In this paper, we propose a nonrigid image registration technique by optimizing a generalized information-theoretic similarity measure using the quasi-Newton method as an optimization scheme and cubic B-splines for modeling the nonrigid deformation field between the fixed and moving 3-D image pairs. To achieve a compromise between the nonrigid registration accuracy and the associated computational cost, we implement a three-level hierarchical multiresolution approach such that the image resolution is increased in a coarse to fine fashion. Experimental results are provided to demonstrate the registration accuracy of our approach. The feasibility of the proposed method is demonstrated on a 3-D magnetic resonance data volume and also on clinically acquired 4-D CT image datasets.