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Research Article
Non-invasive assessment of liver disease in rats using multiparametric magnetic resonance imaging: a feasibility study
Anna M. Hoy, Natasha McDonald, Ross J. Lennen, Matteo Milanesi, Amy H. Herlihy, Timothy J. Kendall, William Mungall, Michael Gyngell, Rajarshi Banerjee, Robert L. Janiczek, Philip S. Murphy, Maurits A. Jansen, Jonathan A. Fallowfield
Biology Open 2018 7: bio033910 doi: 10.1242/bio.033910 Published 2 July 2018
Anna M. Hoy
1MRC/University of Edinburgh Centre for Inflammation Research, Edinburgh EH16 4TJ, UK
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Natasha McDonald
1MRC/University of Edinburgh Centre for Inflammation Research, Edinburgh EH16 4TJ, UK
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Ross J. Lennen
2BHF/University of Edinburgh Centre for Cardiovascular Science, Edinburgh EH16 4TJ, UK
3Edinburgh Preclinical Imaging (EPI), University of Edinburgh, Edinburgh EH16 4TJ, UK
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Matteo Milanesi
4Perspectum Diagnostics, Oxford OX1 2ET, UK
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Amy H. Herlihy
4Perspectum Diagnostics, Oxford OX1 2ET, UK
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Timothy J. Kendall
1MRC/University of Edinburgh Centre for Inflammation Research, Edinburgh EH16 4TJ, UK
5Division of Pathology, University of Edinburgh, Edinburgh EH16 4SA, UK
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William Mungall
6Biomedical Research Resources, University of Edinburgh, Edinburgh EH16 4SB, UK
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Michael Gyngell
4Perspectum Diagnostics, Oxford OX1 2ET, UK
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Rajarshi Banerjee
4Perspectum Diagnostics, Oxford OX1 2ET, UK
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Robert L. Janiczek
7GlaxoSmithKline (Experimental Medicine Imaging), Stevenage SG1 2NY, UK
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Philip S. Murphy
7GlaxoSmithKline (Experimental Medicine Imaging), Stevenage SG1 2NY, UK
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Maurits A. Jansen
2BHF/University of Edinburgh Centre for Cardiovascular Science, Edinburgh EH16 4TJ, UK
3Edinburgh Preclinical Imaging (EPI), University of Edinburgh, Edinburgh EH16 4TJ, UK
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Jonathan A. Fallowfield
1MRC/University of Edinburgh Centre for Inflammation Research, Edinburgh EH16 4TJ, UK
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  • ORCID record for Jonathan A. Fallowfield
  • For correspondence: Jonathan.Fallowfield@ed.ac.uk
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  • Fig. 1.
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    Fig. 1.

    MRI assessment of hepatic fibro-inflammatory injury in rat CCl4 model. (A) Quantification of hepatic collagen content (% area of Picrosirius Red staining). (B) Representative examples of transverse liver MR T1 relaxation maps. (C) T1 relaxation quantification in rats receiving CCl4 or OO for 4 and 12 weeks. (D) Correlation between hepatic collagen content and T1 in rats receiving CCl4 and OO for 12 weeks. Data presented as mean±s.d., analyzed by unpaired t-test (*P<0.05, **P<0.01). Spearman (rs) correlation coefficient was used to examine correlations.

  • Fig. 2.
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    Fig. 2.

    MRI assessment of hepatic steatosis and steatotic inflammatory injury in rat MCD diet model. (A) Representative examples of transverse liver MR PDFF maps. (B) Quantification of Oil Red O (ORO) staining of hepatic fat. (C) Quantification of hepatic PDFF. (D-F) Correlations between hepatic PDFF and (D) histologically assessed steatosis, (E) steatotic inflammatory injury [N(m)AS] and (F) ORO staining in rats receiving MCD or control diet (N) for 4 and 8 weeks. Data presented as mean±s.d., analyzed by unpaired t-test (**P<0.01, ***P<0.001, ****P<0.0001). Spearman (rs) correlation coefficient was used to examine correlations.

  • Fig. 3.
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    Fig. 3.

    MRI assessment of hepatic steatosis and steatohepatitis in rat CCl4 model. (A) Representative examples of transverse liver MR PDFF maps. (B) Quantification of Oil Red O (ORO) staining of hepatic fat. (C) Quantification of hepatic proton density fat fraction (PDFF). (D,E) Correlations between hepatic PDFF and (D) histologically assessed ORO staining and (E) steatotic inflammatory injury [N(m)AS] in rats receiving CCl4 or olive oil (OO) for 4 and 12 weeks. Data presented as mean±s.d., analyzed by unpaired t-test (*P<0.05, **P<0.01). Spearman (rs) correlation coefficient was used to examine correlations.

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    Fig. 4.

    MRI assessment of hepatic steatosis and steatohepatitis in cilostazol-treated rats on MCD diet. Sprague-Dawley rats received MCD diet for 4 weeks plus cliostazol or vehicle for the last 2 weeks of the model. Animals were scanned at baseline and after 4 weeks. (A) Quantification of hepatic fat by morphometry based on H&E staining. (B) Steatotic inflammatory injury [N(m)AS]. (C) Representative examples of transverse liver MR proton density fat fraction (PDFF). (D) Quantification of hepatic PDFF. (E) Correlation between PDFF and steatotic inflammatory injury [N(m)AS]. Data presented as mean±s.d., analyzed by unpaired t-test. Spearman (rs) correlation coefficient was used to examine correlations.

  • Fig. 5.
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    Fig. 5.

    MRI assessment of T2*/R2* relaxation in preclinical liver injury models. (A) Representative examples of transverse liver MR T2* maps. (B) Quantification of R2* (1/T2*) in rats receiving CCl4 or olive oil (OO) for 4 and 12 weeks. (C) Quantification of R2* (1/T2*) in rats receiving MCD or control diet (N) for 4 and 8 weeks. (D) Correlation between R2* and PDFF in animals receiving CCl4 or OO injections and MCD or control diets. Data presented as mean±s.d., analyzed by unpaired t-test (****P<0.0001). Spearman (rs) correlation coefficient was used to examine correlations.

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    Fig. 6.

    Rat models of chronic liver disease. *1 rat euthanized prematurely due to poor health.

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Research Article
Non-invasive assessment of liver disease in rats using multiparametric magnetic resonance imaging: a feasibility study
Anna M. Hoy, Natasha McDonald, Ross J. Lennen, Matteo Milanesi, Amy H. Herlihy, Timothy J. Kendall, William Mungall, Michael Gyngell, Rajarshi Banerjee, Robert L. Janiczek, Philip S. Murphy, Maurits A. Jansen, Jonathan A. Fallowfield
Biology Open 2018 7: bio033910 doi: 10.1242/bio.033910 Published 2 July 2018
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Research Article
Non-invasive assessment of liver disease in rats using multiparametric magnetic resonance imaging: a feasibility study
Anna M. Hoy, Natasha McDonald, Ross J. Lennen, Matteo Milanesi, Amy H. Herlihy, Timothy J. Kendall, William Mungall, Michael Gyngell, Rajarshi Banerjee, Robert L. Janiczek, Philip S. Murphy, Maurits A. Jansen, Jonathan A. Fallowfield
Biology Open 2018 7: bio033910 doi: 10.1242/bio.033910 Published 2 July 2018

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