Numerical image processing based on a model of medical image acquisition of two or more medical images to provide grayscale registration is described. The grayscale registered temporal images may then be displayed for visual comparison and/or further processed by a computer-aided diagnosis system for detection of medical abnormalities therein. A parametric method includes spatially registering two images and performing gray scale registration of the images. A parametric transform model, e.g., analog to analog, digital to digital, analog to digital, or digital to analog model, is selected based on the image acquisition method(s) of the images, i.e., digital or analog/film. Gray scale registration involves generating a joint pixel value histogram from the two images, statistically fitting parameters of the transform model to the joint histogram, generating a lookup table, and using the lookup table to transform and register pixel values of one image to the pixel values of the other image.