Ziying Yin1, Matthew C Murphy1, Jiahui Li1, Kevin J Glaser1, Amy S Mauer2, Taofic Mounajjed3, Terry M Therneau4, Heshan Liu4, Harmeet Malhi2, Armando Manduca1,5, Richard L Ehman1, Meng Yin6. 1. Department of Radiology, Mayo Clinic, 200 First St SW, Rochester, MN, 55905, USA. 2. Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA. 3. Division of Anatomic Pathology, Mayo Clinic, Rochester, MN, USA. 4. Department of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA. 5. Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA. 6. Department of Radiology, Mayo Clinic, 200 First St SW, Rochester, MN, 55905, USA. yin.meng@mayo.edu.
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.
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 NAFLDmouse 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.
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