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The existing differential approaches for localization of 3-D anatomic point landmarks in 3-D images are sensitive to noise and usually extract numerous spurious landmarks. The parametric model-based approaches are not practically usable for localization of landmarks that can not be modeled by simple parametric forms. Some dedicated methods using anatomic knowledge to identify particular landmarks are not general enough to cope with other landmarks. In this paper, we propose a model-based, semi-global segmentation approach to automatically localize 3-D point landmarks in neuroimages. To localize a landmark, the semi-global segmentation (meaning the segmentation of a part of the studied structure in a certain neighborhood of the landmark) is first achieved by an active surface model, and then the landmark is localized by analyzing the segmented part only. The joint use of global model-to-image registration, semi-global structure registration, active surface-based segmentation, and point-anchored surface registration makes our method robust to noise and shape variation. To evaluate the method, we apply it to the localization of ventricular landmarks including curvature extrema, centerline intersections, and terminal points. Experiments with 48 clinical and 18 simulated magnetic resonance (MR) volumetric images show that the proposed approach is able to localize these landmarks with an average accuracy of 1 mm (i.e., at the level of image resolution). We also illustrate the use of the proposed approach to cortical landmark identification and discuss its potential applications ranging from computer-aided radiology and surgery to atlas registration with scans.