Toward a definition of MEG spike: Parametric description of spikes recorded simultaneously by MEG and depth electrodes

AbstractThere is not yet a formal definition of magnetoencephalography (MEG) spike. This study provides a parametric description and definition of clear-cut MEG spikes recorded simultaneously by MEG and depth electrodes (iEEG). A total number of 367 simultaneous MEG/iEEG spikes were selected for analysis. Distribution of morphologic spike parameters and detailed quantitative analysis of the basic morphologic characteristics of MEG spikes is provided

Influence of metallic artifact filtering on MEG signals for source localization during interictal epileptiform activity

Objective. Medical intractable epilepsy is a common condition that affects 40% of epileptic patients that generally have to undergo resective surgery. Magnetoencephalography (MEG) has been increasingly used to identify the epileptogenic foci through equivalent current dipole (ECD) modeling, one of the most accepted methods to obtain an accurate localization of interictal epileptiform discharges (IEDs). Modeling requires that MEG signals are adequately preprocessed to reduce interferences, a task that has been greatly improved by the use of blind source separation (BSS) methods. MEG recordings are highly sensitive to metallic interferences originated inside the head by implanted intracranial electrodes, dental prosthesis, etc and also coming from external sources such as pacemakers or vagal stimulators. To reduce these artifacts, a BSS-based fully automatic procedure was recently developed and validated, showing an effective reduction of metallic artifacts in simulated and real signals (Migliorelli et al 2015 J. Neural Eng. 12 046001). The main objective of this study was to evaluate its effects in the detection of IEDs and ECD modeling of patients with focal epilepsy and metallic interference. Approach. A comparison between the resulting positions of ECDs was performed: without removing metallic interference; rejecting only channels with large metallic artifacts; and after BSS-based reduction. Measures of dispersion and distance of ECDs were defined to analyze the results. Main results. The relationship between the artifact-to-signal ratio and ECD fitting showed that higher values of metallic interference produced highly scattered dipoles. Results revealed a significant reduction on dispersion using the BSS-based reduction procedure, yielding feasible locations of ECDs in contrast to the other two approaches. Significance. The automatic BSS-based method can be applied to MEG datasets affected by metallic artifacts as a processing step to improve the localization of epileptic foci.Postprint (published version

