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

On brain atlas choice and automatic segmentation methods: a comparison of MAPER & FreeSurfer using three atlas databases.

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

Epilepsy-related cytoarchitectonic abnormalities along white matter pathways

Objective Temporal lobe epilepsy (TLE) is one of the most common forms of epilepsy. Unfortunately, the clinical outcomes of TLE cannot be determined based only on current diagnostic modalities. A better understanding of white matter (WM) connectivity changes in TLE may aid the identification of network abnormalities associated with TLE and the phenotypic characterisation of the disease. Methods We implemented a novel approach for characterising microstructural changes along WM pathways using diffusional kurtosis imaging (DKI). Along-the-tract measures were compared for 32 subjects with left TLE and 36 age-matched and gender-matched controls along the left and right fimbria-fornix (FF), parahippocampal WM bundle (PWMB), arcuate fasciculus (AF), inferior longitudinal fasciculus (ILF), uncinate fasciculus (UF) and cingulum bundle (CB). Limbic pathways were investigated in relation to seizure burden and control with antiepileptic drugs. Results By evaluating measures along each tract, it was possible to identify abnormalities localised to specific tract subregions. Compared with healthy controls, subjects with TLE demonstrated pathological changes in circumscribed regions of the FF, PWMB, UF, AF and ILF. Several of these abnormalities were detected only by kurtosis-based and not by diffusivity-based measures. Structural WM changes correlated with seizure burden in the bilateral PWMB and cingulum. Conclusions DKI improves the characterisation of network abnormalities associated with TLE by revealing connectivity abnormalities that are not disclosed by other modalities. Since TLE is a neuronal network disorder, DKI may be well suited to fully assess structural network abnormalities related to epilepsy and thus serve as a tool for phenotypic characterisation of epilepsy

The role of the corpus callosum in seizure spread: MRI lesion mapping in oligodendrogliomas

Our data suggest that the genu of the corpus callosum may be a major pathway for seizure generalization in patients with oligodendrogliomas

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

Energy- and flux-budget (EFB) turbulence closure model for the stably stratified flows. Part I: Steady-state, homogeneous regimes

We propose a new turbulence closure model based on the budget equations for the key second moments: turbulent kinetic and potential energies: TKE and TPE (comprising the turbulent total energy: TTE = TKE + TPE) and vertical turbulent fluxes of momentum and buoyancy (proportional to potential temperature). Besides the concept of TTE, we take into account the non-gradient correction to the traditional buoyancy flux formulation. The proposed model grants the existence of turbulence at any gradient Richardson number, Ri. Instead of its critical value separating - as usually assumed - the turbulent and the laminar regimes, it reveals a transition interval, 0.1< Ri <1, which separates two regimes of essentially different nature but both turbulent: strong turbulence at Ri<<1; and weak turbulence, capable of transporting momentum but much less efficient in transporting heat, at Ri>1. Predictions from this model are consistent with available data from atmospheric and lab experiments, direct numerical simulation (DNS) and large-eddy simulation (LES).Comment: 40 pages, 6 figures, Boundary-layer Meteorology, resubmitted, revised versio