Development of a practical and mobile brain-computer communication device for profoundly paralyzed individuals

Thesis (Ph.D.)--Boston UniversityBrain-computer interface (BCI) technology has seen tremendous growth over the past several decades, with numerous groundbreaking research studies demonstrating technical viability (Sellers et al., 2010; Silvoni et al., 2011). Despite this progress, BCIs have remained primarily in controlled laboratory settings. This dissertation proffers a blueprint for translating research-grade BCI systems into real-world applications that are noninvasive and fully portable, and that employ intelligent user interfaces for communication. The proposed architecture is designed to be used by severely motor-impaired individuals, such as those with locked-in syndrome, while reducing the effort and cognitive load needed to communicate. Such a system requires the merging of two primary research fields: 1) electroencephalography (EEG)-based BCIs and 2) intelligent user interface design. The EEG-based BCI portion of this dissertation provides a history of the field, details of our software and hardware implementation, and results from an experimental study aimed at verifying the utility of a BCI based on the steady-state visual evoked potential (SSVEP), a robust brain response to visual stimulation at controlled frequencies. The visual stimulation, feature extraction, and classification algorithms for the BCI were specially designed to achieve successful real-time performance on a laptop computer. Also, the BCI was developed in Python, an open-source programming language that combines programming ease with effective handling of hardware and software requirements. The result of this work was The Unlock Project app software for BCI development. Using it, a four-choice SSVEP BCI setup was implemented and tested with five severely motor-impaired and fourteen control participants. The system showed a wide range of usability across participants, with classification rates ranging from 25-95%. The second portion of the dissertation discusses the viability of intelligent user interface design as a method for obtaining a more user-focused vocal output communication aid tailored to motor-impaired individuals. A proposed blueprint of this communication "app" was developed in this dissertation. It would make use of readily available laptop sensors to perform facial recognition, speech-to-text decoding, and geo-location. The ultimate goal is to couple sensor information with natural language processing to construct an intelligent user interface that shapes communication in a practical SSVEP-based BCI

An image processing decisional system for the Achilles tendon using ultrasound images

The Achilles Tendon (AT) is described as the largest and strongest tendon in the human body. As for any other organs in the human body, the AT is associated with some medical problems that include Achilles rupture and Achilles tendonitis. AT rupture affects about 1 in 5,000 people worldwide. Additionally, AT is seen in about 10 percent of the patients involved in sports activities. Today, ultrasound imaging plays a crucial role in medical imaging technologies. It is portable, non-invasive, free of radiation risks, relatively inexpensive and capable of taking real-time images. There is a lack of research that looks into the early detection and diagnosis of AT abnormalities from ultrasound images. This motivated the researcher to build a complete system which enables one to crop, denoise, enhance, extract the important features and classify AT ultrasound images. The proposed application focuses on developing an automated system platform. Generally, systems for analysing ultrasound images involve four stages, pre-processing, segmentation, feature extraction and classification. To produce the best results for classifying the AT, SRAD, CLAHE, GLCM, GLRLM, KPCA algorithms have been used. This was followed by the use of different standard and ensemble classifiers trained and tested using the dataset samples and reduced features to categorize the AT images into normal or abnormal. Various classifiers have been adopted in this research to improve the classification accuracy. To build an image decisional system, a 57 AT ultrasound images has been collected. These images were used in three different approaches where the Region of Interest (ROI) position and size are located differently. To avoid the imbalanced misleading metrics, different evaluation metrics have been adapted to compare different classifiers and evaluate the whole classification accuracy. The classification outcomes are evaluated using different metrics in order to estimate the decisional system performance. A high accuracy of 83% was achieved during the classification process. Most of the ensemble classifies worked better than the standard classifiers in all the three ROI approaches. The research aim was achieved and accomplished by building an image processing decisional system for the AT ultrasound images. This system can distinguish between normal and abnormal AT ultrasound images. In this decisional system, AT images were improved and enhanced to achieve a high accuracy of classification without any user intervention

Unsupervised learning for vascular heterogeneity assessment of glioblastoma based on magnetic resonance imaging: The Hemodynamic Tissue Signature

