Interictal and ictal source localization for epilepsy surgery using high-density EEG with MEG: a prospective long-term study.

Drug-resistant focal epilepsy is a major clinical problem and surgery is under-used. Better non-invasive techniques for epileptogenic zone localization are needed when MRI shows no lesion or an extensive lesion. The problem is interictal and ictal localization before propagation from the epileptogenic zone. High-density EEG (HDEEG) and magnetoencephalography (MEG) offer millisecond-order temporal resolution to address this but co-acquisition is challenging, ictal MEG studies are rare, long-term prospective studies are lacking, and fundamental questions remain. Should HDEEG-MEG discharges be assessed independently [electroencephalographic source localization (ESL), magnetoencephalographic source localization (MSL)] or combined (EMSL) for source localization? Which phase of the discharge best characterizes the epileptogenic zone (defined by intracranial EEG and surgical resection relative to outcome)? Does this differ for interictal and ictal discharges? Does MEG detect mesial temporal lobe discharges? Thirteen patients (10 non-lesional, three extensive-lesional) underwent synchronized HDEEG-MEG (72-94 channel EEG, 306-sensor MEG). Source localization (standardized low-resolution tomographic analysis with MRI patient-individualized boundary-element method) was applied to averaged interictal epileptiform discharges (IED) and ictal discharges at three phases: 'early-phase' (first latency 90% explained variance), 'mid-phase' (first of 50% rising-phase, 50% mean global field power), 'late-phase' (negative peak). 'Earliest-solution' was the first of the three early-phase solutions (ESL, MSL, EMSL). Prospective follow-up was 3-21 (median 12) months before surgery, 14-39 (median 21) months after surgery. IEDs (n = 1474) were recorded, seen in: HDEEG only, 626 (42%); MEG only, 232 (16%); and both 616 (42%). Thirty-three seizures were captured, seen in: HDEEG only, seven (21%); MEG only, one (3%); and both 25 (76%). Intracranial EEG was done in nine patients. Engel scores were I (9/13, 69%), II (2/13,15%), and III (2/13). MEG detected baso-mesial temporal lobe epileptogenic zone sources. Epileptogenic zone OR [odds ratio(s)] were significantly higher for earliest-solution versus early-phase IED-surgical resection and earliest-solution versus all mid-phase and late-phase solutions. ESL outperformed EMSL for ictal-surgical resection [OR 3.54, 95% confidence interval (CI) 1.09-11.55, P = 0.036]. MSL outperformed EMSL for IED-intracranial EEG (OR 4.67, 95% CI 1.19-18.34, P = 0.027). ESL outperformed MSL for ictal-surgical resection (OR 3.73, 95% CI 1.16-12.03, P = 0.028) but was outperformed by MSL for IED-intracranial EEG (OR 0.18, 95% CI 0.05-0.73, P = 0.017). Thus, (i) HDEEG and MEG source solutions more accurately localize the epileptogenic zone at the earliest resolvable phase of interictal and ictal discharges, not mid-phase (as is common practice) or late peak-phase (when signal-to-noise ratios are maximal); (ii) from empirical observation of the differential timing of HDEEG and MEG discharges and based on the superiority of ESL plus MSL over either modality alone and over EMSL, concurrent HDEEG-MEG signals should be assessed independently, not combined; (iii) baso-mesial temporal lobe sources are detectable by MEG; and (iv) MEG is not 'more accurate' than HDEEG-emphasis is best placed on the earliest signal (whether HDEEG or MEG) amenable to source localization. Our findings challenge current practice and our reliance on invasive monitoring in these patients. 10.1093/brain/awz015_video1 awz015media1 6018582479001.

Accurate source imaging based on high resolution scalp electroencephalography and individualized finite difference head models in epilepsy pre-surgical workup.

PURPOSE: High-density electroencephalographic source imaging (HD-ESI) has emerged as a useful tool for pre-surgical epilepsy workup. However, it is not routinely used in clinical evaluations due to several factors, one of which is the challenge associated with creating anatomically accurate head models. Reasonable solutions now exist and the present study aims to evaluate the use of these highly resolved individual head models in pre-surgical epilepsy evaluation. METHODS: Nine patients with intractable epilepsy who were candidates for resective epilepsy surgeries participated in the study. For each patient, 256-channel electroencephalography data were acquired along with individual structural MRI data that was used to construct individual finite difference models (iFDM). Accuracy of HD-ESI based on iFDM (HD-ESI-iFDM) was evaluated using multiple criteria, including concordance with intracranial electroencephalography (icEEG) and location of surgical resection. Performance of HD-ESI-iFDM was also compared against MRI and positron emission tomography (PET) results. RESULTS: In all but one patient resective surgeries resulted in seizure-free outcome. Source locations derived from HD-ESI-iFDM demonstrated concordance with surgical resection and with icEEG data, when available. The HD-ESI-iFDM also contributed to the planning of intracranial electrodes implantation. Compared to MRI or PET, HD-ESI-iFDM provided more accurate localization of the epileptogenic zone. CONCLUSION: When acquired with high-density sensor arrays and source imaging is performed with anatomically accurate head models, electroencephalography can contribute meaningfully to epilepsy pre-surgical workup for localization of the epileptogenic zone. Now that both high-density electroencephalography and individualized FDM models can be routinely obtained, it can be incorporated as part of clinical practice.

Application of 256-channel dense array electroencephalographic source imaging in presurgical workup of temporal lobe epilepsy.

