Traditional fuzzy clustering algorithms have been successfully applied in MR image segmentation for quantitative morphological analysis. However, the clustering results might be biased due to the variability of tissue intensities and anatomical structures. For example, clustering-based algorithms tend to over-segment white matter tissues of MR brain images. To solve this problem, we introduce a tissue probability map constrained clustering algorithm and apply it to serialMR brain image segmentation for longitudinal study of human brains. The tissue probability maps consist of segmentation priors obtained from a population and reflect the probability of different tissue types. More accurate image segmentation can be achieved by using these segmentation priors in the clustering algorithm. Experimental results of both simulated longitudinal MR brain data and the Alzheimer's Disease Neuroimaging Initiative (ADNI) data using the new serial image segmentation algorithm in the framework of CLASSIC show more accurate and robust longitudinal measures.