The invention provides, in some aspects, methods and apparatus for registering 3D image volumes by utilizing a graphics processing unit (GPU) to facilitate maximizing the "mutual information" of the two image volumes being registered. Particularly, the GPU is used to compute a histogram representing a probability that a pixel value in one of the images being registered coincides with a pixel value in a transform of the other image. In one aspect, this histogram is generated by a two-step approach including (i) "drawing" a polygon covering a two-component render target having as many pixels as there are samples, where the value of each pixel in the target includes the intensities of the respective pixels of the first and second images, (ii) interpreting that render target as a buffer of vertex positions and, for each sample, rendering into a new render target, a single vertex using coordinates from that buffer.