[ES] El futuro de la imagen médica está ligado a la inteligencia artificial. El análisis manual de imágenes médicas es hoy en día una tarea ardua, propensa a errores y a menudo inasequible para los humanos, que ha llamado la atención de la comunidad de Aprendizaje Automático (AA). La Imagen por Resonancia Magnética (IRM) nos proporciona una rica variedad de representaciones de la morfología y el comportamiento de lesiones inaccesibles sin una intervención invasiva arriesgada. Sin embargo, explotar la potente pero a menudo latente información contenida en la IRM es una tarea muy complicada, que requiere técnicas de análisis computacional inteligente. Los tumores del sistema nervioso central son una de las enfermedades más críticas estudiadas a través de IRM. Específicamente, el glioblastoma representa un gran desafío, ya que, hasta la fecha, continua siendo un cáncer letal que carece de una terapia satisfactoria. Del conjunto de características que hacen del glioblastoma un tumor tan agresivo, un aspecto particular que ha sido ampliamente estudiado es su heterogeneidad vascular. La fuerte proliferación vascular del glioblastoma, así como su robusta angiogénesis han sido consideradas responsables de la alta letalidad de esta neoplasia. Esta tesis se centra en la investigación y desarrollo del método Hemodynamic Tissue Signature (HTS): un método de AA no supervisado para describir la heterogeneidad vascular de los glioblastomas mediante el análisis de perfusión por IRM. El método HTS se basa en el concepto de hábitat, que se define como una subregión de la lesión con un perfil de IRM que describe un comportamiento fisiológico concreto. El método HTS delinea cuatro hábitats en el glioblastoma: el hábitat HAT, como la región más perfundida del tumor con captación de contraste; el hábitat LAT, como la región del tumor con un perfil angiogénico más bajo; el hábitat IPE, como la región adyacente al tumor con índices de perfusión elevados; y el hábitat VPE, como el edema restante de la lesión con el perfil de perfusión más bajo. La investigación y desarrollo de este método ha originado una serie de contribuciones enmarcadas en esta tesis. Primero, para verificar la fiabilidad de los métodos de AA no supervisados en la extracción de patrones de IRM, se realizó una comparativa para la tarea de segmentación de gliomas de grado alto. Segundo, se propuso un algoritmo de AA no supervisado dentro de la familia de los Spatially Varying Finite Mixture Models. El algoritmo propone una densidad a priori basada en un Markov Random Field combinado con la función probabilística Non-Local Means, para codificar la idea de que píxeles vecinos tienden a pertenecer al mismo objeto. Tercero, se presenta el método HTS para describir la heterogeneidad vascular del glioblastoma. El método se ha aplicado a casos reales en una cohorte local de un solo centro y en una cohorte internacional de más de 180 pacientes de 7 centros europeos. Se llevó a cabo una evaluación exhaustiva del método para medir el potencial pronóstico de los hábitats HTS. Finalmente, la tecnología desarrollada en la tesis se ha integrado en la plataforma online ONCOhabitats (https://www.oncohabitats.upv.es). La plataforma ofrece dos servicios: 1) segmentación de tejidos de glioblastoma, y 2) evaluación de la heterogeneidad vascular del tumor mediante el método HTS. Los resultados de esta tesis han sido publicados en diez contribuciones científicas, incluyendo revistas y conferencias de alto impacto en las áreas de Informática Médica, Estadística y Probabilidad, Radiología y Medicina Nuclear y Aprendizaje Automático. También se emitió una patente industrial registrada en España, Europa y EEUU. Finalmente, las ideas originales concebidas en esta tesis dieron lugar a la creación de ONCOANALYTICS CDX, una empresa enmarcada en el modelo de negocio de los companion diagnostics de compuestos farmacéuticos.