Egocentric Computer Vision and Machine Learning for Simulated Prosthetic Vision

Las prótesis visuales actuales son capaces de proporcionar percepción visual a personas con cierta ceguera. Sin pasar por la parte dañada del camino visual, la estimulación eléctrica en la retina o en el sistema nervioso provoca percepciones puntuales conocidas como “fosfenos”. Debido a limitaciones fisiológicas y tecnológicas, la información que reciben los pacientes tiene una resolución muy baja y un campo de visión y rango dinámico reducido afectando seriamente la capacidad de la persona para reconocer y navegar en entornos desconocidos. En este contexto, la inclusión de nuevas técnicas de visión por computador es un tema clave activo y abierto. En esta tesis nos centramos especialmente en el problema de desarrollar técnicas para potenciar la información visual que recibe el paciente implantado y proponemos diferentes sistemas de visión protésica simulada para la experimentación.Primero, hemos combinado la salida de dos redes neuronales convolucionales para detectar bordes informativos estructurales y siluetas de objetos. Demostramos cómo se pueden reconocer rápidamente diferentes escenas y objetos incluso en las condiciones restringidas de la visión protésica. Nuestro método es muy adecuado para la comprensión de escenas de interiores comparado con los métodos tradicionales de procesamiento de imágenes utilizados en prótesis visuales.Segundo, presentamos un nuevo sistema de realidad virtual para entornos de visión protésica simulada más realistas usando escenas panorámicas, lo que nos permite estudiar sistemáticamente el rendimiento de la búsqueda y reconocimiento de objetos. Las escenas panorámicas permiten que los sujetos se sientan inmersos en la escena al percibir la escena completa (360 grados).En la tercera contribución demostramos cómo un sistema de navegación de realidad aumentada para visión protésica ayuda al rendimiento de la navegación al reducir el tiempo y la distancia para alcanzar los objetivos, incluso reduciendo significativamente el número de colisiones de obstáculos. Mediante el uso de un algoritmo de planificación de ruta, el sistema encamina al sujeto a través de una ruta más corta y sin obstáculos. Este trabajo está actualmente bajo revisión.En la cuarta contribución, evaluamos la agudeza visual midiendo la influencia del campo de visión con respecto a la resolución espacial en prótesis visuales a través de una pantalla montada en la cabeza. Para ello, usamos la visión protésica simulada en un entorno de realidad virtual para simular la experiencia de la vida real al usar una prótesis de retina. Este trabajo está actualmente bajo revisión.Finalmente, proponemos un modelo de Spiking Neural Network (SNN) que se basa en mecanismos biológicamente plausibles y utiliza un esquema de aprendizaje no supervisado para obtener mejores algoritmos computacionales y mejorar el rendimiento de las prótesis visuales actuales. El modelo SNN propuesto puede hacer uso de la señal de muestreo descendente de la unidad de procesamiento de información de las prótesis retinianas sin pasar por el análisis de imágenes retinianas, proporcionando información útil a los ciegos. Esté trabajo está actualmente en preparación.<br /

A Wireless, High-Voltage Compliant, and Energy-Efficient Visual Intracortical Microstimulator

