Otolaryngology

Multimodal Handheld Probe for Characterizing Otitis Media — Integrating Raman Spectroscopy and Optical Coherence Tomography

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Otitis media (OM) is a common disease of the middle ear, affecting 80% of children before the age of three. The otoscope, a simple illuminated magnifier, is the standard clinical diagnostic tool to observe the middle ear. However, it has limited contrast to detect signs of infection, such as clearly identifying and characterizing middle ear fluid or biofilms that accumulate within the middle ear. Likewise, invasive sampling of every subject is not clinically indicated nor practical. Thus, collecting accurate noninvasive diagnostic factors is vital for clinicians to deliver a precise diagnosis and effective treatment regimen. To address this need, a combined benchtop Raman spectroscopy (RS) and optical coherence tomography (OCT) system was developed. Together, RS-OCT can non-invasively interrogate the structural and biochemical signatures of the middle ear under normal and infected conditions.In this paper, in vivo RS scans from pediatric clinical human subjects presenting with OM we...

Rabbit tympanic membrane thickness distribution obtained via optical coherence tomography

Knowing the precise tympanic membrane (TM) thickness variation is crucial in understanding the functional properties of the TM and has a significant effect on the accuracy of computational models. Using optical coherence tomography, we imaged five left and five right TMs of domestic New Zealand rabbits. From these data, ten thickness distribution maps were computed. Although inter-specimen variability is present, similar features could be observed in all samples: The rabbit TM is thickest around the umbo, with values of 150 ±32 µm. From the umbo towards the TM annulus, the thickness gradually decreases down to 38 ± 7 µm around the midway location, but increases up to 54 ± 19 µm at the TM annulus. The thickness values at the umbo are comparable to literature data for humans, but the rabbit TM is thinner at the TM annulus and in-between the umbo and annulus. Moreover, the rabbit TM thickness distribution is highly symmetrical, which is not the case for the human TM. The results improv...

University of Alabama at Birmingham Receives NIH Grant for Functional Categorization of Ciliary Motion in PCDt

University of Alabama at Birmingham Receives a 2023 NIH Grant for $159,882 for Functional Categorization of Ciliary Motion in PCDt.  The principal investigator is George Solomon.  Below is a summary of the proposed study. Primary Ciliary Dyskinesia (PCD) is a genetically heterogeneous disorder of motile cilia that results in progressive lung disease due to abrogated mucociliary clearance. While new understandings of the genetics have been helpful for clinical diagnostics, functional testing of cilia are needed to understand and predict phenotypic variation and response to therapy. Recent work in our laboratory has identified a link between ciliary genetics and novel ciliary phenotypes using one-micron optical coherence tomography (µOCT). We have phenotyped the ciliary beating pattern of known and novel murine PCD models. We have extended this work to humans through the use of human nasal epithelial cells. Using these technologies, we will characterize and quantify functional cili...

University of Southern California Receives NIH Grant for Mechanisms of cochlear synaptopathy after noise or blast trauma

University of Southern California Receives a 2023 NIH Grant for $516,926 for Mechanisms of cochlear synaptopathy after noise or blast trauma.  The principal investigator is John S. Oghalai.  Below is a summary of the proposed study. About 15% of Americans have hearing loss due to noise exposure. The classical explanation is trauma to the cochlear hair cells. An additional mechanism of noise-induced hearing loss is cochlear synaptopathy. There are no effective treatments used clinically to prevent hearing loss via either mechanism after traumatic noise exposure. Recently, we identified that endolymphatic hydrops occurs after blast or noise trauma, and that endolymphatic hydrops correlated with cochlear synaptopathy. Our central hypothesis is that endolymphatic hydrops is a surrogate marker for swelling of auditory nerve dendrites that occurs in response to glutamate excitotoxicity. We will test this hypothesis with three aims. First, we will determine whether swelling of auditory ...

Medical College of Wisconsin Receives NIH Grant for Otitis Media Diagnosis and Treatment

Medical College of Wisconsin Receives a 2023 NIH Grant for $497,472 for Otitis Media Diagnosis and Treatment.  The principal investigator is Joseph Kerchner.  Below is a summary of the proposed study Otitis media (OM) is the most common diagnosis in pediatric patients seen for illness in the United States (1,2), affects 90% of all children (3,4) and is the most common indication for antimicrobial therapy and surgery (5) in young children. Despite many attempts to improve diagnosis, treatment, and prevention, OM continues its highly prevalent impact on children and substantial ongoing morbidity (1,3,6-30). OM continues as the most common cause of hearing loss (HL) in children and leads to speech, educational and other developmental delays (31-37). OM causes life-threatening complications (22,27) and is expensive, resulting in over $5 billion annually in U.S. health care expenditures (3,38). Despite the prevalence and difficulties with OM, diagnostic accuracy to allow appropriate t...

