Seizure detection in subdural recordings using nonlinear decision functions

This dissertation proposed a new approach to seizure detection in intracranial EEG recordings using nonlinear decision functions. It implemented well-established features that were designed to deal with complex signals such as brain recordings, and proposed a 2-D domain of analysis. Since the features considered assume both the time and frequency domains, the analysis was carried out both temporally and as a function of different frequency ranges in order to ascertain those measures that were most suitable for seizure detection. In retrospect, this study established a generalized approach to seizure detection that works across several features and across patients. ^ Clinical experiments involved 8 patients with intractable seizures that were evaluated for potential surgical interventions. A total of 35 iEEG data files collected were used in a training phase to ascertain the reliability of the formulated features. The remaining 69 iEEG data files were then used in the testing phase. ^ The testing phase revealed that the correlation sum is the feature that performed best across all patients with a sensitivity of 92% and an accuracy of 99%. The second best feature was the gamma power with a sensitivity of 92% and an accuracy of 96%. In the frequency domain, all of the 5 other spectral bands considered, revealed mixed results in terms of low sensitivity in some frequency bands and low accuracy in other frequency bands, which is expected given that the dominant frequencies in iEEG are those of the gamma band. In the time domain, other features which included mobility, complexity, and activity, all performed very well with an average a sensitivity of 80.3% and an accuracy of 95%. ^ The computational requirement needed for these nonlinear decision functions to be generated in the training phase was extremely long. It was determined that when the duration dimension was rescaled, the results improved and the convergence rates of the nonlinear decision functions were reduced dramatically by more than a 100 fold. Through this rescaling, the sensitivity of the correlation sum improved to 100% and the sensitivity of the gamma power to 97%, which meant that there were even less false negatives and false positives detected. ^

A research platform for artificial neural networks with applications in pediatric epilepsy

This dissertation established a state-of-the-art programming tool for designing and training artificial neural networks (ANNs) and showed its applicability to brain research. The developed tool, called NeuralStudio, allows users without programming skills to conduct studies based on ANNs in a powerful and very user friendly interface. A series of unique features has been implemented in NeuralStudio, such as ROC analysis, cross-validation, network averaging, topology optimization, and optimization of the activation function’s slopes. It also included a Support Vector Machines module for comparison purposes. Once the tool was fully developed, it was applied to two studies in brain research. In the first study, the goal was to create and train an ANN to detect epileptic seizures from subdural EEG. This analysis involved extracting features from the spectral power in the gamma frequencies. In the second application, a unique method was devised to link EEG recordings to epileptic and nonepileptic subjects. The contribution of this method consisted of developing a descriptor matrix that can be used to represent any EEG file regarding its duration and the number of electrodes. The first study showed that the inter-electrode mean of the spectral power in the gamma frequencies and its duration above a specific threshold performs better than the other frequencies in seizure detection, exhibiting an accuracy of 95.90%, a sensitivity of 92.59%, and a specificity of 96.84%. The second study yielded that Hjorth’s parameter activity is sufficient to accurately relate EEG to epileptic and non-epileptic subjects. After testing, accuracy, sensitivity and specificity of the classifier were all above 0.9667. Statistical tests measured the superiority of activity at over 99.99 % certainty. It was demonstrated that (1) the spectral power in the gamma frequencies is highly effective in locating seizures from EEG and (2) activity can be used to link EEG recordings to epileptic and non-epileptic subjects. These two studies required high computational load and could be addressed thanks to NeuralStudio. From a medical perspective, both methods proved the merits of NeuralStudio in brain research applications. For its outstanding features, NeuralStudio has been recently awarded a patent (US patent No. 7502763).

A Research Platform for Artificial Neural Networks with Applications in Pediatric Epilepsy