RÉSUMÉ L’objectif général de ce projet de recherche est la conception, la mise en oeuvre et la validation d’une interface sans fil intracorticale implantable en technologie CMOS avancée pour aider les personnes ayant une déficience visuelle. Les défis majeurs de cette recherche sont de répondre à la conformité à haute tension nécessaire à travers l’interface d’électrode-tissu (IET), augmenter la flexibilité dans la microstimulation et la surveillance multicanale, minimiser le budget de puissance pour un dispositif biomédical implantable, réduire la taille de l’implant et améliorer le taux de transmission sans fil des données. Par conséquent, nous présentons dans cette thèse un système de microstimulation intracorticale multi-puce basée sur une nouvelle architecture pour la transmission des données sans fil et le transfert de l’énergie se servant de couplages inductifs et capacitifs. Une première puce, un générateur de stimuli (SG) éconergétique, et une autre qui est un amplificateur de haute impédance se connectant au réseau de microélectrodes de l’étage de sortie. Les 4 canaux de générateurs de stimuli produisent des impulsions rectangulaires, demi-sinus (DS), plateau-sinus (PS) et autres types d’impulsions de courant à haut rendement énergétique. Le SG comporte un contrôleur de faible puissance, des convertisseurs numérique-analogiques (DAC) opérant en mode courant, générateurs multi-forme d’ondes et miroirs de courants alimentés sous 1.2 et 3.3V se servant pour l’interface entre les deux technologies utilisées. Le courant de stimulation du SG varie entre 2.32 et 220μA pour chaque canal. La deuxième puce (pilote de microélectrodes (MED)), une interface entre le SG et de l’arrangement de microélectrodes (MEA), fournit quatre niveaux différents de courant avec la valeur maximale de 400μA par entrée et 100μA par canal de sortie simultanément pour 8 à 16 sites de stimulation à travers les microélectrodes, connectés soit en configuration bipolaire ou monopolaire. Cette étage de sortie est hautement configurable et capable de délivrer une tension élevée pour satisfaire les conditions de l’interface à travers l’impédance de IET par rapport aux systèmes précédemment rapportés. Les valeurs nominales de plus grandes tensions d’alimentation sont de ±10V. La sortie de tension mesurée est conformément 10V/phase (anodique ou cathodique) pour les tensions d’alimentation spécifiées. L’incrémentation de tensions d’alimentation à ±13V permet de produire un courant de stimulation de 220μA par canal de sortie permettant d’élever la tension de sortie jusqu’au 20V par phase. Cet étage de sortie regroupe un commutateur haute tension pour interfacer une matrice des miroirs de courant (3.3V /20V), un registre à décalage de 32-bits à entrée sérielle, sortie parallèle, et un circuit dédié pour bloquer des états interdits.----------ABSTRACT The general objective of this research project is the design, implementation and validation of an implantable wireless intracortical interface in advanced CMOS technology to aid the visually impaired people. The major challenges in this research are to meet the required highvoltage compliance across electrode-tissue interface (ETI), increase lexibility in multichannel microstimulation and monitoring, minimize power budget for an implantable biomedical device, reduce the implant size, and enhance the data rate in wireless transmission. Therefore, we present in this thesis a multi-chip intracortical microstimulation system based on a novel architecture for wireless data and power transmission comprising inductive and capacitive couplings. The first chip is an energy-efficient stimuli generator (SG) and the second one is a highimpedance microelectrode array driver output-stage. The 4-channel stimuli-generator produces rectangular, half-sine (HS), plateau-sine (PS), and other types of energy-efficient current pulse. The SG is featured with low-power controller, current mode source- and sinkdigital- to-analog converters (DACs), multi-waveform generators, and 1.2V/3.3V interface current mirrors. The stimulation current per channel of the SG ranges from 2.32 to 220μA per channel. The second chip (microelectrode driver (MED)), an interface between the SG and the microelectrode array (MEA), supplies four different current levels with the maximum value of 400μA per input and 100μA per output channel. These currents can be delivered simultaneously to 8 to 16 stimulation sites through microelectrodes, connected either in bipolar or monopolar configuration. This output stage is highly-configurable and able to deliver higher compliance voltage across ETI impedance compared to previously reported designs. The nominal values of largest supply voltages are ±10V. The measured output compliance voltage is 10V/phase (anodic or cathodic) for the specified supply voltages. Increment of supply voltages to ±13V allows 220μA stimulation current per output channel enhancing the output compliance voltage up to 20V per phase. This output-stage is featured with a high-voltage switch-matrix, 3.3V/20V current mirrors, an on-chip 32-bit serial-in parallel-out shift register, and the forbidden state logic building blocks. The SG and MED chips have been designed and fabricated in IBM 0.13μm CMOS and Teledyne DALSA 0.8μm 5V/20V CMOS/DMOS technologies with silicon areas occupied by them 1.75 x 1.75mm2 and 4 x 4mm2 respectively. The measured DC power budgets consumed by low-and mid-voltage microchips are 2.56 and 2.1mW consecutively

Visual activity evoked by infrared in humans after dark adaptation

We evaluated the visual response to infrared (IR) in humans after dark adaptation. In seven adult participants, visual perception, visual sensitivity, and the visual response to IR after light adaptation were tested. Over the course of dark adaptation, we found visual perception and sensitivity to our experimental IR stimulus increased, while the relative IR intensity necessary for perception decreased. Visual perception of the IR stimulus was abolished during a transient light exposure; however, when turned back off, perception to the IR stimulus returned for all participants. These novel findings may be relevant for both pre-clinical and clinical visual research

