| 1. |
- Ciumas, C., et al.
(författare)
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White matter development in children with benign childhood epilepsy with centro-temporal spikes
- 2014
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Ingår i: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 137:4, s. 1095-1106
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Tidskriftsartikel (refereegranskat)abstract
- Benign childhood epilepsy with centro-temporal spikes (BCECTS) is associated with cognitive disturbances thought to reflect interference between the epileptic focus and brain development. Using diffusion tensor imaging, Ciumas et al. demonstrate abnormal maturation of white matter at the epileptic focus, which correlates with duration of epilepsy and cognitive performance.Benign childhood epilepsy with centro-temporal spikes (BCECTS) is a unique form of non-lesional age-dependent epilepsy with rare seizures, focal electroencepalographic abnormalities affecting the same well delineated cortical region in most patients, and frequent mild to moderate cognitive dysfunctions. In this condition, it is hypothesized that interictal electroencepalographic discharges might interfere with local brain maturation, resulting in altered cognition. Diffusion tensor imaging allows testing of this hypothesis by investigating the white matter microstructure, and has previously proved sensitive to epilepsy-related alterations of fractional anisotropy and diffusivity. However, no diffusion tensor imaging study has yet been performed with a focus on BCECTS. We investigated 25 children suffering from BCECTS and 25 age-matched control subjects using diffusion tensor imaging, 3D-T-1 magnetic resonance imaging, and a battery of neuropsychological tests including Conner's scale and Wechsler Intelligence Scale for Children (fourth revision). Electroencephalography was also performed in all patients within 2 months of the magnetic resonance imaging assessment. Parametric maps of fractional anisotropy, mean-, radial-, and axial diffusivity were extracted from diffusion tensor imaging data. Patients were compared with control subjects using voxel-based statistics and family-wise error correction for multiple comparisons. Each patient was also compared to control subjects. Fractional anisotropy and diffusivity images were correlated to neuropsychological and clinical variables. Group analysis showed significantly reduced fractional anisotropy and increased diffusivity in patients compared with control subjects, predominantly over the left pre- and postcentral gyri and ipsilateral to the electroencephalographic focus. At the individual level, regions of significant differences were observed in 10 patients (40%) for anisotropy (eight reduced fractional anisotropy, one increased fractional anisotropy, one both), and 17 (56%) for diffusivity (13 increased, one reduced, three both). There were significant negative correlations between fractional anisotropy maps and duration of epilepsy in the precentral gyri, bilaterally, and in the left postcentral gyrus. Accordingly, 9 of 12 patients (75%) with duration of epilepsy > 12 months showed significantly reduced fractional anisotropy versus none of the 13 patients with duration of epilepsy 12 months. Diffusivity maps positively correlated with duration of epilepsy in the cuneus. Children with BCECTS demonstrate alterations in the microstructure of the white matter, undetectable with conventional magnetic resonance imaging, predominating over the regions displaying chronic interictal epileptiform discharges. The association observed between diffusion tensor imaging changes, duration of epilepsy and cognitive performance appears compatible with the hypothesis that interictal epileptic activity alters brain maturation, which could in turn lead to cognitive dysfunction. However, such cross-sectional association does not demonstrate causality, and other hitherto unidentified factors could represent the common cause to part or all of the observed findings.
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| 2. |
- Ledig, C., et al.
