Carrie Newbold

An in vitro model for investigating impedance changes with cell growth and electrical stimulation: implications for cochlear implants

The impedance of stimulating electrodes used in cochlear implants and other neural prostheses often increases post-implantation, and is thought to be due to fibrous tissue encapsulation of the electrode array. Increased impedance results in higher power requirements to stimulate target neurons at set charge densities. We developed an in vitro model to investigate the electrode-tissue interface in a highly controlled environment. This model was tested using three cell types, with and without charge-balanced biphasic electrical stimulation. Under standard tissue culture conditions, a monolayer of cells was grown over the electrode surface. Electrode impedance increased in proportion to the extent of cell coverage of the electrode. Cell type was a significant factor in the amount of impedance increase, with kidney epithelial cells (MDCK) creating the greatest impedance, followed by dissociated rat skin fibroblasts and then macrophages (J774). The application of electrical stimulation to cell-covered electrodes caused impedance fluctuations similar to that seen in vivo, with a lowering of impedance immediately following stimulation, and a recovery to pre-stimulation levels during inactive periods. Examination of these electrodes suggests that the stimulation-induced impedance changes were due to the amount of cell cover over the electrodes. This in vitro technique accurately models the changes in impedance observed with neural prostheses in vivo, and shows the close relationship between impedance and tissue coverage adjacent to the electrode surface. We believe that this in vitro approach holds great promise to further our knowledge of the mechanisms contributing to electrode impedance.

Changes in biphasic electrode impedance with protein adsorption and cell growth

This study was undertaken to assess the contribution of protein adsorption and cell growth to increases in electrode impedance that occur immediately following implantation of cochlear implant electrodes and other neural stimulation devices. An in vitro model of the electrode-tissue interface was used. Radiolabelled albumin in phosphate buffered saline was added to planar gold electrodes and electrode impedance measured using a charge-balanced biphasic current pulse. The polarization impedance component increased with protein adsorption, while no change to access resistance was observed. The maximum level of protein adsorbed was measured at 0.5 µg cm(-2), indicating a tightly packed monolayer of albumin molecules on the gold electrode and resin substrate. Three cell types were grown over the electrodes, macrophage cell line J774, dissociated fibroblasts and epithelial cell line MDCK, all of which created a significant increase in electrode impedance. As cell cover over electrodes increased, there was a corresponding increase in the initial rise in voltage, suggesting that cell cover mainly contributes to the access resistance of the electrodes. Only a small increase in the polarization component of impedance was seen with cell cover.

Development of a safe dexamethasone-eluting electrode array for cochlear implantation

Abstract Objectives Cochlear implantation can result in trauma leading to increased tissue response and loss of residual hearing. A single intratympanic application of the corticosteroid dexamethasone is sometimes used clinically during surgery to combat the potential effect of trauma on residual hearing. This project looked at the safety and efficacy of dexamethasone eluted from an intracochlear array in vivo. Methods Three trials were conducted using normal hearing adult guinea pigs implanted with successive iterations of dexamethasone-eluting (DX1, DX2, and DX3) or non-eluting (control) intracochlear electrode arrays. The experimental period for each animal was 90 days during which hearing tests were performed at multiple time points. Results There was no significant difference between matched control array and dexamethasone array groups in terms of spiral ganglion neuron density, organ of Corti condition, or fibrosis and ossification. A cochleostomy seal was present in all implanted cochleae. There were no differences in the degree of hearing threshold shifts between DX1 and DX3 and their respective control arrays. Cochleae implanted with DX2 arrays showed less hearing loss and marginally better spiral ganglion neuron survival than their control array counterparts. Post-explant inspection of the DX2 and DX3 arrays revealed a difference in pore density following dexamethasone elution. Conclusion The dexamethasone doses used were safe in the guinea pig cochlea. Dexamethasone did not inhibit formation of a cochleostomy seal. The level of hearing protection afforded by dexamethasone eluting from an intracochlear array may depend upon the degree of elution and level of trauma inflicted.

