High Fidelity Bioelectric Modelling of the Implanted Cochlea

Cochlear implants are medical devices that can restore sound perception in individuals with sensorineural hearing loss (SHL). Since their inception, improvements in performance have largely been driven by advances in signal processing, but progress has plateaued for almost a decade. This suggests that there is a bottleneck at the electrode-tissue interface, which is responsible for enacting the biophysical changes that govern neuronal recruitment. Understanding this interface is difficult because the cochlea is small, intricate, and difficult to access. As such, researchers have turned to modelling techniques to provide new insights. The state-of-the-art involves calculating the electric field using a volume conduction model of the implanted cochlea and coupling it with a neural excitation model to predict the response. However, many models are unable to predict patient outcomes consistently. This thesis aims to improve the reliability of these models by creating high fidelity reconstructions of the inner ear and critically assessing the validity of the underlying and hitherto untested assumptions. Regarding boundary conditions, the evidence suggests that the unmodelled monopolar return path should be accounted for, perhaps by applying a voltage offset at a boundary surface. Regarding vasculature, the models show that large modiolar vessels like the vein of the scala tympani have a strong local effect near the stimulating electrode. Finally, it appears that the oft-cited quasi-static assumption is not valid due to the high permittivity of neural tissue. It is hoped that the study improves the trustworthiness of all bioelectric models of the cochlea, either by validating the claims of existing models, or by prompting improvements in future work. Developing our understanding of the underlying physics will pave the way for advancing future electrode array designs as well as patient-specific simulations, ultimately improving the quality of life for those with SHL

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

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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 <it>et al</it>. 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.</p> <p>Results</p> <p>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.</p> <p>Conclusions</p> <p>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.</p

An Instrumented Cochlea Model for the Evaluation of Cochlear Implant Electrical Stimulus Spread.

Cochlear implants use electrical stimulation of the auditory nerve to restore the sensation of hearing to deaf people. Unfortunately, the stimulation current spreads extensively within the cochlea, resulting in "blurring" of the signal, and hearing that is far from normal. Current spread can be indirectly measured using the implant electrodes for both stimulating and sensing, but this provides incomplete information near the stimulating electrode due to electrode-electrolyte interface effects. Here, we present a 3D-printed "unwrapped" physical cochlea model with integrated sensing wires. We integrate resistors into the walls of the model to simulate current spread through the cochlear bony wall, and "tune" these resistances by calibration with an in-vivo electrical measurement from a cochlear implant patient. We then use this model to compare electrical current spread under different stimulation modes including monopolar, bipolar and tripolar configurations. Importantly, a trade-off is observed between stimulation amplitude and current focusing among different stimulation modes. By combining different stimulation modes and changing intracochlear current sinking configurations in the model, we explore this trade-off between stimulation amplitude and focusing further. These results will inform clinical strategies for use in delivering speech signals to cochlear implant patients

Three-dimensional models of cochlear implants : a review of their development and how they could support management and maintenance of cochlear implant performance

Three-dimensional (3D) computational modelling of the auditory periphery forms an integral part of modern-day research in cochlear implants (CIs). These models consist of a volume conduction description of implanted stimulation electrodes and the current distribution around these, coupled to auditory nerve fibre models. Cochlear neural activation patterns can then be predicted for a given input stimulus. The objective of this article is to present the context of 3D modelling within the field of CIs, the different models and approaches to models that have been developed over the years, as well as the applications and potential applications of these models. The process of development of 3D models is discussed, and the article places specific emphasis on the complementary roles of generic models and user-specific models, as the latter is important for translation of these models into clinical application.http://tandfonline.com/toc/inet202017-05-31hb2016Electrical, Electronic and Computer Engineerin

Proceedings of the Conference on Progress in Electrically Active Implants - Tissue and Functional Regeneration (ELAINE 2020)

The conference on Progress in Electrically Active Implants - Tissue and Functional Regeneration (ELAINE 2020) focused on novel methods in the electric stimulation of bio-material compounds of living cells and implantable electric stimulation devices. ELAINE 2020 provided international scientists a virtual platform to discuss the latest achievements in the form of invited presentations, selected talks from abstract submissions, and virtual poster sessions. In addition, we particularly invited critical reviews and contributions with negative results or unsuccessful replications to foster the scientific discussion and explicitly encourage young scientists to contribute and submit their work

Bioactive Conducting Polymer Coatings for Implantable Neural and Cochlear Electrodes.