(författare)
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Robust whole-brain segmentation: Application to traumatic brain injury
- 2015
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Ingår i: Medical Image Analysis. - : Elsevier BV. - 1361-8415. ; 21:1, s. 40-58
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Tidskriftsartikel (refereegranskat)abstract
- We propose a framework for the robust and fully-automatic segmentation of magnetic resonance (MR) brain images called "Multi-Atlas-Label Propagation with Expectation-Maximisation based refinement" (MALP-EM). The presented approach is based on a robust registration approach (MAPER), highly performant label fusion (joint label fusion) and intensity-based label refinement using EM. We further adapt this framework to be applicable for the segmentation of brain images with gross changes in anatomy. We propose to account for consistent registration errors by relaxing anatomical priors obtained by multi-atlas propagation and a weighting scheme to locally combine anatomical atlas priors and intensity-refined posterior probabilities. The method is evaluated on a benchmark dataset used in a recent MICCAI segmentation challenge. In this context we show that MALP-EM is competitive for the segmentation of MR brain scans of healthy adults when compared to state-of-the-art automatic labelling techniques. To demonstrate the versatility of the proposed approach, we employed MALP-EM to segment 125 MR brain images into 134 regions from subjects who had sustained traumatic brain injury (TBI). We employ a protocol to assess segmentation quality if no manual reference labels are available. Based on this protocol, three independent, blinded raters confirmed on 13 MR brain scans with pathology that MALP-EM is superior to established label fusion techniques. We visually confirm the robustness of our segmentation approach on the full cohort and investigate the potential of derived symmetry-based imaging biomarkers that correlate with and predict clinically relevant variables in TBI such as the Marshall Classification (MC) or Glasgow Outcome Score (GOS). Specifically, we show that we are able to stratify TBI patients with favourable outcomes from non-favourable outcomes with 64.7% accuracy using acute-phase MR images and 66.8% accuracy using follow-up MR images. Furthermore, we are able to differentiate subjects with the presence of a mass lesion or midline shift from those with diffuse brain injury with 76.0% accuracy. The thalamus, putamen, pallidum and hippocampus are particularly affected. Their involvement predicts TBI disease progression.
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| 3. |
- Prange, S., et al.
(författare)
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Early limbic microstructural alterations in apathy and depression in de novo Parkinson's disease
- 2019
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 34:11, s. 1644-1654
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Tidskriftsartikel (refereegranskat)abstract
- Background Whether structural alterations underpin apathy and depression in de novo parkinsonian patients is unknown. The objectives of this study were to investigate whether apathy and depression in de novo parkinsonian patients are related to structural alterations and how structural abnormalities relate to serotonergic or dopaminergic dysfunction. Methods We compared the morphological and microstructural architecture in gray matter using voxel-based morphometry and diffusion tensor imaging coupled with white matter tract-based spatial statistics in a multimodal imaging case-control study enrolling 14 apathetic and 13 nonapathetic patients with de novo Parkinson's disease and 15 age-matched healthy controls, paired with PET imaging of the presynaptic dopaminergic and serotonergic systems. Results De novo parkinsonian patients with apathy had bilateral microstructural alterations in the medial corticostriatal limbic system, exhibiting decreased fractional anisotropy and increased mean diffusivity in the anterior striatum and pregenual anterior cingulate cortex in conjunction with serotonergic dysfunction. Furthermore, microstructural alterations extended to the medial frontal cortex, the subgenual anterior cingulate cortex and subcallosal gyrus, the medial thalamus, and the caudal midbrain, suggesting disruption of long-range nondopaminergic projections originating in the brainstem, in addition to microstructural alterations in callosal interhemispheric connections and frontostriatal association tracts early in the disease course. In addition, microstructural abnormalities related to depressive symptoms in apathetic and nonapathetic patients revealed a distinct, mainly right-sided limbic subnetwork involving limbic and frontal association tracts. Conclusions Early limbic microstructural alterations specifically related to apathy and depression emphasize the role of early disruption of ascending nondopaminergic projections and related corticocortical and corticosubcortical networks which underpin the variable expression of nonmotor and neuropsychiatric symptoms in Parkinson's disease. (c) 2019 International Parkinson and Movement Disorder Society
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| 4. |
- Rizzo, G., et al.