This dissertation established a state-of-the-art programming tool for designing and training artificial neural networks (ANNs) and showed its applicability to brain research. The developed tool, called NeuralStudio, allows users without programming skills to conduct studies based on ANNs in a powerful and very user friendly interface. A series of unique features has been implemented in NeuralStudio, such as ROC analysis, cross-validation, network averaging, topology optimization, and optimization of the activation function’s slopes. It also included a Support Vector Machines module for comparison purposes. Once the tool was fully developed, it was applied to two studies in brain research. In the first study, the goal was to create and train an ANN to detect epileptic seizures from subdural EEG. This analysis involved extracting features from the spectral power in the gamma frequencies. In the second application, a unique method was devised to link EEG recordings to epileptic and non-epileptic subjects. The contribution of this method consisted of developing a descriptor matrix that can be used to represent any EEG file regarding its duration and the number of electrodes. The first study showed that the inter-electrode mean of the spectral power in the gamma frequencies and its duration above a specific threshold performs better than the other frequencies in seizure detection, exhibiting an accuracy of 95.90%, a sensitivity of 92.59%, and a specificity of 96.84%. The second study yielded that Hjorth’s parameter activity is sufficient to accurately relate EEG to epileptic and non-epileptic subjects. After testing, accuracy, sensitivity and specificity of the classifier were all above 0.9667. Statistical tests measured the superiority of activity at over 99.99 % certainty. It was demonstrated that 1) the spectral power in the gamma frequencies is highly effective in locating seizures from EEG and 2) activity can be used to link EEG recordings to epileptic and non-epileptic subjects. These two studies required high computational load and could be addressed thanks to NeuralStudio. From a medical perspective, both methods proved the merits of NeuralStudio in brain research applications. For its outstanding features, NeuralStudio has been recently awarded a patent (US patent No. 7502763).

Automated detection of hematological abnormalities through classification of flow cytometric data patterns

Flow Cytometry analyzers have become trusted companions due to their ability to perform fast and accurate analyses of human blood. The aim of these analyses is to determine the possible existence of abnormalities in the blood that have been correlated with serious disease states, such as infectious mononucleosis, leukemia, and various cancers. Though these analyzers provide important feedback, it is always desired to improve the accuracy of the results. This is evidenced by the occurrences of misclassifications reported by some users of these devices. It is advantageous to provide a pattern interpretation framework that is able to provide better classification ability than is currently available. Toward this end, the purpose of this dissertation was to establish a feature extraction and pattern classification framework capable of providing improved accuracy for detecting specific hematological abnormalities in flow cytometric blood data. ^ This involved extracting a unique and powerful set of shift-invariant statistical features from the multi-dimensional flow cytometry data and then using these features as inputs to a pattern classification engine composed of an artificial neural network (ANN). The contribution of this method consisted of developing a descriptor matrix that can be used to reliably assess if a donor’s blood pattern exhibits a clinically abnormal level of variant lymphocytes, which are blood cells that are potentially indicative of disorders such as leukemia and infectious mononucleosis. ^ This study showed that the set of shift-and-rotation-invariant statistical features extracted from the eigensystem of the flow cytometric data pattern performs better than other commonly-used features in this type of disease detection, exhibiting an accuracy of 80.7%, a sensitivity of 72.3%, and a specificity of 89.2%. This performance represents a major improvement for this type of hematological classifier, which has historically been plagued by poor performance, with accuracies as low as 60% in some cases. This research ultimately shows that an improved feature space was developed that can deliver improved performance for the detection of variant lymphocytes in human blood, thus providing significant utility in the realm of suspect flagging algorithms for the detection of blood-related diseases.^

A framework for automatic feature extraction from airborne light detection and ranging data

Recent advances in airborne Light Detection and Ranging (LIDAR) technology allow rapid and inexpensive measurements of topography over large areas. Airborne LIDAR systems usually return a 3-dimensional cloud of point measurements from reflective objects scanned by the laser beneath the flight path. This technology is becoming a primary method for extracting information of different kinds of geometrical objects, such as high-resolution digital terrain models (DTMs), buildings and trees, etc. In the past decade, LIDAR gets more and more interest from researchers in the field of remote sensing and GIS. Compared to the traditional data sources, such as aerial photography and satellite images, LIDAR measurements are not influenced by sun shadow and relief displacement. However, voluminous data pose a new challenge for automated extraction the geometrical information from LIDAR measurements because many raster image processing techniques cannot be directly applied to irregularly spaced LIDAR points. ^ In this dissertation, a framework is proposed to filter out information about different kinds of geometrical objects, such as terrain and buildings from LIDAR automatically. They are essential to numerous applications such as flood modeling, landslide prediction and hurricane animation. The framework consists of several intuitive algorithms. Firstly, a progressive morphological filter was developed to detect non-ground LIDAR measurements. By gradually increasing the window size and elevation difference threshold of the filter, the measurements of vehicles, vegetation, and buildings are removed, while ground data are preserved. Then, building measurements are identified from no-ground measurements using a region growing algorithm based on the plane-fitting technique. Raw footprints for segmented building measurements are derived by connecting boundary points and are further simplified and adjusted by several proposed operations to remove noise, which is caused by irregularly spaced LIDAR measurements. To reconstruct 3D building models, the raw 2D topology of each building is first extracted and then further adjusted. Since the adjusting operations for simple building models do not work well on 2D topology, 2D snake algorithm is proposed to adjust 2D topology. The 2D snake algorithm consists of newly defined energy functions for topology adjusting and a linear algorithm to find the minimal energy value of 2D snake problems. Data sets from urbanized areas including large institutional, commercial, and small residential buildings were employed to test the proposed framework. The results demonstrated that the proposed framework achieves a very good performance. ^

