Study of the origin and development of cerebellar tumours has been hampered by the complexity and heterogeneity of cerebellar cells that change over the course of development. Here we use single-cell ...transcriptomics to study more than 60,000 cells from the developing mouse cerebellum and show that different molecular subgroups of childhood cerebellar tumours mirror the transcription of cells from distinct, temporally restricted cerebellar lineages. The Sonic Hedgehog medulloblastoma subgroup transcriptionally mirrors the granule cell hierarchy as expected, while group 3 medulloblastoma resembles Nestin
stem cells, group 4 medulloblastoma resembles unipolar brush cells, and PFA/PFB ependymoma and cerebellar pilocytic astrocytoma resemble the prenatal gliogenic progenitor cells. Furthermore, single-cell transcriptomics of human childhood cerebellar tumours demonstrates that many bulk tumours contain a mixed population of cells with divergent differentiation. Our data highlight cerebellar tumours as a disorder of early brain development and provide a proximate explanation for the peak incidence of cerebellar tumours in early childhood.
The regional distribution of white matter (WM) abnormalities in schizophrenia remains poorly understood, and reported disease effects on the brain vary widely between studies. In an effort to ...identify commonalities across studies, we perform what we believe is the first ever large-scale coordinated study of WM microstructural differences in schizophrenia. Our analysis consisted of 2359 healthy controls and 1963 schizophrenia patients from 29 independent international studies; we harmonized the processing and statistical analyses of diffusion tensor imaging (DTI) data across sites and meta-analyzed effects across studies. Significant reductions in fractional anisotropy (FA) in schizophrenia patients were widespread, and detected in 20 of 25 regions of interest within a WM skeleton representing all major WM fasciculi. Effect sizes varied by region, peaking at (d=0.42) for the entire WM skeleton, driven more by peripheral areas as opposed to the core WM where regions of interest were defined. The anterior corona radiata (d=0.40) and corpus callosum (d=0.39), specifically its body (d=0.39) and genu (d=0.37), showed greatest effects. Significant decreases, to lesser degrees, were observed in almost all regions analyzed. Larger effect sizes were observed for FA than diffusivity measures; significantly higher mean and radial diffusivity was observed for schizophrenia patients compared with controls. No significant effects of age at onset of schizophrenia or medication dosage were detected. As the largest coordinated analysis of WM differences in a psychiatric disorder to date, the present study provides a robust profile of widespread WM abnormalities in schizophrenia patients worldwide. Interactive three-dimensional visualization of the results is available at www.enigma-viewer.org.
A first-ever spinal cord imaging meeting was sponsored by the International Spinal Research Trust and the Wings for Life Foundation with the aim of identifying the current state-of-the-art of spinal ...cord imaging, the current greatest challenges, and greatest needs for future development. This meeting was attended by a small group of invited experts spanning all aspects of spinal cord imaging from basic research to clinical practice. The greatest current challenges for spinal cord imaging were identified as arising from the imaging environment itself; difficult imaging environment created by the bone surrounding the spinal canal, physiological motion of the cord and adjacent tissues, and small crosssectional dimensions of the spinal cord, exacerbated by metallic implants often present in injured patients. Challenges were also identified as a result of a lack of “critical mass” of researchers taking on the development of spinal cord imaging, affecting both the rate of progress in the field, and the demand for equipment and software to manufacturers to produce the necessary tools. Here we define the current state-of-the-art of spinal cord imaging, discuss the underlying theory and challenges, and present the evidence for the current and potential power of these methods. In two review papers (part I and part II), we propose that the challenges can be overcome with advances in methods, improving availability and effectiveness of methods, and linking existing researchers to create the necessary scientific and clinical network to advance the rate of progress and impact of the research.
