A Comparison of Cranial Cavity Extraction Tools for Non-contrast Enhanced CT Scans in Acute Stroke Patients

Cranial cavity extraction is often the first step in quantitative neuroimaging analyses. However, few automated, validated extraction tools have been developed for non-contrast enhanced CT scans (NECT). The purpose of this study was to compare and contrast freely available tools in an unseen dataset of real-world clinical NECT head scans in order to assess the performance and generalisability of these tools. This study included data from a demographically representative sample of 428 patients who had completed NECT scans following hospitalisation for stroke. In a subset of the scans (n = 20), the intracranial spaces were segmented using automated tools and compared to the gold standard of manual delineation to calculate accuracy, precision, recall, and dice similarity coefficient (DSC) values. Further, three readers independently performed regional visual comparisons of the quality of the results in a larger dataset (n = 428). Three tools were found; one of these had unreliable performance so subsequent evaluation was discontinued. The remaining tools included one that was adapted from the FMRIB software library (fBET) and a convolutional neural network- based tool (rBET). Quantitative comparison showed comparable accuracy, precision, recall and DSC values (fBET: 0.984 ± 0.002; rBET: 0.984 ± 0.003; p = 0.99) between the tools; however, intracranial volume was overestimated. Visual comparisons identified characteristic regional differences in the resulting cranial cavity segmentations. Overall fBET had highest visual quality ratings and was preferred by the readers in the majority of subject results (84%). However, both tools produced high quality extractions of the intracranial space and our findings should improve confidence in these automated CT tools. Pre- and post-processing techniques may further improve these results. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12021-021-09534-7

tDCS induced GABA change is associated with the simulated electric field in M1, an effect mediated by grey matter volume in the MRS voxel

Background and objective Transcranial direct current stimulation (tDCS) has wide ranging applications in neuro-behavioural and physiological research, and in neurological rehabilitation. However, it is currently limited by substantial inter-subject variability in responses, which may be explained, at least in part, by anatomical differences that lead to variability in the electric field (E-field) induced in the cortex. Here, we tested whether the variability in the E-field in the stimulated cortex during anodal tDCS, estimated using computational simulations, explains the variability in tDCS induced changes in GABA, a neurophysiological marker of stimulation effect. Methods Data from five previously conducted MRS studies were combined. The anode was placed over the left primary motor cortex (M1, 3 studies, N = 24) or right temporal cortex (2 studies, N = 32), with the cathode over the contralateral supraorbital ridge. Single voxel spectroscopy was performed in a 2x2x2cm voxel under the anode in all cases. MRS data were acquired before and either during or after 1 mA tDCS using either a sLASER sequence (7T) or a MEGA-PRESS sequence (3T). sLASER MRS data were analysed using LCModel, and MEGA-PRESS using FID-A and Gannet. E-fields were simulated in a finite element model of the head, based on individual structural MR images, using SimNIBS. Separate linear mixed effects models were run for each E-field variable (mean and 95th percentile; magnitude, and components normal and tangential to grey matter surface, within the MRS voxel). The model included effects of time (pre or post tDCS), E-field, grey matter volume in the MRS voxel, and a 3-way interaction between time, E-field and grey matter volume. Additionally, we ran a permutation analysis using PALM to determine whether E-field anywhere in the brain, not just in the MRS voxel, correlated with GABA change. Results In M1, higher mean E-field magnitude was associated with greater anodal tDCS-induced decreases in GABA (t(24) = 3.24, p = 0.003). Further, the association between mean E-field magnitude and GABA change was moderated by the grey matter volume in the MRS voxel (t(24) = −3.55, p = 0.002). These relationships were consistent across all E-field variables except the mean of the normal component. No significant relationship was found between tDCS-induced GABA decrease and E-field in the temporal voxel. No significant clusters were found in the whole brain analysis. Conclusions Our data suggest that the electric field induced by tDCS within the brain is variable, and is significantly related to anodal tDCS-induced decrease in GABA, a key neurophysiological marker of stimulation. These findings strongly support individualised dosing of tDCS, at least in M1. Further studies examining E-fields in relation to other outcome measures, including behaviour, will help determine the optimal E-fields required for any desired effects

Association between tDCS induced GABA change and estimated electric field in the cortex

Transcranial direct current stimulation (tDCS) has wide ranging applications in neuro- behavioural and physiological research, and in neurological rehabilitation. However, it is currently limited by inter-subject variability in responses, which may be explained, at least in part, by anatomical differences that lead to variability in the actual electric field in the cortex. Our aim was to examine whether the variability in electric fields, estimated using computational simulations, explains the variability in tDCS induced GABA changes measured using magnetic resonance spectroscopy (MRS). Data from five studies (total N = 56 complete cases) were combined. The anode and cathode were placed over the left M1 (3 studies, N = 24) or right temporal cortex (2 studies, N = 32), and contralateral supraorbital ridge respectively. GABA to total Creatine ratios were measured and estimated, before and after tDCS application. sLASER MRS data were analysed using LCModel, and MEGA-PRESS using FID-A and Gannet. The electric fields were simulated in a finite element model of the head, based on individual MPRAGE images, using SimNIBS. Twelve linear mixed effects models were run, one for each E-field variable (mean and 95th percentile of magnitude, normal and tangential components), and separately for the M1 and temporal data. We found that in M1, E-field in the MRS voxel is related to the GABA drop, adding to the accumulating evidence that supports individualised dosing of tDCS. We also found an interaction with grey matter volume within the MRS voxel, emphasising the need to appropriately choose and evaluate any outcome measures which we expect to be related to E-field. While we did not find a similar association in the temporal region, given the challenges of modelling the E-field in this region and possible homeostatic metaplastic effects, such an association cannot be ruled out

tDCS induced GABA change is associated with the simulated electric field in M1, an effect mediated by grey matter volume in the MRS voxel

