Automatic arterial input function (AIF) area determination is provided that can be used to facilitate the generation of parametric maps for perfusion studies based on various imaging modalities and covering a variety of tissues. Automatic AIF determination can be accomplished by extracting characteristic parameters such as maximum slope, maximum enhancement, time to peak, time to wash-out, and wash-out slope. Characteristic parameter maps are generated to show relationships among the extracted characteristic parameters, and the characteristic parameter maps are converted to a plurality of two-dimensional plots. Automated segmentation of non-AIF tissues and determination of AIF areas can be accomplished by automatically finding peaks and valleys of each phase of AIF areas on the plurality of two-dimensional plots.