Neural prostheses facilitate communication with the nervous system for the diagnosis, treatment, and recovery from neurological illness or trauma. These devices require permanently implanted electrodes that provide a stable electrical connection to the nervous system and do not produce adverse effects. Unfortunately, the biological reaction to implanted electrodes often leads to the formation of fibrous tissue that limits charge transfer and renders longterm performance unreliable. This dissertation presents the development and characterization of novel electrode coatings that promote functional integration at the tissue-electrode interface. The primary constituent of these coatings is the conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT). PEDOT is a suitable material for interfacing electrodes with tissue because it is biocompatible, conducts both electronic and ionic charge, is easily functionalized with cells and biomolecules, and mediates the mechanical differences between electrodes and tissue. In addition, deposition of PEDOT-based coatings on individual electrode sites is rapid and reproducible. To form electrode coatings containing live cells or cellular components, PEDOT was deposited around living neuroblastoma and primary cortical neurons. These coated electrodes had 73% lower 1 kHz impedance than uncoated metal while delivering live cells to direct the tissue response. Spongy coatings were made from PEDOT deposited in alginate hydrogel containing live cells and were capable of delivering over 25 times more current than electrodes without PEDOT. Laser-patterning of PEDOT was performed to produce electrode coatings capable of directing neuronal growth. Laser interference patterning of PEDOT resulted in the alignment of up to 87% of neurites in the direction of the pattern without affecting electrical conductivity. Evaluation of conducting polymer and hydrogel coatings on cochlear implants was performed. Coatings on cochlear electrodes reduced the electrode impedance by 80% at and 99% at 1 kHz and 10.7 Hz, respectively. These coated electrodes also delivered BDNF directly within the cochlea, increasing levels of the neurotrophin to 30.3 ng/ml after one week from a baseline of 1.7 ng/ml. In deafened guinea pigs, coated cochlear implants had less chance of failure than uncoated implants. After 6 months, their final average 1 kHz impedance was 5870 Ω compared to 1.2*106 Ω for uncoated implants.Ph.D.Biomedical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/61684/1/jlhendri_1.pd

Electrochemical Safety Studies of Cochlear Implant Electrodes Using the Finite Element Method

Cochlear implants, amongst other neural prostheses, utilise platinum electrodes as an interface between the synthetic implant and the biological tissue environment. If excessive electrical charge is injected via these electrodes, injury to the tissue may result. Empirically derived stimulation limits have been defined to prevent tissue damage, however the injurious mechanisms are still unclear. Evidence suggests that the non-uniform distribution of charge on electrodes influences the electrochemical generation of toxic by-products. However, in vivo and in vitro techniques are limited in their ability to systematically explore the factors and mechanisms that contribute to stimulation-induced tissue injury. To this end, an in silico approach was used to develop a time-domain model of cochlear implant stimulation electrodes. A constant phase angle impedance was used to model the reversible processes on the electrode surface, and Butler-Volmer reaction kinetics were used to define the behaviour of the water window irreversible electrochemical reactions. The resulting model provided time-domain responses of the current density distributions, and net charge consumed by the hydrolysis reactions. This model was then used to perform systematic evaluations of various electrode geometries and stimulation parameters. The modelling results showed the current associated with irreversible reactions was non-uniform and tended towards the periphery of the electrode. A comparison of electrode geometries revealed interactions between electrode size, shape and recess depth. Stimulation mode, electrode position, and electrolyte conductivity were found to impact the shape of the electric field and the extent of irreversible reactions. This emphasised the influence of the physiological environment on the stimulation safety. In vitro experiments were conducted to validate the model. The implications of the results described in this thesis can be used to inform the design of safer electrodes

Flexible Wirelessly Powered Implantable Device

Brain implantable devices have various limitations in terms of size, power, biocompatibility and mechanical properties that need to be addressed. This paper presents a neural implant that is powered wirelessly using a flexible biocompatible antenna. This delivers power to an LED at the end of the shaft to provide a highly efficient demonstration. The proposed design in this study combines mechanical properties and practicality given the numerous constraints of this implant typology. We have applied a modular structure approach to the design of this device considering three modules of antenna, conditioner circuit and shank. The implant was fabricated using a flexible substrate of Polyimide and encapsulated by PDMS for chronic implantation. In addition, finite element method COMSOL Multiphysics simulation of mechanical forces acting on the implant and shank was carried out to validate a viable shank conformation-encapsulation combination that will safely work under operational stress with a satisfactory margin of safety

Modelling of the electrode-auditory nerve fibre interface in cochlear prostheses

The objective of this thesis is to provide additional insight into the electrode array-nerve fibre interface that exists in the implanted cochlea and to facilitate investigation of new electrode arrays in interaction with the cochlea and auditory nerve fibres. The focus is on potential distributions and excitation profiles generated by different electrode array types and factors that could have an influence on these distributions and profiles. Research contributions made by the thesis are the creation of a detailed 3-D model of the implanted cochlea that accurately predicts measurable effects in cochlear implant wearers and facilitates effortless simulation of existing and new electrode array variations; the establishment of the important anatomical structures required in a 3-D representation of the implanted cochlea; establishment of evidence that array location is the primary parameter that controls spread of excitation; definition of the critical focussing intensity of intracochlear electrode pairs; confirmation thatmonopolar stimulation could deliver focussed stimulation to approximately the same degree than that delivered by widely spaced electrode configurations and that the use of monopolar configurations over bipolar configurations are therefore advantageous under certain conditions; explanation of the effect that encapsulation tissue around cochlear implant electrodes could have on neural excitation profiles; extension of the information available on the focussing ability of multipolar intracochlear electrode configurations; and establishment of evidence that a higher lateral electrode density could facilitate better focussing of excitation, continuous shaping of excitation profiles and postoperative customization of electrode arrays for individual implant wearers.Dissertation (PhD(Electronic Engineering))--University of Pretoria, 2001.Electrical, Electronic and Computer EngineeringUnrestricte