Unbiased group-wise image registration: applications in brain fiber tract atlas construction and functional connectivity analysis.

We propose an unbiased implicit-reference group-wise (IRG) image registration method and demonstrate its applications in the construction of a brain white matter fiber tract atlas and the analysis of resting-state functional MRI (fMRI) connectivity. Most image registration techniques pair-wise align images to a selected reference image and group analyses are performed in the reference space, which may produce bias. The proposed method jointly estimates transformations, with an elastic deformation model, registering all images to an implicit reference corresponding to the group average. The unbiased registration is applied to build a fiber tract atlas by registering a group of diffusion tensor images. Compared to reference-based registration, the IRG registration improves the fiber track overlap within the group. After applying the method in the fMRI connectivity analysis, results suggest a general improvement in functional connectivity maps at a group level in terms of larger cluster size and higher average t-scores.