Microanatomy of the human tunnel of Corti structures and cochlear partition-tonotopic variations and transcellular signaling.

Auditory sensitivity and frequency resolution depend on the optimal transfer of sound-induced vibrations from the basilar membrane (BM) to the inner hair cells (IHCs), the principal auditory receptors. There remains a paucity of information on how this is accomplished along the frequency range in the human cochlea. Most of the current knowledge is derived either from animal experiments or human tissue processed after death, offering limited structural preservation and optical resolution. In our study, we analyzed the cytoarchitecture of the human cochlear partition at different frequency locations using high-resolution microscopy of uniquely preserved normal human tissue. The results may have clinical implications and increase our understanding of how frequency-dependent acoustic vibrations are carried to human IHCs. A 1-micron-thick plastic-embedded section (mid-modiolar) from a normal human cochlea uniquely preserved at lateral skull base surgery was analyzed using light and transmission electron microscopy (LM, TEM). Frequency locations were estimated using synchrotron radiation phase-contrast imaging (SR-PCI). Archival human tissue prepared for scanning electron microscopy (SEM) and super-resolution structured illumination microscopy (SR-SIM) were also used and compared in this study. Microscopy demonstrated great variations in the dimension and architecture of the human cochlear partition along the frequency range. Pillar cell geometry was closely regulated and depended on the reticular lamina slope and tympanic lip angle. A type II collagen-expressing lamina extended medially from the tympanic lip under the inner sulcus, here named "accessory basilar membrane." It was linked to the tympanic lip and inner pillar foot, and it may contribute to the overall compliance of the cochlear partition. Based on the findings, we speculate on the remarkable microanatomic inflections and geometric relationships which relay different sound-induced vibrations to the IHCs, including their relevance for the evolution of human speech reception and electric stimulation with auditory implants. The inner pillar transcellular microtubule/actin system's role of directly converting vibration energy to the IHC cuticular plate and ciliary bundle is highlighted.

Synchrotron Phase-Contrast Imaging and Cochlear Otosclerosis: A Case Report.

INTRODUCTION: Otosclerosis is a bone disorder affecting the labyrinthine capsule that leads to conductive and occasionally sensorineural hearing loss. The etiology of otosclerosis remains unknown; factors such as infection, hormones, inflammation, genetics, and autoimmunity have been discussed. Treatment consists primarily of surgical stapes replacement and cochlear implantation. High-resolution computed tomography is routinely used to visualize bone pathology. In the present study, we used synchrotron radiation phase-contrast imaging (SR-PCI) to examine otosclerosis plaques in a temporal bone for the first time. The primary aim was to study their three-dimensional (3D) outline, vascular interrelationships, and connections to the middle ear. METHODS: A donated ear from a patient with otosclerosis who had undergone partial stapedectomy with the insertion of a stapes wire prosthesis was investigated using SR-PCI and compared with a control ear. Otosclerotic lesions were 3D rendered using the composite with shading technique. Scalar opacity and color mapping were adjusted to display volume properties with the removal of bones to enhance surfaces. Vascular bone channels were segmented, and the communications between lesions and the middle ear were established. RESULTS: Fenestral, cochlear, meatal, and vestibular lesions were outlined three-dimensionally. Vascular bone channels were found to be frequently connected to the middle ear mucosa, perilabyrinthine air spaces, and facial nerve vessels. Round window lesions partly embedded the cochlear aqueduct which was pathologically narrowed, while the inferior cochlear vein was significantly dilated in its proximal part. CONCLUSION: Otosclerotic/otospongiotic lesions were imaged for the first time using SR-PCI and 3D rendering. The presence of shunts and abnormal vascular connections to the labyrinth appeared to result in hyper-vascularization, overloading the venous system, and leading to sensorineural hearing loss. We speculate about possible local treatments to alleviate the impact of such critical lesions on the labyrinthine microcirculation.

Micro-CT of the human ossicular chain: Statistical shape modeling and implications for otologic surgery.

The ossicular chain is a middle ear structure consisting of the small incus, malleus and stapes bones, which transmit tympanic membrane vibrations caused by sound to the inner ear. Despite being shown to be highly variable in shape, there are very few morphological studies of the ossicles. The objective of this study was to use a large sample of cadaveric ossicles to create a set of three-dimensional models and study their statistical variance. Thirty-three cadaveric temporal bone samples were scanned using micro-computed tomography (µCT) and segmented. Statistical shape models (SSMs) were then made for each ossicle to demonstrate the divergence of morphological features. Results revealed that ossicles were most likely to vary in overall size, but that more specific feature variability was found at the manubrium of the malleus, the long process and lenticular process of the incus, and the crura and footplate of the stapes. By analyzing samples as whole ossicular chains, it was revealed that when fixed at the malleus, changes along the chain resulted in a wide variety of final stapes positions. This is the first known study to create high-quality, three-dimensional SSMs of the human ossicles. This information can be used to guide otological surgical training and planning, inform ossicular prosthesis development, and assist with other ossicular studies and applications by improving automated segmentation algorithms. All models have been made publicly available.

