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Imaging Non-alcoholic Fatty Liver Disease Model Using H-1 and F-19 MRI

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Abstract

Purpose

We explore the use of intravenously delivered perfluorocarbon (PFC) nanoemulsion and 19F MRI for detecting inflammation in a mouse model of non-alcoholic fatty liver disease (NAFLD). Correlative studies of 1H-based liver proton density fat fraction (PDFF) and T1 measurements and histology are also evaluated.

Procedures

C57BL/6 mice were fed standard or high-fat diet (HFD) for 6 weeks to induce NAFLD. 1H MRI measurements of PDFF and T1 relaxation time were performed at baseline to assess NAFLD onset prior to administration of a PFC nanoemulsion to enable 19F MRI of liver PFC uptake. 1H and 19F MRI biomarkers were acquired at 2, 21, and 42 days post-PFC to assess changes. Histopathology of liver tissue was performed at experimental endpoint.

Results

Significant increases in liver volume, PDFF, and total PFC uptake were noted in HFD mice compared to Std diet mice. Liver fluorine density and T1 relaxation time were significantly reduced in HFD mice.

Conclusions

We demonstrated longitudinal quantification of multiple MRI biomarkers of disease in NAFLD mice. The changes in liver PFC uptake in HFD mice were compared with healthy mice that suggests that 19F MRI may be a viable biomarker of liver pathology.

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Data Availability

Data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

We thank Hongyan Xu for biology assistance and Benjamin Leach for critical reading of the manuscript.

Funding

Funding for ETA was provided by National Institutes of Health (NIH) grants R01-EB024015, R01-CA139579, and Bristol-Meyers Squibb.

Author information

Authors and Affiliations

  1. Department of Radiology, University of California, 9500 Gilman Dr. #0695, La Jolla, San Diego, CA, 92093-0695, USA

    Deanne Lister, Claude B. Sirlin & Eric T. Ahrens

  2. Department of Biology, University of California, La Jolla, San Diego, CA, USA

    Gabrielle Blizard

  3. Department of Pathology, University of California, La Jolla, San Diego, CA, USA

    Mojgan Hosseini

  4. Department of Family Medicine and Public Health, University of California, La Jolla, San Diego, CA, USA

    Karen Messer

  5. Bristol-Meyers Squibb, San Diego, CA, USA

    Jeremy Wellen

Authors
  1. Deanne Lister
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  2. Gabrielle Blizard
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  3. Mojgan Hosseini
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  4. Karen Messer
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  5. Jeremy Wellen
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  6. Claude B. Sirlin
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  7. Eric T. Ahrens
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Contributions

D.L. conducted animal studies, collected and analyzed MRI data, and wrote initial draft. G.B. performed pulse sequence development, data analysis, and helped write draft. M.H. was responsible for histopathological analyses and manuscript editing. K.M. assisted with statistical analyses. J.W. provided experimental design and edited the manuscript. C.S. helped analyze data and write manuscript. E.A. conceptualized project, assisted with MRI experiments, and wrote final copy of manuscript.

Corresponding author

Correspondence to Eric T. Ahrens.

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The authors declare no competing interests.

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Lister, D., Blizard, G., Hosseini, M. et al. Imaging Non-alcoholic Fatty Liver Disease Model Using H-1 and F-19 MRI. Mol Imaging Biol 25, 443–449 (2023). https://doi.org/10.1007/s11307-022-01798-y

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  • DOI: https://doi.org/10.1007/s11307-022-01798-y

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