Numerical 
image processing of two or more medical images to provide 
grayscale registration thereof is described, the numerical 
image processing algorithms being based at least in part on a model of medical 
image acquisition. The 
grayscale registered temporal images may then be displayed for 
visual comparison by a clinician and / or further processed by a computer-
aided diagnosis (CAD) 
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. The models take into account the most relevant 
image acquisition parameters that influence pixel value differences between images, e.g., 
tissue compression, incident 
radiation intensity, 
exposure time, film and digitizer characteristic curves for analog image, and digital 
detector response for 
digital image. The method facilitates temporal comparisons of medical images such as mammograms and / or comparisons of analog with digital images.