Prediction of nonalcoholic fatty liver disease (NAFLD) activity score (NAS) with multiparametric hepatic magnetic resonance imaging and elastography

Ziying Yin, Matthew Murphy, Jiahui Li, Kevin J. Glaser, Amy S. Mauer, Taofic Mounajjed, Terry M Therneau, Heshan Liu, Harmeet M Malhi, Armando Manduca, Richard Lorne Ehman, Meng Yin

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Abstract

Objectives: To investigate the use of MR elastography (MRE)–derived mechanical properties (shear stiffness (|G*|) and loss modulus (G″)) and MRI-derived fat fraction (FF) to predict the nonalcoholic fatty liver disease (NAFLD) activity score (NAS) in a NAFLD mouse model. Methods: Eighty-nine male mice were studied, including 64 training and 25 independent testing animals. An MRI/MRE exam and histologic evaluation were performed. Pairwise, nonparametric comparisons and multivariate analyses were used to evaluate the relationships between the three imaging parameters (FF, |G*|, and G″) and histologic features. A virtual NAS score (vNAS) was generated by combining three imaging parameters with an ordinal logistic model (OLM) and a generalized linear model (GLM). The prediction accuracy was evaluated by ROC analyses. Results: The combination of FF, |G*|, and G″ predicted NAS > 1 with excellent accuracy in both training and testing sets (AUROC > 0.84). OLM and GLM predictive models misclassified 3/54 and 6/54 mice in the training, and 1/25 and 1/25 in the testing cohort respectively, in distinguishing between “not-NASH” and “definite-NASH.” “Borderline-NASH” prediction was poorer in the training set, and no borderline-NASH mice were available in the testing set. Conclusion: This preliminary study shows that multiparametric MRI/MRE can be used to accurately predict the NAS score in a NAFLD animal model, representing a promising alternative to liver biopsy for assessing NASH severity and treatment response. Key Points: • MRE-derived liver stiffness and loss modulus and MRI-assessed fat fraction can be used to predict NAFLD activity score (NAS) in our preclinical mouse model (AUROC > 0.84 for all NAS levels greater than 1). • The overall agreement between the histological-determined NASH diagnosis and the imaging-predicted NASH diagnosis is 80–92%. • The multiparametric hepatic MRI/MRE has great potential for noninvasively assessing liver disease severity and treatment efficacy.

Original languageEnglish (US)
JournalEuropean radiology
DOIs
StatePublished - Jan 1 2019

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Elasticity Imaging Techniques
Magnetic Resonance Imaging
Liver
Fats
Linear Models
Logistic Models
Non-alcoholic Fatty Liver Disease
ROC Curve
Liver Diseases
Multivariate Analysis
Animal Models
Biopsy

Keywords

  • Elastography
  • Magnetic resonance imaging
  • Nonalcoholic fatty liver disease
  • Nonalcoholic steatohepatitis

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

@article{f08432226fb94a3b986102bb919f69ce,
title = "Prediction of nonalcoholic fatty liver disease (NAFLD) activity score (NAS) with multiparametric hepatic magnetic resonance imaging and elastography",
abstract = "Objectives: To investigate the use of MR elastography (MRE)–derived mechanical properties (shear stiffness (|G*|) and loss modulus (G″)) and MRI-derived fat fraction (FF) to predict the nonalcoholic fatty liver disease (NAFLD) activity score (NAS) in a NAFLD mouse model. Methods: Eighty-nine male mice were studied, including 64 training and 25 independent testing animals. An MRI/MRE exam and histologic evaluation were performed. Pairwise, nonparametric comparisons and multivariate analyses were used to evaluate the relationships between the three imaging parameters (FF, |G*|, and G″) and histologic features. A virtual NAS score (vNAS) was generated by combining three imaging parameters with an ordinal logistic model (OLM) and a generalized linear model (GLM). The prediction accuracy was evaluated by ROC analyses. Results: The combination of FF, |G*|, and G″ predicted NAS > 1 with excellent accuracy in both training and testing sets (AUROC > 0.84). OLM and GLM predictive models misclassified 3/54 and 6/54 mice in the training, and 1/25 and 1/25 in the testing cohort respectively, in distinguishing between “not-NASH” and “definite-NASH.” “Borderline-NASH” prediction was poorer in the training set, and no borderline-NASH mice were available in the testing set. Conclusion: This preliminary study shows that multiparametric MRI/MRE can be used to accurately predict the NAS score in a NAFLD animal model, representing a promising alternative to liver biopsy for assessing NASH severity and treatment response. Key Points: • MRE-derived liver stiffness and loss modulus and MRI-assessed fat fraction can be used to predict NAFLD activity score (NAS) in our preclinical mouse model (AUROC > 0.84 for all NAS levels greater than 1). • The overall agreement between the histological-determined NASH diagnosis and the imaging-predicted NASH diagnosis is 80–92{\%}. • The multiparametric hepatic MRI/MRE has great potential for noninvasively assessing liver disease severity and treatment efficacy.",
keywords = "Elastography, Magnetic resonance imaging, Nonalcoholic fatty liver disease, Nonalcoholic steatohepatitis",
author = "Ziying Yin and Matthew Murphy and Jiahui Li and Glaser, {Kevin J.} and Mauer, {Amy S.} and Taofic Mounajjed and Therneau, {Terry M} and Heshan Liu and Malhi, {Harmeet M} and Armando Manduca and Ehman, {Richard Lorne} and Meng Yin",
year = "2019",
month = "1",
day = "1",
doi = "10.1007/s00330-019-06076-0",
language = "English (US)",
journal = "European Radiology",
issn = "0938-7994",
publisher = "Springer Verlag",

