Brain charts for the human lifespan.

Over the past few decades, neuroimaging has become a ubiquitous tool in basic research and clinical studies of the human brain. However, no reference standards currently exist to quantify individual differences in neuroimaging metrics over time, in contrast to growth charts for anthropometric traits such as height and weight1. Here we assemble an interactive open resource to benchmark brain morphology derived from any current or future sample of MRI data ( http://www.brainchart.io/ ). With the goal of basing these reference charts on the largest and most inclusive dataset available, acknowledging limitations due to known biases of MRI studies relative to the diversity of the global population, we aggregated 123,984 MRI scans, across more than 100 primary studies, from 101,457 human participants between 115 days post-conception to 100 years of age. MRI metrics were quantified by centile scores, relative to non-linear trajectories2 of brain structural changes, and rates of change, over the lifespan. Brain charts identified previously unreported neurodevelopmental milestones3, showed high stability of individuals across longitudinal assessments, and demonstrated robustness to technical and methodological differences between primary studies. Centile scores showed increased heritability compared with non-centiled MRI phenotypes, and provided a standardized measure of atypical brain structure that revealed patterns of neuroanatomical variation across neurological and psychiatric disorders. In summary, brain charts are an essential step towards robust quantification of individual variation benchmarked to normative trajectories in multiple, commonly used neuroimaging phenotypes.

Investigation of Brain Iron in Niemann-Pick Type C: A 7T Quantitative Susceptibility Mapping Study.

BACKGROUND AND PURPOSE: While brain iron dysregulation has been observed in several neurodegenerative disorders, its association with the progressive neurodegeneration in Niemann-Pick type C is unknown. Systemic iron abnormalities have been reported in patients with Niemann-Pick type C and in animal models of Niemann-Pick type C. In this study, we examined brain iron using quantitative susceptibility mapping MR imaging in individuals with Niemann-Pick type C compared with healthy controls. MATERIALS AND METHODS: A cohort of 10 patients with adolescent- and adult-onset Niemann-Pick type C and 14 age- and sex-matched healthy controls underwent 7T brain MR imaging with T1 and quantitative susceptibility mapping acquisitions. A probing whole-brain voxelwise comparison of quantitative susceptibility mapping between groups was conducted. Mean quantitative susceptibility mapping in the ROIs (thalamus, hippocampus, putamen, caudate nucleus, and globus pallidus) was further compared. The correlations between regional volume, quantitative susceptibility mapping values, and clinical features, which included disease severity on the Iturriaga scale, cognitive function, and the Social and Occupational Functioning Assessment Scale, were explored as secondary analyses. RESULTS: We observed lower volume in the thalamus and voxel clusters of higher quantitative susceptibility mapping in the pulvinar nuclei bilaterally in patients with Niemann-Pick type C compared with the control group. In patients with Niemann-Pick type C, higher quantitative susceptibility mapping in the pulvinar nucleus clusters correlated with lower volume of the thalamus on both sides. Moreover, higher quantitative susceptibility mapping in the right pulvinar cluster was associated with greater disease severity. CONCLUSIONS: Our findings suggest iron deposition in the pulvinar nucleus in Niemann-Pick type C disease, which is associated with thalamic atrophy and disease severity. This preliminary evidence supports the link between iron and neurodegeneration in Niemann-Pick type C, in line with existing literature on other neurodegenerative disorders.

Altered neurotransmission and neuroimaging biomarkers of chronic arsenic poisoning in wild muskrats (Ondatra zibethicus) and red squirrels (Tamiasciurus hudsonicus) breeding near the City of Yellowknife, Northwest Territories (Canada).

