AbstractLiver disease is increasing in prevalence across the globe. We present here a multiparametric ultrasound (mpUS) imaging approach for assessing nonalcoholic fatty liver disease (NALFD). This study was performed using rats (N = 21) that were fed either a control or methionine and choline deficient (MCD) diet. A mpUS imaging approach that includes H-scan ultrasound (US), shear wave elastography, and contrast-enhanced US measurements were then performed at 0 (baseline), 2, and 6 weeks. Thereafter, animals were euthanized and livers excised for histological processing. A support vector machine (SVM) was used to find a decision plane that classifies normal and fatty liver conditions. In vivo mpUS results from control and MCD diet fed animals reveal that all mpUS measures were different at week 6 (P < 0.05). Principal component analysis (PCA) showed that the H-scan US data contributed the highest percentage to the classification among the mpUS measurements. The SVM resulted in 100% accuracy for classification of normal and high fat livers and 92% accuracy for classification of normal, low fat, and high fat livers. Histology findings found considerable steatosis in the MCD diet fed animals. This study suggests that mpUS examinations have the potential to provide a comprehensive estimation of the main components of early stage NAFLD.