Synchrotron Radiation-Based Reconstruction of the Human Spiral Ganglion: Implications for Cochlear Implantation.

OBJECTIVE: To three-dimensionally reconstruct Rosenthal's canal (RC) housing the human spiral ganglion (SG) using synchrotron radiation phase-contrast imaging (SR-PCI). Straight cochlear implant electrode arrays were inserted to better comprehend the electro-cochlear interface in cochlear implantation (CI). DESIGN: SR-PCI was used to reconstruct the human cochlea with and without cadaveric CI. Twenty-eight cochleae were volume rendered, of which 12 underwent cadaveric CI with a straight electrode via the round window (RW). Data were input into the 3D Slicer software program and anatomical structures were modeled using a threshold paint tool. RESULTS: The human RC and SG were reproduced three-dimensionally with artefact-free imaging of electrode arrays. The anatomy of the SG and its relationship to the sensory organ (Corti) and soft and bony structures were assessed. CONCLUSIONS: SR-PCI and computer-based three-dimensional reconstructions demonstrated the relationships among implanted electrodes, angular insertion depths, and the SG for the first time in intact, unstained, and nondecalcified specimens. This information can be used to assess stimulation strategies and future electrode designs, as well as create place-frequency maps of the SG for optimal stimulation strategies of the human auditory nerve in CI.

Three-dimensional imaging of the human internal acoustic canal and arachnoid cistern: a synchrotron study with clinical implications.

A thorough knowledge of the gross and micro-anatomy of the human internal acoustic canal (IAC) is essential in vestibular schwannoma removal, cochlear implantation (CI) surgery, vestibular nerve section, and decompression procedures. Here, we analyzed the acoustic-facial cistern of the human IAC, including nerves and anastomoses using synchrotron phase contrast imaging (SR-PCI). A total of 26 fresh human temporal bones underwent SR-PCI. Data were processed using volume-rendering software to create three-dimensional (3D) reconstructions allowing soft tissue analyses, orthogonal sectioning, and cropping. A scalar opacity mapping tool was used to enhance tissue surface borders, and anatomical structures were color-labeled for improved 3D comprehension of the soft tissues. SR-PCI reproduced, for the first time, the variable 3D anatomy of the human IAC, including cranial nerve complexes, anastomoses, and arachnoid membrane invagination (acoustic-facial cistern; an extension of the cerebellopontine cistern) in unprocessed, un-decalcified specimens. An unrecognized system of arachnoid pillars and trabeculae was found to extend between the arachnoid and cranial nerves. We confirmed earlier findings that intra-meatal vestibular schwannoma may grow unseparated from adjacent nerves without duplication of the arachnoid layers. The arachnoid pillars may support and stabilize cranial nerves in the IAC and could also play a role in local fluid hydrodynamics.

Effects of object-to-detector distance and beam energy on synchrotron radiation phase-contrast imaging of implanted cochleae.

