Quantitative relaxometry and diffusion MRI for lateralization in MTS and non-MTS temporal lobe epilepsy.

We developed novel methodology for investigating the use of quantitative relaxometry (T1 and T2) and diffusion tensor imaging (DTI) for lateralization in temporal lobe epilepsy. Patients with mesial temporal sclerosis confirmed by pathology (N=8) and non-MTS unilateral temporal lobe epilepsy (N=6) were compared against healthy controls (N=19) using voxel-based analysis restricted to the anterior temporal lobes, and laterality indices for each MRI metric (T1, T2, fractional anisotropy (FA), mean diffusivity, axial and radial diffusivities) were computed based on the proportion of significant voxels on each side. The diffusivity metrics were the most lateralizing MRI metrics in MTS and non-MTS subsets, with significant differences also seen with FA, T1 and T2. Patient-specific multi-modal laterality indices were also computed and were shown to clearly separate the left-onset and right-onset patients. Marked differences between left-onset and right-onset patients were also observed, with left-onset patients exhibiting stronger laterality indices. Finally, neocortical abnormalities were found to be more common in the non-MTS patients. These preliminary results on a small sample size support the further investigation of quantitative MRI and multi-modal image analysis in clinical determination of seizure onset. The presence of more neocortical abnormalities in the non-MTS group suggests a role in seizure onset or propagation and motivates the investigation of more sensitive histopathological analysis to detect and delineate potentially subtle neocortical pathology

Registration of in-vivo to ex-vivo MRI of surgically resected specimens: A pipeline for histology to in-vivo registration.

BACKGROUND: Advances in MRI have the potential to improve surgical treatment of epilepsy through improved identification and delineation of lesions. However, validation is currently needed to investigate histopathological correlates of these new imaging techniques. The purpose of this work is to develop and evaluate a protocol for deformable image registration of in-vivo to ex-vivo resected brain specimen MRI. This protocol, in conjunction with our previous work on ex-vivo to histology registration, completes a registration pipeline for histology to in-vivo MRI, enabling voxel-based validation of novel and existing MRI techniques with histopathology. NEW METHOD: A combination of image-based and landmark-based 3D registration was used to register in-vivo MRI and the ex-vivo MRI from patients (N=10) undergoing epilepsy surgery. Target registration error (TRE) was used to assess accuracy and the added benefit of deformable registration. RESULTS: A mean TRE of 1.35±0.11 and 1.41±0.33mm was found for neocortical and hippocampal specimens respectively. Statistical analysis confirmed that the deformable registration significantly improved the registration accuracy for both specimens. COMPARISON WITH EXISTING METHODS: Image registration of surgically resected brain specimens is a unique application which presents numerous technical challenges and that have not been fully addressed in previous literature. Our computed TRE are comparable to previous attempts tackling similar applications, as registering in-vivo MRI to whole brain or serial histology. CONCLUSION: The presented registration pipeline finds dense and accurate spatial correspondence between in-vivo MRI and histology and allows for the spatially local and quantitative assessment of pathological correlates in MRI

Magnetic resonance imaging and histology correlation in the neocortex in temporal lobe epilepsy.

OBJECTIVE: To investigate the histopathological correlates of quantitative relaxometry and diffusion tensor imaging (DTI) and to determine their efficacy in epileptogenic lesion detection for preoperative evaluation of focal epilepsy. METHODS: We correlated quantitative relaxometry and DTI with histological features of neuronal density and morphology in 55 regions of the temporal lobe neocortex, selected from 13 patients who underwent epilepsy surgery. We made use of a validated nonrigid image registration protocol to obtain accurate correspondences between in vivo magnetic resonance imaging and histology images. RESULTS: We found T1 to be a predictor of neuronal density in the neocortical gray matter (GM) using linear mixed effects models with random effects for subjects. Fractional anisotropy (FA) was a predictor of neuronal density of large-caliber neurons only (pyramidal cells, layers 3 and 5). Comparing multivariate to univariate mixed effects models with nested variables demonstrated that employing T1 and FA together provided a significantly better fit than T1 or FA alone in predicting density of large-caliber neurons. Correlations with clinical variables revealed significant positive correlations between neuronal density and age (rs  = 0.726, pfwe  = 0.021). This study is the first to relate in vivo T1 and FA values to the proportion of neurons in GM. INTERPRETATION: Our results suggest that quantitative T1 mapping and DTI may have a role in preoperative evaluation of focal epilepsy and can be extended to identify GM pathology in a variety of neurological disorders

Investigation of hippocampal substructures in focal temporal lobe epilepsy with and without hippocampal sclerosis at 7T.

