This paper deals with topology preservation in three-dimensional (3-D) deformable image registration. This work is a nontrivial extension of , which addresses the case of two-dimensional (2-D) topology preserving mappings. In both cases, the deformation map is modeled as a hierarchical displacement field, decomposed on a multiresolution B-spline basis. Topology preservation is enforced by controlling the Jacobian of the transformation. Finding the optimal displacement parameters amounts to solving a constrained optimization problem: The residual energy between the target image and the deformed source image is minimized under constraints on the Jacobian. Unlike the 2-D case, in which simple linear constraints are derived, the 3-D B-spline-based deformable mapping yields a difficult (until now, unsolved) optimization problem. In this paper, we tackle the problem by resorting to interval analysis optimization techniques. Care is taken to keep the computational burden as low as possible. Results on multipatient 3-D MRI registration illustrate the ability of the method to preserve topology on the continuous image domain.