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This paper presents a set of validation procedures for nonrigid registration of functional EPI to anatomical MRI brain images. Although various registration techniques have been developed and validated for high-resolution anatomical MRI images, due to a lack of quantitative and qualitative validation procedures, the use of nonrigid registration between functional EPI and anatomical MRI images has not yet been deployed in neuroimaging studies. In this paper, the performance of a robust formulation of a nonrigid registration technique is evaluated in a quantitative manner based on simulated data and is further evaluated in a quantitative and qualitative manner based on in vivo data as compared to the commonly used rigid and affine registration techniques in the neuroimaging software packages. The nonrigid registration technique is formulated as a second-order constrained optimization problem using a free-form deformation model and mutual information similarity measure. Bound constraints, resolution level and cross-validation issues have been discussed to show the degree of accuracy and effectiveness of the nonrigid registration technique. The analyses performed reveal that the nonrigid approach provides a more accurate registration, in particular when the functional regions of interest lie in regions distorted by susceptibility artifacts.