A chemo-mechanical cochleostomy preserves hearing for the in vivo functional imaging of cochlear cells

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In vivo and real-time multicellular imaging enables the decoding of sensory circuits and the tracking of systemic drug uptake. However, in vivo imaging of the auditory periphery remains technically challenging owing to the deep location, mechanosensitivity and fluid-filled, bone-encased nature of the cochlear structure. Existing methods that expose the cochlea invariably cause irreversible damage to auditory function, severely limiting the experimental measurements possible in living animals. Here we present an in vivo surgical protocol that permits the imaging of cochlear cells in hearing mice. Our protocol describes a ventro-lateral approach for preserving external and middle ear structures while performing surgery, the correct mouse positioning for imaging cochlear cells with effective sound transmission into the ear, the chemo-mechanical cochleostomy for creating the imaging window in the otic capsule bone that prevents intracochlear fluid leakage by maintaining an intact endost...

Optical Coherence Tomography-Based Atlas of the Human Cochlear Hook Region

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Advancements in intracochlear diagnostics, as well as prosthetic and regenerative inner ear therapies, rely on a good understanding of cochlear microanatomy. The human cochlea is very small and deeply embedded within the densest skull bone, making nondestructive visualization of its internal microstructures extremely challenging. Current imaging techniques used in clinical practice, such as MRI and CT, fall short in their resolution to visualize important intracochlear landmarks, and histological analysis of the cochlea cannot be performed on living patients without compromising their hearing. Recently, optical coherence tomography (OCT) has been shown to be a promising tool for nondestructive micrometer resolution imaging of the mammalian inner ear. Various studies performed on human cadaveric tissue and living animals demonstrated the ability of OCT to visualize important cochlear microstructures (scalae, organ of Corti, spiral ligament, and osseous spiral lamina) at micrometer ...

Multimodal Handheld Probe for Characterizing Otitis Media – Integrating Raman Spectroscopy and Optical Coherence Tomography

, , , , , , , , , , , ,

Otitis media (OM) is a common disease of the middle ear, affecting 80% of children before the age of three. The otoscope, a simple illuminated magnifier, is the standard clinical diagnostic tool to observe the middle ear. However, it has limited contrast to detect signs of infection, such as clearly identifying and characterizing middle ear fluid or biofilms that accumulate within the middle ear. Likewise, invasive sampling of every subject is not clinically indicated nor practical. Thus, collecting accurate noninvasive diagnostic factors is vital for clinicians to deliver a precise diagnosis and effective treatment regimen. To address this need, a combined benchtop Raman spectroscopy (RS) and optical coherence tomography (OCT) system was developed. Together, RS-OCT can non-invasively interrogate the structural and biochemical signatures of the middle ear under normal and infected conditions.In this paper, in vivo RS scans from pediatric clinical human subjects presenting with OM we...

Intraoperative Use of Wide-Field Optical Coherence Tomography to Evaluate Tissue Microstructure in the Oral Cavity and Oropharynx

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Importance: Involvement of deep margins represents a significant challenge in the treatment of oropharyngeal cancer, and given practical limitations of frozen-section analysis, a need exists for real-time, nondestructive intraoperative margin analysis. Wide-field optical coherence tomography (WF-OCT) has been evaluated as a tool for high-resolution adjunct specimen imaging in breast surgery, but its clinical application in head and neck surgery has not been explored. Objective: To evaluate the utility of WF-OCT for visualizing microstructures at margins of excised oral and oropharyngeal tissue. Design, setting, and participants: This nonrandomized, investigator-initiated qualitative study evaluated the feasibility of the Perimeter Medical Imaging AI Otis WF-OCT device at a single academic center. Included participants were adults undergoing primary ablative surgery of the oral cavity or oropharynx for squamous cell carcinoma in 2018 and 2019. Data were analyzed in October 2019. Expo...

Organ of Corti vibrations are dominated by longitudinal motion in vivo

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Recent observations of sound-evoked vibrations of the cochlea’s sensory organ of Corti (ooC) using optical coherence tomography (OCT) have revealed unanticipated and complex motions. Interpreting these results in terms of the micromechanical inner-ear processes that precede hair-cell transduction is not trivial since OCT only measures a projection of the true motion, which may include transverse and longitudinal displacements. We measure ooC motions at multiple OCT beam angles relative to the longitudinal axis of the basilar membrane (BM) by using the cochlea’s natural curvature and find that the relative phase between outer hair cells (OHC) and BM varies with this angle. This includes a relatively abrupt phase reversal where OHC lead (lag) the BM by ~0.25 cycles for negative (positive) beam angles, respectively. We interpret these results as evidence for significant longitudinal motion within the ooC, which should be considered when interpreting (relative) ooC vibration...

