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

RGB-D Scene Representations for Prosthetic Vision

This thesis presents a new approach to scene representation for prosthetic vision. Structurally salient information from the scene is conveyed through the prosthetic vision display. Given the low resolution and dynamic range of the display, this enables robust identification and reliable interpretation of key structural features that are missed when using standard appearance-based scene representations. Specifically, two different types of salient structure are investigated: salient edge structure, for depiction of scene shape to the user; and salient object structure, for emulation of biological attention deployment when viewing a scene. This thesis proposes and evaluates novel computer vision algorithms for extracting salient edge and salient object structure from RGB-D input. Extraction of salient edge structure from the scene is first investigated through low-level analysis of surface shape. Our approach is based on the observation that regions of irregular surface shape, such as the boundary between the wall and the floor, tend to be more informative of scene structure than uniformly shaped regions. We detect these surface irregularities through multi-scale analysis of iso-disparity contour orientations, providing a real time method that robustly identifies important scene structure. This approach is then extended by using a deep CNN to learn high level information for distinguishing salient edges from structural texture. A novel depth input encoding called the depth surface descriptor (DSD) is presented, which better captures scene geometry that corresponds to salient edges, improving the learned model. These methods provide robust detection of salient edge structure in the scene. The detection of salient object structure is first achieved by noting that salient objects often have contrasting shape from their surroundings. Contrasting shape in the depth image is captured through the proposed histogram of surface orientations (HOSO) feature. This feature is used to modulate depth and colour contrast in a saliency detection framework, improving the precision of saliency seed regions and through this the accuracy of the final detection. After this, a novel formulation of structural saliency is introduced based on the angular measure of local background enclosure (LBE). This formulation addresses fundamental limitations of depth contrast methods and is not reliant on foreground depth contrast in the scene. Saliency is instead measured through the degree to which a candidate patch exhibits foreground structure. The effectiveness of the proposed approach is evaluated through both standard datasets as well as user studies that measure the contribution of structure-based representations. Our methods are found to more effectively measure salient structure in the scene than existing methods. Our approach results in improved performance compared to standard methods during practical use of an implant display

Simulating and optimizing electrical current flow and neuronal activation in retinal implants

© 2018 Dr Timothy Bede Esler[Abstract Withheld

Towards clinical trials of a novel Bionic Eye: Building evidence of safety and efficacy

In the quest for therapeutic solutions for the visually impaired, electrical stimulation of the retina is, and has been, the focus of intense research. Some of these efforts have led to the development of the Phoenix99 Bionic Eye, a device which combines promising technological features with novel stimulation strategies. For medical devices, considerable challenges must be overcome before they’re allowed to be trialled in their target population. The requirements for a study to be performed include the demonstration of a positive risk-benefit ratio of the research. The present dissertation is an attempt to address how pre-clinical trials in animals can be used to understand and minimise risks. A positive risk-benefit ratio means that the potential benefits of the research outweigh the risks of the intervention. In the case of retinal prostheses, the risks include the surgical intervention, the immune response to the device, the safety of the electrical stimuli, and the effects of device ageing. In this work, successful demonstration of the surgical safety and biocompatibility of passive Phoenix99 devices during long-term implantation in sheep called for the evaluation of the chronic effects of the novel stimulation paradigms it can deliver. As preparation for this study, the techniques used to evaluate the safety and efficacy of the stimuli in animals were refined. A systematic approach to minimise the impact of anaesthesia on the experimental results is presented, as well as a novel in vivo retinal recording technique. To maximise the clinical relevance of all animal trials, a computer model for the prediction of thresholds was developed. Finally, in vitro device ageing was performed to deepen our understanding of the design’s potential for long-term implantation. Protocols for a long-term device safety study in sheep and for an acute human trial are also presented, thus taking concrete and sensible steps towards the first clinical use of the Phoenix99 Bionic Eye

