Visualizing motions within the cochlea's organ of Corti and illuminating cochlear mechanics with optical coherence tomography.

Beginning in 2006, optical coherence tomography (OCT) has been adapted for use as a vibrometer for hearing research. The application of OCT in this field, particularly for studying cochlear mechanics, represents a revolutionary advance over previous technologies. OCT provides detailed evidence of the motions of components within the organ of Corti, extending beyond the first-encountered surface of observation.

Endolymphatic hydrops and cochlear synaptopathy after noise exposure are distinct sequelae of hair cell stereociliary bundle trauma.

Endolymphatic hydrops, increased endolymphatic fluid within the cochlea, is the key pathologic finding in patients with Meniere's disease, a disease of episodic vertigo, fluctuating hearing loss, tinnitus, and aural fullness. Endolymphatic hydrops also can occur after noise trauma and its presence correlates with cochlear synaptopathy, a form of hearing loss caused by reduced numbers of synapses between hair cells and auditory nerve fibers. Here we tested whether there is a mechanistic link between these two phenomena by using multimodal imaging techniques to analyze the cochleae of transgenic mice exposed to blast and osmotic challenge.

Generation of a zebrafish neurofibromatosis model via inducible knockout of nf2a/b.

Neurofibromatosis type 2 (NF-2) is a dominantly inherited genetic disorder that results from variants in the tumor suppressor gene, neurofibromin 2 (NF2). Here, we report the generation of a conditional zebrafish model of neurofibromatosis established by inducible genetic knockout of nf2a/b, the zebrafish homologs of human NF2. Analysis of nf2a and nf2b expression revealed ubiquitous expression of nf2b in the early embryo, with overlapping expression in the neural crest and its derivatives and in the cranial mesenchyme.

Optical coherence tomography otoscope for imaging of tympanic membrane and middle ear pathology.

Significance: Pathologies within the tympanic membrane (TM) and middle ear (ME) can lead to hearing loss. Imaging tools available in the hearing clinic for diagnosis and management are limited to visual inspection using the classic otoscope. The otoscopic view is limited to the surface of the TM, especially in diseased ears where the TM is opaque.

Automated Segmentation of Optical Coherence Tomography Images of the Human Tympanic Membrane Using Deep Learning.

Optical Coherence Tomography (OCT) is a light-based imaging modality that is used widely in the diagnosis and management of eye disease, and it is starting to become used to evaluate for ear disease. However, manual image analysis to interpret the anatomical and pathological findings in the images it provides is complicated and time-consuming. To streamline data analysis and image processing, we applied a machine learning algorithm to identify and segment the key anatomical structure of interest for medical diagnostics, the tympanic membrane.

Electronic frequency shifting enables long, variable working distance optical coherence tomography.

Increased imaging range is of growing interest in many applications of optical coherence tomography to reduce constraints on sample location, size, and topography. The design of optical coherence tomography systems with sufficient imaging range (e.g.

Multi-window approach enables two-fold improvement in OCT axial resolution with strong side-lobe suppression and improved phase sensitivity.

A common processing approach for optical coherence tomography (OCT) uses a window function (e.g., Hann or rectangular window) for spectral shaping prior to calculating the Fourier transform.

Optical Coherence Tomography as a Tool for Imaging the Sinonasal Mucosa in Patients: A Systematic Review.

To summarize the current applications and potential uses of optical coherence tomography (OCT), a noninvasive imaging modality that uses near-infrared light to produce cross-sectional, high-resolution images of biologic tissues, for evaluating the sinonasal mucosa in patients. Original articles utilizing OCT to image the sinonasal mucosa in patients were identified from the PubMed, Embase, Cochrane Library, Web of Science, and Scopus databases using the search phrase: "Optical Coherence Tomography" AND (sinonasal OR intranasal OR sinus OR nose OR sinusitis OR rhinitis OR olfactory). Strength of evidence, quality of evidence, and risk of bias were measured using validated scales.

High-spatial density snapshot imaging spectrometer enabled by 2-photon fabricated custom fiber bundles.

We report on a proof-of-concept snapshot imaging spectrometer developed using an array of optical fibers fabricated with 2-photon polymerization (2PP). The dense input array maps to an output array with engineered void spaces for spectral information. Previously, the development and fabrication of custom fiber arrays for imaging spectrometers have been a complex, time-consuming, and costly process, requiring a semi-manual assembly of commercial components.

Fabrication of waveguide directional couplers using 2-photon lithography.

Advances in 2-photon lithography have enabled in-lab production of sub-micron resolution and millimeter scale 3D optical components. The potential complex geometries are well suited to rapid prototyping and production of waveguide structures, interconnects, and waveguide directional couplers, furthering future development and miniaturization of waveguide-based imaging technologies. System alignment is inherent to the 2-photon process, obviating the need for manual assembly and allowing precise micron scale waveguide geometries not possible in traditional fused fiber coupler fabrication.

COVID-19 in the Clinic: Trial of an Aerosol Containment Mask for Endoscopic Clinic Procedures.

Objective: Create an aerosol containment mask (ACM) for common otolaryngologic endoscopic procedures which also provides nanoparticle-level protection to patients.

Study Design: Prospective feasibility study.

Setting: In-person testing with a novel ACM.

Porcine vocal fold elasticity evaluation using Brillouin spectroscopy.

