Clinical and Translational Research
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 21, 2021; 27(7): 609-623
Published online Feb 21, 2021. doi: 10.3748/wjg.v27.i7.609
Quantitative multiparametric magnetic resonance imaging can aid non-alcoholic steatohepatitis diagnosis in a Japanese cohort
Kento Imajo, Louise Tetlow, Andrea Dennis, Elizabeth Shumbayawonda, Sofia Mouchti, Timothy J Kendall, Eve Fryer, Shogi Yamanaka, Yasushi Honda, Takaomi Kessoku, Yuji Ogawa, Masato Yoneda, Satoru Saito, Catherine Kelly, Matt D Kelly, Rajarshi Banerjee, Atsushi Nakajima
Kento Imajo, Yasushi Honda, Takaomi Kessoku, Yuji Ogawa, Satoru Saito, Atsushi Nakajima, Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine, Yokohama 236-0004, Japan
Louise Tetlow, Andrea Dennis, Elizabeth Shumbayawonda, Sofia Mouchti, Catherine Kelly, Matt D Kelly, Rajarshi Banerjee, Innovation, Perspectum, Oxford OX4 2LL, United Kingdom
Timothy J Kendall, Centre for Inflammation Research, University of Edinburgh, Edinburgh, United Kingdom, Edinburgh EH16 4TJ, United Kingdom
Eve Fryer, Department of Cellular Pathology, Oxford University Hospitals NHS Foundation Trust, Oxford OX3 9DU, United Kingdom
Shogi Yamanaka, Anatomic and Clinical Pathology Department, Yokohoma City University Hospital, Yokohoma 236-0004, Japan
Masato Yoneda, Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan
Author contributions: Imajo K and Nakajima A developed the study concept, protocols and initiated the project; Kelly MD and Banerjee R assisted in the further development of the protocol and drafting the clinical study protocol; Imajo K, Nakajima A, Fryer E, Kendall TJ, Yamanaka S, Honda Y, Kessoku T, Ogawa Y, Yoneda M and Saito S contributed to the data collection; Tetlow L, Dennis AM, Shumbayawonda E to the data analysis; Imajo K, Tetlow L, Nakajima A, Dennis AM, Shumbayawonda E, Kelly C, Kelly MD and Banerjee R drafted and completed the manuscript. All authors contributed to the final manuscript.
Institutional review board statement: The study was conducted in accordance with the ethical principles of the Declaration of Helsinki 2013, was approved by the Ethics Committee of Yokohama City University Hospital and was registered as a clinical trial (UMIN Clinical Trials Registry: UMIN000026145).
Conflict-of-interest statement: Perspectum Ltd is a privately funded commercial enterprise that develops medical devices to address unmet clinical needs, including LiverMultiScan®. LT, ES, AD, MK are all employees of Perspectum. RB is CEO of Perspectum. KI, and AN have no relevant disclosures to this study. TK and EF undertake consultancy work for Perspectum.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Andrea Dennis, PhD, Research Scientist, Innovation, Perspectum, Gemini One, 5520 John Smith Drive, Oxford OX4 2LL, United Kingdom.
Received: August 28, 2020
Peer-review started: August 28, 2020
First decision: November 3, 2020
Revised: November 17, 2020
Accepted: December 28, 2020
Article in press: December 28, 2020
Published online: February 21, 2021

Non-invasive assessment of non-alcoholic steatohepatitis (NASH) is increasing in desirability due to the invasive nature and costs associated with the current form of assessment; liver biopsy. Quantitative multiparametric magnetic resonance imaging (mpMRI) to measure liver fat (proton density fat fraction) and fibroinflammatory disease [iron-corrected T1 (cT1)], as well as elastography techniques [vibration-controlled transient elastography (VCTE) liver stiffness measure], magnetic resonance elastography (MRE) and 2D Shear-Wave elastography (SWE) to measure stiffness and fat (controlled attenuated parameter, CAP) are emerging alternatives which could be utilised as safe surrogates to liver biopsy.


To evaluate the agreement of non-invasive imaging modalities with liver biopsy, and their subsequent diagnostic accuracy for identifying NASH patients.


From January 2019 to February 2020, Japanese patients suspected of NASH were recruited onto a prospective, observational study and were screened using non-invasive imaging techniques; mpMRI with LiverMultiScan®, VCTE, MRE and 2D-SWE. Patients were subsequently biopsied, and samples were scored by three independent pathologists. The diagnostic performances of the non-invasive imaging modalities were assessed using area under receiver operating characteristic curve (AUC) with the median of the histology scores as the gold standard diagnoses. Concordance between all three independent pathologists was further explored using Krippendorff’s alpha (a) from weighted kappa statistics.


N = 145 patients with mean age of 60 (SD: 13 years.), 39% females, and 40% with body mass index ≥ 30 kg/m2 were included in the analysis. For identifying patients with NASH, MR liver fat and cT1 were the strongest performing individual measures (AUC: 0.80 and 0.75 respectively), and the mpMRI metrics combined (cT1 and MR liver fat) were the overall best non-invasive test (AUC: 0.83). For identifying fibrosis ≥ 1, MRE performed best (AUC: 0.97), compared to VCTE-liver stiffness measure (AUC: 0.94) and 2D-SWE (AUC: 0.94). For assessment of steatosis ≥ 1, MR liver fat was the best performing non-invasive test (AUC: 0.92), compared to controlled attenuated parameter (AUC: 0.75). Assessment of the agreement between pathologists showed that concordance was best for steatosis (a = 0.58), moderate for ballooning (a = 0.40) and fibrosis (a = 0.40), and worst for lobular inflammation (a = 0.11).


Quantitative mpMRI is an effective alternative to liver biopsy for diagnosing NASH and non-alcoholic fatty liver, and thus may offer clinical utility in patient management.

Keywords: Corrected T1, Fibro-inflammation, Non-invasive imaging, Non-alcoholic steatohepatitis, Multiparametric magnetic resonance imaging, Non-alcoholic fatty liver disease

Core Tip: There is growing interest in the utility of non-invasive tests in the management of non-alcoholic steatohepatitis (NASH). We explored how magnetic resonance imaging technology can stratify patients with simple fatty liver disease from those with NASH. Our results showed that quantitative magnetic resonance imaging derived metrics showed the strongest correlations to the histological pathological components of NASH with very few technical failures. We also observed very high levels of inter-reader disagreement in histopathological biopsy reads, highlighting the pressing need for alternative diagnostic tests for NASH. Our work therefore supports the use of this non-invasive technology in day-to-day practice.