Abstract: This invention describes methods to compute coronary physiology indexes using a high precision registration model, which consists of acquiring coronary angiography images of coronary vessels, performing intravascular imaging, and registering the coronary angiography images with intravascular images to create a high precision registration model, based upon which the coronary flow, fractional flow reserve (FFR) and index of microcirculation resistance (IMR) can be computed. The methods described in this invention to compute coronary flow, FFR, IMR are based on both coronary angiography and intravascular images, and the accuracy is better than those derived from coronary angiography alone or intravascular imaging alone, and have high practical values.