Multiparametric magnetic resonance imaging/magnetic resonance elastography assesses progression and regression of steatosis, inflammation, and fibrosis in alcohol‐associated liver disease
Abstract Background Magnetic resonance imaging (MRI) and MRI‐based elastography (MRE) are the most promising noninvasive techniques in assessing liver diseases. The purpose of this study was to evaluate an advanced multiparametric imaging method for staging disease and assessing treatment response in realistic preclinical alcohol‐associated liver disease (ALD). Methods We utilized four different preclinical mouse models in our study: Model 1—mice were fed a fast‐food diet and fructose water for 48 weeks to induce nonalcoholic fatty liver disease; Model 2—mice were fed chronic‐binge ethanol (EtOH) for 10 days or 8 weeks to induce liver steatosis/inflammation. Two groups of mice were treated with interleukin‐22 at different time points to induce disease regression; Model 3—mice were administered CCl 4 for 2 to 4 weeks to establish liver fibrosis followed by 2 or 4 weeks of recovery; and Model 4—mice were administered EtOH plus CCl 4 for 12 weeks. Mouse liver imaging biomarkers including proton density fat fraction (PDFF), liver stiffness (LS), loss modulus (LM), and damping ratio (DR) were assessed. Liver and serum samples were obtained for histologic and biochemical analyses. Ordinal logistic regression and generalized linear regression analyses were used to model the severity of steatosis, inflammation, and fibrosis, and to assess the regression of these conditions. Results Multiparametric models with combinations of biomarkers (LS, LM, DR, and PDFF) used noninvasively to predict the histologic severity and regression of steatosis, inflammation, and fibrosis were highly accurate (area under the curve > 0.84 for all). A three‐parameter model that incorporates LS, DR, and ALT predicted histologic fibrosis progression ( r = 0.84, p < 0.0001) and regression ( r = 0.79, p < 0.0001) as measured by collagen content in livers. Conclusion This preclinical study provides evidence that multiparametric MRI/MRE can be used noninvasively to assess disease severity and monitor treatment response in ALD.
3D MR Elastography of Hepatocellular Carcinomas as a Potential Biomarker for Predicting Tumor Recurrence
BackgroundPreoperative prediction of tumor recurrence is important in the management of patients with hepatocellular carcinoma (HCC).PurposeTo investigate whether tumor stiffness derived by magnetic resonance elastography (MRE) could predict early recurrence of HCC after hepatic resection.Study TypeRetrospective.PopulationIn all, 99 patients with pathologically confirmed HCCs after surgical resection.Field Strength/Sequence3.0T; preoperative MRE with 60‐Hz mechanical vibrations using an active acoustic driver.AssessmentRegions of interest (ROIs) were manually drawn in the tumors to measure mean tumor stiffness. Surgical specimens were reviewed for histological grade, capsule, vascular invasion, and surgical margins. The early recurrence of HCC was defined as that occurring within 2 years after resection.Statistical TestsCox proportional hazard models were used to evaluate risk factors associated with the time to early recurrence.ResultsHCCs with recurrence had higher tumor stiffness, higher rate of advanced T stage, vascular invasion, lower rate of capsule formation, larger tumor size, higher aspartate aminotransferase (AST), and hepatitis B virus (HBV)‐DNA level and aspartate aminotransferase / alanine aminotransferase ratio (P = 0.031, 0.007, 0.01, <0.001, 0.015, 0.034, 0.01, and 0.014, respectively) than HCCs without recurrence. Vascular invasion (hazard ratio [HR] = 2.922; 95% confidence interval [CI]: [1.079, 7.914], P = 0.035) and mean tumor stiffness (HR = 1.163; 95% CI: [1.055, 1.282], P = 0.002) were risk factors associated with early recurrence. Each 1‐kPa increase in tumor stiffness was associated with a 16.3% increase in the risk for tumor recurrence.Data ConclusionThe mean stiffness of HCCs may be a useful, noninvasive, quantitative biomarker for the prediction of early HCC recurrence after hepatic resection.Level of Evidence: 4Technical Efficacy: Stage 5J. Magn. Reson. Imaging 2019;49:719–730.