In this paper we report the set-up and results of the Multimodal Brain Tumor Image Segmentation Benchmark (BRATS) organized in conjunction with the MICCAI 2012 and 2013 conferences. Twenty state-of-the-art tumor segmentation algorithms were applied to a set of 65 multi-contrast MR scans of low- and high-grade glioma patients - manually annotated by up to four raters - and to 65 comparable scans generated using tumor image simulation software. Quantitative evaluations revealed considerable disagreement between the human raters in segmenting various tumor sub-regions (Dice scores in the range 74%-85%), illustrating the difficulty of this task. We found that different algorithms worked best for different sub-regions (reaching performance comparable to human inter-rater variability), but that no single algorithm ranked in the top for all sub-regions simultaneously. Fusing several good algorithms using a hierarchical majority vote yielded segmentations that consistently ranked above all individual algorithms, indicating remaining opportunities for further methodological improvements. The BRATS image data and manual annotations continue to be publicly available through an online evaluation system as an ongoing benchmarking resource.

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.

Adaptive immune dysfunction, in particular interferon-γ, is implicated in disorders characterized by social dysfunction and suggests interferon-γ signalling may provide a co-evolutionary link between social behaviour and an anti-pathogen immune response. It was shown recently that immune dysfunction can influence spatial learning and memory. Jonathan Kipnis and colleagues now show that mice deficient in adaptive immunity exhibit defects in social behaviour. They find that interferon-γ controls neural circuits and social behaviour by signalling neurons to tune GABAergic signalling in the prefrontal cortex. This work suggests that interferon-γ signalling may provide a co-evolutionary link between social behaviour and an anti-pathogen immune response. Immune dysfunction is commonly associated with several neurological and mental disorders. Although the mechanisms by which peripheral immunity may influence neuronal function are largely unknown, recent findings implicate meningeal immunity influencing behaviour, such as spatial learning and memory1. Here we show that meningeal immunity is also critical for social behaviour; mice deficient in adaptive immunity exhibit social deficits and hyper-connectivity of fronto-cortical brain regions. Associations between rodent transcriptomes from brain and cellular transcriptomes in response to T-cell-derived cytokines suggest a strong interaction between social behaviour and interferon-γ (IFN-γ)-driven responses. Concordantly, we demonstrate that inhibitory neurons respond to IFN-γ and increase GABAergic (γ-aminobutyric-acid) currents in projection neurons, suggesting that IFN-γ is a molecular link between meningeal immunity and neural circuits recruited for social behaviour. Meta-analysis of the transcriptomes of a range of organisms reveals that rodents, fish, and flies elevate IFN-γ/JAK-STAT-dependent gene signatures in a social context, suggesting that the IFN-γ signalling pathway could mediate a co-evolutionary link between social/aggregation behaviour and an efficient anti-pathogen response. This study implicates adaptive immune dysfunction, in particular IFN-γ, in disorders characterized by social dysfunction and suggests a co-evolutionary link between social behaviour and an anti-pathogen immune response driven by IFN-γ signalling.

Publicly available scientific resources help establish evaluation standards, provide a platform for teaching and improve reproducibility. Version 4 of the Insight ToolKit ( ITK4 ) seeks to es- tablish new standards in publicly available image registration methodology. ITK4 makes severaladvances in comparison to previous versions of ITK. ITK4 supports both multivariate images and objective functions; it also unifies high-dimensional (deformation field) and low-dimensional (affine) transformations with metrics that are reusable across transform types and with com- posite transforms that allow arbitrary series of geometric mappings to be chained together seamlessly. Metrics and optimizers take advantage of multi-core resources, when available.Furthermore, ITK4 reduces the parameter optimization burden via principled heuristics that automatically set scaling across disparate parameter types (rotations versus translations). A related approach also constrains steps sizes for gradient-based optimizers. The result is that tuning for different metrics and/or image pairs is rarely necessary allowing the researcher tomore easily focus on design/comparison of registration strategies. In total, the ITK4 contribu- tion is intended as a structure to support reproducible research practices, will provide a more extensive foundation against which to evaluate new work in image registration and also enable application level programmers a broad suite of tools on which to build. Finally, we contextu- alize this work with a reference registration evaluation study with application to pediatric brainlabeling.