Both brain size and biological sex contribute to variation in white matter microstructure in middle-aged healthy adults.

Whether head size and/or biological sex influence proxies of white matter (WM) microstructure such as fractional anisotropy (FA) and mean diffusivity (MD) remains controversial. Diffusion tensor imaging (DTI) indices are also associated with age, but there are large discrepancies in the spatial distribution and timeline of age-related differences reported. The aim of this study was to evaluate the associations between intracranial volume (ICV), sex, and age and DTI indices from WM in a population-based study of healthy individuals (n = 812) aged 50-66 in the Nord-Trøndelag health survey. Semiautomated tractography and tract-based spatial statistics (TBSS) analyses were performed on the entire sample and in an ICV-matched sample of men and women. The tractography results showed a similar positive association between ICV and FA in all major WM tracts in men and women. Associations between ICV and MD, radial diffusivity and axial diffusivity were also found, but to a lesser extent than FA. The TBSS results showed that both men and women had areas of higher and lower FA when controlling for age, but after controlling for age and ICV only women had areas with higher FA. The ICV matched analysis also demonstrated that only women had areas of higher FA. Age was negatively associated with FA across the entire WM skeleton in the TBSS analysis, independent of both sex and ICV. Combined, these findings demonstrated that both ICV and sex contributed to variation in DTI indices and emphasized the importance of considering ICV as a covariate in DTI analysis.

Evidence for a novel subcortical mechanism for posterior cingulate cortex atrophy in HIV peripheral neuropathy.

We previously reported that neuropathic pain was associated with smaller posterior cingulate cortical (PCC) volumes, suggesting that a smaller/dysfunctional PCC may contribute to development of pain via impaired mind wandering. A gap in our previous report was lack of evidence for a mechanism for the genesis of PCC atrophy in HIV peripheral neuropathy. Here we investigate if volumetric differences in the subcortex for those with neuropathic paresthesia may contribute to smaller PCC volumes, potentially through deafferentation of ascending white matter tracts resulting from peripheral nerve damage in HIV neuropathy. Since neuropathic pain and paresthesia are highly correlated, statistical decomposition was used to separate pain and paresthesia symptoms to determine which regions of brain atrophy are associated with both pain and paresthesia and which are associated separately with pain or paresthesia. HIV+ individuals (N = 233) with and without paresthesia in a multisite study underwent structural brain magnetic resonance imaging. Voxel-based morphometry and a segmentation/registration tool were used to investigate regional brain volume changes associated with paresthesia. Analysis of decomposed variables found that smaller midbrain and thalamus volumes were associated with paresthesia rather than pain. However, atrophy in the PCC was related to both pain and paresthesia. Peak thalamic atrophy (p = 0.004; MNI x = - 14, y = - 24, z = - 2) for more severe paresthesia was in a region with reciprocal connections with the PCC. This provides initial evidence that smaller PCC volumes in HIV peripheral neuropathy are related to ascending white matter deafferentation caused by small fiber damage observed in HIV peripheral neuropathy.

Automated segmentation of the substantia nigra, subthalamic nucleus and red nucleus in 7T data at young and old age.

With recent developments in MR acquisition at 7T, smaller brainstem structures such as the red nuclei, substantia nigra and subthalamic nuclei can be imaged with good contrast and resolution. These structures have important roles both in the study of the healthy brain and in diseases such as Parkinson's disease, but few methods have been described to automatically segment them. In this paper, we extend a method that we have previously proposed for segmentation of the striatum and globus pallidus to segment these deeper and smaller structures. We modify the method to allow more direct control over segmentation smoothness by using a Markov random field prior. We investigate segmentation performance in three age groups and show that the method produces consistent results that correspond well with manual segmentations. We perform a vertex-based analysis to identify changes with age in the shape of the structures and present results suggesting that the method may be at least as effective as manual delineation in capturing differences between subjects.

Automatic segmentation of the striatum and globus pallidus using MIST: Multimodal Image Segmentation Tool.

Accurate segmentation of the subcortical structures is frequently required in neuroimaging studies. Most existing methods use only a T1-weighted MRI volume to segment all supported structures and usually rely on a database of training data. We propose a new method that can use multiple image modalities simultaneously and a single reference segmentation for initialisation, without the need for a manually labelled training set. The method models intensity profiles in multiple images around the boundaries of the structure after nonlinear registration. It is trained using a set of unlabelled training data, which may be the same images that are to be segmented, and it can automatically infer the location of the physical boundary using user-specified priors. We show that the method produces high-quality segmentations of the striatum, which is clearly visible on T1-weighted scans, and the globus pallidus, which has poor contrast on such scans. The method compares favourably to existing methods, showing greater overlap with manual segmentations and better consistency.

