The current document is directed to methods and systems that refine anatomical models to sub-voxel resolution. In certain implementations, sophisticated, composite, digital anatomical atlases provide detailed three-dimensional models of the contents of three-dimensional medical images. However, three-dimensional medical images have limited resolutions characterized by a smallest volume, referred to as a voxel, to which an intensity is assigned by the imaging process. The currently disclosed methods employ computed percentages of different types of tissue within voxel volumes to adjust a three-dimensional model of the contents of the voxel volumes to more accurately model the contents of the voxel volumes.