•Clinical challenges encountered in imaging of the spinal cord are presented.•Description of functional MRI of the spinal cord applications•Description of diffusion tensor imaging of the spinal cord applications•Specific findings in spinal cord pathologies
The human hippocampal formation can be divided into a set of cytoarchitecturally and functionally distinct subregions, involved in different aspects of memory formation. Neuroanatomical disruptions ...within these subregions are associated with several debilitating brain disorders including Alzheimer's disease, major depression, schizophrenia, and bipolar disorder. Multi-center brain imaging consortia, such as the Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) consortium, are interested in studying disease effects on these subregions, and in the genetic factors that affect them. For large-scale studies, automated extraction and subsequent genomic association studies of these hippocampal subregion measures may provide additional insight. Here, we evaluated the test–retest reliability and transplatform reliability (1.5T versus 3T) of the subregion segmentation module in the FreeSurfer software package using three independent cohorts of healthy adults, one young (Queensland Twins Imaging Study, N=39), another elderly (Alzheimer's Disease Neuroimaging Initiative, ADNI-2, N=163) and another mixed cohort of healthy and depressed participants (Max Planck Institute, MPIP, N=598). We also investigated agreement between the most recent version of this algorithm (v6.0) and an older version (v5.3), again using the ADNI-2 and MPIP cohorts in addition to a sample from the Netherlands Study for Depression and Anxiety (NESDA) (N=221). Finally, we estimated the heritability (h2) of the segmented subregion volumes using the full sample of young, healthy QTIM twins (N=728). Test–retest reliability was high for all twelve subregions in the 3T ADNI-2 sample (intraclass correlation coefficient (ICC)=0.70–0.97) and moderate-to-high in the 4T QTIM sample (ICC=0.5–0.89). Transplatform reliability was strong for eleven of the twelve subregions (ICC=0.66–0.96); however, the hippocampal fissure was not consistently reconstructed across 1.5T and 3T field strengths (ICC=0.47–0.57). Between-version agreement was moderate for the hippocampal tail, subiculum and presubiculum (ICC=0.78–0.84; Dice Similarity Coefficient (DSC)=0.55–0.70), and poor for all other subregions (ICC=0.34–0.81; DSC=0.28–0.51). All hippocampal subregion volumes were highly heritable (h2=0.67–0.91). Our findings indicate that eleven of the twelve human hippocampal subregions segmented using FreeSurfer version 6.0 may serve as reliable and informative quantitative phenotypes for future multi-site imaging genetics initiatives such as those of the ENIGMA consortium.
•FreeSurfer v6.0 produced reliable volume estimates for 11 hippocampal subregions.•Agreement between v5.3 and v6.0 was poor for small subregions (e.g. fimbria).•All hippocampal subregion volumes were highly heritable (h2=0.67–0.91).•Hippocampal subregions may be useful quantitative phenotypes for future GWA studies.
Abstract
We present the first data release of the James Clerk Maxwell Telescope Plane Survey (JPS), the JPS Public Release 1. JPS is an 850-μm continuum survey of six fields in the northern inner ...Galactic plane in a longitude range of ℓ = 7°–63°, made with the Submillimetre Common-User Bolometer Array 2. This first data release consists of emission maps of the six JPS regions with an average pixel-to-pixel noise of 7.19 mJy beam−1, when smoothed over the beam, and a compact source catalogue containing 7813 sources. The 95 per cent completeness limits of the catalogue are estimated at 0.04 Jy beam−1 and 0.3 Jy for the peak and integrated flux densities, respectively. The emission contained in the compact source catalogue is 42 ± 5 per cent of the total and, apart from the large-scale (greater than 8 arcmin) emission, there is excellent correspondence with features in the 500-μm Herschel maps. We find that, with two-dimensional matching, 98 ± 2 per cent of sources within the fields centred at ℓ = 20°, 30°, 40° and 50° are associated with molecular clouds, with 91 ± 3 per cent of the ℓ = 30° and 40° sources associated with dense molecular clumps. Matching the JPS catalogue to Herschel 70-μm sources, we find that 38 ± 1 per cent of sources show evidence of ongoing star formation. The JPS Public Release 1 images and catalogue will be a valuable resource for studies of star formation in the Galaxy and the role of environment and spiral arms in the star formation process.
