In order to assess coronary artery disease from medical image data, an anatomical model of a coronary artery is generated from the medical image data. A velocity of blood in the coronary artery is estimated based on a spatio-temporal representation of contrast agent propagation in the medical image data. Blood flow is simulated in the anatomical model of the coronary artery using a computational fluid dynamics (CFD) simulation using the estimated velocity of the blood in the coronary artery as a boundary condition.