Abstract: Systems and methods are provided for computing a longitudinal change in a structure of a brain. The method may include receiving a first image of the brain, wherein the first image is captured at a first time; receiving a second image of the brain, wherein the second image is captured at a second time; aligning the first and second images; generating at least one displacement from a location in the first image back to a corresponding location in the second image; and determining an optimized matching deformation between the first and second images based on an energy function that incorporates spatially varying estimates of a likelihood of tissue edge presence at the location in the first image, wherein the matching deformation is one of the generated displacements.