Actuators for the cochlear implant

The multi-channeled cochlear implant device has been proved safe and effective with simultaneous multi electrical stimulation delivered to the inner ear. It provides profoundly deaf people with the opportunity for a life transforming experience by placing them in the world of hearing. But for optimal hearing restoration a proper surgical insertion process and the close placement of the array to the heating nerves are required. To achieve this, a conducting polymer electroactuator has been developed. The electroactuator can either be inserted into the lumen of a commonly used Nucleus 24 Contour electrode or can be attached to the outside of the electrode. By varying the applied potential it is possible to steer or bend the electrode in a controllable manner. Electrosynthesis, interconnection and actuator fabrication will be discussed in detail.

Impedance changes in chronically implanted and stimulated cochlear implant electrodes

Abstract Objectives Electrode impedance increases following implantation and undergoes transitory reduction with onset of electrical stimulation. The studies in this paper measured the changes in access resistance and polarization impedance in vivo before and following electrical stimulation, and recorded the time course of these changes. Design Impedance measures recorded in (a) four cats following 6 months of cochlear implant use, and (b) three cochlear implant recipients with 1.5–5 years cochlear implant experience. Results Both the experimental and clinical data exhibited a reduction in electrode impedance, 20 and 5% respectively, within 15–30 minutes of stimulation onset. The majority of these changes occurred through reduction in polarization impedance. Cessation of stimulation was followed by an equivalent rise in impedance measures within 6–12 hours. Conclusions Stimulus-induced reductions in impedance exhibit a rapid onset and are evident in both chronic in vivo models tested, even several years after implantation. Given the impedance changes were dominated by the polarization component, these findings suggest that the electrical stimulation altered the electrode surface rather than the bulk tissue and fluid in the cochlea.

Electrical stimulation causes rapid changes in electrode impedance of cell-covered electrodes

Animal and clinical observations of a reduction in electrode impedance following electrical stimulation encouraged the development of an in vitro model of the electrode-tissue interface. This model was used previously to show an increase in impedance with cell and protein cover over electrodes. In this paper, the model was used to assess the changes in electrode impedance and cell cover following application of a charge-balanced biphasic current pulse train. Following stimulation, a large and rapid drop in total impedance (Z(t)) and access resistance (R(a)) occurred. The magnitude of this impedance change was dependent on the current amplitude used, with a linear relationship determined between R(a) and the resulting cell cover over the electrodes. The changes in impedance due to stimulation were shown to be transitory, with impedance returning to pre-stimulation levels several hours after cessation of stimulation. A loss of cells over the electrode surface was observed immediately after stimulation, suggesting that the level of stimulation applied was creating localized changes to cell adhesion. Similar changes in electrode impedance were observed for in vivo and in vitro work, thus helping to verify the in vitro model, although the underlying mechanisms may differ. A change in the porosity of the cellular layer was proposed to explain the alterations in electrode impedance in vitro. These in vitro studies provide insight into the possible mechanisms occurring at the electrode-tissue interface in association with electrical stimulation.

Seeing electrode movement in the cochlea Micro-focus fluoroscopy — A great tool for electrode development

Abstract The aim of this study was to utilise micro-focus X-ray fluoroscopy for viewing electrode movement in the cochlea. Various prototypes of newly designed cochlear implant electrodes were evaluated during insertion studies on human cadaver temporal bones. The magnified fluoroscopic images were observed in real-time and recorded for retrospective studies. In 30 insertions of hearing preservation (Hybrid-L) arrays, fluoroscopy provided crucial information on the tip design, length of array and stiffening stylet. In 44 insertions of Contour Advance enhanced (CAe) arrays, the length, curvature, depth of insertion and degree of stiffness were assessed. CAe arrays were successfully inserted to the designated depth and positioned close to the modiolus. High quality microfocus fluoroscopic images of electrode movement in the cochlea greatly assisted in the validation of newly designed intra-cochlear electrode arrays. Copyright

Long-term electrode impedance changes and failure prevalence in cochlear implants

