Systems and methods for processing medical image data with increased sensitivity to facilitate comparisons among groups of subjects are disclosed herein. In one embodiment, a method comprises receiving a first three-dimensional image comprising a plurality of voxels, reducing a regional trend within the three-dimensional image, computing a semivariogram for a region of interest, defining at least one block of spatially correlated voxels, calculating voxel weights for each voxel within the at least one block, and determining a block average count and variance for the at least one block.