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"Sinclair, Benjamin"
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The Immortal Men : the end of forever
\"The superstar creative team of comics legend Jim Lee (Batman, Justice League) and James Tynion IV (Detective Comics) unite to tell the tale of the secret history of heroes who have protected humanity from the shadows since the dawn of time...and who can live forever. There is a secret history to the DC Universe of heroes who have protected humanity from the shadows since the dawn of time...and who can live forever. Enter the Immortal Men! The team, headed by the Immortal Man, has waged a secret war against the House of Conquest for countless years--but Conquest has dealt a devastating blow. When their base of operations, known as the Campus, is savagely attacked, the Immortal Men must seek out their last hope--an emerging metahuman known as Caden Park! With the Batman Who Laughs lurking in the shadows things get serious quickly.\"-- Provided by publisher.
Book
Automated segmentation of epilepsy surgical resection cavities: Comparison of four methods to manual segmentation
•The SPM-based automated epilepsy surgery segmentation tools performed better than the deep learning-based tools on our mixed cohort of subjects who had either temporal or extratemporal epilepsy surgery.•All four tools performed similarly well on the temporal epilepsy subgroup.•The accuracy of each model improved as the size of the resection cavity increased.•Quality control is an important step when implementing the tools, as no algorithm was able to segment every epilepsy surgery resection cavity.
Accurate resection cavity segmentation on MRI is important for neuroimaging research involving epilepsy surgical outcomes. Manual segmentation, the gold standard, is highly labour intensive. Automated pipelines are an efficient potential solution; however, most have been developed for use following temporal epilepsy surgery. Our aim was to compare the accuracy of four automated segmentation pipelines following surgical resection in a mixed cohort of subjects following temporal or extra temporal epilepsy surgery. We identified 4 open-source automated segmentation pipelines. Epic-CHOP and ResectVol utilise SPM-12 within MATLAB, while Resseg and Deep Resection utilise 3D U-net convolutional neural networks. We manually segmented the resection cavity of 50 consecutive subjects who underwent epilepsy surgery (30 temporal, 20 extratemporal). We calculated Dice similarity coefficient (DSC) for each algorithm compared to the manual segmentation. No algorithm identified all resection cavities. ResectVol (n = 44, 88 %) and Epic-CHOP (n = 42, 84 %) were able to detect more resection cavities than Resseg (n = 22, 44 %, P < 0.001) and Deep Resection (n = 23, 46 %, P < 0.001). The SPM-based pipelines (Epic-CHOP and ResectVol) performed better than the deep learning-based pipelines in the overall and extratemporal surgery cohorts. In the temporal cohort, the SPM-based pipelines had higher detection rates, however there was no difference in the accuracy between methods. These pipelines could be applied to machine learning studies of outcome prediction to improve efficiency in pre-processing data, however human quality control is still required.
Journal Article
Batman by Grant Morrison omnibus
\"One of the greatest storytellers of his generation, Grant Morrison's arrival onto the Dark Knight was one of the most hyped debuts in industry history. This collection includes time-spanning epic graphic novels featuring the cataclysmic events of FINAL CRISIS and the introduction of Batman's son, Damian Wayne! These blockbuster stories featured a deconstruction of super hero comics like never before, with challenging, thought-provoking takes on the modern, four-color icons.\"-- Provided by publisher.
Book
A critical guide to the automated quantification of perivascular spaces in magnetic resonance imaging
The glymphatic system is responsible for waste clearance in the brain. It is comprised of perivascular spaces (PVS) that surround penetrating blood vessels. These spaces are filled with cerebrospinal fluid and interstitial fluid, and can be seen with magnetic resonance imaging. Various algorithms have been developed to automatically label these spaces in MRI. This has enabled volumetric and morphological analyses of PVS in healthy and disease cohorts. However, there remain inconsistencies between PVS measures reported by different methods of automated segmentation. The present review emphasizes that importance of voxel-wise evaluation of model performance, mainly with the Sørensen Dice similarity coefficient. Conventional count correlations for model validation are inadequate if the goal is to assess volumetric or morphological measures of PVS. The downside of voxel-wise evaluation is that it requires manual segmentations that require large amounts of time to produce. One possible solution is to derive these semi-automatically. Additionally, recommendations are made to facilitate rigorous development and validation of automated PVS segmentation models. In the application of automated PVS segmentation tools, publication of image quality metrics, such as the contrast-to-noise ratio, alongside descriptive statistics of PVS volumes and counts will facilitate comparability between studies. Lastly, a head-to-head comparison between two algorithms, applied to two cohorts of astronauts reveals how results can differ substantially between techniques.
