The epilepsies are commonly accompanied by widespread abnormalities in cerebral white matter. ENIGMA-Epilepsy is a large quantitative brain imaging consortium, aggregating data to investigate ...patterns of neuroimaging abnormalities in common epilepsy syndromes, including temporal lobe epilepsy, extratemporal epilepsy, and genetic generalized epilepsy. Our goal was to rank the most robust white matter microstructural differences across and within syndromes in a multicentre sample of adult epilepsy patients. Diffusion-weighted MRI data were analysed from 1069 healthy controls and 1249 patients: temporal lobe epilepsy with hippocampal sclerosis (n = 599), temporal lobe epilepsy with normal MRI (n = 275), genetic generalized epilepsy (n = 182) and non-lesional extratemporal epilepsy (n = 193). A harmonized protocol using tract-based spatial statistics was used to derive skeletonized maps of fractional anisotropy and mean diffusivity for each participant, and fibre tracts were segmented using a diffusion MRI atlas. Data were harmonized to correct for scanner-specific variations in diffusion measures using a batch-effect correction tool (ComBat). Analyses of covariance, adjusting for age and sex, examined differences between each epilepsy syndrome and controls for each white matter tract (Bonferroni corrected at P < 0.001). Across 'all epilepsies' lower fractional anisotropy was observed in most fibre tracts with small to medium effect sizes, especially in the corpus callosum, cingulum and external capsule. There were also less robust increases in mean diffusivity. Syndrome-specific fractional anisotropy and mean diffusivity differences were most pronounced in patients with hippocampal sclerosis in the ipsilateral parahippocampal cingulum and external capsule, with smaller effects across most other tracts. Individuals with temporal lobe epilepsy and normal MRI showed a similar pattern of greater ipsilateral than contralateral abnormalities, but less marked than those in patients with hippocampal sclerosis. Patients with generalized and extratemporal epilepsies had pronounced reductions in fractional anisotropy in the corpus callosum, corona radiata and external capsule, and increased mean diffusivity of the anterior corona radiata. Earlier age of seizure onset and longer disease duration were associated with a greater extent of diffusion abnormalities in patients with hippocampal sclerosis. We demonstrate microstructural abnormalities across major association, commissural, and projection fibres in a large multicentre study of epilepsy. Overall, patients with epilepsy showed white matter abnormalities in the corpus callosum, cingulum and external capsule, with differing severity across epilepsy syndromes. These data further define the spectrum of white matter abnormalities in common epilepsy syndromes, yielding more detailed insights into pathological substrates that may explain cognitive and psychiatric co-morbidities and be used to guide biomarker studies of treatment outcomes and/or genetic research.
White matter and hypoxic hypobaria in humans McGuire, Stephen A.; Ryan, Meghann C.; Sherman, Paul M. ...
Human brain mapping,
August 1, 2019, Volume:
40, Issue:
11
Journal Article
Peer reviewed
Open access
Occupational exposure to hypobaria (low atmospheric pressure) is a risk factor for reduced white matter integrity, increased white matter hyperintensive burden, and decline in cognitive function. We ...tested the hypothesis that a discrete hypobaric exposure will have a transient impact on cerebral physiology. Cerebral blood flow, fractional anisotropy of water diffusion in cerebral white matter, white matter hyperintensity volume, and concentrations of neurochemicals were measured at baseline and 24 hr and 72 hr postexposure in N = 64 healthy aircrew undergoing standard US Air Force altitude chamber training and compared to N = 60 controls not exposed to hypobaria. We observed that hypobaric exposure led to a significant rise in white matter cerebral blood flow (CBF) 24 hr postexposure that remained elevated, albeit not significantly, at 72 hr. No significant changes were observed in structural measurements or gray matter CBF. Subjects with higher baseline concentrations of neurochemicals associated with neuroprotection and maintenance of normal white matter physiology (glutathione, N‐acetylaspartate, glutamate/glutamine) showed proportionally less white matter CBF changes. Our findings suggest that discrete hypobaric exposure may provide a model to study white matter injury associated with occupational hypobaric exposure.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Studies of the central sulcus (CS) often use observer-dependent procedures to assess CS morphology and sulcal landmarks. Here, we applied a novel method combining automated sulcus reconstruction, ...surface parameterization, and an observer-independent depth measurement to study the CS. This facilitated the quantitative assessment of the spatial position and intersubject variability of several sulcal landmarks. Sulcal depth profiles also allowed us to develop an algorithm for the clear identification of several landmarks, including the pli de passage fronto-pariétal moyen (PPFM), first described by Broca. Using this algorithm, the PPFM was identified in the majority of sulci, but exhibited limited spatial variability. This appears to support Cunningham's theory that this landmark may be a developmental remnant, and may argue against its role as a guide to the more variable somatotopic hand area. Sulcal depth profiles were also utilized to assess the influence of sex, handedness, and age on CS morphology. These profiles revealed leftward depth asymmetry in the superior extent of the CS of male subjects and near the midpoint of the CS in female subjects. Age correlations were performed for these asymmetries, and a significant correlation was seen only in the male subgroup.