(författare)
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The predictive power of brain mRNA mappings for in vivo protein density: a positron emission tomography correlation study
- 2014
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Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 0271-678X .- 1559-7016. ; 34:5, s. 827-835
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Tidskriftsartikel (refereegranskat)abstract
- Substantial efforts are being spent on postmortem mRNA transcription mapping on the assumption that in vivo protein distribution can be predicted from such data. We tested this assumption by comparing mRNA transcription maps from the Allen Human Brain Atlas with reference protein concentration maps acquired with positron emission tomography (PET) in two representative systems of neurotransmission (opioid and serotoninergic). We found a tight correlation between mRNA expression and specific binding with 5-HT1A receptors measured with PET, but for opioid receptors, the correlation was weak. The discrepancy can be explained by differences in expression regulation between the two systems: transcriptional mechanisms dominate the regulation in the serotoninergic system, whereas in the opioid system proteins are further modulated after transcription. We conclude that mRNA information can be exploited for systems where translational mechanisms predominantly regulate expression. Where posttranscriptional mechanisms are important, mRNA data have to be interpreted with caution. The methodology developed here can be used for probing assumptions about the relationship of mRNA and protein in multiple neurotransmission systems.
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| 5. |
- Heckemann, Rolf A., et al.
(författare)
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Brain Extraction Using Label Propagation and Group Agreement: Pincram
- 2015
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 10:7
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Tidskriftsartikel (refereegranskat)abstract
- Accurately delineating the brain on magnetic resonance (MR) images of the head is a prerequisite for many neuroimaging methods. Most existing methods exhibit disadvantages in that they are laborious, yield inconsistent results, and/or require training data to closely match the data to be processed. Here, we present pincram, an automatic, versatile method for accurately labelling the adult brain on T1-weighted 3D MR head images. The method uses an iterative refinement approach to propagate labels from multiple atlases to a given target image using image registration. At each refinement level, a consensus label is generated. At the subsequent level, the search for the brain boundary is constrained to the neighbourhood of the boundary of this consensus label. The method achieves high accuracy (Jaccard coefficient > 0.95 on typical data, corresponding to a Dice similarity coefficient of > 0.97) and performs better than many state-of-the-art methods as evidenced by independent evaluation on the Segmentation Validation Engine. Via a novel self-monitoring feature, the program generates the " success index," a scalar metadatum indicative of the accuracy of the output label. Pincram is available as open source software.
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| 6. |
- Ledig, C., et al.
(författare)
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Structural brain imaging in Alzheimer's disease and mild cognitive impairment: biomarker analysis and shared morphometry database
- 2018
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Magnetic resonance (MR) imaging is a powerful technique for non-invasive in-vivo imaging of the human brain. We employed a recently validated method for robust cross-sectional and longitudinal segmentation of MR brain images from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. Specifically, we segmented 5074 MR brain images into 138 anatomical regions and extracted time-point specific structural volumes and volume change during follow-up intervals of 12 or 24 months. We assessed the extracted biomarkers by determining their power to predict diagnostic classification and by comparing atrophy rates to published meta-studies. The approach enables comprehensive analysis of structural changes within the whole brain. The discriminative power of individual biomarkers (volumes/atrophy rates) is on par with results published by other groups. We publish all quality-checked brain masks, structural segmentations, and extracted biomarkers along with this article. We further share the methodology for brain extraction (pincram) and segmentation (MALPEM, MALPEM4D) as open source projects with the community. The identified biomarkers hold great potential for deeper analysis, and the validated methodology can readily be applied to other imaging cohorts.
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| 7. |
- McGinnity, Colm J, et al.
(författare)
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Αlpha 5 subunit-containing GABAA receptors in temporal lobe epilepsy with normal MRI.
