Translational approaches to measurement and analysis of the cochlear implant-tissue interface

Abstract

Cochlear implants (CI) are highly successful neuroprosthetic devices, which restore hearing function in children and adults with severe-profound hearing loss. Despite the great potential for improved communication and quality of life, a high degree of performance variability is observed across CI users over time. Clinical outcomes depend on complex interactions between many pre, peri and post-surgical factors. The present work focusses on the interface between the CI electrode array and the cochlea. The tissue response to CI surgery and long-term implantation is not fully understood. The CI-tissue interface is an attractive target for investigation because it can be interrogated using objective measures in humans and animal models. Chapter 2 presents a case study of a migration related CI failure resulting in device explant and reimplantation. The extra-cochlea tissue, which had developed around the array during extrusion was analysed using immunohistochemistry. The study included a wider range of marker-specific antibodies than other published studies of the fibrotic sheath. Light microscopy imaging showed clear evidence of unresolved active inflammation alongside proliferating cells forming new tissue and blood vessels. This profile of wound-healing in human CI represents a novel finding among studies of similar design. Chapter 3 presents a retrospective study of electrode impedance (EI) data from 221 CI users. Evidence suggests that EI can indicate the type and volume of newly developed tissue around the electrode array. The study describes EI trends over five years: greater EI levels in basal electrodes compared to apical, adults showed steady EI reduction in apical electrodes whereas children showed plateau or slight increase. A thresholding method allowed detection of cases exhibiting significant deviation from the sample median. 8% of adults and 5% of children exhibited significantly raised EI, often in mid and apical electrodes, which may be explained by localised fibrotic or bony tissue growth. The case study and retrospective population study prompted research questions regarding underlying mechanisms. For example, is unresolved inflammation a common but under-reported feature of the CI wound healing response? Are the localised increases in EI associated with surgical micro-trauma? Such questions can be investigated using a non-human animal model. Chapter 4 presents method developments towards a mouse model of CI. Immunohistochemical staining was carried out alongside X-ray PCT imaging to create a three-dimensional model of a C57BL/6 mouse cochlea. This combined approach, known as 3D X-ray histology, will provide high spatial resolution and cell-marker specificity for ongoing investigations of the CI-tissue interface. Mouse models greatly benefit from genetic tractability and well established immune challenge paradigms. They allow controlled investigation of factors that influence human CI outcomes such as specific hearing loss aetiology. The statistical approach to data processing applied in Chapter 3 could be used to improve monitoring of the CI-tissue interface with minimal cost and could guide prophylactic anti-inflammatory treatment. Clinical decision making will be enhanced by knowledge of the cochlear wound healing response gained from current and future work using the mouse model and explanted human fibrotic tissue.

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Identifiers

ORCID for Tracey Newman: orcid.org/0000-0002-3727-9258

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