[EN] The future of medical imaging is linked to Artificial Intelligence (AI). The manual analysis of medical images is nowadays an arduous, error-prone and often unaffordable task for humans, which has caught the attention of the Machine Learning (ML) community. Magnetic Resonance Imaging (MRI) provides us with a wide variety of rich representations of the morphology and behavior of lesions completely inaccessible without a risky invasive intervention. Nevertheless, harnessing the powerful but often latent information contained in MRI acquisitions is a very complicated task, which requires computational intelligent analysis techniques. Central nervous system tumors are one of the most critical diseases studied through MRI. Specifically, glioblastoma represents a major challenge, as it remains a lethal cancer that, to date, lacks a satisfactory therapy. Of the entire set of characteristics that make glioblastoma so aggressive, a particular aspect that has been widely studied is its vascular heterogeneity. The strong vascular proliferation of glioblastomas, as well as their robust angiogenesis and extensive microvasculature heterogeneity have been claimed responsible for the high lethality of the neoplasm. This thesis focuses on the research and development of the Hemodynamic Tissue Signature (HTS) method: an unsupervised ML approach to describe the vascular heterogeneity of glioblastomas by means of perfusion MRI analysis. The HTS builds on the concept of habitats. A habitat is defined as a sub-region of the lesion with a particular MRI profile describing a specific physiological behavior. The HTS method delineates four habitats within the glioblastoma: the HAT habitat, as the most perfused region of the enhancing tumor; the LAT habitat, as the region of the enhancing tumor with a lower angiogenic profile; the potentially IPE habitat, as the non-enhancing region adjacent to the tumor with elevated perfusion indexes; and the VPE habitat, as the remaining edema of the lesion with the lowest perfusion profile. The research and development of the HTS method has generated a number of contributions to this thesis. First, in order to verify that unsupervised learning methods are reliable to extract MRI patterns to describe the heterogeneity of a lesion, a comparison among several unsupervised learning methods was conducted for the task of high grade glioma segmentation. Second, a Bayesian unsupervised learning algorithm from the family of Spatially Varying Finite Mixture Models is proposed. The algorithm integrates a Markov Random Field prior density weighted by the probabilistic Non-Local Means function, to codify the idea that neighboring pixels tend to belong to the same semantic object. Third, the HTS method to describe the vascular heterogeneity of glioblastomas is presented. The HTS method has been applied to real cases, both in a local single-center cohort of patients, and in an international retrospective cohort of more than 180 patients from 7 European centers. A comprehensive evaluation of the method was conducted to measure the prognostic potential of the HTS habitats. Finally, the technology developed in this thesis has been integrated into an online open-access platform for its academic use. The ONCOhabitats platform is hosted at https://www.oncohabitats.upv.es, and provides two main services: 1) glioblastoma tissue segmentation, and 2) vascular heterogeneity assessment of glioblastomas by means of the HTS method. The results of this thesis have been published in ten scientific contributions, including top-ranked journals and conferences in the areas of Medical Informatics, Statistics and Probability, Radiology & Nuclear Medicine and Machine Learning. An industrial patent registered in Spain, Europe and EEUU was also issued. Finally, the original ideas conceived in this thesis led to the foundation of ONCOANALYTICS CDX, a company framed into the business model of companion diagnostics for pharmaceutical compounds.