This paper presents a new methodology for the automatic segmentation and characterization of object changes in time series of three-dimensional data sets. The purpose of the analysis is a detection and characterization of objects based on their dynamic changes. The technique was inspired by procedures developed for the analysis of functional MRI data sets. After precise registration of serial volume data sets to 4-D data, we applied a new time series analysis taking into account the characteristic time function of variable lesions. The images were preprocessed with a correction of image field inhomogeneities and a normalization of the brightness function over the whole time series. This leads to the hypothesis that static regions remain unchanged over time, whereas local changes in tissue characteristics cause typical functions in the voxel’s time series. A set of features are derived from the time series and their derivatives, expressing probabilities for membership to the sought structures. These multiple sources of uncertain evidence were combined to a single evidence value using Dempster Shafer’s theory. Individual processing of a series of 3-D data sets is therefore replaced by a fully 4-D processing. To explore the sensitivity of time information, active lesions are segmented solely based on time fluctuation, neglecting absolute intensity information. The project is driven by the objective of improving the segmentation and characterization of white matter lesions in serial MR data of multiple sclerosis patients. Pharmaceutical research and patient follow-up requires efficient and robust methods with high degree of automation. Further, an enhanced set of morphometric parameters might give a better insight into the course of the disease and therefore leads to a better understanding of the disease mechanism and of drug effects. The new method has been applied to two time series from different patient studies, covering time resolutions of 12 and 24 data sets over a period of roughly one year. The results demonstrate that time evolution is a highly sensitive feature to detect fluctuating structures.