A variant of the popular nonparametric nonuniform intensity normalization (N3) algorithm is proposed for bias field correction. Given the superb performance of N3 and its public availability, it has been the subject of several evaluation studies. These studies have demonstrated the importance of certain parameters associated with the B -spline least-squares fitting. We propose the substitution of a recently developed fast and robust B-spline approximation routine and a modified hierarchical optimization scheme for improved bias field correction over the original N3 algorithm. Similar to the N3 algorithm, we also make the source code, testing, and technical documentation of our contribution, which we denote as ¿N4ITK,¿ available to the public through the Insight Toolkit of the National Institutes of Health. Performance assessment is demonstrated using simulated data from the publicly available Brainweb database, hyperpolarized ³ He lung image data, and 9.4T postmortem hippocampus data.

Multi-atlas segmentation is an effective approach for automatically labeling objects of interest in biomedical images. In this approach, multiple expert-segmented example images, called atlases, are registered to a target image, and deformed atlas segmentations are combined using label fusion. Among the proposed label fusion strategies, weighted voting with spatially varying weight distributions derived from atlas-target intensity similarity have been particularly successful. However, one limitation of these strategies is that the weights are computed independently for each atlas, without taking into account the fact that different atlases may produce similar label errors. To address this limitation, we propose a new solution for the label fusion problem in which weighted voting is formulated in terms of minimizing the total expectation of labeling error and in which pairwise dependency between atlases is explicitly modeled as the joint probability of two atlases making a segmentation error at a voxel. This probability is approximated using intensity similarity between a pair of atlases and the target image in the neighborhood of each voxel. We validate our method in two medical image segmentation problems: hippocampus segmentation and hippocampus subfield segmentation in magnetic resonance (MR) images. For both problems, we show consistent and significant improvement over label fusion strategies that assign atlas weights independently.

We evaluate a fully automatic technique for labeling hippocampal subfields and cortical subregions in the medial temporal lobe in in vivo 3 Tesla MRI. The method performs segmentation on a T2‐weighted MRI scan with 0.4 × 0.4 × 2.0 mm³ resolution, partial brain coverage, and oblique orientation. Hippocampal subfields, entorhinal cortex, and perirhinal cortex are labeled using a pipeline that combines multi‐atlas label fusion and learning‐based error correction. In contrast to earlier work on automatic subfield segmentation in T2‐weighted MRI [Yushkevich et al., 2010], our approach requires no manual initialization, labels hippocampal subfields over a greater anterior‐posterior extent, and labels the perirhinal cortex, which is further subdivided into Brodmann areas 35 and 36. The accuracy of the automatic segmentation relative to manual segmentation is measured using cross‐validation in 29 subjects from a study of amnestic mild cognitive impairment (aMCI) and is highest for the dentate gyrus (Dice coefficient is 0.823), CA1 (0.803), perirhinal cortex (0.797), and entorhinal cortex (0.786) labels. A larger cohort of 83 subjects is used to examine the effects of aMCI in the hippocampal region using both subfield volume and regional subfield thickness maps. Most significant differences between aMCI and healthy aging are observed bilaterally in the CA1 subfield and in the left Brodmann area 35. Thickness analysis results are consistent with volumetry, but provide additional regional specificity and suggest nonuniformity in the effects of aMCI on hippocampal subfields and MTL cortical subregions. Hum Brain Mapp, 36:258–287, 2015.

Obtaining quantitative measures from biomedical images often requires segmentation, i.e., finding and outlining the structures of interest. Multi-modality imaging datasets, in which multiple imaging measures are available at each spatial location, are increasingly common, particularly in MRI. In applications where fully automatic segmentation algorithms are unavailable or fail to perform at desired levels of accuracy, semi-automatic segmentation can be a time-saving alternative to manual segmentation, allowing the human expert to guide segmentation, while minimizing the effort expended by the expert on repetitive tasks that can be automated. However, few existing 3D image analysis tools support semi-automatic segmentation of multi-modality imaging data. This paper describes new extensions to the ITK-SNAP interactive image visualization and segmentation tool that support semi-automatic segmentation of multi-modality imaging datasets in a way that utilizes information from all available modalities simultaneously. The approach combines Random Forest classifiers, trained by the user by placing several brushstrokes in the image, with the active contour segmentation algorithm. The new multi-modality semi-automatic segmentation approach is evaluated in the context of high-grade glioblastoma segmentation.