Early detection of fatty liver disease in mice via quantitative ultrasound

Nonalcoholic fatty liver disease (NAFLD) is estimated to have a 25-30% incidence among obese individuals and can lead to inflammation (nonalcoholic steatohepatitis, NASH) and fibrosis. While conventional ultrasound and other imaging techniques can diagnose advanced stages of fatty liver and hepatic cirrhosis (one NASH outcome), even though pathology is the gold standard, existing techniques are not currently able to detect early stages of NAFLD. The objective is to develop a method for early detection of NAFLD in humans by first examining the model-free quantitative ultrasound (QUS) parameters of livers in diet-controlled mice. Two studies were conducted, each with 25 male C57BL/6J mice; 20 fed an atherogenic (Ath) diet and 5 fed a control diet. In Study 1 (a non-QUS study), 10 mice each were fed the Ath diet for 4 and 8 weeks, respectively; there was significant liver steatosis and inflammation of the Ath-diet-fed mice. Therefore, Study 2 was conducted with reduced feeding times to moderate the Ath diet's liver effect for which 10 mice each were on the Ath diet for 2 and 4 weeks, respectively. For Study 2, liver lipids compared somewhat favorably to pathologist steatosis grades. QUS model-free parameters were functionally related to liver lipids. These preliminary findings suggest that early detection of NAFLD is feasible with QUS.