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.

Interpretation of neuronal response properties with simplified neuron models

Laurent Badel

Computational neuroscience is a branch of the neurosciences that attempts to elucidate the principles underlying the operation of neurons with the help of mathematical modeling. In contrast with a number of fields pursuing a tightly related goal, such as machine learning or statistical learning, computational neuroscience emphasizes the realistic description of neuronal function and organization, and therefore requires a collaboration with experimental research in order to design new models and test their predictions. With the growing computational power available in modern computers, the simulation of neuronal networks with realistic numbers of neurons and functional organization is becoming routinely accessible. For the accurate design of such network models, the experimental characterization of neuronal response properties is required to probe the structural layout of biological networks at the single cell level. We develop here a novel method, the dynamic I-V method, that allows for the extraction of cellular response properties, and requires only a small amount of experimental data. Using this technique a simplified model of the neuronal response is obtained that is shown to accurately fit the experimental data. We demonstrate the use of the dynamic I-V method on both cortical pyramidal cells and inhibitory interneurons, and give the distributions of cellular parameters for the studied sample of cells. We also give theoretical results on the spike-triggered average, a quantity that is easily measured experimentally, which relate the neuronal response properties to identifiable features of the spike-triggered average, and can potentially be helpful to extend the dynamic I-V method in order to derive more accurate models. Potential applications and extensions of our results are discussed.

EPFL2009

Simulation of epiretinal prostheses - Evaluation of geometrical factors affecting stimulation thresholds

Arnaud Bertsch, Grégoire Cosendai, Willyan Hasenkamp Carreira, Sri Harsha Kasi Raj, Philippe Renaud

Background An accurate understanding of the electrical interaction between retinal prostheses and retinal tissue is important to design effective devices. Previous studies have used modelling approaches to simulate electric fields generated by epiretinal prostheses in saline and to simulate retinal ganglion cell (RGC) activation using passive or/and active biophysical models of the retina. These models have limited scope for studying an implanted human retinal prosthesis as they often do not account for real geometry and composition of the prosthesis-retina interface. This interface consists of real dimensions and location of stimulation and ground electrodes that are separated by the retinal tissue and surrounded by physiological fluids. Methods In this study, we combined the prosthesis-retina interface elements into a framework to evaluate the geometrical factors affecting stimulation thresholds for epiretinal prostheses used in clinical human trials, as described by Balthasar et al. in their Investigative Ophthalmology and Visual Science (IOVS) paper published in 2008 using the Argus I epiretinal implants. Finite element method (FEM) based computations were used to estimate threshold currents based on a threshold criterion employing a passive electric model of the retina. Results Threshold currents and impedances were estimated for different electrode-retina distances. The profiles and the values for thresholds and impedances obtained from our simulation framework are within the range of measured values in the only elaborate published clinical trial until now using Argus I epiretinal implants. An estimation of resolution for the electrodes used in these trials was provided. Our results reiterate the importance of close proximity between electrodes and retina for safe and efficient retinal stimulation. Conclusions The validation of our simulation framework being relevant for epiretinal prosthesis research is derived from the good agreement of the computed trends and values of the current study with measurements demonstrated in existing clinical trials on humans (Argus I). The proposed simulation framework could be used to generate the relationship between threshold and impedance for any electrode geometry and consequently be an effective tool for design engineers, surgeons and electrophysiologists.

BioMed Central2011

Assessment of mechanical properties in unirradiated and irradiated zircaloys and steels with non-standard tests and finite element calculations