Previous investigations of cerebral anatomy in persistent developmental stutterers have reported bilateral anomalies in the perisylvian region and atypical patterns of cerebral asymmetry. In this ...study, perisylvian sulcal patterns were analyzed to compare subjects with persistent developmental stuttering (PDS) and an age-, hand-, and gender-matched control group. This analysis was accomplished using software designed for 3-dimensional sulcal identification and extraction. Patterns of cerebral asymmetry were also investigated with standard planimetric measurements. PDS subjects showed a small but significant increase in both the number of sulci connecting with the second segment of the right Sylvian fissure and in the number of suprasylvian gyral banks (of sulci) along this segment. No differences were seen in the left perisylvian region for either sulcal number or gyral bank number. Measurements of asymmetry revealed typical patterns of cerebral asymmetry in both groups with no significant differences in frontal and occipital width asymmetry, frontal and occipital pole asymmetry, or planum temporale and Sylvian fissure asymmetries. The subtle difference in cortical folding of the right perisylvian region observed in PDS subjects may correlate with functional imaging studies that have reported increased right-hemisphere activity during stuttered speech.
Objective
Demonstrate that occupational exposure to nonhypoxic hypobaria is associated with subcortical white matter hyperintensities (WMHs) on fluid‐attenuated inversion recovery magnetic resonance ...imaging (MRI).
Methods
Eighty‐three altitude chamber personnel (PHY), 105 U‐2 pilots (U2P), and 148 age‐ controlled and health‐matched doctorate degree controls (DOC) underwent high‐resolution MRI. Subcortical WMH burden was quantified as count and volume of subcortical WMH lesions after transformation of images to the Talairach atlas–based stereotactic frame.
Results
Subcortical WMHs were more prevalent in PHY (volume p = 0.011/count p = 0.019) and U2P (volume p < 0.001/count p < 0.001) when compared to DOC, whereas PHY were not significantly different than U2P.
Interpretation
This study provides strong evidence that nonhypoxic hypobaric exposure may induce subcortical WMHs in a young, healthy population lacking other risk factors for WMHs and adds this occupational exposure to other environmentally related potential causes of WMHs. Ann Neurol 2014;76:719–726
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
OBJECTIVE:Determine whether United States Air Force (USAF) U-2 pilots (U2Ps) with occupational exposure to repeated hypobaria had lower neurocognitive performance compared to pilots without repeated ...hypobaric exposure and whether U2P neurocognitive performance correlated with white matter hyperintensity (WMH) burden.
METHODS:We collected Multidimensional Aptitude Battery–II (MAB-II) and MicroCogAssessment of Cognitive Functioning (MicroCog) neurocognitive data on USAF U2Ps with a history of repeated occupational exposure to hypobaria and compared these with control data collected from USAF pilots (AFPs) without repeated hypobaric exposure (U2Ps/AFPs MAB-II 87/83; MicroCog 93/80). Additional comparisons were performed between U2Ps with high vs low WMH burden.
RESULTS:U2Ps with repeated hypobaric exposure had significantly lower scores than control pilots on reasoning/calculation (U2Ps/AFPs 99.4/106.5), memory (105.5/110.9), information processing accuracy (102.1/105.8), and general cognitive functioning (103.5/108.5). In addition, U2Ps with high whole-brain WMH count showed significantly lower scores on reasoning/calculation (high/low 96.8/104.1), memory (102.9/110.2), general cognitive functioning (101.5/107.2), and general cognitive proficiency (103.6/108.8) than U2Ps with low WMH burden (high/low WMH mean volume 0.213/0.003 cm and mean count 14.2/0.4).
