Nathaniel T. Greene, PhD - US grants

Project Summary/Abstract Many surgical procedures, including otological procedures intended to restore hearing, involve substantial manipulation of components of the middle and inner ear. In particular cochlear implants (CIs), which are increasingly indicated for patients with some residual acoustic hearing, involves direct manipulation of the contents of the inner ear. Unfortunately, up to ~50% of these patients lose their residual acoustic hearing, and a substantial proportion of all CI patients experience balance dysfunction either immediately or some time after surgery. Several studies aimed at determining the cause of the immediate hearing loss have suggested that while the presence of a CI electrode does not substantially alter sound transmission in the cochlea, high-level transients are generated in the cochlea during insertion. These intracochlear pressure (PIC) transients can show peak pressures in excess of 170 dB SPL peak equivalent ear canal SPL (PEAC), thus could cause noise- induced hearing or vestibular loss. These studies were the first to identify the presence of PIC transients, but failed to identify the sources and the risks to hearing from these exposures. The goal of this proposal is to overcome these previous shortcomings using two techniques. First (aim 1), we will further characterize PIC transients during CI surgery in cadaveric human specimens. PIC measurements will be conducted during insertion, manipulation, and removal of CI electrodes to quantify the number of PIC transients generated, and correlate with features such as CI electrode manufacturer, geometry, and insertion style (i.e. with a sheath or stylet or via forceps). The source of PIC transients will be investigated with live fluoroscopic imaging in a subset of these experiments to correlate PIC events with electrode position in the cochlea. Second (aim 2), the risk of hearing loss from these PIC transients will be determined in chinchillas. PIC transients recorded in aim 1 will be translating into acoustic stimuli that produce identical intracochlear exposures in chinchilla using the recently quantified relationship between sound transmission into the inner ear in chinchillas and humans. This technique, which will generate acoustic stimuli that produce PIC in chinchillas that are identical to the PIC in human cochlea observed during CI surgery, requires use of two recent innovations:1) characterization of this relationship, and 2) development of a loudspeaker capable of generating the necessary high-level acoustic stimuli. The experiments thereafter follow a standard noise-exposure protocol in which physiological measures of animal hearing are assessed before, and at several time points after noise exposure to assess the resulting permanent hearing loss. These measurements will thus provide a quantitative estimate of the hearing loss expected from exposure to PIC transients generated during CI surgery that may lead to improved electrode design and surgical techniques. This proposal will thereby develop and validate an animal model for assessing human noise induced hearing loss risk. Furthermore, since PIC may be measured for any source that stimulates the inner ear, this proposal develops a technique that may be used to assess noise-induced hearing loss risk for non-traditional (non-air-conducted) noise sources.

Project Summary We request in this proposal partial support to cover the expenses of the 9th International Meeting of the Middle Ear Mechanics in Research and Otology (MEMRO) 2021 conference, which will be held in June of 2021 at the University of Colorado's Boulder campus. Consistent with the goals of the first MEMRO meeting in 1996 the purpose of this triennial meeting is to bring together experts in middle ear science and engineering, with clinical otologists, in order to foster an exchange between these related but too often independent groups. Recent MEMRO meetings were held in Shanghai (2018) and Aalborg, Denmark (2015) and each attracted ~200 participants from over 20 countries. A goal of the 2021 meeting will be to continue to facilitate the free exchange of ideas between basic and clinical scientists, and to provide a framework for novel collaborative efforts in order to advance our clinical and scientific understanding of middle ear function, dysfunction and repair. The theme of the 2021 MEMRO meeting will be ?Advances in Middle Ear Science and OTO surgery?, highlighting our focus on the intersection between the two fields. An important goal of this meeting is to increase diversity in the attendees. In particular, we intend to specifically target otology residents and faculty by hosting a ?Middle-Ear Surgical Lab and Seminar? the day immediately prior to the formal MEMRO 2021 meeting. The 2021 MEMRO meeting is being organized by the University of Colorado School of Medicine and the meeting will be held on the nearby University of Colorado Boulder campus, chosen because of its convenient location allowing easy travel, idyllic campus and surroundings, and very reasonable costs with on- campus housing and dining options adjacent to the conference venue available for attendees.