Journal Article
Volumetric MRI and FDG-PET hypometabolism biomarkers of frontotemporal dementia: protocol for a systematic review and meta-analysis
IntroductionFrontotemporal dementia (FTD) remains challenging to diagnose owing to the marked clinical heterogeneity associated with the disease. This heterogeneity stems from the complex interplay of various clinical phenotypes, genetic mutations and underlying neuropathologies, such as TDP-43 and tau proteinopathies. Currently, there is no single confirmed biomarker that can reliably diagnose disease, specifically disease stage, disease subtype and underlying neuropathology. Recent research has indicated that neuroimaging techniques hold the most promise for the discovery of FTD biomarkers. We propose a protocol for a systematic review and meta-analysis to identify MRI and fluorodeoxyglucose positron emission tomography (FDG-PET) biomarkers associated with clinical, genetic and pathological subtypes of FTD. We aim to address the following research questions: can regional MRI volumetry and FDG-PET hypometabolism differentiate (1) FTD patients from healthy controls; (2) sporadic cases of FTD from healthy controls; (3) genetic cases of FTD (MAPT, GRN, and C9orf72 mutations); and (4) underlying neuropathology, specifically discriminating between tau- and TDP-43-based FTD?MethodsLiterature searches will be performed across three databases: Ovid Medline, Ovid Embase and Web of Science. Publications that have fewer than five participants, are non-human-based, not written in the English language or contain unpublished data will be excluded. Two independent investigators will screen and subsequently evaluate which publications to include. Should any disagreements arise, a third investigator will settle the discrepancy. After the random-effects meta-analysis has been used to extract and pool the data, I2 analysis will be used to quantify heterogeneity.Ethics and disseminationEthics approval will not be required for this research. On completion, the systematic review and meta-analysis will be published in a peer-reviewed journal.PROSPERO registration numberCRD42024545302.
Journal Article
Heritability of the network architecture of intrinsic brain functional connectivity
The brain's functional network exhibits many features facilitating functional specialization, integration, and robustness to attack. Using graph theory to characterize brain networks, studies demonstrate their small-world, modular, and “rich-club” properties, with deviations reported in many common neuropathological conditions. Here we estimate the heritability of five widely used graph theoretical metrics (mean clustering coefficient (γ), modularity (Q), rich-club coefficient (ϕnorm), global efficiency (λ), small-worldness (σ)) over a range of connection densities (k=5–25%) in a large cohort of twins (N=592, 84 MZ and 89 DZ twin pairs, 246 single twins, age 23±2.5). We also considered the effects of global signal regression (GSR). We found that the graph metrics were moderately influenced by genetic factors h2 (γ=47–59%, Q=38–59%, ϕnorm=0–29%, λ=52–64%, σ=51–59%) at lower connection densities (≤15%), and when global signal regression was implemented, heritability estimates decreased substantially h2 (γ=0–26%, Q=0–28%, ϕnorm=0%, λ=23–30%, σ=0–27%). Distinct network features were phenotypically correlated (|r|=0.15–0.81), and γ, Q, and λ were found to be influenced by overlapping genetic factors. Our findings suggest that these metrics may be potential endophenotypes for psychiatric disease and suitable for genetic association studies, but that genetic effects must be interpreted with respect to methodological choices.
•Graph metrics were moderately influenced by genetic factors (h2=0–64%).•When global signal regression was implemented, heritability estimates decreased substantially.•γ, Q, and λ were found to be influenced by overlapping genetic factors.
Journal Article
Role of the glymphatic system and perivascular spaces as a potential biomarker for post‐stroke epilepsy
Stroke is one of the most common causes of acquired epilepsy, which can also result in disability and increased mortality rates particularly in elderly patients. No preventive treatment for post-stroke epilepsy is currently available. Development of such treatments has been greatly limited by the lack of biomarkers to reliably identify high-risk patients. The glymphatic system, including perivascular spaces (PVS), is the brain's waste clearance system, and enlargement or asymmetry of PVS (ePVS) is hypothesized to play a significant role in the pathogenesis of several neurological conditions. In this article, we discuss potential mechanisms for the role of perivascular spaces in the development of post-stroke epilepsy. Using advanced MR-imaging techniques, it has been shown that there is asymmetry and impairment of glymphatic function in the setting of ischemic stroke. Furthermore, studies have described a dysfunction of PVS in patients with different focal and generalized epilepsy syndromes. It is thought that inflammatory processes involving PVS and the blood-brain barrier, impairment of waste clearance, and sustained hypertension affecting the glymphatic system during a seizure may play a crucial role in epileptogenesis post-stroke. We hypothesize that impairment of the glymphatic system and asymmetry and dynamics of ePVS in the course of a stroke contribute to the development of PSE. Automated ePVS detection in stroke patients might thus assist in the identification of high-risk patients for post-stroke epilepsy trials. PLAIN LANGUAGE SUMMARY: Stroke often leads to epilepsy and is one of the main causes of epilepsy in elderly patients, with no preventative treatment available. The brain's waste removal system, called the glymphatic system which consists of perivascular spaces, may be involved. Enlargement or asymmetry of perivascular spaces could play a role in this and can be visualised with advanced brain imaging after a stroke. Detecting enlarged perivascular spaces in stroke patients could help identify those at risk for post-stroke epilepsy.
