1. A method of determining a tissue perfusion response, comprising: perfusing a predetermined contrast agent into a subject; acquiring data using a predetermined modality as a function of time; determining a time-related parameter value based upon the acquired data for each of a predetermined set of voxels consisting of adjacent voxels and at least one voxel of interest; excluding some of the acquired data corresponding to any one of the adjacent voxels based upon the time-related parameter value along a predetermined blood flow direction to the voxel of interest, the remaining acquired data defining selected adjacent voxels; determining a local input function based the acquired data of the selected adjacent voxels; and determining the tissue perfusion response based upon the local input function and an output function according to the acquired data.