Estimating the thickness of the cerebral cortex is a key step in many brain imaging studies, revealing valuable information on development or disease progression. In this work, we present a framework for measuring the cortical thickness, based on minimizing line integrals over the probability map of the gray matter in the MRI volume. We first prepare a probability map that contains the probability of each voxel belonging to the gray matter. Then, the thickness is basically defined for each voxel as the minimum line integral of the probability map on line segments centered at the point of interest. In contrast to our approach, previous methods often perform a binary-valued hard segmentation of the gray matter before measuring the cortical thickness. Because of image noise and partial volume effects, such a hard classification ignores the underlying tissue class probabilities assigned to each voxel, discarding potentially useful information. We describe our proposed method and demonstrate its performance on both artificial volumes and real 3D brain MRI data from subjects with Alzheimer's disease and healthy individuals. Hum Brain Mapp 2009. © 2009 Wiley-Liss, Inc.