Chronic arsenic poisoning has been shown to be a risk factor for the development of intellectual disability. Numerous human and animal studies have also confirmed that low-level arsenic exposure has deleterious effects on neurotransmission and brain structures which have been further linked to neurobehavioral disorders. The aim of this present work was to comparatively assess structural brain volume changes and alteration of two (2) neurotransmitters, specifically dopamine (DA) and serotonin (5-HT) in the brains of wild muskrats and squirrels breeding in arsenic endemic areas, near the vicinity of the abandoned Giant mine site in Yellowknife and in reference locations between 52 and 105 km from the city of Yellowknife. The levels of DA and 5-HT were measured in the brain tissues, and Magnetic Resonance Imaging (MRI) was used to attempt brain volume measurements. The results revealed that the concentrations of DA and 5-HT were slightly increased in the brains of squirrels from the arsenic endemic areas compared to the reference site. Further, DA and 5-HT were slightly reduced in the brains of muskrats from the arsenic endemic areas compared to the reference location. In general, no statistically significant neurotransmission changes and differences were observed in the brain tissues of muskrats and squirrels from both arsenic endemic areas and non-endemic sites. Although MRI results showed that the brain volumes of squirrels and muskrats were not statistically different between sites after multiple comparison correction; it was noted that core brain regions were substantially affected in muskrats, in particular the hippocampal memory circuit, striatum and thalamus. Squirrel brains showed more extensive neuroanatomical changes, likely due to their relatively smaller body mass, with extensive shrinkage of the core brain structures, and the cortex, even after accounting for differences in overall brain size. The results of this present study constitute the first observation of neuroanatomical changes in wild small mammal species breeding in arsenic endemic areas of Canada.

The effect of crack cocaine addiction and age on the microstructure and morphology of the human striatum and thalamus using shape analysis and fast diffusion kurtosis imaging.

The striatum and thalamus are subcortical structures intimately involved in addiction. The morphology and microstructure of these have been studied in murine models of cocaine addiction (CA), showing an effect of drug use, but also chronological age in morphology. Human studies using non-invasive magnetic resonance imaging (MRI) have shown inconsistencies in volume changes, and have also shown an age effect. In this exploratory study, we used MRI-based volumetric and novel shape analysis, as well as a novel fast diffusion kurtosis imaging sequence to study the morphology and microstructure of striatum and thalamus in crack CA compared to matched healthy controls (HCs), while investigating the effect of age and years of cocaine consumption. We did not find significant differences in volume and mean kurtosis (MKT) between groups. However, we found significant contraction of nucleus accumbens in CA compared to HCs. We also found significant age-related changes in volume and MKT of CA in striatum and thalamus that are different to those seen in normal aging. Interestingly, we found different effects and contributions of age and years of consumption in volume, displacement and MKT changes, suggesting that each measure provides different but complementing information about morphological brain changes, and that not all changes are related to the toxicity or the addiction to the drug. Our findings suggest that the use of finer methods and sequences provides complementing information about morphological and microstructural changes in CA, and that brain alterations in CA are related cocaine use and age differently.

The role of substrate surface alteration in the fabrication of vertically aligned CdTe nanowires.

Previously we have described the deposition of vertically aligned wurtzite CdTe nanowires derived from an unusual catalytically driven growth mode. This growth mode could only proceed when the surface of the substrate was corrupted with an alcohol layer, although the role of the corruption was not fully understood. Here, we present a study detailing the remarkable role that this substrate surface alteration plays in the development of CdTe nanowires; it dramatically improves the size uniformity and largely eliminates lateral growth. These effects are demonstrated to arise from the altered surface's ability to limit Ostwald ripening of the catalytic seed material and by providing a surface unable to promote the epitaxial relationship needed to sustain a lateral growth mode. The axial growth of the CdTe nanowires is found to be exclusively driven through the direct impingement of adatoms onto the catalytic seeds leading to a self-limiting wire height associated with the sublimation of material from the sidewall facets. The work presented furthers the development of the mechanisms needed to promote high quality substrate-based vertically aligned CdTe nanowires. With our present understanding of the growth mechanism being a combination of selective area epitaxy and a catalytically driven vapour-liquid-solid growth mode, these results also raise the intriguing possibility of employing this growth mode in other material systems in an effort to produce superior nanowires.