OBJECTIVES: To demonstrate that synchrotron radiation phase-contrast imaging (SR-PCI) can be used to visualize the intrascalar structures in implanted human cochleae and to find the optimal combination of the parameters object-to-detector distance (ODD) and beam energy (E) for visualization. MATERIALS AND METHODS: Three cadaveric implanted human temporal bones underwent SR-PCI with varying combinations of parameters ODD (3, 2 and 1 m) and E (47, 60 and 72 keV). All images were then reconstructed to a three-dimensional (3D) stack of slices. The acquired 3D images were compared using contrast-to-noise ratios (CNRs) of the basilar membrane ( CNRBM ) and the electrode array (CNRE ) and the standard deviation of the beam streaks ( σS ). Postprocessing calculations were performed using Matlab (Version 2017b, MathWorks Inc., Natick, MA, U.S.A.) with a standard significance level p < 0.05 to determine the most optimal combination of parameters. RESULTS: SR-PCI with computed tomography reconstruction provided good visualization of the anatomical features of the implanted cochleae, specifically the exact location of the electrode with respect to the BM. A single-factor ANOVA revealed a significant difference of variance for both CNRE and CNRBM , but failed to show significance for σS . A two-sample t-test failed to show any significant difference between CNRE columns of (3 m, 72 keV) and (2 m, 60 keV). The CNRBM was significantly different only at two pairs of columns, when (1 m, 72 keV) was compared against (2 m, 72 keV) and (3 m, 72 keV). CONCLUSIONS: The results of this study show that SR-PCI is a viable method to visualize implanted human cochleae. SR-PCI is less invasive, less labour intensive and is associated with a much lower acquisition time compared to other methods for postimplantation imaging in humans, such as histological sectioning. We found that the optimal combination of E and ODD parameters was 72 keV and 2 m, respectively. These parameters resulted in high-contrast images of the electrode as well as all internal structures of the cochleae. LAY DESCRIPTION: Cochlear implants (CI) are currently the preferred method of treatment for hearing loss. Cochlear implantation surgery involves placement of a metallic, wire-shaped electrode inside the cochlea, the main organ of the human hearing system. Knowledge of the exact location of the electrode after implantation is beneficial in improving the extent of restored hearing. Common clinical imaging modalities such as computed-tomography (CT) are not ideal for providing such information, due to lack of resolution and streaking caused by the metallic electrode. Recent studies have developed algorithms to extract the electrode location from clinical computed-tomography images and have been validated using histology or micro computed-tomography (micro-CT). Synchrotron radiation phase contrast imaging (SR-PCI) is a high-resolution imaging technique used to visualize small structures in three dimensions. Recently, SR-PCI has been shown to be an alternative to histology or micro-CT for imaging the human cochlea. However, it has not been optimized for imaging implanted human cochleae. The main objective of the present work was to find the optimal organization of imaging parameters (i.e., object-to-detector distance and beam energy) for using SR-PCI to image implanted human cochleae. Three cadaveric human cochleae were imaged using five different combinations of imaging parameters at the Canadian Light Source Inc., Saskatoon, SK, Canada. The resulting images were compared both quantitatively and qualitatively. An optimal combination of parameters was found to produce high-contrast images of the both the CI electrode and all internal structures of the cochlea with minimal streaking. SR-PCI is therefore a viable alternative to histological or micro-CT studies for post-surgical imaging of implanted human cochleae.

Effects of Various Trajectories on Tissue Preservation in Cochlear Implant Surgery: A Micro-Computed Tomography and Synchrotron Radiation Phase-Contrast Imaging Study.

OBJECTIVES: The purpose of this study was to evaluate the three-dimensional (3D) anatomy and potential damage to the hook region of the human cochlea following various trajectories at cochlear implantation (CI). The goal was to determine which of the approaches can avoid lesions to the soft tissues, including the basilar membrane and its suspension to the lateral wall. Currently, there is increased emphasis on conservation of inner ear structures, even in nonhearing preservation CI surgery. DESIGN: Micro-computed tomography and various CI approaches were made in an archival collection of macerated and freshly fixed human temporal bones. Furthermore, synchrotron radiation phase-contrast imaging was used to reproduce the soft tissues. The 3D anatomy was investigated using bony and soft tissue algorithms, and influences on inner ear structures were examined. RESULTS: Micro-computed tomography with 3D rendering demonstrated the topography of the round window (RW) and osseous spiral laminae, while synchrotron imaging allowed reproduction of soft tissues such as the basilar membrane and its suspension around the RW membrane. Anterior cochleostomies and anteroinferior cochleostomies invariably damaged the intracochlear soft tissues while inferior cochleostomies sporadically left inner ear structures unaffected. CONCLUSIONS: Results suggest that cochleostomy approaches often traumatize the soft tissues at the hook region at CI surgery. For optimal structural preservation, the RW approach is, therefore, recommended.

Morphologic Analysis of the Scala Tympani Using Synchrotron: Implications for Cochlear Implantation.

OBJECTIVES: To use synchrotron radiation phase-contrast imaging (SR-PCI) to visualize and measure the morphology of the entire cochlear scala tympani (ST) and assess cochlear implant (CI) electrode trajectories. METHODS: SR-PCI images were used to obtain geometric measurements of the cochlear scalar diameter and area at 5-degree increments in 35 unimplanted and three implanted fixed human cadaveric cochleae. RESULTS: The cross-sectional diameter and area of the cochlea were found to decrease from the base to the apex. This study represents a wide variability in cochlear morphology and suggests that even in the smallest cochlea, the ST can accommodate a 0.4 mm diameter electrode up to 720°. Additionally, all lateral wall array trajectories were within the anatomically accommodating insertion zone. CONCLUSION: This is the first study to use SR-PCI to visualize and quantify the entire ST morphology, from the round window to the apical tip, and assess the post-operative trajectory of electrodes. These high-resolution anatomical measurements can be used to inform the angular insertion depth that can be accommodated in CI patients, accounting for anatomical variability. LEVEL OF EVIDENCE: N/A. Laryngoscope, 134:2889-2897, 2024.