[CA] El futur de la imatge mèdica està lligat a la intel·ligència artificial. L'anàlisi manual d'imatges mèdiques és hui dia una tasca àrdua, propensa a errors i sovint inassequible per als humans, que ha cridat l'atenció de la comunitat d'Aprenentatge Automàtic (AA). La Imatge per Ressonància Magnètica (IRM) ens proporciona una àmplia varietat de representacions de la morfologia i el comportament de lesions inaccessibles sense una intervenció invasiva arriscada. Tanmateix, explotar la potent però sovint latent informació continguda a les adquisicions de IRM esdevé una tasca molt complicada, que requereix tècniques d'anàlisi computacional intel·ligent. Els tumors del sistema nerviós central són una de les malalties més crítiques estudiades a través de IRM. Específicament, el glioblastoma representa un gran repte, ja que, fins hui, continua siguent un càncer letal que manca d'una teràpia satisfactòria. Del conjunt de característiques que fan del glioblastoma un tumor tan agressiu, un aspecte particular que ha sigut àmpliament estudiat és la seua heterogeneïtat vascular. La forta proliferació vascular dels glioblastomes, així com la seua robusta angiogènesi han sigut considerades responsables de l'alta letalitat d'aquesta neoplàsia. Aquesta tesi es centra en la recerca i desenvolupament del mètode Hemodynamic Tissue Signature (HTS): un mètode d'AA no supervisat per descriure l'heterogeneïtat vascular dels glioblastomas mitjançant l'anàlisi de perfusió per IRM. El mètode HTS es basa en el concepte d'hàbitat, que es defineix com una subregió de la lesió amb un perfil particular d'IRM, que descriu un comportament fisiològic concret. El mètode HTS delinea quatre hàbitats dins del glioblastoma: l'hàbitat HAT, com la regió més perfosa del tumor amb captació de contrast; l'hàbitat LAT, com la regió del tumor amb un perfil angiogènic més baix; l'hàbitat IPE, com la regió adjacent al tumor amb índexs de perfusió elevats, i l'hàbitat VPE, com l'edema restant de la lesió amb el perfil de perfusió més baix. La recerca i desenvolupament del mètode HTS ha originat una sèrie de contribucions emmarcades a aquesta tesi. Primer, per verificar la fiabilitat dels mètodes d'AA no supervisats en l'extracció de patrons d'IRM, es va realitzar una comparativa en la tasca de segmentació de gliomes de grau alt. Segon, s'ha proposat un algorisme d'AA no supervisat dintre de la família dels Spatially Varying Finite Mixture Models. L'algorisme proposa un densitat a priori basada en un Markov Random Field combinat amb la funció probabilística Non-Local Means, per a codificar la idea que els píxels veïns tendeixen a pertànyer al mateix objecte semàntic. Tercer, es presenta el mètode HTS per descriure l'heterogeneïtat vascular dels glioblastomas. El mètode HTS s'ha aplicat a casos reals en una cohort local d'un sol centre i en una cohort internacional de més de 180 pacients de 7 centres europeus. Es va dur a terme una avaluació exhaustiva del mètode per mesurar el potencial pronòstic dels hàbitats HTS. Finalment, la tecnologia desenvolupada en aquesta tesi s'ha integrat en una plataforma online ONCOhabitats (https://www.oncohabitats.upv.es). La plataforma ofereix dos serveis: 1) segmentació dels teixits del glioblastoma, i 2) avaluació de l'heterogeneïtat vascular dels glioblastomes mitjançant el mètode HTS. Els resultats d'aquesta tesi han sigut publicats en deu contribucions científiques, incloent revistes i conferències de primer nivell a les àrees d'Informàtica Mèdica, Estadística i Probabilitat, Radiologia i Medicina Nuclear i Aprenentatge Automàtic. També es va emetre una patent industrial registrada a Espanya, Europa i els EEUU. Finalment, les idees originals concebudes en aquesta tesi van donar lloc a la creació d'ONCOANALYTICS CDX, una empresa emmarcada en el model de negoci dels companion diagnostics de compostos farmacèutics.En este sentido quiero agradecer a las diferentes instituciones y estructuras de financiación de investigación que han contribuido al desarrollo de esta tesis. En especial quiero agradecer a la Universitat Politècnica de València, donde he desarrollado toda mi carrera acadèmica y científica, así como al Ministerio de Ciencia e Innovación, al Ministerio de Economía y Competitividad, a la Comisión Europea, al EIT Health Programme y a la fundación Caixa ImpulseJuan Albarracín, J. (2020). Unsupervised learning for vascular heterogeneity assessment of glioblastoma based on magnetic resonance imaging: The Hemodynamic Tissue Signature [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/149560TESI

