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Biomedical image registration, or geometric alignment of two-dimensional and/or three-dimensional (3D) image data, is becoming increasingly important in diagnosis, treatment planning, functional studies, computer-guided therapies, and in biomedical research. Registration based on intensity values usually requires optimization of some similarity metric between the images. Local optimization techniques frequently fail because functions of these metrics with respect to transformation parameters are generally nonconvex and irregular and, therefore, global methods are often required. In this paper, a new evolutionary approach, particle swarm optimization, is adapted for single-slice 3D-to-3D biomedical image registration. A new hybrid particle swarm technique is proposed that incorporates initial user guidance. Multimodal registrations with initial orientations far from the ground truth were performed on three volumes from different modalities. Results of optimizing the normalized mutual information similarity metric were compared with various evolutionary strategies. The hybrid particle swarm technique produced more accurate registrations than the evolutionary strategies in many cases, with comparable convergence. These results demonstrate that particle swarm approaches, along with evolutionary techniques and local methods, are useful in image registration, and emphasize the need for hybrid approaches for difficult registration problems.