Correcting dynamic distortions in 7T echo planar imaging using a jittered echo time sequence.

PURPOSE: To develop a distortion correction method for echo planar imaging (EPI) that is able to measure dynamic changes in B0 . THEORY AND METHODS: The approach we propose is based on single-echo EPI with a jittering of the echo time between two values for alternate time points. Field maps are calculated between phase images from adjacent volumes and are used to remove distortion from corresponding magnitude images. The performance of our approach was optimized using an analytical model and by comparison with field maps from dual-echo EPI. The method was tested in functional MRI experiments at 7T with motor tasks and compared with the conventional static approach. RESULTS: Unwarping using our method was accurate even for head rotations up to 8.2°, where the static approach introduced errors up to 8.2 mm. Jittering the echo time between 19 and 25 ms had no measurable effect on blood oxygenation level-dependent (BOLD) sensitivity. Our approach reduced the distortions in activated regions to <1 mm and repositioned active voxels correctly. CONCLUSION: This method yields accurate distortion correction in the presence of motion. No reduction in BOLD sensitivity was observed. As such, it is suitable for application in a wide range of functional MRI experiments. Magn Reson Med 76:1388-1399, 2016. © 2015 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Atypical vertical sound localization and sound-onset sensitivity in people with autism spectrum disorders.

BACKGROUND: Autism spectrum disorders (ASDs) are associated with auditory hyper- or hyposensitivity; atypicalities in central auditory processes, such as speech-processing and selective auditory attention; and neural connectivity deficits. We sought to investigate whether the low-level integrative processes underlying sound localization and spatial discrimination are affected in ASDs. METHODS: We performed 3 behavioural experiments to probe different connecting neural pathways: 1) horizontal and vertical localization of auditory stimuli in a noisy background, 2) vertical localization of repetitive frequency sweeps and 3) discrimination of horizontally separated sound stimuli with a short onset difference (precedence effect). RESULTS: Ten adult participants with ASDs and 10 healthy control listeners participated in experiments 1 and 3; sample sizes for experiment 2 were 18 adults with ASDs and 19 controls. Horizontal localization was unaffected, but vertical localization performance was significantly worse in participants with ASDs. The temporal window for the precedence effect was shorter in participants with ASDs than in controls. LIMITATIONS: The study was performed with adult participants and hence does not provide insight into the developmental aspects of auditory processing in individuals with ASDs. CONCLUSION: Changes in low-level auditory processing could underlie degraded performance in vertical localization, which would be in agreement with recently reported changes in the neuroanatomy of the auditory brainstem in individuals with ASDs. The results are further discussed in the context of theories about abnormal brain connectivity in individuals with ASDs.

Reference-free unwarping of EPI data using dynamic off-resonance correction with multiecho acquisition (DOCMA).

Inhomogeneities of the main magnetic field cause geometric distortion in echo-planar imaging, a method central to functional MRI. A number of correction methods have been proposed, most of which are based on the acquisition of a fieldmap providing the local offsets to the main magnetic field. Here, accelerated multiecho echo-planar imaging is used, with echo times short enough to enable the construction of a fieldmap of comparable quality from the data themselves. This way, each volume in a time series can be unwarped using a fieldmap obtained from that volume, avoiding volume-to-volume field-motion interactions that invalidate reference data in conventional approaches that use a single, static, fieldmap. The combination of accelerated acquisition with dynamic distortion correction yields volumes with very low distortion at repetition times similar to conventional echo-planar imaging. The method is applied to data acquired at 3 and 7 T and is shown to effectively correct image geometry. Furthermore, it is shown that dynamic distortion correction yields better temporal signal stability than correction using a static fieldmap in the presence of subject motion.

Partition-based mass clustering of tractography streamlines.

We describe a novel scalable clustering framework for streamlines obtained from diffusion tractography. Clustering is an attractive means of segmenting a large set of streamlines into anatomically relevant bundles. For most existing methods, however, the large datasets produced in high resolution or multiple subject studies are problematical. To achieve good scalability, our method repeatedly divides the data into subsets, which are then partitioned using hierarchical clustering. A final partition is obtained by recombining the subsets. In addition, the recombination scheme provides a consistency measure for cluster assignment of individual streamlines, which is used to clean up the final result. The clusters have good anatomical plausibility and we show that three clusters corresponding to the three known segments of the arcuate fasciculus show excellent agreement with literature. A major advantage of the method is the fact that it can find clusters in datasets of essentially arbitrary size. This fact is exploited to find consistent clusters in concatenated tractography data from multiple subjects. We expect the identification of bundles across subjects to be an important application of the method.