Significance: The vocal folds are critically important structures within the larynx which serve the essential functions of supporting the airway, preventing aspiration, and phonation. The vocal fold mucosa has a unique multilayered architecture whose layers have discrete viscoelastic properties facilitating sound production. Perturbations in these properties lead to voice loss.

The impact of targeted ablation of one row of outer hair cells and Deiters' cells on cochlear amplification.

The mammalian cochlea contains three rows of outer hair cells (OHCs) that amplify the basilar membrane traveling wave with high gain and exquisite tuning. The pattern of OHC loss caused by typical methods of producing hearing loss in animal models (noise, ototoxic exposure, or aging) is variable and not consistent along the length of the cochlea. Thus, it is difficult to use these approaches to understand how forces from multiple OHCs summate to create normal cochlear amplification.

Interplay between traveling wave propagation and amplification at the apex of the mouse cochlea.

Sounds entering the mammalian ear produce waves that travel from the base to the apex of the cochlea. An electromechanical active process amplifies traveling wave motions and enables sound processing over a broad range of frequencies and intensities. The cochlear amplifier requires combining the global traveling wave with the local cellular processes that change along the length of the cochlea given the gradual changes in hair cell and supporting cell anatomy and physiology.

Vector of motion measurements in the living cochlea using a 3D OCT vibrometry system.

Optical coherence tomography (OCT) has become an important tool for measuring the vibratory response of the living cochlea. It stands alone in its capacity to measure the intricate motion of the hearing organ through the surrounding otic capsule bone. Nevertheless, as an extension of phase-sensitive OCT, it is only capable of measuring motion along the optical axis.

Unloading outer hair cell bundles in vivo does not yield evidence of spontaneous oscillations in the mouse cochlea.

Along with outer hair cell (OHC) somatic electromotility as the actuator of cochlear amplification, active hair bundle motility may be a complementary mechanism in the mammalian auditory system. Here, we searched the mouse cochlea for the presence of spontaneous bundle oscillations that have been observed in non-mammalian ears. In those systems, removal of the overlying membrane is necessary for spontaneous bundle oscillations to manifest.

Cochlear outer hair cell electromotility enhances organ of Corti motion on a cycle-by-cycle basis at high frequencies in vivo.

Mammalian hearing depends on an amplification process involving prestin, a voltage-sensitive motor protein that enables cochlear outer hair cells (OHCs) to change length and generate force. However, it has been questioned whether this prestin-based somatic electromotility can operate fast enough in vivo to amplify cochlear vibrations at the high frequencies that mammals hear. In this study, we measured sound-evoked vibrations from within the living mouse cochlea and found that the top and bottom of the OHCs move in opposite directions at frequencies exceeding 20 kHz, consistent with fast somatic length changes.

In vivo functional imaging of the human middle ear with a hand-held optical coherence tomography device.

We describe an optical coherence tomography and vibrometry system designed for portable hand-held usage in the otology clinic on awake patients. The system provides clinically relevant point-of-care morphological imaging with 14-44 µm resolution and functional vibratory measures with sub-nanometer sensitivity. We evaluated various new approaches for extracting functional information including a multi-tone stimulus, a continuous chirp stimulus, and alternating air and bone stimulus.

COVID-19 in the Clinic: Human Testing of an Aerosol Containment Mask for Endoscopic Clinic Procedures.

Objective: To create an aerosol containment mask (ACM) for common otolaryngologic endoscopic procedures that also provides nanoparticle-level protection to patients.

Study Design: Prospective feasibility study .

Setting: In-person testing with a novel ACM.

COVID-19 in the Clinic: Aerosol Containment Mask for Endoscopic Otolaryngologic Clinic Procedures.

Objective: To create an aerosol containment mask (ACM) that contains aerosols during common otolaryngologic endoscopic procedures while protecting patients from environmental aerosols.

Study Design: Bench testing.

Setting: Mannequin testing.

Development and Characterization of PLGA-Based Multistage Delivery System for Enhanced Payload Delivery to Targeted Vascular Endothelium.

Vascular-targeted drug delivery remains an attractive platform for therapeutic and diagnostic interventions in human diseases. This work focuses on the development of a poly-lactic-co-glycolic-acid (PLGA)-based multistage delivery system (MDS). MDS consists of two stages: a micron-sized PLGA outer shell and encapsulated drug-loaded PLGA nanoparticles.

In Vivo Cochlear imaging provides a tool to study endolymphatic hydrops.

Exposure to noise trauma, such as that from improvised explosive devices, can lead to sensorineural hearing loss and a reduced quality of life. In order to elucidate the mechanisms underlying noise-induced hearing loss, we have adapted optical coherence tomography (OCT) for real-time cochlear visualization in live mice after blast exposure. We demonstrated that endolymphatic hydrops develops following blast injury, and that this phenomenon may be associated with glutamate excitotoxicity and cochlear synaptopathy.

Dual-modality optical coherence tomography and frequency-domain fluorescence lifetime imaging microscope system for intravascular imaging.

Significance: Detailed biochemical and morphological imaging of the plaque burdened coronary arteries holds the promise of improved understanding of atherosclerosis plaque development, ultimately leading to better diagnostics and therapies.

Aim: Development of a dual-modality intravascular catheter supporting swept-source optical coherence tomography (OCT) and frequency-domain fluorescence lifetime imaging (FD-FLIM) of endogenous fluorophores with UV excitation.

Approach: We instituted a refined approach to endoscope development that combines simulation in a commercial ray tracing program, fabrication, and a measurement method for optimizing ball-lens performance.