A method (12) of estimating one or more physiological parameters, in particular of a cardiac region, based on medical imaging data. An input time series of three-dimensional medical images is received (14), representative of a cardiac region of a patient. A meshless simulation frame-work is applied (16) for simulating blood flow through at least a portion of the anatomical area captured by the images. The simulation framework comprises in particular simulating force interactions between individual elements of a simulated fluid (representing blood) and individual patches of a tissue structure of the imaged cardiac region. One or more physiological parameters (18) are derived based on the simulated blood flow.