Subregional hippocampal deformations in major depressive disorder.

BACKGROUND: Hippocampal atrophy is a well reported feature of major depressive disorder, although the evidence has been mixed. The present study sought to examine hippocampal volume and subregional morphology in patients with major depressive disorder, who were all medication-free and in an acute depressive episode of moderate severity. METHODS: Structural magnetic resonance imaging scans were acquired in 37 patients (mean age 42 years) and 37 age, gender and IQ-matched healthy individuals. Hippocampal volume and subregional structural differences were measured by manual tracings and identification of homologous surface points to the central core of each hippocampus. RESULTS: Both right (P=0.001) and left (P=0.005) hippocampal volumes were reduced in patients relative to healthy controls (n=37 patients and n=37 controls), while only the right hippocampus (P=0.016) showed a reduced volume in a subgroup of first-episode depression patients (n=13) relative to healthy controls. Shape analysis localised the subregional deformations to the subiculum and CA1 subfield extending into the CA2-3 subfields predominantly in the tail regions in the right (P=0.017) and left (P=0.011) hippocampi. LIMITATIONS: As all patients were in an acute depressive episode, effects associated with depressive state cannot be distinguished from trait effects. CONCLUSIONS: Subregional hippocampal deficits are present early in the course of major depression. The deformations may reflect structural correlates underlying functional memory impairments and distinguish depression from other psychiatric disorders.

Online resource for validation of brain segmentation methods.

One key issue that must be addressed during the development of image segmentation algorithms is the accuracy of the results they produce. Algorithm developers require this so they can see where methods need to be improved and see how new developments compare with existing ones. Users of algorithms also need to understand the characteristics of algorithms when they select and apply them to their neuroimaging analysis applications. Many metrics have been proposed to characterize error and success rates in segmentation, and several datasets have also been made public for evaluation. Still, the methodologies used in analyzing and reporting these results vary from study to study, so even when studies use the same metrics their numerical results may not necessarily be directly comparable. To address this problem, we developed a web-based resource for evaluating the performance of skull-stripping in T1-weighted MRI. The resource provides both the data to be segmented and an online application that performs a validation study on the data. Users may download the test dataset, segment it using whichever method they wish to assess, and upload their segmentation results to the server. The server computes a series of metrics, displays a detailed report of the validation results, and archives these for future browsing and analysis. We applied this framework to the evaluation of 3 popular skull-stripping algorithms--the Brain Extraction Tool [Smith, S.M., 2002. Fast robust automated brain extraction. Hum. Brain Mapp. 17 (3),143-155 (Nov)], the Hybrid Watershed Algorithm [Ségonne, F., Dale, A.M., Busa, E., Glessner, M., Salat, D., Hahn, H.K., Fischl, B., 2004. A hybrid approach to the skull stripping problem in MRI. NeuroImage 22 (3), 1060-1075 (Jul)], and the Brain Surface Extractor [Shattuck, D.W., Sandor-Leahy, S.R., Schaper, K.A., Rottenberg, D.A., Leahy, R.M., 2001. Magnetic resonance image tissue classification using a partial volume model. NeuroImage 13 (5), 856-876 (May) under several different program settings. Our results show that with proper parameter selection, all 3 algorithms can achieve satisfactory skull-stripping on the test data.

Construction of a 3D probabilistic atlas of human cortical structures.

We describe the construction of a digital brain atlas composed of data from manually delineated MRI data. A total of 56 structures were labeled in MRI of 40 healthy, normal volunteers. This labeling was performed according to a set of protocols developed for this project. Pairs of raters were assigned to each structure and trained on the protocol for that structure. Each rater pair was tested for concordance on 6 of the 40 brains; once they had achieved reliability standards, they divided the task of delineating the remaining 34 brains. The data were then spatially normalized to well-known templates using 3 popular algorithms: AIR5.2.5's nonlinear warp (Woods et al., 1998) paired with the ICBM452 Warp 5 atlas (Rex et al., 2003), FSL's FLIRT (Smith et al., 2004) was paired with its own template, a skull-stripped version of the ICBM152 T1 average; and SPM5's unified segmentation method (Ashburner and Friston, 2005) was paired with its canonical brain, the whole head ICBM152 T1 average. We thus produced 3 variants of our atlas, where each was constructed from 40 representative samples of a data processing stream that one might use for analysis. For each normalization algorithm, the individual structure delineations were then resampled according to the computed transformations. We next computed averages at each voxel location to estimate the probability of that voxel belonging to each of the 56 structures. Each version of the atlas contains, for every voxel, probability densities for each region, thus providing a resource for automated probabilistic labeling of external data types registered into standard spaces; we also computed average intensity images and tissue density maps based on the three methods and target spaces. These atlases will serve as a resource for diverse applications including meta-analysis of functional and structural imaging data and other bioinformatics applications where display of arbitrary labels in probabilistically defined anatomic space will facilitate both knowledge-based development and visualization of findings from multiple disciplines.