Automated tractography in patients with temporal lobe epilepsy using TRActs Constrained by UnderLying Anatomy (TRACULA)

Purpose A detailed understanding of white matter tract alterations in patients with temporal lobe epilepsy (TLE) is important as it may provide useful information for likely side of seizure onset, cognitive impairment and postoperative prognosis. However, most diffusion-tensor imaging (DTI) studies have relied on manual reconstruction of tract bundles, despite the recent development of automated techniques. In the present study, we used an automated white matter tractography analysis approach to quantify temporal lobe white matter tract alterations in TLE and determine the relationships between tract alterations, the extent of hippocampal atrophy and the chronicity and severity of the disorder. Methods We acquired preoperative T1-weighted and DTI data in 64 patients with well-characterized TLE, with imaging and histopathological evidence of hippocampal sclerosis. Identical acquisitions were collected for 44 age- and sex-matched healthy controls. We employed automatic probabilistic tractography DTI analysis using TRActs Constrained by UnderLying Anatomy (TRACULA) available in context of Freesurfer software for the reconstruction of major temporal lobe tract bundles. We determined the factors influencing probabilistic tract reconstruction and investigated alterations of DTI scalar metrics along white matter tracts with respect to hippocampal volume, which was automatically estimated using Freesurfer's morphometric pipelines. We also explored the relationships between white matter tract alterations and duration of epilepsy, age of onset of epilepsy and seizure burden (defined as a function of seizure frequency and duration of epilepsy). Results Whole-tract diffusion characteristics of patients with TLE differed according to side of epilepsy and were significantly different between patients and controls. Waypoint comparisons along each tract revealed that patients had significantly altered tissue characteristics of the ipsilateral inferior-longitudinal, uncinate fasciculus, superior longitudinal fasciculus and cingulum relative to controls. Changes were more widespread (ipsilaterally and contralaterally) in patients with left TLE while patients with right TLE showed changes that remained spatially confined in ipsilateral tract regions. We found no relationship between DTI alterations and volume of the epileptogenic hippocampus. DTI alterations of anterior ipsilateral uncinate and inferior-longitudinal fasciculus correlated with duration of epilepsy (over and above effects of age) and age at onset of epilepsy. Seizure burden correlated with tissue characteristics of the uncinate fasciculus. Conclusion This study shows that TRACULA permits the detection of alterations of DTI tract scalar metrics in patients with TLE. It also provides the opportunity to explore relationships with structural volume measurements and clinical variables along white matter tracts. Our data suggests that the anterior temporal lobe portions of the uncinate and inferior-longitudinal fasciculus may be particularly vulnerable to pathological alterations in patients with TLE. These alterations are unrelated to the extent of hippocampal atrophy (and therefore potentially mediated by independent mechanisms) but influenced by chronicity and severity of the disorder

Preoperative automated fibre quantification predicts postoperative seizure outcome in temporal lobe epilepsy

Approximately one in every two patients with pharmacoresistant temporal lobe epilepsy will not be rendered completely seizure-free after temporal lobe surgery. The reasons for this are unknown and are likely to be multifactorial. Quantitative volumetric magnetic resonance imaging techniques have provided limited insight into the causes of persistent postoperative seizures in patients with temporal lobe epilepsy. The relationship between postoperative outcome and preoperative pathology of white matter tracts, which constitute crucial components of epileptogenic networks, is unknown. We investigated regional tissue characteristics of preoperative temporal lobe white matter tracts known to be important in the generation and propagation of temporal lobe seizures in temporal lobe epilepsy, using diffusion tensor imaging and automated fibre quantification. We studied 43 patients with mesial temporal lobe epilepsy associated with hippocampal sclerosis and 44 healthy controls. Patients underwent preoperative imaging, amygdalohippocampectomy and postoperative assessment using the International League Against Epilepsy seizure outcome scale. From preoperative imaging, the fimbria-fornix, parahippocampal white matter bundle and uncinate fasciculus were reconstructed, and scalar diffusion metrics were calculated along the length of each tract. Altogether, 51.2% of patients were rendered completely seizure-free and 48.8% continued to experience postoperative seizure symptoms. Relative to controls, both patient groups exhibited strong and significant diffusion abnormalities along the length of the uncinate bilaterally, the ipsilateral parahippocampal white matter bundle, and the ipsilateral fimbria-fornix in regions located within the medial temporal lobe. However, only patients with persistent postoperative seizures showed evidence of significant pathology of tract sections located in the ipsilateral dorsal fornix and in the contralateral parahippocampal white matter bundle. Using receiver operating characteristic curves, diffusion characteristics of these regions could classify individual patients according to outcome with 84% sensitivity and 89% specificity. Pathological changes in the dorsal fornix were beyond the margins of resection, and contralateral parahippocampal changes may suggest a bitemporal disorder in some patients. Furthermore, diffusion characteristics of the ipsilateral uncinate could classify patients from controls with a sensitivity of 98%; importantly, by co-registering the preoperative fibre maps to postoperative surgical lacuna maps, we observed that the extent of uncinate resection was significantly greater in patients who were rendered seizure-free, suggesting that a smaller resection of the uncinate may represent insufficient disconnection of an anterior temporal epileptogenic network. These results may have the potential to be developed into imaging prognostic markers of postoperative outcome and provide new insights for why some patients with temporal lobe epilepsy continue to experience postoperative seizures

Thalamohippocampal atrophy in focal epilepsy of unknown cause at the time of diagnosis.

