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A portable single-sided magnetic-resonance sensor for the grading of liver steatosis and fibrosis

Nature Biomedical Engineering volume 5, pages 240–251 (2021)Cite this article

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Abstract

Low-cost non-invasive diagnostic tools for staging the progression of non-alcoholic chronic liver failure from fatty liver disease to steatohepatitis are unavailable. Here, we describe the development and performance of a portable single-sided magnetic-resonance sensor for grading liver steatosis and fibrosis using diffusion-weighted multicomponent T2 relaxometry. In a diet-induced mouse model of non-alcoholic fatty liver disease, the sensor achieved overall accuracies of 92% (Cohen’s kappa, κ = 0.89) and 86% (κ = 0.78) in the ex vivo grading of steatosis and fibrosis, respectively. Localization of the measurements in living mice through frequency-dependent spatial encoding led to an overall accuracy of 87% (κ = 0.81) for the grading of steatosis. In human liver samples, the sensor graded steatosis with an overall accuracy of 93% (κ = 0.88). The use of T2 relaxometry as a sensitive measure in fully automated low-cost magnetic-resonance devices at the point of care would alleviate the accessibility and cost limits of magnetic-resonance imaging for diagnosing liver disease and assessing liver health before liver transplantation.

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Fig. 1: A portable MR sensor can accurately quantify fat content.
Fig. 2: A diet-induced model of NAFLD/NASH leads to progressive steatosis followed by fibrosis in mouse livers.
Fig. 3: The portable MR sensor accurately stages steatosis and fibrosis using multicomponent T2 relaxometry analysis of excised livers.
Fig. 4: The portable MR sensor accurately stages steatosis from excised human livers.
Fig. 5: The portable MR sensor accurately stages steatosis in vivo using multicomponent T2 relaxometry.

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Data availability

The main data supporting the results in this study are available within the paper and its Supplementary Information. The raw and analysed datasets generated during the study are too large to be publicly shared, yet they are available for research purposes from the corresponding author on reasonable request.

Code availability

All code used for the analysis of data generated during the study is available from the corresponding author on reasonable request.

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Acknowledgements

We thank staff at the Koch Institute Swanson Biotechnology Center for technical support, specifically W. Huang and V. Spanoudaki at Animal Imaging and Preclinical Testing and K. Cormier at Histology; A. Warren, K. Nayak, M. Rosen, E. Adalsteinsson, S. Carrasco, K. Subramanyam, M. Cotler, E. Rousseau and K. Ramadi for discussions; staff at the New England Donor Services and the patients and families that made this study possible. This work was supported in part by the Koch Institute Support (core) grant no. P30-CA14051 from the National Cancer Institute, the National Institutes of Health grant nos. R01DK096075 and R01DK107875, and National Science Foundation (ATP-Bio 1941543). A.B. was supported by a Fannie & John Hertz Foundation Graduate Fellowship and a National Science Foundation Graduate Fellowship.

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Author notes

  1. These authors contributed equally: Ashvin Bashyam, Chris J. Frangieh.

Authors and Affiliations

  1. David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA

    Ashvin Bashyam, Chris J. Frangieh, Jeremy Sogo & Michael J. Cima

  2. Electrical Engineering & Computer Science, Massachusetts Institute of Technology, Cambridge, MA, USA

    Ashvin Bashyam, Chris J. Frangieh & Jeremy Sogo

  3. Division of Transplantation, Department of Surgery, Massachusetts General Hospital, Boston, MA, USA

    Siavash Raigani & Heidi Yeh

  4. Department of Microbiology and Immunobiology, Division of Immunology, Harvard Medical School, Boston, MA, USA

    Roderick T. Bronson

  5. Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Boston, MA, USA

    Korkut Uygun

  6. Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA

    Dennis A. Ausiello

  7. Center for Assessment Technology and Continuous Health, Massachusetts General Hospital, Boston, MA, USA

    Dennis A. Ausiello

  8. Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA

    Michael J. Cima

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Contributions

A.B. constructed the portable MR sensor. A.B. and C.J.F. characterized the portable MR sensor, performed all of the experiments and wrote the manuscript. J.S. performed ex vivo experiments. A.B. prepared figures. A.B., C.J.F. and M.J.C. designed the experiments and interpreted results. A.B., C.J.F., S.R. and M.J.C. edited the manuscript. R.T.B. conducted pathology analysis of all tissues. M.J.C., D.A.A., H.Y. and K.U. supervised the research.

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Correspondence to Michael J. Cima.

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Competing interests

A.B. and M.J.C. are inventors on a patent application (US20180306879) submitted by MIT that describes the design of the permanent magnet array within the portable MR sensor. K.U. has a financial interest in Organ Solutions, a company that is focused on developing organ preservation technology. These interests are managed by the Mass General Brigham in accordance with their conflict of interest policies.

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Supplementary Figs. 1–15, Table 1, discussion, methods and references.

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Bashyam, A., Frangieh, C.J., Raigani, S. et al. A portable single-sided magnetic-resonance sensor for the grading of liver steatosis and fibrosis. Nat Biomed Eng 5, 240–251 (2021). https://doi.org/10.1038/s41551-020-00638-0

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