Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is one of the most common chronic liver disorders worldwide and can lead to inflammation, fibrosis, and liver cancer. To better understand the impact of an unbalanced hypercaloric diet on liver phenotype in impaired autophagy, the study compared C57BL/6J wild type (WT) and MAPK15-ERK8 knockout (KO) male mice with C57BL/6J background fed for 17 weeks with "Western-type" (WD) or standard diet (SD). Liver features were monitored in vivo by high-frequency ultrasound (HFUS) using a semi-quantitative and parametric assessment of pathological changes in the parenchyma complemented by computer-aided diagnosis (CAD) methods. Liver histology was considered the reference standard. WD induced liver steatosis in both genotypes, although KO mice showed more pronounced dietary effects than WT mice. Overall, HFUS reliably detected steatosis-related parenchymal changes over time in the two mouse genotypes examined, consistent with histology. Furthermore, this study demonstrated the feasibility of extracting quantitative features from conventional B-mode ultrasound images of the liver in murine models at early clinical stages of MASLD using a computationally efficient and vendor-independent CAD method. This approach may contribute to the non-invasive characterization of genetically engineered mouse models of MASLD according to the principles of replacement, reduction, and refinement (3Rs), with interesting translational implications.