- 2021
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Ingår i: Brain communications. - : Oxford University Press (OUP). - 2632-1297. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- GABAA receptors containing the α5 subunit mediate tonic inhibition and are widely expressed in the limbic system. In animals, activation of α5-containing receptors impairs hippocampus-dependent memory. Temporal lobe epilepsy is associated with memory impairments related to neuron loss and other changes. The less selective PET ligand [11C]flumazenil has revealed reductions in GABAA receptors. The hypothesis that α5 subunit receptor alterations are present in temporal lobe epilepsy and could contribute to impaired memory is untested. We compared α5 subunit availability between individuals with temporal lobe epilepsy and normal structural MRI ('MRI-negative') and healthy controls, and interrogated the relationship between α5 subunit availability and episodic memory performance, in a cross-sectional study. Twenty-three healthy male controls (median ± interquartile age 49 ± 13 years) and 11 individuals with MRI-negative temporal lobe epilepsy (seven males; 40 ± 8) had a 90-min PET scan after bolus injection of [11C]Ro15-4513, with arterial blood sampling and metabolite correction. All those with epilepsy and six controls completed the Adult Memory and Information Processing Battery on the scanning day. 'Bandpass' exponential spectral analyses were used to calculate volumes of distribution separately for the fast component [VF; dominated by signal from α1 (α2, α3)-containing receptors] and the slow component (VS; dominated by signal from α5-containing receptors). We made voxel-by-voxel comparisons between: the epilepsy and control groups; each individual case versus the controls. We obtained parametric maps of VF and VS measures from a single bolus injection of [11C]Ro15-4513. The epilepsy group had higher VS in anterior medial and lateral aspects of the temporal lobes, the anterior cingulate gyri, the presumed area tempestas (piriform cortex) and the insulae, in addition to increases of ∼24% and ∼26% in the ipsilateral and contralateral hippocampal areas (P < 0.004). This was associated with reduced VF:VS ratios within the same areas (P < 0.009). Comparisons of VS for each individual with epilepsy versus controls did not consistently lateralize the epileptogenic lobe. Memory scores were significantly lower in the epilepsy group than in controls (mean ± standard deviation -0.4 ± 1.0 versus 0.7 ± 0.3; P = 0.02). In individuals with epilepsy, hippocampal VS did not correlate with memory performance on the Adult Memory and Information Processing Battery. They had reduced VF in the hippocampal area, which was significant ipsilaterally (P = 0.03), as expected from [11C]flumazenil studies. We found increased tonic inhibitory neurotransmission in our cohort of MRI-negative temporal lobe epilepsy who also had co-morbid memory impairments. Our findings are consistent with a subunit shift from α1/2/3 to α5 in MRI-negative temporal lobe epilepsy.
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| 8. |
- Scott, G., et al.
(författare)
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Amyloid pathology and axonal injury after brain trauma
- 2016
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Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 86:9, s. 821-828
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Tidskriftsartikel (refereegranskat)abstract
- Objective:To image -amyloid (A) plaque burden in long-term survivors of traumatic brain injury (TBI), test whether traumatic axonal injury and A are correlated, and compare the spatial distribution of A to Alzheimer disease (AD).Methods:Patients 11 months to 17 years after moderate-severe TBI underwent C-11-Pittsburgh compound B (C-11-PiB)-PET, structural and diffusion MRI, and neuropsychological examination. Healthy aged controls and patients with AD underwent PET and structural MRI. Binding potential (BPND) images of C-11-PiB, which index A plaque density, were computed using an automatic reference region extraction procedure. Voxelwise and regional differences in BPND were assessed. In TBI, a measure of white matter integrity, fractional anisotropy, was estimated and correlated with C-11-PiB BP(ND.)Results:Twenty-eight participants (9 with TBI, 9 controls, 10 with AD) were assessed. Increased C-11-PiB BPND was found in TBI vs controls in the posterior cingulate cortex and cerebellum. Binding in the posterior cingulate cortex increased with decreasing fractional anisotropy of associated white matter tracts and increased with time since injury. Compared to AD, binding after TBI was lower in neocortical regions but increased in the cerebellum.Conclusions:Increased A burden was observed in TBI. The distribution overlaps with, but is distinct from, that of AD. This suggests a mechanistic link between TBI and the development of neuropathologic features of dementia, which may relate to axonal damage produced by the injury.