An efficient telemetry system for restoring sight

PhD ThesisThe human nervous system can be damaged as a result of disease or trauma, causing conditions such as Parkinson’s disease. Most people try pharmaceuticals as a primary method of treatment. However, drugs cannot restore some cases, such as visual disorder. Alternatively, this impairment can be treated with electronic neural prostheses. A retinal prosthesis is an example of that for restoring sight, but it is not efficient and only people with retinal pigmentosa benefit from it. In such treatments, stimulation of the nervous system can be achieved by electrical or optical means. In the latter case, the nerves need to be rendered light sensitive via genetic means (optogenetics). High radiance photonic devices are then required to deliver light to the target tissue. Such optical approaches hold the potential to be more effective while causing less harm to the brain tissue. As these devices are implanted in tissue, wireless means need to be used to communicate with them. For this, IEEE 802.15.6 or Bluetooth protocols at 2.4GHz are potentially compatible with most advanced electronic devices, and are also safe and secure. Also, wireless power delivery can operate the implanted device. In this thesis, a fully wireless and efficient visual cortical stimulator was designed to restore the sight of the blind. This system is likely to address 40% of the causes of blindness. In general, the system can be divided into two parts, hardware and software. Hardware parts include a wireless power transfer design, the communication device, power management, a processor and the control unit, and the 3D design for assembly. The software part contains the image simplification, image compression, data encoding, pulse modulation, and the control system. Real-time video streaming is processed and sent over Bluetooth, and data are received by the LPC4330 six layer implanted board. After retrieving the compressed data, the processed data are again sent to the implanted electrode/optrode to stimulate the brain’s nerve cells

Attention and Social Cognition in Virtual Reality:The effect of engagement mode and character eye-gaze

Technical developments in virtual humans are manifest in modern character design. Specifically, eye gaze offers a significant aspect of such design. There is need to consider the contribution of participant control of engagement. In the current study, we manipulated participants’ engagement with an interactive virtual reality narrative called Coffee without Words. Participants sat over coffee opposite a character in a virtual café, where they waited for their bus to be repaired. We manipulated character eye-contact with the participant. For half the participants in each condition, the character made no eye-contact for the duration of the story. For the other half, the character responded to participant eye-gaze by making and holding eye contact in return. To explore how participant engagement interacted with this manipulation, half the participants in each condition were instructed to appraise their experience as an artefact (i.e., drawing attention to technical features), while the other half were introduced to the fictional character, the narrative, and the setting as though they were real. This study allowed us to explore the contributions of character features (interactivity through eye-gaze) and cognition (attention/engagement) to the participants’ perception of realism, feelings of presence, time duration, and the extent to which they engaged with the character and represented their mental states (Theory of Mind). Importantly it does so using a highly controlled yet ecologically valid virtual experience

Analysis of Factors Affecting the Performance of Retinal Prostheses Using Finite Element Modelling of Electric Field Distribution in the Retina

This dissertation proposes a computational framework targeted at improving the design of currently employed retinal prostheses. The framework was used for analysing factors impacting the performance of prostheses in terms of electrical stimulation for retinal neurons, which might lead to a perception of pixelated vision. Despite their demonstrated effectiveness, the chronic and safe usage of these retinal prostheses in human and animal trials is jeopardised due to high stimulation thresholds. This is related to the distance between the stimulating electrodes and the retinal neurons resulting from the implantation procedure. The major goal of this dissertation was to evaluate the stimulation efficacy in current implantable planar microelectrode-based retinal prostheses and consequently demonstrate their weakness, thereby providing scope for the development of future implants. The effect of geometrical factors i.e., electrode-retina distance and electrode size on stimulation applied to the retina by retinal prostheses was studied. To this end, a finite element method based simulation framework to compute electric field distribution in the retina was constructed. An electrical model of the retina was an integral part of the framework, essentially represented by a resistivity profile of the multi-layered retina. The elements of a retinal prosthesis were modelled by incorporating realistic electrode sizes, an anatomical and electrical model of the retina, a precise positioning of stimulation and return electrodes and the location of the implant with respect to the retina representing the epiretinal and subretinal stimulation schemes. The simulations were carried out both in quasi-static and direct current (DC) modes. It was observed that electrode-electrolyte interface and tissue capacitance could be safely neglected in our model based on the magnitude of the applied voltage stimulus and frequencies under consideration. Therefore, all simulations were conducted in DC mode. Thresholds and lateral extents of the stimulation were computed for electrode sizes corresponding to existing and self-fabricated implants. The values and trends obtained were in agreement with experiments from literature and our collaborators at the les Hôpitaux Universitaires de Genève (HUG). In the subretinal stimulation scheme, the computed variation of impedance with electrode-retina distance correlated well with time varying in vivo impedance measurements in rats conducted in collaboration with the Institut de la Vision, INSERM, Paris. Finally, it was also reiterated that the currently employed retinal prostheses are not very efficient due to a significant distance between the stimulation electrode and the retinal cells. In addition, I present a new experimental technique for measuring the absolute and local resistivity profile in high-resolution along the retinal depth, based on impedance spectroscopy using a bipolar microprobe. This experiment was devised to extract the resistivity profile of an embryonic chick retina to construct an electrical model for the simulation framework to simulate in vitro retinal stimulation experiments conducted by HUG collaborators. We validated the capability of the technique in rat and embryonic chick retinas. In conclusion, the computational framework presented in this dissertation is more realistic than those found in literature, but represents only a preliminary step towards an accurate model of a real implantation scenario in vivo. The simulation results are in agreement with results from clinical trials in humans for epiretinal configuration (literature) and with in vitro results for epiretinal and subretinal stimulation applied to chick retinas (HUG). The developed simulation framework computes quantities that can form a reference for quality control during surgery while inserting implants in the eye and functionality checks by electrophysiologists. Furthermore, this framework is useful in deciding the specifications of stimulation electrodes such as optimal size, shape, material, array density, and the position of the reference electrode to name a few. The work presented here offers to aid in optimising retinal prostheses and implantation procedures for patients and eventually contributes towards improving their quality of life

