Processing of longitudinal diffusion tensor imaging (DTI) data is a crucial challenge to better understand pathological mechanisms of complex brain diseases such as multiple sclerosis (MS) where white-matter (WM) fiber bundles are variably altered by inflammatory events. In this study, we propose a new fully automated method to detect longitudinal changes in diffusivity metrics along WM fiber bundles. The proposed method is divided in three main parts: 1) preprocessing of longitudinal diffusion acquisitions, 2) WM fiber-bundle extraction, and 3) application of nonnegative matrix factorization and density-based local outliers algorithms to detect and delineate longitudinal variations appearing in the cross section of the WM fiber bundle. In order to validate our method, we introduce a new model to simulate real longitudinal changes based on a generalized Gaussian probability density function. Moreover, we applied our method on longitudinal data. High level of performances were obtained for the detection of small longitudinal changes along the WM fiber bundles in MS patients.