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| 9. |
- Wild, H. M., et al.
(författare)
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Gyri of the human parietal lobe: Volumes, spatial extents, automatic labelling, and probabilistic atlases
- 2017
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:8
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Tidskriftsartikel (refereegranskat)abstract
- Accurately describing the anatomy of individual brains enables interlaboratory communication of functional and developmental studies and is crucial for possible surgical interventions. The human parietal lobe participates in multimodal sensory integration including language processing and also contains the primary somatosensory area. We describe detailed protocols to subdivide the parietal lobe, analyze morphological and volumetric characteristics, and create probabilistic atlases in MNI152 stereotaxic space. The parietal lobe was manually delineated on 3D T1 MR images of 30 healthy subjects and divided into four regions: supramarginal gyrus (SMG), angular gyrus (AG), superior parietal lobe (supPL) and postcentral gyrus (postCG). There was the expected correlation of male gender with larger brain and intracranial volume. We examined a wide range of anatomical features of the gyri and the sulci separating them. At least a rudimentary primary intermediate sulcus of Jensen (PISJ) separating SMG and AG was identified in nearly all (59/60) hemispheres. Presence of additional gyri in SMG and AG was related to sulcal features and volumetric characteristics. The parietal lobe was slightly (2%) larger on the left, driven by leftward asymmetries of the postCG and SMG. Intersubject variability was highest for SMG and AG, and lowest for postCG. Overall the morphological characteristics tended to be symmetrical, and volumes also tended to covary between hemispheres. This may reflect developmental as well as maturation factors. To assess the accuracy with which the labels can be used to segment newly acquired (unlabelled) T1-weighted brain images, we applied multi-atlas label propagation software (MAPER) in a leave-one-out experiment and compared the resulting automatic labels with the manually prepared ones. The results showed strong agreement (mean Jaccard index 0.69, corresponding to a mean Dice index of 0.82, average mean volume error of 0.6%). Stereotaxic probabilistic atlases of each subregion were obtained. They illustrate the physiological brain torque, with structures in the right hemisphere positioned more anteriorly than in the left, and right/left positional differences of up to 10 mm. They also allow an assessment of sulcal variability, e.g. low variability for parietooccipital fissure and cingulate sulcus. Illustrated protocols, individual label sets, probabilistic atlases, and a maximum-probability atlas which takes into account surrounding structures are available for free download under academic licences.
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| 10. |
- Yaakub, S. N., et al.
(författare)
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On brain atlas choice and automatic segmentation methods: a comparison of MAPER & FreeSurfer using three atlas databases
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Several automatic image segmentation methods and few atlas databases exist for analysing structural T1-weighted magnetic resonance brain images. The impact of choosing a combination has not hitherto been described but may bias comparisons across studies. We evaluated two segmentation methods (MAPER and FreeSurfer), using three publicly available atlas databases (Hammers_mith, Desikan-Killiany-Tourville, and MICCAI 2012 Grand Challenge). For each combination of atlas and method, we conducted a leave-one-out cross-comparison to estimate the segmentation accuracy of FreeSurfer and MAPER. We also used each possible combination to segment two datasets of patients with known structural abnormalities (Alzheimer’s disease (AD) and mesial temporal lobe epilepsy with hippocampal sclerosis (HS)) and their matched healthy controls. MAPER was better than FreeSurfer at modelling manual segmentations in the healthy control leave-one-out analyses in two of the three atlas databases, and the Hammers_mith atlas database transferred to new datasets best regardless of segmentation method. Both segmentation methods reliably identified known abnormalities in each patient group. Better separation was seen for FreeSurfer in the AD and left-HS datasets, and for MAPER in the right-HS dataset. We provide detailed quantitative comparisons for multiple anatomical regions, thus enabling researchers to make evidence-based decisions on their choice of atlas and segmentation method. © 2020, The Author(s).
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