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

doi:10.1242/bio.033910

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

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Abstract / Description of output

Non-invasive quantitation of liver disease using multiparametric MRI could refine clinical care pathways, trial design and preclinical drug development. The aim of the study was to evaluate the use of multiparametric MRI in experimental models of liver disease. Liver injury was induced in rats using 4 or 12 weeks carbon tetrachloride (CCl4) intoxication and 4 or 8 weeks methionine and choline deficient (MCD) diet. Liver MRI was performed using a 7.0 Tesla small animal scanner at baseline and specified timepoints after liver injury. Multiparametric liver MRI parameters (T1 mapping, T2* mapping and proton density fat fraction (PDFF)) were correlated with gold standard histopathological measures. Mean hepatic T1 increased significantly in rats treated with CCl4 for 12 weeks compared to controls (1122±78 ms vs. 959±114 ms; d=162.7, 95% CI (11.92, 313.4), P=0.038) and correlated strongly with histological collagen content (rs=0.717, P=0.037). In MCD diet-treated rats, hepatic PDFF correlated strongly with histological fat content (rs=0.819, P<0.0001), steatosis grade (rs=0.850, P<0.0001) and steatohepatitis score (rs=0.818, P<0.0001). Although there was minimal histological iron, progressive fat accumulation in MCD diet-treated liver significantly shortened T2*. In preclinical models, quantitative MRI markers correlated with histopathological assessments, especially for fatty liver disease. Validation in longitudinal studies is required.

Original language	English
Pages (from-to)	bio033910
Journal	Biology Open
Volume	7
Issue number	7
DOIs	https://doi.org/10.1242/bio.033910
Publication status	Published - 15 Jul 2018

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Hoy, A. M., Mcdonald, N., Lennen, R. J., Milanesi, M., Herlihy, A. H., Kendall, T. J., Mungall, W., Gyngell, M., Banerjee, R., Janiczek, R. L., Murphy, P. S., Jansen, M. A., & Fallowfield, J. A. (2018). Non-invasive assessment of liver disease in rats using multiparametric magnetic resonance imaging: a feasibility study. Biology Open, 7(7), bio033910. https://doi.org/10.1242/bio.033910

@article{6d84c80c618943c8905377726971ba55,

title = "Non-invasive assessment of liver disease in rats using multiparametric magnetic resonance imaging: a feasibility study",

abstract = "Non-invasive quantitation of liver disease using multiparametric MRI could refine clinical care pathways, trial design and preclinical drug development. The aim of the study was to evaluate the use of multiparametric MRI in experimental models of liver disease. Liver injury was induced in rats using 4 or 12 weeks carbon tetrachloride (CCl4) intoxication and 4 or 8 weeks methionine and choline deficient (MCD) diet. Liver MRI was performed using a 7.0 Tesla small animal scanner at baseline and specified timepoints after liver injury. Multiparametric liver MRI parameters (T1 mapping, T2* mapping and proton density fat fraction (PDFF)) were correlated with gold standard histopathological measures. Mean hepatic T1 increased significantly in rats treated with CCl4 for 12 weeks compared to controls (1122±78 ms vs. 959±114 ms; d=162.7, 95% CI (11.92, 313.4), P=0.038) and correlated strongly with histological collagen content (rs=0.717, P=0.037). In MCD diet-treated rats, hepatic PDFF correlated strongly with histological fat content (rs=0.819, P<0.0001), steatosis grade (rs=0.850, P<0.0001) and steatohepatitis score (rs=0.818, P<0.0001). Although there was minimal histological iron, progressive fat accumulation in MCD diet-treated liver significantly shortened T2*. In preclinical models, quantitative MRI markers correlated with histopathological assessments, especially for fatty liver disease. Validation in longitudinal studies is required. ",

author = "Hoy, {Anna M.} and Natasha Mcdonald and Lennen, {Ross J.} and Matteo Milanesi and Herlihy, {Amy H.} and Kendall, {Timothy J.} and William Mungall and Michael Gyngell and Rajarshi Banerjee and Janiczek, {Robert L.} and Murphy, {Philip S.} and Jansen, {Maurits A.} and Fallowfield, {Jonathan A.}",

year = "2018",

month = jul,

day = "15",

doi = "10.1242/bio.033910",

language = "English",

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Hoy, AM, Mcdonald, N, Lennen, RJ, Milanesi, M, Herlihy, AH, Kendall, TJ, Mungall, W, Gyngell, M, Banerjee, R, Janiczek, RL, Murphy, PS, Jansen, MA & Fallowfield, JA 2018, 'Non-invasive assessment of liver disease in rats using multiparametric magnetic resonance imaging: a feasibility study', Biology Open, vol. 7, no. 7, pp. bio033910. https://doi.org/10.1242/bio.033910