Development and validation of a surgical planning tool for bone-conduction implants.

Background: The BONEBRIDGE® (Med-El GmbH) is a bone-conduction device comprising an external audio processor and an internal Bone Conduction-Floating Mass Transducer (BC-FMT) surgically anchored to the temporal bone. Due to the implant's size, its placement may be challenging in certain anatomies, necessitating thorough surgical planning. Manual planning methods are laborious, time-intensive, and prone to errors. This study aimed to develop and validate an automated algorithm for determining skull thickness, aiding in the surgical planning of the BONEBRIDGE and other devices requiring similar bone thickness estimations. Materials and methods: Twelve cadaveric temporal bones underwent clinical computed tomography (CT). A custom Python algorithm was developed to automatically segment bone from soft tissue, generate 3D models, and perform ray-tracing to estimate bone thickness. Two thickness colormaps were generated for each sample: the cortical thickness to the first air cell and the total thickness down to the dura. The algorithm was validated against expert manual measurements to achieve consensus interpretation. Results: The algorithm estimated bone-to-air thicknesses (mean = 4.7 mm, 95% Confidence Interval [CI] of 4.3-5.0 mm) that closely matched the expert measurements (mean = 4.7 mm, CI of 4.4-5.0 mm), with a mean absolute difference (MAD) of 0.3 mm. Similarly, the algorithm's estimations to the dura (6.0 mm, CI of 5.4-6.5 mm) were comparable to the expert markings (5.9 mm, CI of 5.4-6.5 mm), with a MAD of 0.3 mm. Conclusions: The first automated algorithm to calculate skull thickness to both the air cells and dura in the temporal bone was developed. Colormaps were optimized to aid with the surgical planning of BONEBRIDGE implantation, however the tool can be generalized to aid in the surgical planning of any bone thickness application. The tool was published as a freely available extension to the open-source 3D Slicer software program (www.slicer.org).

Immuno-surveillance and protection of the human cochlea.

Background: Despite its location near infection-prone areas, the human inner ear demonstrates remarkable resilience. This suggests that there are inherent instruments deterring the invasion and spread of pathogens into the inner ear. Here, we combined high-resolution light microscopy, super-resolution immunohistochemistry (SR-SIM) and synchrotron phase contrast imaging (SR-PCI) to identify the protection and barrier systems in the various parts of the human inner ear, focusing on the lateral wall, spiral ganglion, and endolymphatic sac. Materials and methods: Light microscopy was conducted on mid-modiolar, semi-thin sections, after direct glutaraldehyde/osmium tetroxide fixation. The tonotopic locations were estimated using SR-PCI and 3D reconstruction in cadaveric specimens. The sections were analyzed for leucocyte and macrophage activity, and the results were correlated with immunohistochemistry using confocal microscopy and SR-SIM. Results: Light microscopy revealed unprecedented preservation of cell anatomy and several macrophage-like cells that were localized in the cochlea. Immunohistochemistry demonstrated IBA1 cells frequently co-expressing MHC II in the spiral ganglion, nerve fibers, lateral wall, spiral limbus, and tympanic covering layer at all cochlear turns as well as in the endolymphatic sac. RNAscope assays revealed extensive expression of fractalkine gene transcripts in type I spiral ganglion cells. CD4 and CD8 cells occasionally surrounded blood vessels in the modiolus and lateral wall. TMEM119 and P2Y12 were not expressed, indicating that the cells labeled with IBA1 were not microglia. The round window niche, compact basilar membrane, and secondary spiral lamina may form protective shields in the cochlear base. Discussion: The results suggest that the human cochlea is surveilled by dwelling and circulating immune cells. Resident and blood-borne macrophages may initiate protective immune responses via chemokine signaling in the lateral wall, spiral lamina, and spiral ganglion at different frequency locations. Synchrotron imaging revealed intriguing protective barriers in the base of the cochlea. The role of the endolymphatic sac in human inner ear innate and adaptive immunity is discussed.

Virtual Reality Simulation for the Middle Cranial Fossa Approach: A Validation Study.