Background and objectiveTranscranial direct current stimulation (tDCS) has wide ranging applications in neuro-behavioural and physiological research, and in neurological rehabilitation. However, it is currently limited by substantial inter-subject variability in responses, which may be explained, at least in part, by anatomical differences that lead to variability in the electric field (E-field) induced in the cortex. Here, we tested whether the variability in the E-field in the stimulated cortex during anodal tDCS, estimated using computational simulations, explains the variability in tDCS induced changes in GABA, a neurophysiological marker of stimulation effect. MethdsData from five previously conducted MRS studies were combined. The anode was placed over the left primary motor cortex (M1, 3 studies, N = 24) or right temporal cortex (2 studies, N = 32), with the cathode over the contralateral supraorbital ridge. Single voxel spectroscopy was performed in a 2x2x2cm voxel under the anode in all cases. MRS data were acquired before and either during or after 1 mA tDCS using either a sLASER sequence (7T) or a MEGA-PRESS sequence (3T). sLASER MRS data were analysed using LCModel, and MEGA-PRESS using FID-A and Gannet. E-fields were simulated in a finite element model of the head, based on individual structural MR images, using SimNIBS. Separate linear mixed effects models were run for each E-field variable (mean and 95th percentile; magnitude, and components normal and tangential to grey matter surface, within the MRS voxel). The model included effects of time (pre or post tDCS), E-field, grey matter volume in the MRS voxel, and a 3-way interaction between time, E-field and grey matter volume. Additionally, we ran a permutation analysis using PALM to determine whether E-field anywhere in the brain, not just in the MRS voxel, correlated with GABA change. ResultsIn M1, higher mean E-field magnitude was associated with greater anodal tDCS-induced decreases in GABA (t(24) = 3.24, p = 0.003). Further, the association between mean E-field magnitude and GABA change was moderated by the grey matter volume in the MRS voxel (t(24) = -3.55, p = 0.002). These relationships were consistent across all E-field variables except the mean of the normal component. No significant relationship was found between tDCS-induced GABA decrease and E-field in the temporal voxel. No significant clusters were found in the whole brain analysis. ConclusionsOur data suggest that the electric field induced by tDCS within the brain is variable, and is significantly related to anodal tDCS-induced decrease in GABA, a key neurophysiological marker of stimulation. These findings strongly support individualised dosing of tDCS, at least in M1. Further studies examining E-fields in relation to other outcome measures, including behaviour, will help determine the optimal E-fields required for any desired effects

An expanded set of genome-wide association studies of brain imaging phenotypes in UK Biobank

UK Biobank is a major prospective epidemiological study, including multimodal brain imaging, genetics and ongoing health outcomes. Previously, we published genome-wide associations of 3,144 brain imaging-derived phenotypes, with a discovery sample of 8,428 individuals. Here we present a new open resource of genome-wide association study summary statistics, using the 2020 data release, almost tripling the discovery sample size. We now include the X chromosome and new classes of imaging-derived phenotypes (subcortical volumes and tissue contrast). Previously, we found 148 replicated clusters of associations between genetic variants and imaging phenotypes; in this study, we found 692, including 12 on the X chromosome. We describe some of the newly found associations, focusing on the X chromosome and autosomal associations involving the new classes of imaging-derived phenotypes. Our novel associations implicate, for example, pathways involved in the rare X-linked STAR (syndactyly, telecanthus and anogenital and renal malformations) syndrome, Alzheimer’s disease and mitochondrial disorders

The Digital Brain Bank, an open access platform for post-mortem imaging datasets

Post-mortem magnetic resonance imaging (MRI) provides the opportunity to acquire high-resolution datasets to investigate neuroanatomy and validate the origins of image contrast through microscopy comparisons. We introduce the Digital Brain Bank (open.win.ox.ac.uk/DigitalBrainBank), a data release platform providing open access to curated, multimodal post-mortem neuroimaging datasets. Datasets span three themes—Digital Neuroanatomist: datasets for detailed neuroanatomical investigations; Digital Brain Zoo: datasets for comparative neuroanatomy; and Digital Pathologist: datasets for neuropathology investigations. The first Digital Brain Bank data release includes 21 distinctive whole-brain diffusion MRI datasets for structural connectivity investigations, alongside microscopy and complementary MRI modalities. This includes one of the highest-resolution whole-brain human diffusion MRI datasets ever acquired, whole-brain diffusion MRI in fourteen nonhuman primate species, and one of the largest post-mortem whole-brain cohort imaging studies in neurodegeneration. The Digital Brain Bank is the culmination of our lab’s investment into post-mortem MRI methodology and MRI-microscopy analysis techniques. This manuscript provides a detailed overview of our work with post-mortem imaging to date, including the development of diffusion MRI methods to image large post-mortem samples, including whole, human brains. Taken together, the Digital Brain Bank provides cross-scale, cross-species datasets facilitating the incorporation of post-mortem data into neuroimaging studies