Investigation of upper limb prosthesis functionality using quantitative design tools

Upper limb prostheses offer those with limb loss a solution to restore some of their lost functionality by allowing them to participate in bilateral tasks, especially those required for daily living. Whilst there is a wide range of upper limb prostheses available, there remain high device rejection rates. Low functionality and discomfort are major factors in prosthesis rejection, which had been identified as challenges more than 60 years ago. These issues have not been effectively addressed due the lack of design tools for engineers and clinicians. Upper limb prostheses have seen greater technological advances than the methods to evaluate them effectively, which has resulted in over-engineered designs which do not meet the needs of their user. In this thesis , I aim to improve future upper limb prostheses through the development of three design tools. These design tools seek to quantify the functionality of prosthetic devices using motion capture analysis, virtual environments, and joint optimisation. By developing these tools, there is greater opportunity to optimise prostheses earlier in the design cycle which can result in improved functionality. It is anticipated that improvements in functionality will increase user satisfaction and therefore reduce device rejection rates Motion capture analysis was used to study the compensatory movements that arise from operating an upper limb prosthesis. Using a motion capture suit, the motor strategy of a participant was compared between using their biological hand and using a prosthesis through the use of an able-bodied adaptor. It was found that the shoulder and trunk had to make the most compensatory movements to complete several grasping tasks due to the lack of degrees of freedom at the distal end of the prosthesis. Without forearm supination/pronation and wrist extension/flexion, the participant had to approach the grasping tasks from a different angle, sometimes having to lean backwards and abduct their upper arm. The methodology of utilising a motion capture suit as a design tool to quantitatively assess the compensatory movements caused by a prosthetic device was successfully demonstrated. Virtual environments, in conjunction with quantitative grasp quality metrics, can be used to assess the performance of the upper limb prosthesis extremity alone, uninfluenced by user bias. A dynamic virtual environment is presented to simulate several grasping tasks with five upper limb prosthetic devices. Contact information from these grasping tasks are used to calculate the quality of the grasp and provide an overall grasping functionality score. From the simulation results, it was found that more degrees of freedom do not necessary equate to better grasping performance. The positions of force vectors during grasp formation are vital and they must be well- balanced in order to result in stable grasps. Simulated grasping and quantitative analysis in a virtual environment has been demonstrated, which can be used to better plan grasping paths and therefore improve the grasping functionality of upper limb prosthesis designs. Prosthesis users desire their devices to have a low mass, have a low cost, and have high functionality. However, these are conflicting design objectives and decisions must be made to which design considerations to prioritise. A multi-objective model was used to balance these three objectives and select the most suitable components that make up a prosthesis. A modularity scheme was used to divide an upper limb prosthesis into three categories: socket, forearm, and terminal device. In each category, several components were considered which can either be manufactured by conventional engineering or additive manufacturing. Each component would provide a unique value determined by a several quantitative utility functions. Based on satisfaction studies in the literature, the multi-objective optimisation model found that a Split Hook terminal device with an additively manufactured socket and forearm was the optimal design as it provided a low mass and excellent grasping functionality. This model has been demonstrated to work with different user requirements to intelligently select the most appropriate upper limb components within the modularity scheme. Overall, methods were developed which covered aspects of prosthesis design from clinical testing of prosthetic devices, functionality assessments of Computer Aided Design models, and intelligent selection of prosthesis components for individual requirements. It is hoped that these design tools may enable better communication between engineers and clinicians to ensure that users receive devices that are to their satisfaction