Methodological and clinical aspects of ictal and interictal MEG

During the last years magnetoencephalography (MEG), has become an important part of the pre-surgical epilepsy workup. Interictal activity is usually recorded. Nevertheless, the technological advances now enable ictal MEG recordings as well. The records of 26 pharmaco-resistant focal epilepsy patients, who underwent ictal MEG and epilepsy surgery, were reviewed. In 12 patients prediction of ictal onset zone (IOZ) localization by ictal and interictal MEG was compared with ictal intracranial EEG (icEEG). On the lobar surface level the sensitivity of ictal MEG in IOZ location was 0.71 and the specificity 0.73. The sensitivity of the interictal MEG was 0.40 and specificity 0.77. The records of 34 operated epilepsy patients with focal cortical dysplasia (FCD) were retrospectively evaluated. The resected proportion of the source cluster related to interictal MEG was evaluated in respect to postoperative seizure outcome. 17 out of 34 patients with FCD (50%) achieved seizure freedom. The seizure outcome was similar in patients with MR-invisible and MR-visible FCD. With MEG source clusters and favorable seizure outcome (Engel class I and II) the proportion of the cluster volume resection was 49% - significantly higher (p=0.02) than with MEG clusters but unfavorable outcome (5.5% of cluster volume resection). Median nerve somatosensory evoked MEG responses were processed by movement compensation based on signal space separation (MC-SSS) and on spatio-temporal signal space separation (MC-tSSS). MEG was recorded in standard and deviant head positions. With up to 5 cm head displacement, MC-SSS decreased the mean localization error from 3.97 to 2.13 cm, but increased noise of planar gradiometers from 3.4 to 5.3 fT/cm. MC-tSSS reduced noise from 3.4 to 2.8 fT/cm and reduced the mean localization error from 3.91 to 0.89 cm. The MEG data containing speech-related artifacts and data containing alpha rhythm were processed by tSSS with different correlation limits. The speech artifact was progressively suppressed with the decreasing tSSS correlation limit. The optimal artifact suppression was achieved at correlation of 0.8. The randomly distributed source current (RDCS), and auditory and somatosensory evoked fields (AEFs and SEFs) were simulated. The information was calculated employing Shannon's theory of communication for a standard 306-sensor MEG device and for a virtual MEG helmet (VMH), which was constructed based on simulated MEG measurements in different head positions. With the simulation of 360 recorded events using RDCS model the maximum Shannon's number was 989 for single head position in standard MEG array and 1272 in VMH (28.6% additional information). With AEFs the additional contribution of VMH was 12.6% and with SEFs only 1.1%. To conclude, ictal MEG predicts IOZ location with higher sensitivity than interictal MEG. Resection of larger proportion of the MEG source cluster in patients with FCD is associated with a better seizure outcome, however, complete resection of MEG source cluster is often not required for achievement of favorable seizure outcome. The seizure outcome is similar in patients having MR-positive and MR-negative FCD. MC-tSSS decreases the source localization error to less than 1 cm, when the head is displaced up to 5 cm; however, it is reasonable to limit use of movement compensation for no more than 3-cm head displacement to keep the head inside sensor helmet. The optimization of the tSSS correlation limit to about 0.8 can improve the artifact suppression in MEG without substantial change of brain signals. MEG recording of the same brain activity in different head positions with subsequent construction of VMH can improve the information content of the data.Magnetoenkefalografia (MEG) on menetelmä, jolla mitataan aivojen tuottamia heikkoja magneettikenttiä. Yksi menetelmän tärkeimmistä kliinisistä käyttö-tarkoituksista on paikantaa epilepsiapesäkkeitä aivoissa. Tämä on tärkeää epilepsiakirurgian suunnittelussa. Potilaan liikkeet mittauksen aikana ovat aiheuttaneet epätarkkuutta pesäkkeiden paikannukseen ja häiriösignaaleja mittauksiin. Ongelma on ollut erityisen korostunut lasten mittauksissa ja epileptisten kohtausten rekisteröinneissä. Useimmissa potilaissa MEG-paikannus onkin perustunut kohtausten välisten epileptiformisten aivosähköilmiöiden paikannukseen. Pitkät MEG-rekisteröinnit ovat myös olleet haastavia koska yhteistyökykyisten potilaidenkin on vaikea olla liikkumatta pitkiä aikoja. Viime vuosien tekninen kehitys on mahdollistanut MEG-mittaukset myös pään liikkeiden aikana. Myös aivosignaalien ja kehossa olevien magneettisten materiaalien (esim hammaspaikat, sydämen tahdistimet tai aivostimulaattorit) aiheuttamien magneettisten häiriöiden erottaminen on nykyisin toteutettavissa. Tämä kehitys on mahdollistanut MEG-mittaukset potilailla, joilla aiemmin ei ollut mahdollisuutta hyötyä MEG-paikannuksista ja myös MEG-mittaukset epileptisten kohtausten aikana. Tärkeä osa väitöskirjaa on epilepsiakohtausten aikaisten MEG-mittausten kliinisen hyödyn arviointi. Tulokset osoittavat, että kohtauksenaikaiset MEG-mittaukset paikantavat herkemmin epilepsiakohtauksen lähdealueen aivoissa kuin kohtausten välisten epilepsiailmiöiden lähdepaikannus. Lähdealueiden paikannus on yhtä tarkka sekä aivokuoren pinnalla että 4 cm syvyydessä aivouurteissa. Pää ei kuitenkaan saisi liikkua 3 cm enempää MEG-mittauksen aikana, ja menetelmän herkkyys paranee oilennaisesti magneettikenttien matemaattiseen mallinnukseen perustuvalla magneettisten liikehäiriöiden poistolla. Väitöskirja tutkii lisäksi aivokuoren rakennemuutosten (paikallinen aivokuoridysplasia) aiheuttaman epilepsian kohtausten välisiä MEG-mittauksia. Päinvastoin kuin aiemmin on väitetty, ei aina ole tarpeen poistaa koko epileptisia lähdealueita sisältävää aivojen aluetta hyvän leikkaustuloksen saamiseksi. Väitöskirja esittelee myös laskennallisen MEG-anturiston määritysmenetelmän , joka lisää MEG-mittausten informaatiosisältöä huomioimalla pään liikkeet tulosten analyysissä

