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

3D printed biomimetic cochleae and machine learning co-modelling provides clinical informatics for cochlear implant patients.

Cochlear implants restore hearing in patients with severe to profound deafness by delivering electrical stimuli inside the cochlea. Understanding stimulus current spread, and how it correlates to patient-dependent factors, is hampered by the poor accessibility of the inner ear and by the lack of clinically-relevant in vitro, in vivo or in silico models. Here, we present 3D printing-neural network co-modelling for interpreting electric field imaging profiles of cochlear implant patients. With tuneable electro-anatomy, the 3D printed cochleae can replicate clinical scenarios of electric field imaging profiles at the off-stimuli positions. The co-modelling framework demonstrated autonomous and robust predictions of patient profiles or cochlear geometry, unfolded the electro-anatomical factors causing current spread, assisted on-demand printing for implant testing, and inferred patients' in vivo cochlear tissue resistivity (estimated mean = 6.6 kΩcm). We anticipate our framework will facilitate physical modelling and digital twin innovations for neuromodulation implants

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

In silico study on in vitro experiments to determine the electric membrane properties of a realistic cochlear model for electric field simulations on cochlear implants

To further develop and optimise the design of cochlear implants, a numerical model with precise material properties and authentic geometry is required. Since simulation results strongly depend on the accuracy of the estimates of the electrical properties of cochlear membranes, it is important to have a reliable in vivo method for measuring electrical impedance changes in the cochlear compartments. This work is a preliminary attempt to model, simulate and analyse the behaviour of a novel in-vitro experimental system for conducting plausible in-vivo measurements on mammalian cochlea membranes.Zur Weiterentwicklung und Optimierung des Designs von Cochlea-Implantaten ist ein detailliertes numerisches Modell der Cochlea erforderlich. Da die Simulationsergebnisse stark von den elektrischen Eigenschaften der Cochlea-Membranen abhängen, ist es wichtig, ein zuverlässiges In-vivo-Verfahren zur Messung des elektrischen Impedanzverlaufs zu haben. Diese Arbeit ist eine vorbereitende Studie, das Verhalten eines neuartigen In-vitro-Versuchssystems zur Durchführung plausibler In-vivo-Messungen an Cochlea-Membranen von Säugetieren zu modellieren, zu simulieren und zu analysieren

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

Development of a method to create subject specific cochlear models for electric hearing

Cochlear implants are electronic devices intended for restoring hearing to the profoundly deaf. Unfortunately the degree of restored hearing varies greatly between subjects. To investigate some of the mechanisms that determine this variability, mathematical models of the auditory system are used. The level of detail that these models incorporate varies greatly. The present study describes the development of a method to create high detail, subject specific cochlea models. μ-CT scans and photomicrographs were used to obtain the morphology and histology of a specific guinea pig cochlea. A 3D model was constructed from this data and the finite element method was used to determine the potential distribution inside the cochlea. The potential distribution was calculated for different stimulus protocols applied to different modelled electrodes. A neuron model was then used to obtain neural excitation profiles. The modelled excitation profiles were compared to data from literature and it was found that this model is valid and can be used as a tool in electric hearing research. The model output was also compared to brainstem response data from the specific subject to assess the degree to which this model can predict brain stem data from a specific subject. Possible improvements to the model were also discussed.Dissertation (MEng)--University of Pretoria, 2009.Electrical, Electronic and Computer Engineeringunrestricte

Experimental investigation of promontory motion and intracranial pressure following bone conduction: Stimulation site and coupling type dependence

Objective Investigation of bone conduction sound propagation by osseous and non-osseous pathways and their interactions based upon the stimulation site and coupling method of the actuator from a bone conduction hearing aid (BCHA). Methods Experiments were conducted on five Thiel embalmed whole head cadaver specimens. The electromagnetic actuator from a commercial bone conduction hearing aid (BCHA) (Baha® Cordelle II) was used to provide a stepped sine stimulus in the range of 0.1–10 kHz. Osseous pathways (direct bone stimulation or transcutaneous stimulation) were sequentially activated by stimulation at the mastoid or the BAHA side using several methods including a percutaneously implanted screw, Baha® Attract transcutaneous magnet and a 5-N (5-N) steel headband. Non-osseous pathways (only soft tissue or intra-cranial contents) were activated by actuator stimulation on the eye or neck via attachment to a 5-N steel headband, and were compared with stimulation via equivalent attachment on the mastoid and forehead. The response of the skull was measured as motions of the ipsi- and contralateral promontory and intracranial pressure (ICP) in the central, anterior, posterior, ipsilateral and contralateral temporal regions of the cranial space. Promontory motion was monitored using a 3-dimensional Laser Doppler vibrometer (3D LDV) system. Results The promontory undergoes spatially complex motion with similar contributions from all motion components, regardless of stimulation mode. Combined 3D promontory motion provided lower inter-sample variability than did any individual component. Transcranial transmission showed gain for the low frequencies and attenuation above 1 kHz, independent of stimulation mode This effect was not only for the magnitude but also its spatial composition such that contralateral promontory motion did not follow the direction of ipsilateral stimulation above 0.5 kHz. Non-osseous stimulation on the neck and eye induced comparable ICP relative to percutaneous (via screw) mastoid stimulation. Corresponding phase data indicated lower phase delays for ICP when stimulation was via non-osseous means (i.e., to the eye) versus osseous means (i.e., to the mastoid or forehead). Sound propagation due to skull stimulation passes through the thicker bony sections first before activating the CSF. Conclusion Utilization of 3D promontory motion measurements provides more precise (lower inter-sample variability) information about bone vibrations than does any individual component. It also provides a more detailed description of transcranial attenuation. A comprehensive combination of motion and pressures measurements across the head, combined with a variation of the stimulation condition, could reveal details about sound transmission within the skull

Comparison of Multi-Compartment Cable Models of Human Auditory Nerve Fibers

Background: Multi-compartment cable models of auditory nerve fibers have been developed to assist in the improvement of cochlear implants. With the advancement of computational technology and the results obtained from in vivo and in vitro experiments, these models have evolved to incorporate a considerable degree of morphological and physiological details. They have also been combined with three-dimensional volume conduction models of the cochlea to simulate neural responses to electrical stimulation. However, no specific rules have been provided on choosing the appropriate cable model, and most models adopted in recent studies were chosen without a specific reason or by inheritance. Methods: Three of the most cited biophysical multi-compartment cable models of the human auditory nerve, i.e., Rattay et al. (2001b), Briaire and Frijns (2005), and Smit et al. (2010), were implemented in this study. Several properties of single fibers were compared among the three models, including threshold, conduction velocity, action potential shape, latency, refractory properties, as well as stochastic and temporal behaviors. Experimental results regarding these properties were also included as a reference for comparison. Results: For monophasic single-pulse stimulation, the ratio of anodic vs. cathodic thresholds in all models was within the experimental range despite a much larger ratio in the model by Briaire and Frijns. For biphasic pulse-train stimulation, thresholds as a function of both pulse rate and pulse duration differed between the models, but none matched the experimental observations even coarsely. Similarly, for all other properties including the conduction velocity, action potential shape, and latency, the models presented different outcomes and not all of them fell within the range observed in experiments. Conclusions: While all three models presented similar values in certain single fiber properties to those obtained in experiments, none matched all experimental observations satisfactorily. In particular, the adaptation and temporal integration behaviors were completely missing in all models. Further extensions and analyses are required to explain and simulate realistic auditory nerve fiber responses to electrical stimulation