PURPOSE: To provide a more detailed investigation of hippocampal subfields using 7T magnetic resonance imaging (MRI) for the identification of hippocampal sclerosis in temporal lobe epilepsy (TLE). MATERIALS AND METHODS: Patients (n = 13) with drug-resistant TLE previously identified by conventional imaging as having hippocampal sclerosis (HS) or not (nine without HS, four HS) and 20 age-matched healthy controls were scanned and compared using a 7T MRI protocol. Using a manual segmentation scheme to delineate hippocampal subfields, subfield-specific volume changes and apparent transverse relaxation rate ( R2*) were studied between the two groups. In addition, qualitative assessment at 7T and clinical outcomes were correlated with measured subfield changes. RESULTS: Volumetry of the hippocampus at 7T in HS patients revealed significant ipsilateral subfield atrophy in CA1 (P = 0.001) and CA4+DG (P \u3c 0.001). Volumetry also uncovered subfield atrophy in 33% of patients without HS, which had not been detected using conventional imaging. R2* was significantly lower in the CA4+DG subfields (P = 0.001) and the whole hippocampus (P = 0.029) of HS patients compared to controls but not significantly lower than the group without HS (P = 0.077, P = 0.109). No correlation was found between quantitative volumetry and qualitative assessment as well as surgical outcomes (Sub, P = 0.495, P = 0.567, P = 0.528; CA1, P = 0.104 ± 0.171, P = 0.273, P = 0.554; CA2+CA3, P = 0.517, P = 0.952, P = 0.130 ± 0.256; CA4+DG, P = 0.052 ± 0.173, P = 0.212, P = 0.124 ± 0.204; WholeHipp, P = 0.187, P = 0.132 ± 0.197, P = 0.628). CONCLUSION: These preliminary findings indicate that hippocampal subfield volumetry assessed at 7T is capable of identifying characteristic patterns of hippocampal atrophy in HS patients; however, difficulty remains in using imaging to identify hippocampal pathologies in cases without HS. LEVEL OF EVIDENCE: 2 J. MAGN. RESON. IMAGING 2017;45:1359-1370

Early Observations And Analysis Of The Type Ia SN 2014J In M82

We present optical and near infrared (NIR) observations of the nearby Type Ia SN 2014J. Seventeen optical and 23 NIR spectra were obtained from 10 days before (-10d) to 10 days after (+10d) the time of maximum B-band brightness. The relative strengths of absorption features and their patterns of development can be compared at one day intervals throughout most of this period. Carbon is not detected in the optical spectra, but we identify C I lambda 1.0693 in the NIR spectra. Mg II lines with high oscillator strengths have higher initial velocities than other Mg II lines. We show that the velocity differences can be explained by differences in optical depths due to oscillator strengths. The spectra of SN 2014J show that it is a normal SN Ia, but many parameters are near the boundaries between normal and high-velocity subclasses. The velocities for OI, Mg II, Si II, S Ca a, and Fell suggest that SN 2014J has a layered structure with little or no mixing. That result is consistent with the delayed detonation explosion models. We also report photometric observations, obtained from -10d to +29d, in the UBVRIJH and K-s bands. The template fitting package SNooPy is used to interpret the light curves and to derive photometric parameters. Using R-v = 1.46, which is consistent with previous studies, SNooPy finds that A(v) = 1.80 for E(B - V)(host) = 1.23 +/- 0.06 mag. The maximum B-band brightness of -19.19 +/- 0.10 mag was reached on February 1.74 UT +/- 0.13 days and the supernova has a decline parameter, Delta m(15), of 1.12 +/- 0.02 mag.Department of Space, Government of IndiaHungarian OTKA NN-107637NSF AST-1109801, AST-1151462, AST-1211196NSF Astronomy and Astrophysics Postdoctoral Fellowship AST-1302771NASA through a grant from the Space Telescope Science Institute GO-12540NASA NAS5-26555Swedish Research CouncilSwedish National Space BoardDanish Agency for Science and Technology and Innovation realized through a Sapere Aude Level 2 grantAstronom

In vivo MRI signatures of hippocampal subfield pathology in intractable epilepsy.