The CORNISH project is the highest resolution radio continuum survey of the Galactic plane to date. It is the 5 GHz radio continuum part of a series of multi-wavelength surveys that focus on the ...northern GLIMPSE region (10degrees < l < 65degrees), observed by the Spitzer satellite in the mid-infrared. Observations with the Very Large Array in B and BnA configurations have yielded a 1".5 resolution Stokes I map with a root mean square noise level better than 0.4 mJy beam super(-1). Here we describe the data-processing methods and data characteristics, and present a new, uniform catalog of compact radio emission. This includes an implementation of automatic deconvolution that provides much more reliable imaging than standard CLEANing. A rigorous investigation of the noise characteristics and reliability of source detection has been carried out. We show that the survey is optimized to detect emission on size scales up to 14" and for unresolved sources the catalog is more than 90% complete at a flux density of 3.9 mJy. We have detected 3062 sources above a 7sigma detection limit and present their ensemble properties. The catalog is highly reliable away from regions containing poorly sampled extended emission, which comprise less than 2% of the survey area. Imaging problems have been mitigated by down-weighting the shortest spacings and potential artifacts flagged via a rigorous manual inspection with reference to the Spitzer infrared data. We present images of the most common source types found: H II regions, planetary nebulae, and radio galaxies. The CORNISH data and catalog are available online at http://cornish.leeds.ac.uk.
Subcortical structures, which include the basal ganglia and parts of the limbic system, have key roles in learning, motor control and emotion, but also contribute to higher-order executive functions. ...Prior studies have reported volumetric alterations in subcortical regions in schizophrenia. Reported results have sometimes been heterogeneous, and few large-scale investigations have been conducted. Moreover, few large-scale studies have assessed asymmetries of subcortical volumes in schizophrenia. Here, as a work completely independent of a study performed by the ENIGMA consortium, we conducted a large-scale multisite study of subcortical volumetric differences between patients with schizophrenia and controls. We also explored the laterality of subcortical regions to identify characteristic similarities and differences between them. T1-weighted images from 1680 healthy individuals and 884 patients with schizophrenia, obtained with 15 imaging protocols at 11 sites, were processed with FreeSurfer. Group differences were calculated for each protocol and meta-analyzed. Compared with controls, patients with schizophrenia demonstrated smaller bilateral hippocampus, amygdala, thalamus and accumbens volumes as well as intracranial volume, but larger bilateral caudate, putamen, pallidum and lateral ventricle volumes. We replicated the rank order of effect sizes for subcortical volumetric changes in schizophrenia reported by the ENIGMA consortium. Further, we revealed leftward asymmetry for thalamus, lateral ventricle, caudate and putamen volumes, and rightward asymmetry for amygdala and hippocampal volumes in both controls and patients with schizophrenia. Also, we demonstrated a schizophrenia-specific leftward asymmetry for pallidum volume. These findings suggest the possibility of aberrant laterality in neural pathways and connectivity patterns related to the pallidum in schizophrenia.
Integrated quantum photonic waveguide circuits are a promising approach to realizing future photonic quantum technologies. Here, we present an integrated photonic quantum technology platform ...utilizing the silicon-on-insulator material system, where quantum interference and the manipulation of quantum states of light are demonstrated in components orders of magnitude smaller than previous implementations. Two-photon quantum interference is presented in a multi-mode interference coupler, and the manipulation of entanglement is demonstrated in a Mach-Zehnder interferometer, opening the way to an all-silicon photonic quantum technology platform.
We present a complete sample of molecular clumps containing compact and ultracompact H ii (UC H ii) regions between = 10° and 60° and |b| < 1°, identified by combining the APEX Telescope Large Area ...Survey of the Galaxy submm and CORNISH radio continuum surveys with visual examination of archival infrared data. Our sample is complete to optically thin, compact and UC H ii regions driven by a zero-age main-sequence star of spectral type B0 or earlier embedded within a 1000 M clump. In total we identify 213 compact and UC H ii regions, associated with 170 clumps. Unambiguous kinematic distances are derived for these clumps and used to estimate their masses and physical sizes, as well as the Lyman continuum fluxes and sizes of their embedded H ii regions. We find a clear lower envelope for the surface density of molecular clumps hosting massive star formation of 0.05 g cm−2, which is consistent with a similar sample of clumps associated with 6.7 GHz masers. The mass of the most massive embedded stars is closely correlated with the mass of their natal clump. Young B stars appear to be significantly more luminous in the ultraviolet than predicted by current stellar atmosphere models. The properties of clumps associated with compact and UC H ii regions are very similar to those associated with 6.7 GHz methanol masers and we speculate that there is little evolution in the structure of the molecular clumps between these two phases. Finally, we identify a significant peak in the surface density of compact and UC H ii-regions associated with the W49A star-forming complex, noting that this complex is truly one of the most massive and intense regions of star formation in the Galaxy.
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