Diagnosis and Treatment of Small Bowel Disorders

Over the last few decades, remarkable progress has been made in understanding the aetiology and pathophysiology of diseases and many new theories emphasize the importance of the small bowel ‘ecosystem’ in the pathogenesis of acute and chronic illness. Emerging factors such as microbiome, stem cells, innate intestinal immunity and the enteric nervous system along with mucosal and endothelial barriers have key role in the development of gastrointestinal and extra-intestinal diseases. Therefore, the small intestine is considered key player in metabolic disease development, including diabetes mellitus, and other diet-related disorders such as celiac and non-celiac enteropathies. Another major field is drug metabolism and its interaction with microbiota. Moreover, the emergence of gut-brain, gut-liver and gut-blood barriers points toward the important role of small intestine in the pathogenesis of common disorders, such as liver disease, hypertension and neurodegenerative disease. However, the small bowel remains an organ that is difficult to fully access and assess and accurate diagnosis often poses a clinical challenge. Eventually, the therapeutic potential remains untapped. Therefore, it is due time to direct our interest towards the small intestine and unravel the interplay between small-bowel and other gastrointestinal (GI) and non-GI related maladies

Heterogeneous recognition of bioacoustic signals for human-machine interfaces

Human-machine interfaces (HMI) provide a communication pathway between man and machine. Not only do they augment existing pathways, they can substitute or even bypass these pathways where functional motor loss prevents the use of standard interfaces. This is especially important for individuals who rely on assistive technology in their everyday life. By utilising bioacoustic activity, it can lead to an assistive HMI concept which is unobtrusive, minimally disruptive and cosmetically appealing to the user. However, due to the complexity of the signals it remains relatively underexplored in the HMI field. This thesis investigates extracting and decoding volition from bioacoustic activity with the aim of generating real-time commands. The developed framework is a systemisation of various processing blocks enabling the mapping of continuous signals into M discrete classes. Class independent extraction efficiently detects and segments the continuous signals while class-specific extraction exemplifies each pattern set using a novel template creation process stable to permutations of the data set. These templates are utilised by a generalised single channel discrimination model, whereby each signal is template aligned prior to classification. The real-time decoding subsystem uses a multichannel heterogeneous ensemble architecture which fuses the output from a diverse set of these individual discrimination models. This enhances the classification performance by elevating both the sensitivity and specificity, with the increased specificity due to a natural rejection capacity based on a non-parametric majority vote. Such a strategy is useful when analysing signals which have diverse characteristics, false positives are prevalent and have strong consequences, and when there is limited training data available. The framework has been developed with generality in mind with wide applicability to a broad spectrum of biosignals. The processing system has been demonstrated on real-time decoding of tongue-movement ear pressure signals using both single and dual channel setups. This has included in-depth evaluation of these methods in both offline and online scenarios. During online evaluation, a stimulus based test methodology was devised, while representative interference was used to contaminate the decoding process in a relevant and real fashion. The results of this research provide a strong case for the utility of such techniques in real world applications of human-machine communication using impulsive bioacoustic signals and biosignals in general

Ecological Understanding through Transdisciplinary Art and Participatory Biology

Full version unavailable due to 3rd party copyright restrictionsIn this study evidence is presented that suggests transdisciplinary art practices and participatory biology programs may successfully increase public understanding of ecological phenomenon. As today’s environmental issues are often complex and large-scale, finding effective strategies that encourage public awareness and stewardship are paramount for long-term conservation of species and ecosystems. Although artists and biologists tend to stay confined to their professional boundaries, and their discourses largely remain inaccessible to larger audiences, arguments here are presented for a combined approach, which may disseminate knowledge about ecology to non-specialists through novel art-science participatory research and exhibitions. Moreover, historically several scientists utilized varied creative art forms to disseminate scientific insights to a larger populace of non-specialists, such strategies as engaging writings and visually provocative artworks may still be effective to captivate contemporary audiences. In addition such historic hybrid science-art practitioners may have laid a conceptual terrain for some of today’s transdisciplinary art and citizen science practices. Furthermore, seminal ecological artworks from the 20th Century by Joseph Beuys, Patricia Johanson and Hans Haacke utilized novel strategies to reach audiences with a message of wetland conservation, blurring boundaries between art, ecology and activism. More recently artists like Cornelia Hesse-Honegger, Helen and Newton Harrison and others have integrated biological research into their art practices, which resulted in new scientific discoveries. Through my own transdisciplinary artwork about frogs, data suggests that the visual strategies I employ were effective to increase non-specialist understanding of the ecological phenomenon of amphibian declines and deformations. In addition through my participatory biology programs, Public Bio-Art Laboratories and Eco-Actions, evidence suggests that non-specialists achieved an increased awareness of the challenges amphibians and ecosystems currently face. Likewise, that through such participatory citizen science research new scientific insights about the proximate causes for deformities in anuran amphibians at select localities in middle England and Quebec were achieved. Here laboratory and field evidence, generated with the aid of public volunteers, found that non-lethal predatory injury to tadpoles from odonate nymphs and some fishes resulted in permanent limb deformities in post-metamorphic anurans. From an environmental-education and larger conservation standpoint, these findings are very relevant as they offer novel strategies for experientially engaging non-specialist audiences while generating important insights into biological communities and wetland ecosystems