An automated method for the determination of electroreception thresholds in weakly electric fish

Weakly electric fish produce a dual function electric signal that makes them ideal models for the study of sensory computation and signal evolution. This signal, the electric organ discharge (EOD), is used for communication and navigation. In some families of gymnotiform electric fish, the EOD is a dynamic signal that increases in amplitude during social interactions. Amplitude increase could facilitate communication by increasing the likelihood of being sensed by others or by impressing prospective mates or rivals. Conversely, by increasing its signal amplitude a fish might increase its sensitivity to objects by lowering its electrolocation detection threshold. To determine how EOD modulations elicited in the social context affect electrolocation, I developed an automated and fast method for measuring electroreception thresholds using a classical conditioning paradigm. This method employs a moving shelter tube, which these fish occupy at rest during the day, paired with an electrical stimulus. A custom built and programmed robotic system presents the electrical stimulus to the fish, slides the shelter tube requiring them to follow, and records video of their movements. I trained the electric fish of the genus Sternopygus was trained to respond to a resistive stimulus on this apparatus in 2 days. The motion detection algorithm correctly identifies the responses 91% of the time, with a false positive rate of only 4%. This system allows for a large number of trials, decreasing the amount of time needed to determine behavioral electroreception thresholds. This novel method enables the evaluation the evolutionary interplay between two conflicting sensory forces, social communication and navigation.

Electrochemical Immunosensing of Cortisol in an Automated Microfluidic System Towards Point-of-Care Applications

This dissertation describes the development of a label-free, electrochemical immunosensing platform integrated into a low-cost microfluidic system for the sensitive, selective and accurate detection of cortisol, a steroid hormone co-related with many physiological disorders. Abnormal levels of cortisol is indicative of conditions such as Cushing’s syndrome, Addison’s disease, adrenal insufficiencies and more recently post-traumatic stress disorder (PTSD). Electrochemical detection of immuno-complex formation is utilized for the sensitive detection of Cortisol using Anti-Cortisol antibodies immobilized on sensing electrodes. Electrochemical detection techniques such as cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) have been utilized for the characterization and sensing of the label-free detection of Cortisol. The utilization of nanomaterial’s as the immobilizing matrix for Anti-cortisol antibodies that leads to improved sensor response has been explored. A hybrid nano-composite of Polyanaline-Ag/AgO film has been fabricated onto Au substrate using electrophoretic deposition for the preparation of electrochemical immunosening of cortisol. Using a conventional 3-electrode electrochemical cell, a linear sensing range of 1pM to 1µM at a sensitivity of 66µA/M and detection limit of 0.64pg/mL has been demonstrated for detection of cortisol. Alternately, a self-assembled monolayer (SAM) of dithiobis(succinimidylpropionte) (DTSP) has been fabricated for the modification of sensing electrode to immobilize with Anti-Cortisol antibodies. To increase the sensitivity at lower detection limit and to develop a point-of-care sensing platform, the DTSP-SAM has been fabricated on micromachined interdigitated microelectrodes (µIDE). Detection of cortisol is demonstrated at a sensitivity of 20.7µA/M and detection limit of 10pg/mL for a linear sensing range of 10pM to 200nM using the µIDE’s. A simple, low-cost microfluidic system is designed using low-temperature co-fired ceramics (LTCC) technology for the integration of the electrochemical cortisol immunosensor and automation of the immunoassay. For the first time, the non-specific adsorption of analyte on LTCC has been characterized for microfluidic applications. The design, fabrication technique and fluidic characterization of the immunoassay are presented. The DTSP-SAM based electrochemical immunosensor on µIDE is integrated into the LTCC microfluidic system and cortisol detection is achieved in the microfluidic system in a fully automated assay. The fully automated microfluidic immunosensor hold great promise for accurate, sensitive detection of cortisol in point-of-care applications.