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Cardiac-induced liver deformation as a measure of liver stiffness using dynamic imaging without magnetization tagging—preclinical proof-of-concept, clinical translation, reproducibility and feasibility in patients with cirrhosis

  • Hepatobiliary
  • Published:
Abdominal Radiology Aims and scope Submit manuscript

Abstract

Purpose

MR elastography and magnetization-tagging use liver stiffness (LS) measurements to diagnose fibrosis but require physical drivers, specialist sequences and post-processing. Here we evaluate non-rigid registration of dynamic two-dimensional cine MRI images to measure cardiac-induced liver deformation (LD) as a measure of LS by (i) assessing preclinical proof-of-concept, (ii) clinical reproducibility and inter-reader variability, (iii) the effects of hepatic hemodynamic changes and (iv) feasibility in patients with cirrhosis.

Methods

Sprague–Dawley rats (n = 21 bile duct ligated (BDL), n = 17 sham-operated controls) and fasted patients with liver cirrhosis (n = 11) and healthy volunteers (HVs, n = 10) underwent spoiled gradient-echo short-axis cardiac cine MRI studies at 9.4 T (rodents) and 3.0 T (humans). LD measurements were obtained from intrahepatic sub-cardiac regions-of-interest close to the diaphragmatic margin. One-week reproducibility and prandial stress induced hemodynamic changes were assessed in healthy volunteers.

Results

Normalized LD was higher in BDL (1.304 ± 0.062) compared with sham-operated rats (1.058 ± 0.045, P = 0.0031). HV seven-day reproducibility Bland–Altman (BA) limits-of-agreement (LoAs) were ± 0.028 a.u. and inter-reader variability BA LoAs were ± 0.030 a.u. Post-prandial LD increases were non-significant (+ 0.0083 ± 0.0076 a.u., P = 0.3028) and uncorrelated with PV flow changes (r = 0.42, p = 0.2219). LD measurements successfully obtained from all patients were not significantly higher in cirrhotics (0.102 ± 0.0099 a.u.) compared with HVs (0.080 ± 0.0063 a.u., P = 0.0847).

Conclusion

Cardiac-induced LD is a conceptually reasonable approach from preclinical studies, measurements demonstrate good reproducibility and inter-reader variability, are less likely to be affected by hepatic hemodynamic changes and are feasible in patients with cirrhosis.

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Data availability

The authors confirm that the data supporting the findings of this study are available within the article. Raw data were generated at the UCL Centre for Medical Imaging/UCL Centre for Advanced Biomedical Imaging. Derived data supporting the findings of this study are available from the corresponding author on request.

Code availability

Cardiac cine MRI data were analyzed using GIQuant® (Motilent, London, UK).

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Funding

Wellcome Trust Clinical Research Training Fellowship (Grant WT092186). National Institute of Health Research University College London Hospitals Biomedical Research Centre.

Author information

Authors and Affiliations

  1. Division of Medicine, Centre for Medical Imaging, University College London (UCL), London, UK

    Manil D. Chouhan, Heather E. Fitzke, David Atkinson, Steve Halligan, Alex Menys & Stuart A. Taylor

  2. Wingate Institute of Neurogastroenterology, Neuroscience and Trauma, Queen Mary University of London (QMUL), London, UK

    Heather E. Fitzke

  3. Department of Medical Physics, University College London Hospitals NHS Trust, London, UK

    Alan Bainbridge

  4. Division of Medicine, Institute for Liver and Digestive Health, University College London (UCL), London, UK

    Nathan Davies & Rajeshwar P. Mookerjee

  5. Division of Medicine, Centre for Advanced Biomedical Imaging, University College London (UCL), London, UK

    Mark F. Lythgoe

  6. Motilent, London, UK

    Alex Menys

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  1. Manil D. Chouhan
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Contributions

MDC—guarantor of integrity of the entire study, study concepts and design, literature research, clinical studies, experimental preclinical studies, data analysis, statistical analysis, manuscript preparation, manuscript editing. HEF—study concepts and design, experimental preclinical studies, data analysis, manuscript editing. AB—clinical studies, experimental preclinical studies, data analysis. DA—clinical studies, experimental preclinical studies, data analysis, manuscript editing. SH—statistical analysis, manuscript editing. ND—experimental preclinical studies. MFL—experimental preclinical studies. RPM—clinical studies, experimental preclinical studies, manuscript editing. AM—study concepts and design, experimental preclinical studies, clinical studies, data analysis, manuscript editing. SAT—study concepts and design, manuscript editing.

Corresponding author

Correspondence to Manil D. Chouhan.

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Conflict of interest

Manil D Chouhan—no relevant conflict of interest or competing interest to declare. Heather E Fitzke—BBBSRC funded work placements with Motilent Ltd in 2018 and 2020 (BB/S508019/1). No other relevant conflict of interest or competing interest to declare. Alan Bainbridge, David Atkinson, Steve Halligan, Nathan Davies, Mark F Lythgoe, Rajeshwar P Mookerjee have no relevant conflict of interest or competing interest to declare. Alex Menys—is the CEO of Motilent. No other relevant conflict of interest or competing interest to declare. Stuart A Taylor—has share options in Motilent and is a consultant at Alimentiv. No other relevant conflict of interest or competing interest to declare.

Ethical approval

Preclinical-approval obtained from the Animal Care Ethical Committee of University College London.

Clinical-Research Ethics Committee (Joint RNOH/IOMS, Reference Number 08/H0724/35) approval was obtained.

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Written consent obtained from all clinical study participants.

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Written consent obtained from all clinical study participants, with implied consent from all authors.

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Chouhan, M.D., Fitzke, H.E., Bainbridge, A. et al. Cardiac-induced liver deformation as a measure of liver stiffness using dynamic imaging without magnetization tagging—preclinical proof-of-concept, clinical translation, reproducibility and feasibility in patients with cirrhosis. Abdom Radiol 46, 4660–4670 (2021). https://doi.org/10.1007/s00261-021-03168-8

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