A method for registering digital renal perfusion images includes selecting a volume of interest (VOI) containing a kidney in a reference renal perfusion image, computing 3D intensity gradients for a plurality of points in the VOI of the reference renal perfusion image, computing 3D intensity gradients for a plurality of points in a search window of a current renal perfusion image, and maximizing a similarity measure between the reference image VOI and the current image search window, where the similarity measure is a function of the 3D intensity gradients computed for the reference image and the current image.