Rationale/Objective: Hearing loss is the most common sensory deficit in the world, disabling 466 million people worldwide, and is the most frequent congenital anomaly, affecting 1 in 500 newborns. In addition, its prevalence is steadily increasing; from 2005 to 2015, global prevalence increased from roughly 27% to 29%. Sensorineural hearing loss (SNHL) is the most common type of hearing loss and the most common war-induced injury, along with tinnitus, endured by American military personnel. SNHL is characterized by damage to the delicate mechanosensory and neural structures that reside in the cochlea. SNHL typically remains irreversible today, in part because today's diagnostic tools are imprecise and cannot facilitate visualization of micron-sized cells and nerve fibers inside the cochlea. This unmet need reflects challenges due to the cochlea's small size, fragility, coiled shape, and encasement within the densest bone in the human body.

Our objective is to introduce a novel imaging technology capable of visualizing, for the first time, the fine microstructural defects that cause hearing loss within the inner ears of living humans. Such a technology would revolutionize the way we diagnose and treat a variety of hearing disorders. To this end, we recently demonstrated the ability of a novel, minimally invasive imaging technology called micro-optical coherence tomography (micro-OCT), to visualize individual cells and auditory nerve fibers in a guinea pig cochlea. Subsequently, we have built a preliminary preclinical micro-OCT system and endoscopic probe (0.8 mm in diameter) that can be inserted into the human cochlea of a cadaver through the round window (the only membranous opening into the inner ear) to endoscopically image the cochlea's interior with high resolution. This approach of introducing the micro-OCT probe into the inner ear is the same as currently utilized for placement of cochlear implants (CIs), which are devices used to restore hearing in people with severe to profound SNHL. Based on our preliminary data, we now propose to develop and validate a novel, miniature micro-OCT imaging probe (0.5 mm in diameter) for insertion into the inner ear to obtain the first high-resolution microscopic images and videos of the cochlea's interior in human cadavers (Aim 1) and living non-human primates (Aim 2).

Aims of application: Our specific aims are (1) Develop and test, in human cadavers, preclinical intracochlear micro-OCT probe and system that can diagnose cellular origins of SNHL and ultimately serve as a disposable stylet in a CI; (2) Develop clinical-grade intracochlear micro-OCT probe and system for ultimate integration with a CI electrode array and demonstrate safety and feasibility in non-human primates (namely Rhesus macaque monkeys).

The ultimate integration of our micro-OCT probe with a CI electrode array will improve the safety and efficacy of CIs. Specifically, next-generation CIs enabled by our micro-OCT imaging probe will have superior safety (by preserving the delicate intracochlear microanatomy) and efficacy (by both allowing combined acoustic and electric stimulation as well as facilitating future biological regenerative and restorative therapies).

Anticipated short-term/long-term outcomes: If successful, our micro-OCT probe will dramatically improve the way we diagnose and recommend therapy for SNHL. SNHL often results in isolation and mental health disorders such as depression because it is currently irreversible, and treatments are limited and variable in efficacy. Families of military personnel, Veterans, and civilians who lose their hearing face the challenge of learning to maintain communication without understanding speech, which can be both financially and mentally costly. The clinical tool we develop will remedy these problems by enabling first (a) visualization and quantification of the structural cause of a patient's impairment, such as loss or damage of sensory hair cell or nerve fibers, (b) rational treatment recommendations that target specific cells (such as emerging biological regenerative therapies, including gene therapy), and (c) precise monitoring of response to treatment. This technology will benefit (a) military personnel and Veterans suffering from noise-induced SNHL, (b) civilians experiencing SNHL of any cause, and (c) hearing researchers and otologic surgeons by opening new areas of investigation.

The main short-term outcome will be a clinical grade micro-OCT system by 2023; thus, we hope that our technology will benefit the aforementioned populations within the next 5 to 10 years. Long-term outcomes will include routine use of our micro-OCT imaging probe in (1) next-generation cochlear implants to improve their safety and efficacy, and (2) successfully designed and executed clinical trials involving therapies that restore auditory function based on biological regeneration and repair mechanisms.