BACKGROUND AND PURPOSE:Patients with chronic focal epilepsy may have atrophy of brain structures important for the generation and maintenance of seizures. However, little research has been conducted in patients with newly diagnosed focal epilepsy (NDfE), despite it being a crucial point in time for understanding the underlying biology of the disorder. We aimed to determine whether patients with NDfE show evidence of volumetric abnormalities of subcortical structures. METHODS:Eighty-two patients with NDfE and 40 healthy controls underwent magnetic resonance imaging scanning using a standard clinical protocol. Volume estimation of the left and right hippocampus, thalamus, caudate nucleus, putamen and cerebral hemisphere was performed for all participants and normalised to whole brain volume. Volumes lower than two standard deviations below the control mean were considered abnormal. Volumes were analysed with respect to patient clinical characteristics, including treatment outcome 12 months after diagnosis. RESULTS:Volume of the left hippocampus (p(FDR-corr)  = 0.04) and left (p(FDR-corr)  = 0.002) and right (p(FDR-corr)  = 0.04) thalamus was significantly smaller in patients relative to controls. Relative to the normal volume limits in controls, 11% patients had left hippocampal atrophy, 17% had left thalamic atrophy and 9% had right thalamic atrophy. We did not find evidence of a relationship between volumes and future seizure control or with other clinical characteristics of epilepsy. CONCLUSIONS:Volumetric abnormalities of structures known to be important for the generation and maintenance of focal seizures are established at the time of epilepsy diagnosis and are not necessarily a result of the chronicity of the disorder

Everyday legitimacy and international administration: global governance and local legitimacy in Kosovo

International administrations are a very specific form of statebuilding. This paper examines the limits illustrated by the experience in Kosovo. Here, the international administration faced the same requirements of any legitimate, Liberal government, but without the checks and balances normally associated with Liberal governance. Thus, the international administration was granted full authority and the power thereby associated, but without the legitimacy upon which the Liberal social contract rests. The state-building agenda put forth came to be seen as more exogenous, reinforcing the delegitimization process. This paper will specifically address the influence of the Weberian approach to legitimacy on the statebuilding literature, as well as its limits. It will then propose other possible avenues for statebuilding, more in line with a wider understanding of legitimacy and intervention

Artificial intelligence for classification of temporal lobe epilepsy with ROI-level MRI data: A worldwide ENIGMA-Epilepsy study

Artificial intelligence has recently gained popularity across different medical fields to aid in the detection of diseases based on pathology samples or medical imaging findings. Brain magnetic resonance imaging (MRI) is a key assessment tool for patients with temporal lobe epilepsy (TLE). The role of machine learning and artificial intelligence to increase detection of brain abnormalities in TLE remains inconclusive. We used support vector machine (SV) and deep learning (DL) models based on region of interest (ROI-based) structural (n = 336) and diffusion (n = 863) brain MRI data from patients with TLE with (“lesional”) and without (“non-lesional”) radiographic features suggestive of underlying hippocampal sclerosis from the multinational (multi-center) ENIGMA-Epilepsy consortium. Our data showed that models to identify TLE performed better or similar (68–75%) compared to models to lateralize the side of TLE (56–73%, except structural-based) based on diffusion data with the opposite pattern seen for structural data (67–75% to diagnose vs. 83% to lateralize). In other aspects, structural and diffusion-based models showed similar classification accuracies. Our classification models for patients with hippocampal sclerosis were more accurate (68–76%) than models that stratified non-lesional patients (53–62%). Overall, SV and DL models performed similarly with several instances in which SV mildly outperformed DL. We discuss the relative performance of these models with ROI-level data and the implications for future applications of machine learning and artificial intelligence in epilepsy care

Systematic Grant and Funding Body Acknowledgment Data for Publications: An Examination of New Dimensions and New Controversies for Bibliometrics

