enrolled, at a median of 1.3 years (0.02-12.6 years) post HTx, and compared to 24 controls (13.9 ± 2.6 years of age; 12 girls). The mean histological CVF was 10.0 ± 3.4%. Septal native T1 times and ECV were higher in HTx patients compared to controls (1008 ± 32 ms vs 979 ± 24 ms, p < 0.005 and 0.30 ± 0.03 vs 0.22 ± 0.03, p < 0.0001, respectively). CVF showed a moderate correlation with native T1 (r = 0.53, p < 0.05) as well as ECV (r = 0.46, p < 0.05). Native T1 time, but not ECV and CVF, correlated with ischemia time (r = 0.46, p < 0.05).
  
  
  CONCLUSIONS
  CMR-derived fibrosis markers correlate with histological degree of fibrosis on EmBx in children after HTx. Further, native T1 times are associated with longer ischemia times.
authors.affiliation: Division of Cardiology, Department of Paediatrics, Labatt Family Heart Centre, The Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto, ON, M5G 1X8, Canada.
authors.forename: Seiko
authors.initials: S
authors.lastname: Ide
authors.affiliation: Division of Cardiology, Department of Paediatrics, Labatt Family Heart Centre, The Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto, ON, M5G 1X8, Canada.
authors.forename: Eugenie
authors.initials: E
authors.lastname: Riesenkampff
authors.affiliation: Division of Pathology, Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
authors.forename: David A
authors.initials: DA
authors.lastname: Chiasson
authors.affiliation: Division of Cardiology, Department of Paediatrics, Labatt Family Heart Centre, The Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto, ON, M5G 1X8, Canada.
authors.forename: Anne I
authors.initials: AI
authors.lastname: Dipchand
authors.affiliation: Division of Cardiology, Department of Paediatrics, Labatt Family Heart Centre, The Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto, ON, M5G 1X8, Canada.|Division of Cardiology, Department of Paediatrics, Stollery Children's Hospital, Edmonton, AB, Canada.
authors.forename: Paul F
authors.initials: PF
authors.lastname: Kantor
authors.affiliation: Division of Cardiology, Department of Paediatrics, Labatt Family Heart Centre, The Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto, ON, M5G 1X8, Canada.
authors.forename: Rajiv R
authors.initials: RR
authors.lastname: Chaturvedi
authors.affiliation: Division of Cardiology, Department of Paediatrics, Labatt Family Heart Centre, The Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto, ON, M5G 1X8, Canada.|Department of Diagnostic Imaging, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
authors.forename: Shi-Joon
authors.initials: SJ
authors.lastname: Yoo
authors.affiliation: Division of Cardiology, Department of Paediatrics, Labatt Family Heart Centre, The Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto, ON, M5G 1X8, Canada. lars.grosse-wortmann@sickkids.ca.|Department of Diagnostic Imaging, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada. lars.grosse-wortmann@sickkids.ca.
authors.forename: Lars
authors.identifier: http://orcid.org/0000-0002-1185-3805
authors.initials: L
authors.lastname: Grosse-Wortmann
mesh_terms: D000293:Adolescent; D000367:Age Factors; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D009202:Cardiomyopathies / Q000000981:diagnostic imaging* / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003094:Collagen / Q000032:analysis; D003287:Contrast Media / Q000008:administration & dosage; D005260:Female; D005355:Fibrosis; D019786:Gadolinium DTPA / Q000008:administration & dosage; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D007223:Infant; D019028:Magnetic Resonance Imaging, Cine; D008297:Male; D009206:Myocardium / Q000737:chemistry / Q000473:pathology*; D015588:Observer Variation; D010865:Pilot Projects; D011237:Predictive Value of Tests; D011446:Prospective Studies; D015203:Reproducibility of Results; D012720:Severity of Illness Index; D066027:Transplant Recipients; D016896:Treatment Outcome; D020257:Ventricular Remodeling
chemical_list: D015415:Biomarkers; D003287:Contrast Media; D003094:Collagen; D019786:Gadolinium DTPA
keywords: Cardiovascular magnetic resonance; Diffuse myocardial fibrosis; Extracellular volume fraction; Histological validation; Native T1 time; Paediatric heart transplantation