Methods and systems are described for assessing a vessel obstruction. The methods and systems obtain a volumetric image dataset of a myocardium and at least one coronary vessel, wherein the myocardium comprises muscular tissue of the heart. A three-dimensional (3D) image corresponding to a coronary vessel of interest is created from the volumetric image dataset. Feature data that represents features of both the myocardium and the coronary vessel of interest is generated. At least some of the feature data is determined by a first machine learning-based model based on the 3D image. A second machine learning-based model is used to determine at least one parameter based on the feature data, wherein the at least one parameter represents functionally significant coronary lesion severity of the coronary vessel of interest.