OBJECTIVES: Our aim is to assess the subfield-specific histopathological correlates of hippocampal volume and intensity changes (T1, T2) as well as diff!usion MRI markers in TLE, and investigate the efficacy of quantitative MRI measures in predicting histopathology in vivo. EXPERIMENTAL DESIGN: We correlated in vivo volumetry, T2 signal, quantitative T1 mapping, as well as diffusion MRI parameters with histological features of hippocampal sclerosis in a subfield-specific manner. We made use of on an advanced co-registration pipeline that provided a seamless integration of preoperative 3 T MRI with postoperative histopathological data, on which metrics of cell loss and gliosis were quantitatively assessed in CA1, CA2/3, and CA4/DG. PRINCIPAL OBSERVATIONS: MRI volumes across all subfields were positively correlated with neuronal density and size. Higher T2 intensity related to increased GFAP fraction in CA1, while quantitative T1 and diffusion MRI parameters showed negative correlations with neuronal density in CA4 and DG. Multiple linear regression analysis revealed that in vivo multiparametric MRI can predict neuronal loss in all the analyzed subfields with up to 90% accuracy. CONCLUSION: Our results, based on an accurate co-registration pipeline and a subfield-specific analysis of MRI and histology, demonstrate the potential of MRI volumetry, diffusion, and quantitative T1 as accurate in vivo biomarkers of hippocampal pathology

Deep brain stimulation of the anterior nucleus of the thalamus in drug-resistant epilepsy in the MORE multicenter patient registry

Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background and objectives: The efficacy of deep brain stimulation of the anterior nucleus of the thalamus (ANT DBS) in patients with drug-resistant epilepsy (DRE) was demonstrated in the double-blind Stimulation of the Anterior Nucleus of the Thalamus for Epilepsy randomized controlled trial. The Medtronic Registry for Epilepsy (MORE) aims to understand the safety and longer-term effectiveness of ANT DBS therapy in routine clinical practice. Methods: MORE is an observational registry collecting prospective and retrospective clinical data. Participants were at least 18 years old, with focal DRE recruited across 25 centers from 13 countries. They were followed for at least 2 years in terms of seizure frequency (SF), responder rate (RR), health-related quality of life (Quality of Life in Epilepsy Inventory 31), depression, and safety outcomes. Results: Of the 191 patients recruited, 170 (mean [SD] age of 35.6 [10.7] years, 43% female) were implanted with DBS therapy and met all eligibility criteria. At baseline, 38% of patients reported cognitive impairment. The median monthly SF decreased by 33.1% from 15.8 at baseline to 8.8 at 2 years (p 10 implantations) had 42.8% reduction in median monthly SF by 2 years in comparison with 25.8% in low-volume center. In patients with cognitive impairment, the reduction in median monthly SF was 26.0% by 2 years compared with 36.1% in patients without cognitive impairment. The most frequently reported adverse events were changes (e.g., increased frequency/severity) in seizure (16%), memory impairment (patient-reported complaint, 15%), depressive mood (patient-reported complaint, 13%), and epilepsy (12%). One definite sudden unexpected death in epilepsy case was reported. Discussion: The MORE registry supports the effectiveness and safety of ANT DBS therapy in a real-world setting in the 2 years following implantation. Classification of evidence: This study provides Class IV evidence that ANT DBS reduces the frequency of seizures in patients with drug-resistant focal epilepsy.The MORE registry was sponsored and funded by Medtronic, plc.info:eu-repo/semantics/publishedVersio

Rapidly Rising Transients in the Supernova - Superluminous Supernova Gap

The American Astronomical Society. All rights reserved..We present observations of four rapidly rising (trise ≈ 10 days) transients with peak luminosities between those of supernovae (SNe) and superluminous SNe (Mpeak ap; -20) - one discovered and followed by the Palomar Transient Factory (PTF) and three by the Supernova Legacy Survey. The light curves resemble those of SN 2011kl, recently shown to be associated with an ultra-long-duration gamma-ray burst (GRB), though no GRB was seen to accompany our SNe. The rapid rise to a luminous peak places these events in a unique part of SN phase space, challenging standard SN emission mechanisms. Spectra of the PTF event formally classify it as an SN II due to broad Hα emission, but an unusual absorption feature, which can be interpreted as either high velocity Hα (though deeper than in previously known cases) or Si ii (as seen in SNe Ia), is also observed. We find that existing models of white dwarf detonations, CSM interaction, shock breakout in a wind (or steeper CSM), and magnetar spin down cannot readily explain the observations. We consider the possibility that a "Type 1.5 SN" scenario could be the origin of our events. More detailed models for these kinds of transients and more constraining observations of future such events should help to better determine their nature. © 2016

Surgical Techniques for the Treatment of Temporal Lobe Epilepsy

Temporal lobe epilepsy (TLE) is the most common form of medically intractable epilepsy. Advances in electrophysiology and neuroimaging have led to a more precise localization of the epileptogenic zone within the temporal lobe. Resective surgery is the most effective treatment for TLE. Despite the variability in surgical techniques and in the extent of resection, the overall outcomes of different TLE surgeries are similar. Here, we review different surgical interventions for the management of TLE