A multiparametric MRI protocol for PDFF, ADC, T1 and T2: applications in the NAFLD and NASH disease spectrum evaluated using multiple mouse models

Purpose – Nonalcoholic fatty liver disease (NAFLD) and its subtype, Nonalcoholic steatohepatitis (NASH), are highly prevalent diseases which are characterized by diagnostic limitations and unmet therapeutic need. The disease spectrum in the liver includes hepatic steatosis, inflammation, and fibrosis. In this study we investigate a multiparametric MRI protocol across multiple research standard mouse models of NAFLD and NASH in order to provide biomarkers which can noninvasively and objectively quantify disease progression or regression longitudinallyMethods – Male C57BL/6 mice were subjected to diet- and chemical-based induction of NAFLD and NASH for 12 weeks and imaged at specified time points throughout the disease time course. At each timepoint, a sequence of MRI protocols were acquired at 11.7T which enabled the quantification of MRI-PDFF, ADC, T1, and T2 in the liver. Results – Liver PDFF was found to increase in all experimental diet groups versus control mice on a standard diet over the 12 week time course. In contrast, liver ADC decreased in all experimental diet groups. Liver T1 relaxation time was found to decrease and liver T2 relaxation time increased in all experimental groups. Conclusions – We conclude that PDFF and T1 relaxation time are accurate and robust biomarkers in the quantification of hepatic steatosis. Additionally, ADC may be a viable biomarker in the detection of liver fibrosis while T2 relaxation time has indications in liver inflammation. Our multiparametric MRI protocol has implications in diagnosis, clinical trial stratification, and therapeutic advance