Methods and systems for interactively segmenting 3D image data are provided. An initial segmentation of the 3D image data is obtained, and for each of a plurality of image regions, a segmentation uncertainty indicator for the initial image segmentation is associated with the image region and a strength is assigned to the segmentation uncertainty indicator. A low-confidence region in the 3D image data is identified based at least in part on proximity of the low-confidence region to the image regions and strengths of the corresponding segmentation uncertainty indicators. An optimization routine may be applied to an objective function whose value depends at least in part on proximity of the candidate region to the image regions and the strengths of the corresponding uncertainty indicators to identify the low-confidence region from among a plurality of candidate regions.