Purpose: Multi-atlas segmentation has been shown to be highly robust and accurate across an extraordinary range of potential applications. However, it is limited to the segmentation of structures that are anatomically consistent across a large population of potential target subjects (i.e., multi-atlas segmentation is limited to “in-atlas” applications). Herein, the authors propose a technique to determine the likelihood that a multi-atlas segmentation estimate is representative of the problem at hand, and, therefore, identify anomalous regions that are not well represented within the atlases.

Methods: The authors derive a technique to estimate the out-of-atlas (OOA) likelihood for every voxel in the target image. These estimated likelihoods can be used to determine and localize the probability of an abnormality being present on the target image.

Results: Using a collection of manually labeled whole-brain datasets, the authors demonstrate the efficacy of the proposed framework on two distinct applications. First, the authors demonstrate the ability to accurately and robustly detect malignant gliomas in the human brain—an aggressive class of central nervous system neoplasms. Second, the authors demonstrate how this OOA likelihood estimation process can be used within a quality control context for diffusion tensor imaging datasets to detect large-scale imaging artifacts (e.g., aliasing and image shading).

Conclusions: The proposed OOA likelihood estimation framework shows great promise for robust and rapid identification of brain abnormalities and imaging artifacts using only weak dependencies on anomaly morphometry and appearance. The authors envision that this approach would allow for application-specific algorithms to focus directly on regions of high OOA likelihood, which would (1) reduce the need for human intervention, and (2) reduce the propensity for false positives. Using the dual perspective, this technique would allow for algorithms to focus on regions of normal anatomy to ascertain image quality and adapt to image appearance characteristics.