TY - JOUR

T1 - Non-invasive assessment of liver disease in rats using multiparametric magnetic resonance imaging: a feasibility study

AU - Hoy, Anna M.

AU - Mcdonald, Natasha

AU - Lennen, Ross J.

AU - Milanesi, Matteo

AU - Herlihy, Amy H.

AU - Kendall, Timothy J.

AU - Mungall, William

AU - Gyngell, Michael

AU - Banerjee, Rajarshi

AU - Janiczek, Robert L.

AU - Murphy, Philip S.

AU - Jansen, Maurits A.

AU - Fallowfield, Jonathan A.

PY - 2018/7/15

Y1 - 2018/7/15

N2 - Non-invasive quantitation of liver disease using multiparametric MRI could refine clinical care pathways, trial design and preclinical drug development. The aim of the study was to evaluate the use of multiparametric MRI in experimental models of liver disease. Liver injury was induced in rats using 4 or 12 weeks carbon tetrachloride (CCl4) intoxication and 4 or 8 weeks methionine and choline deficient (MCD) diet. Liver MRI was performed using a 7.0 Tesla small animal scanner at baseline and specified timepoints after liver injury. Multiparametric liver MRI parameters (T1 mapping, T2* mapping and proton density fat fraction (PDFF)) were correlated with gold standard histopathological measures. Mean hepatic T1 increased significantly in rats treated with CCl4 for 12 weeks compared to controls (1122±78 ms vs. 959±114 ms; d=162.7, 95% CI (11.92, 313.4), P=0.038) and correlated strongly with histological collagen content (rs=0.717, P=0.037). In MCD diet-treated rats, hepatic PDFF correlated strongly with histological fat content (rs=0.819, P<0.0001), steatosis grade (rs=0.850, P<0.0001) and steatohepatitis score (rs=0.818, P<0.0001). Although there was minimal histological iron, progressive fat accumulation in MCD diet-treated liver significantly shortened T2*. In preclinical models, quantitative MRI markers correlated with histopathological assessments, especially for fatty liver disease. Validation in longitudinal studies is required.

AB - Non-invasive quantitation of liver disease using multiparametric MRI could refine clinical care pathways, trial design and preclinical drug development. The aim of the study was to evaluate the use of multiparametric MRI in experimental models of liver disease. Liver injury was induced in rats using 4 or 12 weeks carbon tetrachloride (CCl4) intoxication and 4 or 8 weeks methionine and choline deficient (MCD) diet. Liver MRI was performed using a 7.0 Tesla small animal scanner at baseline and specified timepoints after liver injury. Multiparametric liver MRI parameters (T1 mapping, T2* mapping and proton density fat fraction (PDFF)) were correlated with gold standard histopathological measures. Mean hepatic T1 increased significantly in rats treated with CCl4 for 12 weeks compared to controls (1122±78 ms vs. 959±114 ms; d=162.7, 95% CI (11.92, 313.4), P=0.038) and correlated strongly with histological collagen content (rs=0.717, P=0.037). In MCD diet-treated rats, hepatic PDFF correlated strongly with histological fat content (rs=0.819, P<0.0001), steatosis grade (rs=0.850, P<0.0001) and steatohepatitis score (rs=0.818, P<0.0001). Although there was minimal histological iron, progressive fat accumulation in MCD diet-treated liver significantly shortened T2*. In preclinical models, quantitative MRI markers correlated with histopathological assessments, especially for fatty liver disease. Validation in longitudinal studies is required.

U2 - 10.1242/bio.033910

DO - 10.1242/bio.033910

M3 - Article

SN - 2046-6390

VL - 7

SP - bio033910

JO - Biology Open

JF - Biology Open

IS - 7

ER -

Non-invasive assessment of liver disease in rats using multiparametric magnetic resonance imaging: a feasibility study

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