OBJECTIVE: This study evaluated the localization precision of 256-channel dense array electroencephalographic source imaging (dESI) in comparison to conventional noninvasive tools. In addition, the study was designed to analyze the relationship between the 256-channel dESI source patterns and surgical outcome. METHODS: Forty-three patients with temporal lobe epilepsy (TLE) who underwent one-stage resective surgeries were recruited in this study. We compared dESI with other noninvasive evaluation methods by comparing results with resections that eliminate or significantly reduced seizures according to sub-lobule and lobule criteria. Sensitivity and specificity of multiple evaluation methods were calculated. Kaplan-Meier analysis was performed to evaluate the relationship between source patterns and surgical outcome. RESULTS: dESI showed the best sensitivity (sub-lobule, 91.4%; lobule, 97.1%) and specificity (75%) for both sub-lobule and lobule criteria. The Kaplan-Meier survival analysis showed that cases with "single source" had better prognosis than with "multiple sources" (p<0.05); cases of "sources within resection" showed better surgical prognosis than cases of "sources outside resection" (p<0.05). CONCLUSION: In this study, 256-channel dESI provided a higher clinical yield than the other most broadly used noninvasive presurgical workup tools. dESI results with "single source" correlated strongly to good prognosis, while cases with "multiple sources" may cautiously be considered as candidates for one-stage resective surgeries. The resection of the irritative zone identified by interictal epileptiform discharges (IEDs) was related to good surgical prognosis in TLE. SIGNIFICANCE: In the presurgical workup of TLE, the clinical yield of 256-channel dESI is high. Patterns of dESI results are related to surgical prognosis, and they can be instructive for presurgical planning. The resection of the irritative zone can be related to good surgical prognosis in TLE.

In vivo imaging of epileptic foci in rats using a miniature probe integrating diffuse optical tomography and electroencephalographic source localization.

OBJECTIVE: The goal of this work is to establish a new dual-modal brain-mapping technique based on diffuse optical tomography (DOT) and electroencephalographic source localization (ESL) that can chronically/intracranially record optical/electroencephalography (EEG) data to precisely map seizures and localize the seizure-onset zone and associated epileptic brain network. METHODS: The dual-modal imaging system was employed to image seizures in an experimental acute bicuculline methiodide rat model of focal epilepsy. Depth information derived from DOT was used as constraint in ESL to enhance the image reconstruction. Groups of animals were compared based on localization of seizure foci, either at different positions or at different depths. RESULTS: This novel imaging technique successfully localized the seizure-onset zone in rat induced by bicuculline methiodide injected at a depth of 1, 2, and 3 mm, respectively. The results demonstrated that the incorporation of the depth information from DOT into the ESL image reconstruction resulted in more accurate and reliable ESL images. Although the ESL images showed a horizontal shift of the source localization, the DOT identified the seizure focus accurately. In one case, when the bicuculline methiodide (BMI) was injected at a site outside the field of view (FOV) of the DOT/ESL interface, ESL gave false-positive detection of the focus, while DOT showed negative detection. SIGNIFICANCE: This study represents the first to identify seizure-onset zone using implantable DOT. In addition, the combination of DOT/ESL has never been documented in neuroscience and epilepsy imaging. This technology will enable us to precisely measure the neural activity and hemodynamic response at exactly the same tissue site and at both cortical and subcortical levels.

Simplificación del problema inverso electroencefalográfico a una sola región homogénea con condición de Neumann nula / Simplification of the Inverse Electroencephalographic Problem to One Homogeneous Region with Null Neumann Condition

Objetivo: Presentar una simplificación del Problema Inverso Electroencefalográfico (PIE) del caso de varias capas conductoras a una región homogénea con condición de Neumann Nula. Metodología: Se divide el PIE en tres problemas, dos de los cuales se resuelven usando el potencial medido en el cuero cabelludo y con estas soluciones y el tercer problema se lleva a cabo la simplificación. Para validar la simplificación se genera un ejemplo sintético usando el modelo de esferas concéntricas. Resultados: Por medio de la simplificación la fuente se determina a partir de la ecuación de Poisson con una condición de Neumann nula y un dato adicional sobre la frontera de la región homogénea, el cual se obtiene de la medición. Esto es válido para regiones generales con fronteras suficientemente suaves. Adicionalmente, para el caso de esferas concéntricas, se plantea el PIE para el caso de una fuente dipolar (que representa a focos epilépticos) usando esta simplificación y la técnica de la función de Green. Conclusión: La simplificación presentada aquí permite analizar el PIE en una región lo cual simplifica su estudio teórico y numérico. En particular, puede ser útil para el análisis del problema de identificación de los parámetros de una fuente dipolar.

Objective: To give a simplification of the Inverse Electroencephalographic Problem (IEP) from the case of multilayer conductive medium to the case of a homogeneous region with null Neumann condition. Methodology: IEP is divided in three problems, two of which are resolved using the measurements of potential on the scalp and with these solutions and the third problem the simplification is carried out. In order to validate the simplification a synthetic example is generated using the model of concentric spheres. Results: Through of simplification, the source is determined from the Poisson equation with null Neumann condition and an additional data on the boundary of the homogeneous region, which is obtained from the measurement. This is valid for regions with smooth boundary. Additionally, in the case of concentric spheres, it is statement the identification problem for dipolar sources (representing epileptic focus) using this simplification and Green function. Conclusion: The simplification presented here allows us to analyze the inverse problem in one region, which simplifies the theoretical and numerical study. In particular it may be useful to analyze the problem of parameter identification of a dipolar source.