Using x-ray micro computed tomography to quantify intracochlear fibrosis after cochlear implantation in a Guinea pig model

Kady J Braack; Tylah Miles; Farah Amat; Daniel J Brown; Marcus D Atlas; Jafri Kuthubutheen; Wilhelmina H A M Mulders; Cecilia M Prêle

doi:10.1016/j.heliyon.2023.e19343

Using x-ray micro computed tomography to quantify intracochlear fibrosis after cochlear implantation in a Guinea pig model

Heliyon. 2023 Aug 19;9(9):e19343. doi: 10.1016/j.heliyon.2023.e19343. eCollection 2023 Sep.

Authors

Kady J Braack¹, Tylah Miles², Farah Amat¹, Daniel J Brown³, Marcus D Atlas^{3

4

5}, Jafri Kuthubutheen^{4

6}, Wilhelmina H A M Mulders¹, Cecilia M Prêle^{2

5

7}

Affiliations

¹ School of Human Sciences, University of Western Australia, Crawley, WA 6009, Australia.
² Institute for Respiratory Health, University of Western Australia, Nedlands, WA 6009, Australia.
³ Curtin Medical School, Curtin University, Bentley, WA 6102, Australia.
⁴ Medical School, University of Western Australia, Crawley, WA 6009, Australia.
⁵ Ear Science Institute Australia, Subiaco, WA 6008, Australia.
⁶ Department of Otolaryngology Head and Neck Surgery, Sir Charles Gairdner Hospital, Hospital Avenue, Nedlands, WA 6009, Australia.
⁷ School of Medical, Molecular and Forensic Sciences, Murdoch University, Murdoch, WA 6150, Australia.

Abstract

Cochlear implants (CIs) allow individuals with profound hearing loss to understand speech and perceive sounds. However, not all patients obtain the full benefits that CIs can provide and the cause of this disparity is not fully understood. One possible factor for the variability in outcomes after cochlear implantation, is the development of fibrotic scar tissue around the implanted electrode. It has been hypothesised that limiting the extent of fibrosis after implantation may improve overall CI function, and longevity of the device. Currently, histology is often used to quantify the extent of intracochlear tissue growth after implantation however this method is labour intensive, time-consuming, often involves significant user bias, and causes physical distortion of the fibrosis. Therefore, this study aimed to evaluate x-ray micro computed tomography (μCT) as a method to measure the amount and distribution of fibrosis in a guinea pig model of cochlear implantation. Adult guinea pigs were implanted with an inactive electrode, and cochleae harvested eight weeks later (n = 7) and analysed using μCT, to quantify the extent of tissue reaction, followed by histological analysis to confirm that the tissue was indeed fibrotic. Cochleae harvested from an additional six animals following implantation were analysed by μCT, before and after contrast staining with osmium tetroxide (OsO₄), to enhance the visualisation of soft tissues within the cochlea, including the tissue reaction. Independent analysis by two observers showed that the quantification method was robust and provided additional information on the distribution of the response within the cochlea. Histological analysis revealed that μCT visualised dense collagenous material and new bone formation but did not capture loose, areolar fibrotic tissue. Treatment with OsO₄ significantly enhanced the visible tissue reaction detected using μCT. Overall, μCT is an alternative and reliable method that can be used to quantify the extent of the CI-induced intracochlear tissue response and will be a useful tool for the in vivo assessment of novel anti-fibrotic treatments.

Keywords: Cochlea; Cochlear implant; Hearing; Histology; Inner ear; Ossification.