}

TY - JOUR

T1 - Prediction of nonalcoholic fatty liver disease (NAFLD) activity score (NAS) with multiparametric hepatic magnetic resonance imaging and elastography

AU - Yin, Ziying

AU - Murphy, Matthew

AU - Li, Jiahui

AU - Glaser, Kevin J.

AU - Mauer, Amy S.

AU - Mounajjed, Taofic

AU - Therneau, Terry M

AU - Liu, Heshan

AU - Malhi, Harmeet M

AU - Manduca, Armando

AU - Ehman, Richard Lorne

AU - Yin, Meng

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Objectives: To investigate the use of MR elastography (MRE)–derived mechanical properties (shear stiffness (|G*|) and loss modulus (G″)) and MRI-derived fat fraction (FF) to predict the nonalcoholic fatty liver disease (NAFLD) activity score (NAS) in a NAFLD mouse model. Methods: Eighty-nine male mice were studied, including 64 training and 25 independent testing animals. An MRI/MRE exam and histologic evaluation were performed. Pairwise, nonparametric comparisons and multivariate analyses were used to evaluate the relationships between the three imaging parameters (FF, |G*|, and G″) and histologic features. A virtual NAS score (vNAS) was generated by combining three imaging parameters with an ordinal logistic model (OLM) and a generalized linear model (GLM). The prediction accuracy was evaluated by ROC analyses. Results: The combination of FF, |G*|, and G″ predicted NAS > 1 with excellent accuracy in both training and testing sets (AUROC > 0.84). OLM and GLM predictive models misclassified 3/54 and 6/54 mice in the training, and 1/25 and 1/25 in the testing cohort respectively, in distinguishing between “not-NASH” and “definite-NASH.” “Borderline-NASH” prediction was poorer in the training set, and no borderline-NASH mice were available in the testing set. Conclusion: This preliminary study shows that multiparametric MRI/MRE can be used to accurately predict the NAS score in a NAFLD animal model, representing a promising alternative to liver biopsy for assessing NASH severity and treatment response. Key Points: • MRE-derived liver stiffness and loss modulus and MRI-assessed fat fraction can be used to predict NAFLD activity score (NAS) in our preclinical mouse model (AUROC > 0.84 for all NAS levels greater than 1). • The overall agreement between the histological-determined NASH diagnosis and the imaging-predicted NASH diagnosis is 80–92%. • The multiparametric hepatic MRI/MRE has great potential for noninvasively assessing liver disease severity and treatment efficacy.

AB - Objectives: To investigate the use of MR elastography (MRE)–derived mechanical properties (shear stiffness (|G*|) and loss modulus (G″)) and MRI-derived fat fraction (FF) to predict the nonalcoholic fatty liver disease (NAFLD) activity score (NAS) in a NAFLD mouse model. Methods: Eighty-nine male mice were studied, including 64 training and 25 independent testing animals. An MRI/MRE exam and histologic evaluation were performed. Pairwise, nonparametric comparisons and multivariate analyses were used to evaluate the relationships between the three imaging parameters (FF, |G*|, and G″) and histologic features. A virtual NAS score (vNAS) was generated by combining three imaging parameters with an ordinal logistic model (OLM) and a generalized linear model (GLM). The prediction accuracy was evaluated by ROC analyses. Results: The combination of FF, |G*|, and G″ predicted NAS > 1 with excellent accuracy in both training and testing sets (AUROC > 0.84). OLM and GLM predictive models misclassified 3/54 and 6/54 mice in the training, and 1/25 and 1/25 in the testing cohort respectively, in distinguishing between “not-NASH” and “definite-NASH.” “Borderline-NASH” prediction was poorer in the training set, and no borderline-NASH mice were available in the testing set. Conclusion: This preliminary study shows that multiparametric MRI/MRE can be used to accurately predict the NAS score in a NAFLD animal model, representing a promising alternative to liver biopsy for assessing NASH severity and treatment response. Key Points: • MRE-derived liver stiffness and loss modulus and MRI-assessed fat fraction can be used to predict NAFLD activity score (NAS) in our preclinical mouse model (AUROC > 0.84 for all NAS levels greater than 1). • The overall agreement between the histological-determined NASH diagnosis and the imaging-predicted NASH diagnosis is 80–92%. • The multiparametric hepatic MRI/MRE has great potential for noninvasively assessing liver disease severity and treatment efficacy.

KW - Elastography

KW - Magnetic resonance imaging

KW - Nonalcoholic fatty liver disease

KW - Nonalcoholic steatohepatitis

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