Novel Imaging Methodologies for Improved Study and Diagnosis of Sensorineural Hearing Loss

Abstract

Sensorineural hearing loss is the most common sensory deficit in the world. Despite its widespread prevalence, diagnostics and therapeutics for hearing loss remain limited in part due to the lack of an effective clinical imaging technology for visualizing biomarkers of sensorineural hearing loss in humans. Results from experiments conducted in animal models of hearing loss and human cadaveric inner ear specimens suggest that this type of hearing loss is characterized by damage to the cochlea – the small, snail-shaped sensory organ that facilitates hearing – and in particular to the cochlea’s sensory epithelium, which comprises a mosaic of sensory cells and nerve fibers that relay acoustic information from our environments to our brains. These findings are yet to be confirmed in living humans, however, due to the human cochlea’s small size, complex three-dimensional configuration, fragility, and deep encasement in dense bone, which render it inaccessible via conventional clinical imaging techniques such as computed tomography and magnetic resonance imaging. Our inability to visualize these sensory structures, and importantly, the specific morphological and physiological transformations that induce hearing impairment, has precluded personalized and meaningful diagnosis of sensorineural hearing loss in patients, and has slowed therapy development. The present dissertation introduces two novel imaging technologies that are promising for clinical translation and inner ear applications, and demonstrates their efficacy for visualizing the micron-scale structures that are implicated in sensorineural hearing loss in humans. The first, synchrotron radiation phase contrast imaging, leverages the penetration power and resolving capability of synchrotron-facilitated X-ray imaging to enable cellular-level imaging of the cochlea’s interior through its dense bony shell in situ, without contrast enhancement or bone decalcification. The second, micro-optical coherence tomography, is a high-resolution, minimally-invasive interferometric imaging technique that can be interfaced with sub-millimeter-diameter endoscopes to access the cochlea’s internal lumina for micron-scale imaging. Together, the results presented herein motivate further investigation into the utility of high-resolution X-ray- and optical coherence tomography-based imaging techniques for improving both the study and clinical diagnosis of sensorineural hearing loss in humans.