Biomedical Engineering

Biomedical engineering is currently relatively wide scientific area which has been constantly bringing innovations with an objective to support and improve all areas of medicine such as therapy, diagnostics and rehabilitation. It holds a strong position also in natural and biological sciences. In the terms of application, biomedical engineering is present at almost all technical universities where some of them are targeted for the research and development in this area. The presented book brings chosen outputs and results of research and development tasks, often supported by important world or European framework programs or grant agencies. The knowledge and findings from the area of biomaterials, bioelectronics, bioinformatics, biomedical devices and tools or computer support in the processes of diagnostics and therapy are defined in a way that they bring both basic information to a reader and also specific outputs with a possible further use in research and development

Retinal pigment epithelium transplantation in retinal diseases

Age-related macular degeneration (AMD) and inherited macular diseases (IMD) are retinal disorders that can cause blindness through atrophy of the retinal pigment epithelium (RPE) or choroidal neovascularisation (CNV). RPE transplantation in severe forms of neovascular AMD has been performed with promising short-term outcomes. However, this approach has not been evaluated in atrophic types of AMD or IMD. Furthermore, the long-term outcomes of photoreceptors cell function rescue by RPE reconstruction in neovascular AMD is unknown. Current surgical techniques are complex with associated high complication rates. Therefore, other treatment approaches to reconstruct the RPE are required. This thesis aims to examine whether long-term photoreceptor cell function rescue can be achieved through RPE reconstruction by investigating the outcomes of autologous RPE transplantation or full macular translocation in AMD and IMD. A further aim is to determine the feasibility of a new approach to reconstruct the RPE using human embryonic stem cell (hESC). A prospective study of autologous RPE-choroid grafts in 9 patients with atrophic macular disease secondary to AMD or IMD demonstrated that submacular RPE graft can support retinal function and fixation. However, there was a high surgical and post-operative complication rates and the overall visual acuity and reading ability declined. Long-term follow-up demonstrated that the graft can maintain retinal function for over 2 years in some patients. A retrospective review of long-term outcomes following autologous RPE-choroid grafts and full macular translocation in 12 and 40 patients with neovascular AMD, respectively, showed that rescue of retinal function beyond 2 years is possible. A visual acuity of 6/12 was achieved and maintained for over 2 years in 8% and 15% of patients who had patch graft and translocation, respectively. However, overall visual acuity outcomes were limited by delayed post-operative complications such as recurrent CNV and cystoid macular oedema. A prospective porcine experiment showed that subretinal implant of hESC derived-RPE was feasible and human donor cell can survive in vivo for up to 6 weeks. However, there was significant loss of the hESC-RPE which may have occurred intra-operatively or during the first 2 weeks post-operatively. Macrophages were noted at the site of the graft suggesting some inflammatory and immunological responses to the human cells, polyester substrate or surgical trauma. The work in this thesis has provided the proof of principle that reconstruction of the RPE can maintain retinal function in atrophic and neovascular macular diseases over the long-term. A novel approach using hESC-RPE on an artificial substrate may be a more feasible and safer alternative to current clinical techniques of RPE reconstruction

Molecular Therapies for Inherited Retinal Diseases

Following the implementation of next-generation sequencing technologies (e.g., exome and genome sequencing) in molecular diagnostics, the majority of genetic defects underlying inherited retinal disease (IRD) can readily be identified. In parallel, opportunities to counteract the molecular consequences of these defects are rapidly emerging, providing hope for personalized medicine. ‘Classical’ gene augmentation therapy has been under study for several genetic subtypes of IRD and can be considered a safe and sometimes effective therapeutic strategy. The recent market approval of the first retinal gene augmentation therapy product (LuxturnaTM, for individuals with bi-allelic RPE65 mutations) by the FDA has not only demonstrated the potential of this specific approach, but also opened avenues for the development of other strategies. However, every gene—or even every mutation—may need a tailor-made therapeutic approach, in order to obtain the most efficacious strategy with minimal risks associated. In addition to gene augmentation therapy, other subtypes of molecular therapy are currently being designed and/or implemented, including splice modulation, DNA or RNA editing, optogenetics and pharmacological modulation. In addition, the development of proper delivery vectors has gained strong attention, and should not be overlooked when designing and testing a novel therapeutic approach. In this Special Issue, we aim to describe the current state of the art of molecular therapeutics for IRD, and discuss existing and novel therapeutic strategies, from idea to implementation, and from bench to bedside