title: Liver histology and diffusion-weighted MRI in children with nonalcoholic fatty liver disease: A MAGNET study.
abstract: To determine potential associations between histologic features of pediatric nonalcoholic fatty liver disease (NAFLD) and estimated quantitative magnetic resonance diffusion-weighted imaging (DWI) parameters.
  
  
  
  This prospective, cross-sectional study was performed as part of the Magnetic Resonance Assessment Guiding NAFLD Evaluation and Treatment (MAGNET) ancillary study to the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN). Sixty-four children underwent a 3T DWI scan (b-values: 0, 100, and 500 s/mm2) within 180 days of a clinical liver biopsy of the right hepatic lobe. Three parameters were estimated in the right hepatic lobe: apparent diffusion coefficient (ADC), diffusivity (D), and perfusion fraction (F); the first assuming exponential decay and the latter two assuming biexponential intravoxel incoherent motion. Grading and staging of liver histology were done using the NASH CRN scoring system. Associations between histologic scores and DWI-estimated parameters were tested using multivariate linear regression.
  
  
  
  Estimated means ± standard deviations were: ADC: 1.3 (0.94-1.8) × 10-3mm2/s; D: 0.82 (0.56-1.0) × 10-3mm2/s; and F: 17 (6.0-28)%. Multivariate analyses showed ADC and D decreased with steatosis and F decreased with fibrosis (P < 0.05). Associations between DWI-estimated parameters and other histologic features were not significant: ADC: fibrosis (P = 0.12), lobular inflammation (P = 0.20), portal inflammation (P = 0.27), hepatocellular inflammation (P = 0.29), NASH (P = 0.30); D: fibrosis (P = 0.34), lobular inflammation (P = 0.84), portal inflammation (P = 0.76), hepatocellular inflammation (P = 0.38), NASH (P = 0.81); F: steatosis (P = 0.57), lobular inflammation (P = 0.22), portal inflammation (P = 0.42), hepatocellular inflammation (P = 0.59), NASH (P = 0.07).
  
  
  
  In children with NAFLD, steatosis and fibrosis have independent effects on DWI-estimated parameters ADC, D, and F. Further research is needed to determine the underlying mechanisms and clinical implications of these effects.
  
  
  
  1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1149-1158.
authors.affiliation: Liver Imaging Group, Department of Radiology, University of California, San Diego, School of Medicine, San Diego, California, USA.
authors.forename: Paul
authors.identifier: 0000-0002-2947-3894
authors.initials: P
authors.lastname: Manning
authors.affiliation: Liver Imaging Group, Department of Radiology, University of California, San Diego, School of Medicine, San Diego, California, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Murphy
authors.affiliation: Liver Imaging Group, Department of Radiology, University of California, San Diego, School of Medicine, San Diego, California, USA.
authors.forename: Kang
authors.initials: K
authors.lastname: Wang
authors.affiliation: Liver Imaging Group, Department of Radiology, University of California, San Diego, School of Medicine, San Diego, California, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Hooker
authors.affiliation: Computational and Applied Statistics Laboratory (CASL), SDSC, University of California, San Diego, La Jolla, California, USA.
authors.forename: Tanya
authors.initials: T
authors.lastname: Wolfson
authors.affiliation: Liver Imaging Group, Department of Radiology, University of California, San Diego, School of Medicine, San Diego, California, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Middleton
authors.affiliation: Department of Pediatrics, UCSD and Department of Gastroenterology, Rady Children's Hospital, San Diego, California, USA.
authors.forename: Kimberly P
authors.initials: KP
authors.lastname: Newton
authors.affiliation: Department of Pediatrics, UCSD and Department of Gastroenterology, Rady Children's Hospital, San Diego, California, USA.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Behling
authors.affiliation: Department of Pediatrics, UCSD and Department of Gastroenterology, Rady Children's Hospital, San Diego, California, USA.
authors.forename: Hannah I
authors.initials: HI
authors.lastname: Awai
authors.affiliation: Department of Pediatrics, UCSD and Department of Gastroenterology, Rady Children's Hospital, San Diego, California, USA.
authors.forename: Janis
authors.initials: J
authors.lastname: Durelle
authors.affiliation: Department of Pediatrics, UCSD and Department of Gastroenterology, Rady Children's Hospital, San Diego, California, USA.
authors.forename: Melissa N
authors.initials: MN
authors.lastname: Paiz
authors.affiliation: Department of Pediatrics, UCSD and Department of Gastroenterology, Rady Children's Hospital, San Diego, California, USA.
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Angeles
authors.affiliation: Department of Pediatrics, UCSD and Department of Gastroenterology, Rady Children's Hospital, San Diego, California, USA.
authors.forename: Diana
authors.initials: D
authors.lastname: De La Pena
authors.affiliation: Department of Medicine, UCSD, San Diego, California, USA.
authors.forename: J Allen
authors.initials: JA
authors.lastname: McCutchan
authors.affiliation: Department of Pediatrics, UCSD and Department of Gastroenterology, Rady Children's Hospital, San Diego, California, USA.
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Schwimmer
authors.affiliation: Liver Imaging Group, Department of Radiology, University of California, San Diego, School of Medicine, San Diego, California, USA.
authors.forename: Claude B
authors.initials: CB
authors.lastname: Sirlin
mesh_terms: D000293:Adolescent; D002648:Child; D003430:Cross-Sectional Studies; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D005260:Female; D006652:Histological Techniques / Q000379:methods; D006801:Humans; D008099:Liver / Q000000981:diagnostic imaging* / Q000473:pathology*; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease / Q000000981:diagnostic imaging* / Q000473:pathology*; D011446:Prospective Studies
keywords: ADC; DWI; NAFLD; QIBs; children; intravoxel incoherent motion; nonalcoholic fatty liver disease; pediatric; quantitative imaging biomarkers