Detection of High-Frequency EEG Activity in Epileptic Patients

Tato práce se zabývá automatickou detekcí vysokofrekvenčních oscilací jakožto moderního elektrofyziologického biomarkru epileptogenní tkáně v intrakraniálním EEG, jehož vizuální detekce je zdlouhavý proces, který je ovlivněn subjektivitou hodnotitele. Epilepsie je jedním z nejčastějších neurologických onemocnění postihující 1 % obyvatelstva. Přestože jsou přibližně dvě třetiny případů léčitelné farmakologicky, zbylá třetina pacientů je odkázána zejména na léčbu chirurgickým zákrokem, pro nějž je zapotřebí přesně lokalizovat ložisko patologické tkáně. Vysokofrekvenční oscilace jsou v posledním desetiletí studovány pro jejich potenciál lokalizace patologické tkáně. Součástí této práce je shrnutí dosavadního výzkumu vysokofrekvenčních oscilací a výčet detektorů používaných ve výzkumu. V rámci práce byly vyvinuty či vylepšeny tři detektory vysokofrekvenčních oscilací, na jejichž popis navazuje evaluace z hlediska shody s manuální detekcí, přesnosti výpočtu příznaků oscilací a schopnosti lokalizace patologické tkáně. V závěru práce jsou představeny vyvinuté metody vizualizace vysokofrekvenčních výskytu oscilací a stručně uvedeny dosažené vědecké výsledky.This work deals with automated detection of high-frequency oscillations as a novel electrophysiologic biomarker of epileptogenic tissue in intracranial EEG. Visual detection of these oscillations is a time-consuming process and is prone to reviewer bias. Epilepsy is one of the most common neurological diseases affecting 1 % of population. Even though two thirds of cases are successfully treated with anti-epileptic drugs, the rest of the patients are dependent mainly on surgical procedure, which requires precise localization of pathologic focus. High-frequency oscillations have been studied over the last decade for their potential to localize the focus of pathological tissue. Initial part of this work is a summary of the current state of high-frequency oscillations research and a detailed list of detectors used in research. Within the scope of this work three high-frequency oscillation detectors were developed or enhanced. The description of the algorithms is followed by detector evaluation with regard to the concordance with expert reviewed events, feature estimation and the ability to correctly localize pathological tissue. The final part of the work provides an overview of developed visualization methods and a short summary of achieved scientific results.

Automatic Detection of High Frequency Oscillations of Neural Signals in Epileptic Patients

Epilepsy is one the most common neurological disorders. For patients suffering from epilepsy who are medically intractable, in certain cases surgical resection of pathologic brain tissue is one remaining possibility. Prior to surgery, intracranial Electroencephalography (IEEG) study is conducted to localize seizure-generating zones. IEEG typically consists of studying epileptiform spikes and seizure discharges; however some researchers have observed short bursts of high frequency oscillations (HFOs), mostly in the range of 100-500 Hz in the seizure generating areas. A retrospective correlation analysis between the post-surgical outcome and HFO generating tissue supports the idea that HFO events may play a fundamental role in epilepsy and epileptogenesis. Recently, HFO events have been scored visually by clinicians. Typically, it is necessary to record IEEG for several days or weeks to collect sufficient epileptiform activities for precise evaluation. Needless to say, manual review of the data makes visual scoring an extremely tiresome process in which subjectivity is inevitable. Due to the recent explosion of HFO research, the development of algorithms for automatic detection of HFO events poses a great benefit to researchers and clinicians. In the literature, two methods have been widely used for automatic detection of HFO events based on the energy of the signal in the 100-500 Hz frequency band. In this thesis, we present three new methods for automatic detection of HFO events based on the sharpness property of the IEEG signals. By using simulated and real-data signals, the performance of the proposed methods are compared to the existing energy-based approaches using sensitivity and specificity metrics. Additionally, we present the clinical implication of the HFO event detections for four epileptic patients. The results indicate that the performance of the proposed detectors are robust and stable and do not deteriorate in the presence of the noise and artifacts

Kurtosis-based detection of intracranial high-frequency oscillations for the identification of the seizure onset zone

Pathological High-Frequency Oscillations (HFOs) have been recently proposed as potential biomarker of the seizure onset zone (SOZ) and have shown superior accuracy to interictal epileptiform discharges in delineating its anatomical boundaries. Characterization of HFOs is still in its infancy and this is reflected in the heterogeneity of analysis and reporting methods across studies and in clinical practice. The clinical approach to HFOs identification and quantification usually still relies on visual inspection of EEG data. In this study, we developed a pipeline for the detection and analysis of HFOs. This includes preliminary selection of the most informative channels exploiting statistical properties of the pre-ictal and ictal intracranial EEG (iEEG) time series based on spectral kurtosis, followed by wavelet-based characterization of the time-frequency properties of the signal. We performed a preliminary validation analyzing EEG data in the ripple frequency band (80-250[Formula: see text]Hz) from six patients with drug-resistant epilepsy who underwent pre-surgical evaluation with stereo-EEG (SEEG) followed by surgical resection of pathologic brain areas, who had at least two-year positive post-surgical outcome. In this series, kurtosis-driven selection and wavelet-based detection of HFOs had average sensitivity of 81.94% and average specificity of 96.03% in identifying the HFO area which overlapped with the SOZ as defined by clinical presurgical workup. Furthermore, the kurtosis-based channel selection resulted in an average reduction in computational time of 66.60%