An optically-guided cochlear implant sheath for real-time monitoring of electrode insertion into the human cochlea

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In cochlear implant surgery, insertion of perimodiolar electrode arrays into the scala tympani can be complicated by trauma or even accidental translocation of the electrode array within the cochlea. In patients with partial hearing loss, cochlear trauma can not only negatively affect implant performance, but also reduce residual hearing function. These events have been related to suboptimal positioning of the cochlear implant electrode array with respect to critical cochlear walls of the scala tympani (modiolar wall, osseous spiral lamina and basilar membrane). Currently, the position of the electrode array in relation to these walls cannot be assessed during the insertion and the surgeon depends on tactile feedback, which is unreliable and often comes too late. This study presents an image-guided cochlear implant device with an integrated, fiber-optic imaging probe that provides real-time feedback using optical coherence tomography during insertion into the human cochlea. This nov...

Cochlear motion across the reticular lamina implies that it is not a stiff plate

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Within the cochlea, the basilar membrane (BM) is coupled to the reticular lamina (RL) through three rows of piezo-like outer hair cells (OHCs) and supporting cells that endow mammals with sensitive hearing. Anatomical differences across OHC rows suggest differences in their motion. Using optical coherence tomography, we measured in vivo and postmortem displacements through the gerbil round-window membrane from approximately the 40–47 kHz best-frequency (BF) regions. Our high spatial resolution allowed measurements across the RL surface at the tops of the three rows of individual OHCs and their bottoms, and across the BM. RL motion varied radially; the third-row gain was more than 3 times greater than that of the first row near BF, whereas the OHC-bottom motions remained similar. This implies that the RL mosaic, comprised of OHC and phalangeal-process tops joined together by adhesion molecules, is much more flexible than the Deiters’ cells connected to the OHCs at their b...

Overturning the mechanisms of cochlear amplification via area deformations of the organ of Corti

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The mammalian ear embeds a cellular amplifier that boosts sound-induced hydromechanical waves as they propagate along the cochlea. The operation of this amplifier is not fully understood and is difficult to disentangle experimentally. In the prevailing view, cochlear waves are amplified by the piezo-electric action of the outer hair cells (OHCs), whose cycle-by-cycle elongations and contractions inject power into the local motion of the basilar membrane (BM). Concomitant deformations of the opposing (or “top”) side of the organ of Corti are assumed to play a minor role and are generally neglected. However, analysis of intracochlear motions obtained using optical coherence tomography calls this prevailing view into question. In particular, the analysis suggests that (i) the net local power transfer from the OHCs to the BM is either negative or highly inefficient; and (ii) vibration of the top side of the organ of Corti plays a primary role in traveling-wave amplification....

Stanford University Received a 2022 NIH Grant for development of a Human Ear Cellular Atlas

Stanford University Received a 2022 NIH Grant for $803,331 for development of a Human Ear Cellular Atlas. The principal investigator is Alan Cheng. Below is a summary of the proposed study. Hearing and balance disorders disable nearly half a billion people worldwide, yet there are virtually no pharmacological or biological therapies for these disorders. This alarming state of medicine coexist with the brighter state of science where numerous therapeutic approaches have shown efficacy in animal models. This conundrum reflects the fact that there are important differences between animal models and humans, that we have an incomplete understanding of the molecular signatures of the auditory and vestibular organs in the human inner ear, and that adult human inner ear tissues are not readily available to test promising therapeutics. We propose to solve this conundrum by defining the molecular makeup of normal, live human inner ear tissues (Aim 1), describing the three-dimensional (3D) cel...

Compact briefcase OCT system for point-of-care imaging

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A detector for characterizing at least one of a middle ear fluid and a middle ear biofilm includes a handheld probe outputting near-infrared and visible light, an OCT system to obtain A-scans at a plurality of positions on a tympanic membrane, and a camera to obtain surface sub-images at the plurality of positions. A-scans and surface sub-images are synchronized and the surface sub-images are mosaicked to generate a surface image of the tympanic membrane. Cross-sectional scan images or a thickness map are generated from the synchronized A-scans and segmented to extract a plurality of specified features. The specified features are then classified to characterize at least one of the middle ear fluid and the middle ear biofilm. The detector, including handheld probe with camera, OCT system, and a laptop computer, is sized to fit into a handheld, portable, compact, foam-padded briefcase weighing less than 10 kg. ( Read Full Article )

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