title: Stereological Analysis of Liver Biopsy Histology Sections as a Reference Standard for Validating Non-Invasive Liver Fat Fraction Measurements by MRI.
abstract: OBJECTIVE
  Validation of non-invasive methods of liver fat quantification requires a reference standard. However, using standard histopathology assessment of liver biopsies is problematical because of poor repeatability. We aimed to assess a stereological method of measuring volumetric liver fat fraction (VLFF) in liver biopsies and to use the method to validate a magnetic resonance imaging method for measurement of VLFF.
  
  
  METHODS
  VLFFs were measured in 59 subjects (1) by three independent analysts using a stereological point counting technique combined with the Delesse principle on liver biopsy histological sections and (2) by three independent analysts using the HepaFat-Scan® technique on magnetic resonance images of the liver. Bland Altman statistics and intraclass correlation (IC) were used to assess the repeatability of each method and the bias between the methods of liver fat fraction measurement.
  
  
  RESULTS
  Inter-analyst repeatability coefficients for the stereology and HepaFat-Scan® methods were 8.2 (95% CI 7.7-8.8)% and 2.4 (95% CI 2.2-2.5)% VLFF respectively. IC coefficients were 0.86 (95% CI 0.69-0.93) and 0.990 (95% CI 0.985-0.994) respectively. Small biases (≤3.4%) were observable between two pairs of analysts using stereology while no significant biases were observable between any of the three pairs of analysts using HepaFat-Scan®. A bias of 1.4±0.5% VLFF was observed between the HepaFat-Scan® method and the stereological method.
  
  
  CONCLUSIONS
  Repeatability of the stereological method is superior to the previously reported performance of assessment of hepatic steatosis by histopathologists and is a suitable reference standard for validating non-invasive methods of measurement of VLFF.
authors: School of Physics, The University of Western Australia, Crawley, Western Australia, Australia.
authors: Tim G
authors: TG
authors: St Pierre
authors: School of Physics, The University of Western Australia, Crawley, Western Australia, Australia.|Resonance Health Ltd, Claremont, Western Australia, Australia.
authors: Michael J
authors: MJ
authors: House
authors: Resonance Health Ltd, Claremont, Western Australia, Australia.
authors: Sander J
authors: SJ
authors: Bangma
authors: Resonance Health Ltd, Claremont, Western Australia, Australia.
authors: Wenjie
authors: W
authors: Pang
authors: Resonance Health Ltd, Claremont, Western Australia, Australia.
authors: Andrew
authors: A
authors: Bathgate
authors: School of Medicine and Pharmacology, The University of Western Australia, Crawley, Western Australia, Australia.|Department of Gastroenterology, Fremantle Hospital, Fremantle, Western Australia, Australia.
authors: Eng K
authors: EK
authors: Gan
authors: School of Medicine and Pharmacology, The University of Western Australia, Crawley, Western Australia, Australia.|Department of Gastroenterology, Fremantle Hospital, Fremantle, Western Australia, Australia.|Faculty of Health Sciences, Curtin University of Technology, Bentley, Western Australia, Australia.
authors: Oyekoya T
authors: OT
authors: Ayonrinde
authors: Department of Pathology, The University of Melbourne, Melbourne, Victoria, Australia.
authors: Prithi S
authors: PS
authors: Bhathal
authors: Centre for Liver Disease Research, School of Medicine Translational Research Institute, The University of Queensland, Woolloongabba, Queensland, Australia.
authors: Andrew
authors: A
authors: Clouston
authors: School of Medicine and Pharmacology, The University of Western Australia, Crawley, Western Australia, Australia.|Department of Gastroenterology, Fremantle Hospital, Fremantle, Western Australia, Australia.|Faculty of Health Sciences, Curtin University of Technology, Bentley, Western Australia, Australia.|Institute for Immunology & Infectious Diseases, Murdoch University, Murdoch, Western Australia, Australia.
authors: John K
authors: JK
authors: Olynyk
authors: School of Medicine and Pharmacology, The University of Western Australia, Crawley, Western Australia, Australia.|Liver Transplant Unit, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.
authors: Leon A
authors: LA
authors: Adams
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D005234:Fatty Liver / Q000473:pathology* / Q000601:surgery; D005260:Female; D006652:Histological Techniques / Q000379:methods*; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods / Q000592:standards*; D008107:Liver Diseases / Q000473:pathology* / Q000601:surgery; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D012015:Reference Standards; D055815:Young Adult