Abdominal Radiology

, Volume 44, Issue 2, pp 482–492 | Cite as

Inter-reader agreement of magnetic resonance imaging proton density fat fraction and its longitudinal change in a clinical trial of adults with nonalcoholic steatohepatitis

  • Jonathan C. Hooker
  • Gavin Hamilton
  • Charlie C. Park
  • Steven Liao
  • Tanya Wolfson
  • Soudabeh Fazeli Dehkordy
  • Cheng William Hong
  • Adrija Mamidipalli
  • Anthony Gamst
  • Rohit Loomba
  • Claude B. SirlinEmail author



To determine the inter-reader agreement of magnetic resonance imaging proton density fat fraction (PDFF) and its longitudinal change in a clinical trial of adults with nonalcoholic steatohepatitis (NASH).

Study type

We performed a secondary analysis of a placebo-controlled randomized clinical trial of a bile acid sequestrant in 45 adults with NASH. A six-echo spoiled gradient-recalled-echo magnitude-based fat quantification technique was performed at 3 T. Three independent readers measured MRI-PDFF by placing one primary and two additional regions of interest (ROIs) in each segment at both time points. Cross-sectional agreement between the three readers was evaluated using intra-class correlation coefficients (ICCs) and coefficients of variation (CV). Additionally, we used Bland–Altman analyses to examine pairwise agreement between the three readers at baseline, end of treatment (EOT), and for longitudinal change.


Using all ROIs by all readers, mean PDFF at baseline, at EOT, and mean change in PDFF was 16.1%, 16.0%, and 0.07%, respectively. The 27-ROI PDFF measurements had 0.998 ICC and 1.8% CV at baseline, 0.998 ICC and 1.8% CV at EOT, and 0.997 ICC for longitudinal change. The 9-ROI PDFF measurements had corresponding values of 0.997 and 2.6%, 0.996 and 2.4%, and 0.994. Using 27 ROIs, the magnitude of the bias between readers for whole-liver PDFF measurement ranged from 0.03% to 0.06% points at baseline, 0.01% to 0.07% points at EOT, and 0.01% to 0.02% points for longitudinal change.


Inter-reader agreement for measuring whole-liver PDFF and its longitudinal change is high. 9-ROI measurements have only slightly lower agreement than 27-ROI measurements.


Liver Inter-reader agreement Quantitative imaging biomarker Region of interest Proton density fat fraction (PDFF) Reproducibility 


Compliance with ethical standards


The project described was partially supported by the National Institutes of Health Grants K23-DK090303, R01 DK083380-01, and T32EB005970. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Conflict of interest

Jonathan C. Hooker, Dr. Gavin Hamilton, Charlie C. Park, Dr. Steven Liao, Tanya Wolfson, Dr. Soudabeh Fazeli Dehkordy, Dr. Cheng William Hong, Dr. Adrija Mamidipalli, and Dr. Anthony Gamst declare that they have no conflict of interest. Dr. Rohit Loomba has the following disclosure related to this study: Daiichi-Sankyo. Dr. Claude B. Sirlin has the following disclosures not related to this study. Industry service agreements and consultation agreements: Alexion, AstraZeneca, Bioclinica, BMS, Fibrogen, Galmed, Genzyme, Gilead, Fibrogen, Icon, Intercept, Isis, Janssen, NuSirt, Perspectum, Pfizer, Profil, Sanofi, Shire, Synageva, Tobira, Takeda, VirtualScopics.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the Institutional and/or National Research Committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.

Informed consent

Informed consent was obtained from all individual participants included in the study.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Jonathan C. Hooker
    • 1
  • Gavin Hamilton
    • 1
  • Charlie C. Park
    • 1
  • Steven Liao
    • 1
  • Tanya Wolfson
    • 2
  • Soudabeh Fazeli Dehkordy
    • 1
  • Cheng William Hong
    • 1
  • Adrija Mamidipalli
    • 1
  • Anthony Gamst
    • 2
  • Rohit Loomba
    • 3
  • Claude B. Sirlin
    • 1
    Email author
  1. 1.Liver Imaging Group, Department of RadiologyUniversity of California, San DiegoSan DiegoUSA
  2. 2.Computational and Applied Statistics Laboratory (CASL), San Diego Supercomputer Center (SDSC)University of California, San DiegoLa JollaUSA
  3. 3.Division of Epidemiology, Department of Family Medicine and Preventive MedicineUniversity of California at San DiegoLa JollaUSA

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