CONCLUSION:In these otherwise healthy, highly functioning individuals, pilots with occupational exposure to repeated hypobaria demonstrated lower neurocognitive performance, albeit demonstrable on only some tests, than pilots without repeated exposure. Furthermore, within the U2P population, higher WMH burden was associated with lower neurocognitive test performance. Hypobaric exposure may be a risk factor for subtle changes in neurocognition.
Introduction
Quantitative longitudinal magnetic resonance imaging and spectroscopy (MRI/S) is used to assess progress of brain disorders and treatment effects. Understanding the significance of MRI/S ...changes requires knowledge of the inherent technical and physiological consistency of these measurements. This longitudinal study examined the variance and reproducibility of commonly used quantitative MRI/S measurements in healthy subjects while controlling physiological and technical parameters.
Methods
Twenty‐five subjects were imaged three times over 5 days on a Siemens 3T Verio scanner equipped with a 32‐channel phase array coil. Structural (T1, T2‐weighted, and diffusion‐weighted imaging) and physiological (pseudocontinuous arterial spin labeling, proton magnetic resonance spectroscopy) data were collected. Consistency of repeated images was evaluated with mean relative difference, mean coefficient of variation, and intraclass correlation (ICC). Finally, a “reproducibility rating” was calculated based on the number of subjects needed for a 3% and 10% difference.
Results
Structural measurements generally demonstrated excellent reproducibility (ICCs 0.872–0.998) with a few exceptions. Moderate‐to‐low reproducibility was observed for fractional anisotropy measurements in fornix and corticospinal tracts, for cortical gray matter thickness in the entorhinal, insula, and medial orbitofrontal regions, and for the count of the periependymal hyperintensive white matter regions. The reproducibility of physiological measurements ranged from excellent for most of the magnetic resonance spectroscopy measurements to moderate for permeability‐diffusivity coefficients in cingulate gray matter to low for regional blood flow in gray and white matter.
Discussion
This study demonstrates a high degree of longitudinal consistency across structural and physiological measurements in healthy subjects, defining the inherent variability in these commonly used sequences. Additionally, this study identifies those areas where caution should be exercised in interpretation. Understanding this variability can serve as the basis for interpretation of MRI/S data in the assessment of neurological disorders and treatment effects.
This study evaluated the consistency of multiple MRI sequences in 25 healthy subjects over three scans performed over 5 days. This study can serve as a reference for understanding the inherent variability in MRI and thus assist in the interpretation of MRIs in clinical studies of neurological disorders and treatment effects.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Anatomical Global Spatial Normalization Lancaster, Jack L.; Cykowski, Matthew D.; McKay, David Reese ...
Neuroinformatics,
10/2010, Volume:
8, Issue:
3
Journal Article
Peer reviewed
Open access
Anatomical global spatial normalization (aGSN) is presented as a method to scale high-resolution brain images to control for variability in brain size without altering the mean size of other brain ...structures. Two types of mean preserving scaling methods were investigated, “shape preserving” and “shape standardizing”. aGSN was tested by examining 56 brain structures from an adult brain atlas of 40 individuals (LPBA40) before and after normalization, with detailed analyses of cerebral hemispheres, all gyri collectively, cerebellum, brainstem, and left and right caudate, putamen, and hippocampus. Mean sizes of brain structures as measured by volume, distance, and area were preserved and variance reduced for both types of scale factors. An interesting finding was that scale factors derived from each of the ten brain structures were also mean preserving. However, variance was best reduced using whole brain hemispheres as the reference structure, and this reduction was related to its high average correlation with other brain structures. The fractional reduction in variance of structure volumes was directly related to
ρ
2
, the square of the reference-to-structure correlation coefficient. The average reduction in variance in volumes by aGSN with whole brain hemispheres as the reference structure was approximately 32%. An analytical method was provided to directly convert between conventional and aGSN scale factors to support adaptation of aGSN to popular spatial normalization software packages.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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