Multimodality Micro-Optical Coherence Tomography for Imaging the Functional Microanatomy of the Human Cochlea - PROJECT SUMMARY/ABSTRACT Sensorineural hearing loss (SNHL), the most common sensory deficit worldwide, is caused by damage to the fragile mechanosensory and neural structures of the human cochlea. The vast majority of SNHL remains irreversible, in part because the current clinical tools for otologic diagnosis, surgery, and therapy cannot visualize or provide functional information about the micron-sized cochlear cells and nerve fibers deeply embedded in a patient’s dense temporal bone. Thus, there is an urgent unmet need for an imaging tool that can determine the status of cochlear sensorineural cells to identify the underlying pathobiological defect, and ultimately determine the receptiveness of these cells to emerging SNHL treatments such as gene or cell therapy. To address this crucial challenge, we propose to significantly advance our existing intracochlear catheter that images sensorineural cellular structure with a high-resolution, cross-sectional imaging technology termed Micro-OCT (µOCT). Our proposed multimodality µOCT (MM-µOCT) technology will obtain improved images of cellular microstructure and simultaneously acquired and co-localized images of metabolic activity through 1) dynamic µOCT (DµOCT) imaging of intracellular motion and 2) metabolic autofluorescence imaging (AFI) of NADH/FAD. In Aim 1, we will develop and validate MM-µOCT technologies (both DµOCT and AFI) on the benchtop using mouse cochlear explants and whole excised mouse cochleae. Explants will be exposed to agents that simulate oxidative stress or hypoxia occurring during noise-exposure, while whole cochleae from noise- or gentamicin- exposed mice will be imaged in situ. In Aim 2, we will develop a flexible MM-µOCT endomicroscopic probe for imaging the sensorineural cells of the human inner ear, which will be tested in non-human primates following unilateral noise exposure. In parallel in Aim 2, we will develop clinical grade MM-µOCT system and probe using a medical device design control process and will apply for an FDA IDE for conducting a first-in-human study with this technology after the grant is over. Through this robust clinical translation strategy, we will create a minimally invasive tool for determining the microanatomic/metabolic states of critical cells implicated in human SNHL. This new capability will allow hearing loss treatments to be individualized and optimized, improving therapeutic success rates and restoring hearing in many more patients than is currently possible today.