Journal Article
Voxel‐based and surface‐based cortical morphometric MRI applications for identifying the epileptogenic zone: A narrative review
Approximately 40% of patients with drug‐resistant epilepsy referred for surgical evaluation have no epileptogenic lesion on MRI (MRI‐negative). MRI‐negative epilepsy is associated with poorer seizure freedom prognosis and has therefore motivated the development of structural post‐processing methods to “convert” MRI‐negative to MRI‐positive cases. In this article, we review the principles, advances, and challenges of voxel‐ and surface‐based cortical morphometric MRI techniques in detecting the epileptogenic zone. The ground truth for the presumed epileptogenic zone in imaging studies can be classified into lesion‐based (MRI lesion mask or histopathology) or epileptogenicity‐based ground truth (anatomical‐electroclinical correlations or resections that lead to seizure freedom). Voxel‐based techniques are reported to have a 13%–97% concordance rate, while surface‐based techniques have 67%–92% compared to lesion‐based ground truths. Epileptogenicity‐based ground truth may be more relevant in the case of MRI‐negative cases; however, the sensitivity and concordance rate (voxel‐based technique 7.1%–66.7%, and surface‐based technique 62%) are limited by the reliance on scalp EEG and qualitative analysis of seizure‐onset pattern. The use of stereo‐EEG and quantitative EEG analysis may fill this gap to evaluate the correlation between cortical morphometry results and electrophysiological epileptogenic biomarkers of the epileptogenic zone and help improve the yield of structural post‐processing tools. Plain Language Summary Locating the epileptogenic zone (the brain area that is responsible for seizure generation) is important to diagnose and plan epilepsy treatments. An abnormal brain imaging (MRI) result can help clinical decision‐making; however, around 40% of patients have normal MRI results (MRI‐negative). We are reviewing the potential of two advanced MRI methods (voxel‐ and surface‐based cortical morphometry) to localize the epileptogenic zone in the presence or absence of visible MRI abnormalities. We also describe the current challenge of applying the above methods in daily clinical practice and propose using advanced brain recording analysis to aid this translation process.
Journal Article
Relationships between measures of neurovascular integrity and fluid transport in aging: a multi-modal neuroimaging study
Fluid transport in the neurovascular unit is essential for maintaining brain health through nutrient delivery and waste clearance. However, these systems are complex and the inter-dependencies between elements of these systems and how they may change through aging is not well understood. MRI outcomes provide insight into the underlying biological mechanisms of these systems in vivo, including water exchange rate through the neurovascular unit (BBB k
w
), enlarged perivascular spaces (ePVS), cerebral blood flow (CBF), free water (FW), and white matter hyperintensities (WMH). To explore the relationships between functional elements of the neurovascular unit, this study investigated relationships between these MRI measures using Bayesian mixed models, and their variation with chronological age or atrophy-related brain age (brainageR) using linear regression. In 132 non-clinical older adults (mean age = 67 years; 68% female), BBB k
w
positively associated with CBF (β^ = 0.08, 95% credible interval (CI) = [0.02, 0.15]). FW positively associated with both ePVS (β^ = 0.44, CI = [0.30, 0.63]) and WMH (β^ = 0.13, CI = [0.04, 0.21]). BBB k
w
, CBF and ePVS decreased with age, while FW and WMH increased (all
p
< 0.05). There were no associations with atrophy-related brain age (all
p
> 0.05). Relationships between FW, ePVS and WMH likely reflect interconnectivity of fluid regulation within different compartments, while the relationship between BBB k
w
and CBF indicates a link between neurovascular fluid flow and vessel function. While individual metrics of neurovascular integrity are associated with age, their inter-relationships appear stable, providing a baseline for future research in fluid transport and vascular health in neurodegenerative disease.
Graphical Abstract
Journal Article
18F-FDG-PET hypometabolism as a predictor of favourable outcome in epilepsy surgery: protocol for a systematic review and meta-analysis
IntroductionA substantial proportion of patients who undergo surgery for drug resistant focal epilepsy do not become seizure free. While some factors, such as the detection of hippocampal sclerosis or a resectable lesion on MRI and electroencephalogram-MRI concordance, can predict favourable outcomes in epilepsy surgery, the prognostic value of the detection of focal hypometabolism with 18F-fluorodeoxyglucose positive emission tomography (18F-FDG-PET) hypometabolism is uncertain. We propose a protocol for a systematic review and meta-analysis to examine whether localisation with 18F-FDG-PET hypometabolism predicts favourable outcomes in epilepsy surgery.Methods and analysisA systematic literature search of Medline, Embase and Web of Science will be undertaken. Publications which include evaluation with 18F-FDG-PET prior to surgery for drug resistant focal epilepsy, and which report ≥12 months of postoperative surgical outcome data will be included. Non-human, non-English language publications, publications with fewer than 10 participants and unpublished data will be excluded. Screening and full-text review of publications for inclusion will be undertaken by two independent investigators, with discrepancies resolved by consensus or a third investigator. Data will be extracted and pooled using random effects meta-analysis, with heterogeneity quantified using the I2 analysis.Ethics and disseminationEthics approval is not required. Once complete, the systematic review will be published in a peer-reviewed journal.PROSPERO registration numberCRD42022324823.
Journal Article