Abstract Objective: This study assessed the prevalence of electrode failures and electrode impedance measures in Nucleus cochlear implants around initial activation (an average of 16 days after surgery) and after 8 to 12 years of device use. Design: Retrospective data from the Melbourne Cochlear Implant Clinic was collated and analysed. Study sample: Included in this study were 232 adults, all of whom were implanted at the clinic between March 1998 and August 2005. Results: Overall 0.5% of electrodes failed over the entire test period, with 5.6% of devices showing one or more electrode failure. The majority of these failures were recorded by initial activation. The numbers of electrode failures have decreased over time with array type, such that no failures were recorded with the currently available Contour Advance array. Array type was shown to affect electrode impedance at both time points, with the Contour and Contour Advance arrays having significantly higher absolute values than the Banded array. However, the Banded array had significantly higher area-normalized impedances at initial and final measures than the Contour and Contour Advance array. Conclusions: A relatively low incidence of electrode failures were recorded for the Nucleus devices of these recipients. Electrode impedance dropped for all array types after 8 to 12 years of device use.

Meningitis and a safe dexamethasone-eluting intracochlear electrode array

Abstract Objectives To evaluate the potential risk of pneumococcal meningitis associated with the use of a dexamethasone-eluting intracochlear electrode array as compared with a control array. Methods In two phases, adult Hooded–Wistar rats were implanted via the middle ear with an intracochlear array and were inoculated with Streptococcus pneumoniae 5 days post-surgery. Phase I created a dosing curve by implanting five groups (n = 6) with a control array, then inoculating 5 days later with different numbers of S. pneumoniae: 0 CFU, 103 CFU, 104 CFU, 104 CFU repeated, or 105 CFU (colony forming units). A target infection rate of 20% was aimed for and 104 CFU was the closest to this target with 33% infection rate. In phase II, we implanted two groups (n = 10), one with a dexamethasone-eluting array, the other a control array, and both groups were inoculated with 104 CFU of S. pneumoniae 5 days post-surgery. Results The dexamethasone-eluting array group had a 40% infection rate; the control array group had a 60% infection rate. This difference was not statistically significant with a P value of ≥0.5. Conclusion The use of a dexamethasone-eluting intracochlear electrode array did not increase the risk of meningitis in rats when inoculated with S. pneumoniae via the middle ear 5 days following implantation.

Measuring the effective area and charge density of platinum electrodes for bionic devices

OBJECTIVE Neural stimulation is usually performed with fairly large platinum electrodes. Smaller electrodes increase the applied charge density, potentially damaging the electrode. Greater understanding of the charge injection mechanism is required for safe neural stimulation. APPROACH The charge injection mechanism and charge injection capacity were measured by cyclic voltammetry. Electrodes were cleaned mechanically or by potential cycling in acidic solutions. The effective electrode area was measured by hydrogen adsorption or reduction of [Formula: see text]. MAIN RESULTS The water window and safe potential window were affected by changes to electrolyte, electrode size, polishing method and oxygen concentration. Capacitance and Faradaic current contribute to the charge injection capacity. Varying voltammetric scan rate (measurement time), electrode size, polishing method, potential window, electrolyte and oxygen concentration affected the charge injection capacity and ratio of oxidation to reduction charge. Hydrogen adsorption in acidic solutions provided an inaccurate effective electrode area. Reduction of a solution phase redox species with a linear or radial diffusion profile could provide an effective electrode area. The charge density (charge injection capacity divided by electrode area) of a platinum electrode is dependent on the charge injection capacity and electrode area measurement technique. By varying cyclic voltammetric conditions, the charge density of platinum ranged from 0.15 to 5.57 mC cm-2. SIGNIFICANCE The safe potential window, charge injection mechanism, charge injection capacity and charge density of platinum depends on electrolyte, size of the electrode, oxygen concentration and differences in electrode polishing method. The oxidation and reduction charge injection capacities are not equal. Careful control of a platinum electrodes surface may allow larger charge densities and safe use of smaller electrodes. New electrode materials and geometries should be tested in a consistent manner to allow comparison of potential suitability for neural stimulation.