ObjectiveThe incidence of cardiovascular diseases (CVD) is rising rapidly worldwide. Some forms of CVD, such as stroke and heart attack, are more common among patients with certain conditions. Atherosclerosis development is a major factor underlying cardiovascular events, such as heart attack and stroke, and its early detection may prevent such events. Ultrasound imaging of carotid arteries is a useful method for diagnosis of atherosclerotic plaques; however, an automated method to classify atherosclerotic plaques for evaluation of early-stage CVD is needed. Here, we propose an automated method for classification of high-risk atherosclerotic plaque ultrasound images. MethodsFive deep learning (DL) models (VGG16, ResNet-50, GoogLeNet, XceptionNet, and SqueezeNet) were used for automated classification and the results compared with those of a machine learning (ML)-based technique, involving extraction of 23 texture features from ultrasound images and classification using a Support Vector Machine classifier. To enhance model interpretability, output gradient-weighted convolutional activation maps (GradCAMs) were generated and overlayed on original images. ResultsA series of indices, including accuracy, sensitivity, specificity, F1-score, Cohen-kappa index, and area under the curve values, were calculated to evaluate model performance. GradCAM output images allowed visualization of the most significant ultrasound image regions. The GoogLeNet model yielded the highest accuracy (98.20%). ConclusionML models may be also suitable for applications requiring low computational resource. Further, DL models could be more completely automated than ML models.