Human investigators instinctively segment medical images into their anatomical components, drawing upon prior knowledge of anatomy to overcome image artifacts, noise, and lack of tissue contrast. The authors describe: 1) the development and use of a brain tissue probability model for the segmentation of multiple sclerosis (MS) lesions in magnetic resonance (MR) brain images, and 2) an empirical comparison of the performance of statistical and decision tree classifiers, applied to MS lesion segmentation. Based on MR image data obtained from healthy volunteers, the model provides prior probabilities of brain tissue distribution per unit voxel in a standardized 3-D "brain space". In comparison to purely data-driven segmentation, the use of the model to guide the segmentation of MS lesions reduced the volume of false positive lesions by 50-80%