Magnetoencephalography-based approaches to epilepsy classification

Epilepsy is a chronic central nervous system disorder characterized by recurrent seizures. Not only does epilepsy severely affect the daily life of the patient, but the risk of premature death in patients with epilepsy is three times higher than that of the normal population. Magnetoencephalography (MEG) is a non-invasive, high temporal and spatial resolution electrophysiological data that provides a valid basis for epilepsy diagnosis, and used in clinical practice to locate epileptic foci in patients with epilepsy. It has been shown that MEG helps to identify MRI-negative epilepsy, contributes to clinical decision-making in recurrent seizures after previous epilepsy surgery, that interictal MEG can provide additional localization information than scalp EEG, and complete excision of the stimulation area defined by the MEG has prognostic significance for postoperative seizure control. However, due to the complexity of the MEG signal, it is often difficult to identify subtle but critical changes in MEG through visual inspection, opening up an important area of research for biomedical engineers to investigate and implement intelligent algorithms for epilepsy recognition. At the same time, the use of manual markers requires significant time and labor costs, necessitating the development and use of computer-aided diagnosis (CAD) systems that use classifiers to automatically identify abnormal activity. In this review, we discuss in detail the results of applying various different feature extraction methods on MEG signals with different classifiers for epilepsy detection, subtype determination, and laterality classification. Finally, we also briefly look at the prospects of using MEG for epilepsy-assisted localization (spike detection, high-frequency oscillation detection) due to the unique advantages of MEG for functional area localization in epilepsy, and discuss the limitation of current research status and suggestions for future research. Overall, it is hoped that our review will facilitate the reader to quickly gain a general understanding of the problem of MEG-based epilepsy classification and provide ideas and directions for subsequent research

UNSUPERVISED CLASSIFICATION OF HIGH-FREQUENCY OSCILLATIONS IN NEOCORTICAL EPILEPSY AND CONTROL PATIENTS

Quality of life for the more than 15 million people with drug-resistant epilepsy is tied to how precisely the brain areas responsible for generating their seizures can be localized. High-frequency (100-500 Hz) field-potential oscillations (HFOs) are emerging as a candidate biomarker for epileptogenic networks, but quantitative HFO studies are hampered by selection bias arising out of the need to reduce large volumes of data in the absence of capable automated processing methods. In this thesis, I introduce and evaluate an algorithm for the automatic detection and classification of HFOs that can be deployed without human intervention across long, continuous data records from large numbers of patients. I then use the algorithm in analyzing unique macro- and microelectrode intracranial electroencephalographic recordings from human neocortical epilepsy patients and controls. A central finding is that one class of HFOs discovered by the algorithm (median bandpassed spectral centroid ~140 Hz) is more prevalent in the seizure onset zone than outside. The outcomes of this work add to our understanding of epileptogenic networks and are suitable for near-term translation into improved surgical and device-based treatments

RIPPLELAB: A comprehensive application for the detection, analysis and classification of high frequency oscillations in electroencephalographic signals

High Frequency Oscillations (HFOs) in the brain have been associated with different physiological and pathological processes. In epilepsy, HFOs might reflect a mechanism of epileptic phenomena, serving as a biomarker of epileptogenesis and epileptogenicity. Despite the valuable information provided by HFOs, their correct identification is a challenging task. A comprehensive application, RIPPLELAB, was developed to facilitate the analysis of HFOs. RIPPLELAB provides a wide range of tools for HFOs manual and automatic detection and visual validation; all of them are accessible from an intuitive graphical user interface. Four methods for automated detection—as well as several options for visualization and validation of detected events—were implemented and integrated in the application. Analysis of multiple files and channels is possible, and new options can be added by users. All features and capabilities implemented in RIPPLELAB for automatic detection were tested through the analysis of simulated signals and intracranial EEG recordings from epileptic patients (n = 16; 3,471 analyzed hours). Visual validation was also tested, and detected events were classified into different categories. Unlike other available software packages for EEG analysis, RIPPLELAB uniquely provides the appropriate graphical and algorithmic environment for HFOs detection (visual and automatic) and validation, in such a way that the power of elaborated detection methods are available to a wide range of users (experts and non-experts) through the use of this application. We believe that this open-source tool will facilitate and promote the collaboration between clinical and research centers working on the HFOs field. The tool is available under public license and is accessible through a dedicated web site

Automated Detection of High-Frequency Oscillations in Epilepsy Based on a Convolutional Neural Network

Epilepsy is one of the most common chronic neurological diseases. High-frequency oscillations (HFOs) have emerged as promising biomarkers for the epileptogenic zone. However, visual marking of HFOs is a time-consuming and laborious process. Several automated techniques have been proposed to detect HFOs, yet these are still far from being suitable for application in a clinical setting. Here, ripples and fast ripples from intracranial electroencephalograms were detected in six patients with intractable epilepsy using a convolutional neural network (CNN) method. This approach proved more accurate than using four other HFO detectors integrated in RIPPLELAB, providing a higher sensitivity (77.04% for ripples and 83.23% for fast ripples) and specificity (72.27% for ripples and 79.36% for fast ripples) for HFO detection. Furthermore, for one patient, the Cohen's kappa coefficients comparing automated detection and visual analysis results were 0.541 for ripples and 0.777 for fast ripples. Hence, our automated detector was capable of reliable estimates of ripples and fast ripples with higher sensitivity and specificity than four other HFO detectors. Our detector may be used to assist clinicians in locating epileptogenic zone in the future