Bibliographic databases are beginning to provide systematic grant and funding body acknowledgement data for the publications they index. This paper considers how this new data might be used for policy purposes and the key issues that are likely to arise in its use. While the attempt to provide this kind of systematic data is in its relative infancy, there is already sufficient information within the WOS database to examine a number of controversies in science studies. This paper considers one such issue, namely the relationship between the number of funding sources acknowledged and the citation impact of publications where a positive relationship has been assumed to exist. Analyses of sets of publications from 2009 from the journals Cell and Physical Review Letters give contrasting results, suggesting that our understanding of the issue of the relationship between the impact of a publication and the number of funding sources which it acknowledges is not fully understood and may be more complicated that previously considered. It is proposed that scientific research findings are packaged by researchers into papers in a variety of ways for a wide variety of purposes. Individual funding quanta from whatever source are not therefore inputs to papers directly; rather, such funding supports a process that has amongst its outcomes, the production of papers

Event-based modelling in temporal lobe epilepsy demonstrates progressive atrophy from cross-sectional data

OBJECTIVE: Recent work has shown that people with common epilepsies have characteristic patterns of cortical thinning, and that these changes may be progressive over time. Leveraging a large multi-centre cross-sectional cohort, we investigated whether regional morphometric changes occur in a sequential manner, and whether these changes in people with mesial temporal lobe epilepsy and hippocampal sclerosis (MTLE-HS) correlate with clinical features. METHODS: We extracted regional measures of cortical thickness, surface area and subcortical brain volumes from T1-weighted (T1W) MRI scans collected by the ENIGMA-Epilepsy consortium, comprising 804 people with MTLE-HS and 1,625 healthy controls from 25 centres. Features with a moderate case-control effect size (Cohen's d≥0.5) were used to train an Event-Based Model (EBM), which estimates a sequence of disease-specific biomarker changes from cross-sectional data and assigns a biomarker-based fine-grained disease stage to individual patients. We tested for associations between EBM disease stage and duration of epilepsy, age of onset and anti-seizure medicine (ASM) resistance. RESULTS: In MTLE-HS, decrease in ipsilateral hippocampal volume along with increased asymmetry in hippocampal volume was followed by reduced thickness in neocortical regions, reduction in ipsilateral thalamus volume and, finally, increase in ipsilateral lateral ventricle volume. EBM stage was correlated to duration of illness (Spearman's ρ=0.293, p=7.03x10-16 ), age of onset (ρ=-0.18, p=9.82x10-7 ) and ASM resistance (AUC=0.59, p=0.043, Mann-Whitney U test). However, associations were driven by cases assigned to EBM stage zero, which represents MTLE-HS with mild or non-detectable abnormality on T1W MRI. SIGNIFICANCE: From cross-sectional MRI, we reconstructed a disease progression model that highlights a sequence of MRI changes that aligns with previous longitudinal studies. This model could be used to stage MTLE-HS subjects in other cohorts and help establish connections between imaging-based progression staging and clinical features

Harmonizing DTI measurements across scanners to examine the development of white matter microstructure in 803 adolescents of the NCANDA study

Neurodevelopment continues through adolescence, with notable maturation of white matter tracts comprising regional fiber systems progressing at different rates. To identify factors that could contribute to regional differences in white matter microstructure development, large samples of youth spanning adolescence to young adulthood are essential to parse these factors. Recruitment of adequate samples generally relies on multi-site consortia but comes with the challenge of merging data acquired on different platforms. In the current study, diffusion tensor imaging (DTI) data were acquired on GE and Siemens systems through the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA), a multi-site study designed to track the trajectories of regional brain development during a time of high risk for initiating alcohol consumption. This cross-sectional analysis reports baseline Tract-Based Spatial Statistic (TBSS) of regional fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (L1), and radial diffusivity (LT) from the five consortium sites on 671 adolescents who met no/low alcohol or drug consumption criteria and 132 adolescents with a history of exceeding consumption criteria. Harmonization of DTI metrics across manufacturers entailed the use of human-phantom data, acquired multiple times on each of three non-NCANDA participants at each site’s MR system, to determine a manufacturer-specific correction factor. Application of the correction factor derived from human phantom data measured on MR systems from different manufacturers reduced the standard deviation of the DTI metrics for FA by almost a half, enabling harmonization of data that would have otherwise carried systematic error. Permutation testing supported the hypothesis of higher FA and lower diffusivity measures in older adolescents and indicated that, overall, the FA, MD, and L1 of the boys was higher than that of the girls, suggesting continued microstructural development notable in the boys. The contribution of demographic and clinical differences to DTI metrics was assessed with General Additive Models (GAM) testing for age, sex, and ethnicity differences in regional skeleton mean values. The results supported the primary study hypothesis that FA skeleton mean values in the no/low-drinking group were highest at different ages. When differences in intracranial volume were covaried, FA skeleton mean reached a maximum at younger ages in girls than boys and varied in magnitude with ethnicity. Our results, however, did not support the hypothesis that youth who exceeded exposure criteria would have lower FA or higher diffusivity measures than the no/low-drinking group; detecting the effects of excessive alcohol consumption during adolescence on DTI metrics may require longitudinal study