Liver disease is increasing in numbers and relevance across the globe. This disease causes no noticeable symptoms in many cases. After diagnosis, the costs associated with medical care are very high. Patients can be characterized on the nonalcoholic fatty liver disease (NAFLD) spectrum based on the progressive presence of steatosis (i.e. abnormal accumulation of fat within the liver), inflammation, ballooning, and then hepatic fibrosis. Despite the rapid growth and prevalence, the only therapy to treat NAFLD are lifestyle modifications, such as diet and exercise. While the pharmaceutical industry is actively pursuing the discovery and development of candidate drug therapies to address this unmet medical need, there is an urgent clinical need for the ability to noninvasively detect, accurately stage, and reliably monitor NAFLD. To that end, the goal of this research project is to develop a system and method for multiparametric ultrasound (mpUS) imaging of nonalcoholic fatty liver disease (NAFLD) including early pathology progression. Our preliminary findings strongly suggest that a single mpUS test that combines steatosis, ballooning, and inflammation information has the potential to provide a comprehensive estimation of the main components of early stage NAFLD. The main innovation of the proposed research project lies in the implicit link between biophysical models of NAFLD with these coordinated mpUS measurements. The first objective of this project is to develop an integrated ultrasound system and method for performing mpUS imaging. Then we will optimize this new imaging system in healthy rat liver. Lastly, we will evaluate mpUS imaging with a rat model of NAFLD that mirrors disease progression in humans. Here we will also optimize a biophysical model and longitudinal performance in the decision of NAFLD progression. If successful, this research will introduce and validate a safe, cost-effective mpUS imaging technology that can noninvasively detect, accurately stage, and reliably monitor NAFLD.