Non-invasive measurements of ictal and interictal epileptiform activity using optically pumped magnetometers

Magneto- and electroencephalography (MEG/EEG) are important techniques for the diagnosis and pre-surgical evaluation of epilepsy. Yet, in current cryogen-based MEG systems the sensors are offset from the scalp, which limits the signal-to-noise ratio (SNR) and thereby the sensitivity to activity from deep structures such as the hippocampus. This effect is amplified in children, for whom adult-sized fixed-helmet systems are typically too big. Moreover, ictal recordings with fixed-helmet systems are problematic because of limited movement tolerance and/or logistical considerations. Optically Pumped Magnetometers (OPMs) can be placed directly on the scalp, thereby improving SNR and enabling recordings during seizures. We aimed to demonstrate the performance of OPMs in a clinical population. Seven patients with challenging cases of epilepsy underwent MEG recordings using a 12-channel OPM-system and a 306-channel cryogen-based whole-head system: three adults with known deep or weak (low SNR) sources of interictal epileptiform discharges (IEDs), along with three children with focal epilepsy and one adult with frequent seizures. The consistency of the recorded IEDs across the two systems was assessed. In one patient the OPMs detected IEDs that were not found with the SQUID-system, and in two patients no IEDs were found with either system. For the other patients the OPM data were remarkably consistent with the data from the cryogenic system, noting that these were recorded in different sessions, with comparable SNRs and IED-yields overall. Importantly, the wearability of OPMs enabled the recording of seizure activity in a patient with hyperkinetic movements during the seizure. The observed ictal onset and semiology were in agreement with previous video- and stereo-EEG recordings. The relatively affordable technology, in combination with reduced running and maintenance costs, means that OPM-based MEG could be used more widely than current MEG systems, and may become an affordable alternative to scalp EEG, with the potential benefits of increased spatial accuracy, reduced sensitivity to volume conduction/field spread, and increased sensitivity to deep sources. Wearable MEG thus provides an unprecedented opportunity for epilepsy, and given its patient-friendliness, we envisage that it will not only be used for presurgical evaluation of epilepsy patients, but also for diagnosis after a first seizure

Spatio-temporal evolution of interictal epileptic activity : a study with unaveraged multichannel MEG data in association with MRIs.

This thesis addresses issues relating to MEG modelling, analysis and interpretation of results. A source model employing current density distributions, namely Magnetic Field Tomography (MET), is used to obtain the MEG results. The first issue of concern refers to the registration of MEG data with structural MR images in an attempt to improve the localisation capability of MEG/MET. Simulations testing some spatial and tem poral aspects of the reconstruction capability of MET are also provided. A novel way of conducting MET studies in depth is suggested and implemented: the iterative use of a source space designed to cover deep situated structures on either side of the brain. The main bulk of this thesis is concerned with research into interictal epileptic activity as recorded by means of multichannel MEG system s and analysed using MET. The major aim is to investigate whether or not MET analysis of unaveraged MEG data (single epochs) is feasible in cases of pathophysiological signals and more specifically interictal signals from patients with epilepsy of a complex partial type. The investigation is undertaken against the "traditional" view of the impropriety and absurdity of using single epoch records in the MEG analysis due to noise dominance; we provide evidence that analysis of single, unaveraged epileptic spikes is actually feasible: we demonstrate spatio-temporal coherence in the MET results of the various single interictal events and show that activity extracted from the "averaged event" is made up of activity contributions which occur intermittently and at variable latencies. Our statements are drawn from the study of both superficial and deep activity

Methods for noninvasive localization of focal epileptic activity with magnetoencephalography

