Diffusion tensor imaging (DTI) provides a unique source of information about the underlying tissue structure of brain white matter in vivo including both the geometry of major fiber bundles as well as quantitative information about tissue properties represented by derived tensor measures. This paper presents a method for statistical comparison of fiber bundle diffusion properties between populations of diffusion tensor images. Unbiased diffeomorphic atlas building is used to compute a normalized coordinate system for populations of diffusion images. The diffeomorphic transformations between each subject and the atlas provide spatial normalization for the comparison of tract statistics. Diffusion properties, such as fractional anisotropy (FA) and tensor norm, along fiber tracts are modeled as multivariate functions of arc length. Hypothesis testing is performed non-parametrically using permutation testing based on the Hotelling T2 statistic. The linear discriminant embedded in the T2 metric provides an intuitive, localized interpretation of detected differences. The proposed methodology was tested on two clinical studies of neurodevelopment. In a study of one and two year old subjects, a significant increase in FA and a correlated decrease in Frobenius norm was found in several tracts. Significant differences in neonates were found in the splenium tract between controls and subjects with isolated mild ventriculomegaly (MVM) demonstrating the potential of this method for clinical studies