Emiliano Campitelli

Nuclear materials have been successfully employed in commercial fission reactors for many decades. Research and material development for advanced fission system and future thermo-nuclear fusion reactors have acquired maturity while great challenges remain to be taken up. The goal of the material scientist is to understand the way neutron irradiation and aggressive reactor environment alter the original material properties and to safely manage the operation conditions for each particular reactor component. In the framework of surveillance programme, the need has arisen to design experimental methods to be used with a limited amount of material for Post Irradiation Examination (PIE) of reactor components to test the integrity of those on a regular time basis. Having to deal with radioactive material, it is particularly important to devise experimental testing procedures as simple as possible but from which reliable information can be drawn. Within materials development programme, irradiations have continuously been performed either in reactors or with particle accelerators. In both cases, the irradiation volumes are usually limited. The concern was to optimize the volume of the irradiated samples in order to increase their number to obtain a good statistical representation of their mechanical behavior after irradiation, and to have a very definite and homogeneous damage dose and irradiation temperature. The concerns explained above originated the development of small-scale specimen testing methods. Advantage is taken of the fact that, within size and geometry limitations, some mechanical properties of a sample are independent of its absolute size. In this way it is possible to perform mechanical tests on samples of reduced volume that represents big advantages to face the aforementioned challenges. Non-standard test on very small specimen have also been proposed to extract mechanical properties of the bulk. If these non-standard testing methods are to be employed for PIE, it becomes necessary to develop modeling tool to understand under what circumstances they can provide useful information and specially how to obtain it. Finite element modeling (FEM) of the non-standard tests has played a key role in this sense, providing a link between standard test analysis and that of the non-standard ones. The goal of this work was to implement finite element models for non-standard tests to ultimately study the mechanical properties of Zircaloy cladding tube and tempered martensitic steels in the unirradiated and irradiated condition. One model was developed for ring tensile tests. It was first validated with a quite ductile iron-chromium ferritic alloy, for which ring and uniaxial tensile test were performed at room temperature. Using the constitutive behavior determined from the uniaxial tensile tests, the load – displacement curves of the ring tensile tests were very well reproduced. Another model was developed for the so-called small ball punch test, which consists in deforming a 3 mm diameter disk clamped between two dies with a ball puncher and to record the load – displacement curve. In order to validate the model, a series of ball punch tests and of tensile tests were carried out on the austenitic steel 316L at room temperature. In this last case, the ball punch test curves were also well reconstructed with the model. Based upon a simple analysis and simulation results, we showed that it is possible to obtain, by ring tensile tests, a quick and accurate assessment of the constitutive behavior of an unknown material, simply by processing the experimental force-elongation data in the same way as for uniaxial tests, taking half the ring perimeter as initial length and twice the ring cross section as the sample cross section. The ring tensile test method was used to determine the hoop mechanical properties of Zircaloy tubes used in fission reactors. Tensile tests were also performed in the axial direction of the Zircaloy tubes. Differences between the yield stress as well as the post-yield behaviors in the axial direction and those in the circumferential direction of the tube could be measured reflecting some component of the anisotropy of the tube. Ball punch specimens were cut also out of the tube in the radial direction and tested. Using the FE model for punch test, in which the anisotropy of the mechanical properties are taken into account through the Hill's theory, the values of the Hill's yield function parameters were estimated. The irradiation hardening of neutron irradiated Zircaloy tube was finally determined. The ball punch test model was extensively used for numerical investigations, to determine how the constitutive behavior of the materials (uniaxial true stress – true strain) employed as input acts in combination with other experimental factors (specimen thickness, friction coefficient) in mediating the shape of the experimental curves. In the light of the results, we derived calibrations between parameters of the non-standard and standard tests. For instance we proposed a new approach to determine the yield stress from the ball punch test. We also showed how the slope of the punch tests scales with the average flow stress of the material. The calibrations proposed in the past by authors and published in the open literature have been revisited and critically reviewed. Based upon the findings of the numerical studies, we propose a given methodology to unambiguously evaluate the material constitutive behavior of a material in a case where the only available data comes from various non-standard tests. Experimental ball punch test results obtained on proton-irradiated specimen (0.5 dpa and Tirr = 523 K), of the tempered martensitic steel, EUROFER97, have been obtained. The irradiation hardening was found equal to about 150 MPa, consistently with previous data on similar steels and irradiation conditions. From the simulations of the ball punch test curves of the irradiated specimens, it was concluded that the irradiation does not affect the strain hardening at relatively low fluence.