A method for determining functional severity of a stenosis includes: (a) generating a simulated perfusion map from a calculated blood flow; (b) comparing the simulated perfusion map to a measured perfusion map to identify a degree of mismatch therebetween, the measured perfusion map representing perfusion in a patient; (c) modifying a parameter in a model used in calculating the blood flow when the degree of mismatch meets or exceeds a predefined threshold; (d) computing a hemodynamic quantity from the simulated perfusion map when the degree of mismatch is less than the predefined threshold, the hemodynamic quantity being indicative of the functional severity of the stenosis; and (e) displaying the hemodynamic quantity. Systems for determining functional severity of a stenosis are described.