Abstract

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver disease. Patients can be characterized on the NAFLD spectrum by the progressive presence of hepatic steatosis, inflammation, hepatocyte ballooning, and then fibrosis. Currently, liver biopsy remains the only test available to detect the histologic features of NAFLD, but it is limited by its invasiveness, proneness to sampling error, and potential complications. There is an ongoing clinical need for the capability to noninvasively detect, accurately stage, and reliably monitor NAFLD. The objective of this research project was to introduce a multiparametric ultrasound (mpUS) imaging approach and evaluate its use for assessing NALFD, thereby introducing a surrogate biomarker comparable to liver biopsy. The novel method combines contrast-enhanced ultrasound (CEUS), shear wave elastography (SWE), and H-scan ultrasound (US) imaging. This approach integrates information related to liver tissue perfusion, viscoelasticity, and US scatterer size. Using Sprague-Dawley rats that were fed either control or a methionine and choline deficient (MCD) diet ( $N=6$ per group), mpUS imaging was performed at week 0 (baseline), 2 and 6. Thereafter, animals were euthanized and livers excised for histological processing and analysis. In vivo mpUS results from control and diet fed animals revealed that all parametric measures were statistically different at 6 weeks. Histological results revealed the presence of steatosis and mild fibrosis in animals fed the MCD diet. Overall, mpUS imaging was shown to be a promising approach for the early assessment of NAFLD.

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