The present invention provides a system and method for performing a single-scan rest-stress cardiac measurement. In one aspect, the system includes a positron emission tomography (PET) imaging system, a source of a first PET radiotracer for administration to a subject, a source of a second PET radiotracer for administration to a subject, and a processor. The processor has non-transient computer readable media programmed with instructions to obtain PET images of the subject administered with the radiotracer. Furthermore, the computer readable media is programmed with instructions to process the PET images with a non-steady-state, multi-compartment parametric model. An output of the non-steady-state, multi-compartment parametric model is a measure of myocardial blood flow for both a rest state and a stress state of the subject.