Magnetoencephalography (MEG) is a noninvasive brain signal acquisition technique that provides excellent temporal resolution and a whole-head coverage allowing the spatial mapping of sources. These characteristics make MEG an appropriate technique to localize the epileptogenic zone (EZ) in the preoperative evaluation of refractory epilepsy. Presurgical evaluation with MEG can guide the placement of intracranial EEG (iEEG), the current gold standard in the clinical practice, and even supply sufficient information for a surgical intervention without invasive recordings, reducing invasiveness, discomfort, and cost of the presurgical epilepsy diagnosis. However, MEG signals have low signal-to-noise ratio compared with iEEG and can sometimes be affected by noise that masks or distorts the brain activity. This may prevent the detection of interictal epileptiform discharges (IEDs) and high-frequency oscillations (HFOs), two important biomarkers used in the preoperative evaluation of epilepsy. In this thesis, the reduction of two kinds of interference is aimed to improve the signal-to-noise ratio of MEG signals: metallic artifacts mask the activity of IEDs; and the high-frequency noise, that masks HFO activity. Considering the large number of MEG channels and the long duration of the recordings, reducing noise and marking events manually is a time-consuming task. The algorithms presented in this thesis provide automatic solutions aimed at the reduction of interferences and the detection of HFOs. Firstly, a novel automatic BSS-based algorithm to reduce metallic interference is presented and validated using simulated and real MEG signals. Three methods are tested: AMUSE, a second-order BSS technique; and INFOMAX and FastICA, based on high-order statistics. The automatic detection algorithm exploits the known characteristics of metallic-related interferences. Results indicate that AMUSE performes better when recovering brain activity and allows an effective removal of artifactual components.Secondly, the influence of metallic artifact filtering using the developed algorithm is evaluated in the source localization of IEDs in patients with refractory focal epilepsy. A comparison between the resulting positions of equivalent current dipoles (ECDs) produced by IEDs is performed: without removing metallic interference, rejecting only channels with large metallic artifacts, and after BSS-based reduction. The results show that a significant reduction on dispersion is achieved using the BSS-based reduction procedure, yielding feasible locations of ECDs in contrast to the other approaches. Finally, an algorithm for the automatic detection of epileptic ripples in MEG using beamformer-based virtual sensors is developed. The automatic detection of ripples is performed using a two-stage approach. In the first step, beamforming is applied to the whole head to determine a region of interest. In the second step, the automatic detection of ripples is performed using the time-frequency characteristics of these oscillations. The performance of the algorithm is evaluated using simultaneous intracranial EEG recordings as gold standard.The novel approaches developed in this thesis allow an improved noninvasive detection and localization of interictal epileptic biomarkers, which can help in the delimitation of the epileptogenic zone and guide the placement of intracranial electrodes, or even to determine these areas without additional invasive recordings. As a consequence of this improved detection, and given that interictal biomarkers are much more frequent and easy to record than ictal episodes, the presurgical evaluation process can be more comfortable for the patient and in a more economic way.La magnetoencefalografía (MEG) es una técnica no invasiva de adquisición de señales cerebrales que proporciona una excelente resolución temporal y una cobertura total de la cabeza, permitiendo el mapeo espacial de las fuentes cerebrales. Estas características hacen del MEG una técnica apropiada para localizar la zona epileptogénica (EZ) en la evaluación preoperatoria de la epilepsia refractaria. La evaluación prequirúrgica con MEG puede orientar la colocación del EEG intracraneal (iEEG), el actual modelo de referencia en la práctica clínica, e incluso suministrar información suficiente para una intervención quirúrgica sin registros invasivos; reduciendo la invasividad, la incomodidad y el costo del diagnóstico de la epilepsia prequirúrgica. Sin embargo, las señales MEG tienen baja relación señal ruido en comparación con el iEEG pudiendo imposibilitar la detección de descargas epileptiformes interictales (IEDs) y oscilaciones de alta frecuencia (HFOs), dos importantes biomarcadores utilizados en la evaluación preoperatoria de la epilepsia.En esta tesis, la reducción de dos tipos de interferencia está dirigida a mejorar la relación señal-ruido de la señal MEG: los artefactos metálicos que enmascaran la actividad de las IEDs; y el ruido de alta frecuencia, que enmascara la actividad de las HFOs. Debido al gran número de canales MEG y la larga duración de los registros, tanto reducir el ruido como seleccionar los biomarcadores manualmente es una tarea que consume mucho tiempo. Los algoritmos presentados en esta tesis aportan soluciones automáticas dirigidas a la reducción de interferencias y la detección de HFOs. En primer lugar, se presenta y valida un nuevo algoritmo automático basado en BSS para reducir interferencias metálicas mediante señales simuladas y reales. Se prueban tres métodos: AMUSE, una técnica BSS de segundo orden; y INFOMAX y FastICA, basados en estadísticos de orden superior. El algoritmo de detección automático utiliza las características conocidas de la señal producida por la interferencia metálica. Los resultados indican que AMUSE recupera mejor la actividad cerebral y permite una eliminación efectiva de componentes artefactuales.Posteriormente, se evalúa la influencia del filtrado de artefactos metálicos en la localización de IEDs en pacientes con epilepsia focal refractaria. Se realiza una comparación entre las posiciones resultantes de dipolos de corriente equivalentes (ECDs) producidos por IEDs: sin eliminar interferencias metálicas, rechazando solamente canales con elevados artefactos metálicos y, por último, después de una reducción utilizando el algoritmo BSS desarrollado. Los resultados muestran que se logra una reducción significativa en la dispersión utilizando el procedimiento de reducción basado en BSS, lo que produce ubicaciones factibles de los dipolos en contraste con los otros enfoques.En segundo lugar, se desarrolla un algoritmo para la detección automática ripples epilépticos en MEG utilizando sensores virtuales basados en la técnica de beamformer. La detección de ripples se realiza mediante un enfoque en dos etapas. Primero, se determina el área de interés usando beamformer. Posteriormente, se realiza la detección automática de ripples utilizando las características en tiempo-frecuencia. El rendimiento del algoritmo se evalúa utilizando registros iEEG simultáneos.Los nuevos enfoques desarrollados en esta tesis permiten una detección no invasiva mejor de los biomarcadores interictales, que pueden ayudar a delimitar la zona epileptogénica y guiar la colocación de electrodos intracraneales, o incluso determinar estas áreas sin este tipo de registros. Como consecuencia de esta mejora en la detección, y dado que los biomarcadores interictales son mucho más frecuentes y fáciles de registrar que los episodios ictales, la evaluación prequirúrgica puede ser más cómoda y menos costosa para el paciente.Postprint (published version

