BACKGROUND AND AIMS: Ultrasound imaging and shear wave elastography (SWE) can be used to noninvasively stage hepatopathologies and are widespread in clinical practice. These techniques have recently been adapted for small animal use in a novel 3D in vivo imaging system capable of high-throughput automated scanning. Our goal was to evaluate the feasibility of using this imaging tool in the murine Western diet (WD) model, a highly translatable preclinical model of obesity, metabolic disease and liver fibrosis. METHODS: Female C57BL/6 mice (N = 48) were placed on WD or chow diet and imaged longitudinally for a period of 48 weeks. Imaging consisted of 3D B-mode and targeted SWE captures. Liver volume, liver echogenicity and liver stiffness were quantified from in vivo imaging data. A subset of mice was sacrificed at various timepoints (0, 12, 24 and 48 weeks) for histological workup. Correlation analysis was performed between in vivo imaging and histological measurements to determine level of agreement. RESULTS: Noninvasive imaging showed statistically significant increases in liver volume and echogenicity, but non-significant increase in liver stiffness in the WD-fed cohort, suggesting development of hepatomegaly and steatosis, but negligible fibrosis. Ex vivo analysis confirmed significant increases in liver weight, liver triglycerides and ALT, but limited increases in fibrosis corroborating noninvasive imaging results. Correlation analysis between imaging and histology demonstrated good agreement between liver volume/liver weight (R(2) = 0.85) and echogenicity/triglycerides (R(2) = 0.76). CONCLUSIONS: This study demonstrated that noninvasive ultrasound liver assessments are feasible in the WD mouse model and closely reflect the underlying pathological state of the animal. Automated ultrasound can serve as a high-throughput noninvasive screening method for preclinical liver disease research and drug development.