Movement correction and clinical implementation of wearable magnetoencephalography (MEG)

Magnetoencephalography (MEG) is the non-invasive measurement of magnetic fields due to neuronal current flow. The magnitude of the magnetic fields (10 fT to 1000 fT) is millions of times smaller than the Earth’s static field. Consequently, highly sensitive magnetic sensors are required for MEG. Until recently, MEG systems have been based on sensors requiring cryogenic cooling. Hardware limitations from this cooling have made MEG systems large, immobile and expensive. In recent years, Optically Pumped Magnetometers (OPMs) have become viable sensors with which to measure neuromagnetic fields. These can be placed directly on the scalp. This wearability means that the participant is no longer required to remain still and the cost of the system, both financial and in terms of space, is generally lower. The freedom of movement opens up new neuroscientific and clinical applications. However, this new system is not without limitations. Movement in particular leads to artefacts unlike those previously seen in MEG; the OPM properties (gain, sensitive axis orientation, phase) are dependent on the ambient magnetic field at the sensor, which changes with position. In this thesis, we look at the impact of movement on OPM based MEG (OP-MEG) and how it can be reduced. In Chapter 2, we look into the cause of movement artefacts in OP-MEG, by mapping the spatial variation in the background magnetic field in our OP-MEG system. We show that the field varies both spatially and temporally, and that by modelling it we can reduce the interference in an OP-MEG recording. In Chapters 3 and 4, we correct for this changing field in real-time, first in simulation and then empirically. Based on the simulation results, we updated our empirical method to remove reliance on recording the position of the participant and to minimise time delays in providing the correction. Finally, in Chapters 5 and 6, we record interictal (between seizure) and ictal (seizure) OP-MEG in patients with epilepsy, while considering the impact movement has on the recordings and interictal event detection

Magnetoencephalography

This is a practical book on MEG that covers a wide range of topics. The book begins with a series of reviews on the use of MEG for clinical applications, the study of cognitive functions in various diseases, and one chapter focusing specifically on studies of memory with MEG. There are sections with chapters that describe source localization issues, the use of beamformers and dipole source methods, as well as phase-based analyses, and a step-by-step guide to using dipoles for epilepsy spike analyses. The book ends with a section describing new innovations in MEG systems, namely an on-line real-time MEG data acquisition system, novel applications for MEG research, and a proposal for a helium re-circulation system. With such breadth of topics, there will be a chapter that is of interest to every MEG researcher or clinician