BACKGROUND AND OBJECTIVES: Virtual reality (VR) surgical rehearsal is an educational tool that exists in a safe environment. Validation is necessary to establish the educational value of this platform. The middle cranial fossa (MCF) is ideal for simulation because trainees have limited exposure to this approach and it has considerable complication risk. Our objectives were to assess the face, content, and construct validities of an MCF VR simulation, as well as the change in performance across serial simulations. METHODS: Using high-resolution volumetric data sets of human cadavers, the authors generated a high-fidelity visual and haptic rendering of the MCF approach using CardinalSim software. Trainees from Neurosurgery and Otolaryngology-Head and Neck Surgery at two Canadian academic centers performed MCF dissections on this VR platform. Randomization was used to assess the effect of enhanced VR interaction. Likert scales were used to assess the face and content validities. Performance metrics and pre- and postsimulation test scores were evaluated. Construct validity was evaluated by examining the effect of the training level on simulation performance. RESULTS: Twenty trainees were enrolled. Face and content validities were achieved in all domains. Construct validity, however, was not demonstrated. Postsimulation test scores were significantly higher than presimulation test scores ( P < .001 ). Trainees demonstrated statistically significant improvement in the time to complete dissections ( P < .001 ), internal auditory canal skeletonization ( P < .001 ), completeness of the anterior petrosectomy ( P < .001 ), and reduced number of injuries to critical structures ( P = .001 ). CONCLUSION: This MCF VR simulation created using CardinalSim demonstrated face and content validities. Construct validity was not established because no trainee included in the study had previous MCF approach experience, which further emphasizes the importance of simulation. When used as a formative educational adjunct in both Neurosurgery and Otolaryngology-Head and Neck Surgery, this simulation has the potential to enhance understanding of the complex anatomic relationships of critical neurovascular structures.

Finite element modelling of the human middle ear using synchrotron-radiation phase-contrast imaging.

Finite element (FE) models of the middle ear often lack accurate geometry of soft tissue structures, such as the suspensory ligaments, as they can be difficult to discern using conventional imaging modalities, such as computed tomography. Synchrotron-radiation phase-contrast imaging (SR-PCI) is a non-destructive imaging modality that has been shown to produce excellent visualization of soft tissue structures without the need for extensive sample preparation. The objectives of the investigation were to firstly use SR-PCI to create and evaluate a biomechanical FE model of the human middle ear that includes all soft tissue structures, and secondly, to investigate how modelling assumptions and simplifications of ligament representations affect the simulated biomechanical response of the FE model. The FE model included the suspensory ligaments, ossicular chain, tympanic membrane, the incudostapedial and incudomalleal joints, and the ear canal. Frequency responses obtained from the SR-PCI-based FE model agreed well with published laser doppler vibrometer measurements on cadaveric samples. Revised models with exclusion of the superior malleal ligament (SML), simplification of the SML, and modification of the stapedial annular ligament were studied, as these revised models represented modelling assumptions that have been made in literature.

Influence of the Frequency-to-Place Function on Recognition with Place-Based Cochlear Implant Maps.

OBJECTIVE: Comparison of acute speech recognition for cochlear implant (CI) alone and electric-acoustic stimulation (EAS) users listening with default maps or place-based maps using either a spiral ganglion (SG) or a new Synchrotron Radiation-Artificial Intelligence (SR-AI) frequency-to-place function. METHODS: Thirteen adult CI-alone or EAS users completed a task of speech recognition at initial device activation with maps that differed in the electric filter frequency assignments. The three map conditions were: (1) maps with the default filter settings (default map), (2) place-based maps with filters aligned to cochlear SG tonotopicity using the SG function (SG place-based map), and (3) place-based maps with filters aligned to cochlear Organ of Corti (OC) tonotopicity using the SR-AI function (SR-AI place-based map). Speech recognition was evaluated using a vowel recognition task. Performance was scored as the percent correct for formant 1 recognition due to the rationale that the maps would deviate the most in the estimated cochlear place frequency for low frequencies. RESULTS: On average, participants had better performance with the OC SR-AI place-based map as compared to the SG place-based map and the default map. A larger performance benefit was observed for EAS users than for CI-alone users. CONCLUSION: These pilot data suggest that EAS and CI-alone users may experience better performance with a patient-centered mapping approach that accounts for the variability in cochlear morphology (OC SR-AI frequency-to-place function) in the individualization of the electric filter frequencies (place-based mapping procedure). LEVEL OF EVIDENCE: 3 Laryngoscope, 133:3540-3547, 2023.

High-Fidelity Virtual Reality Simulation for the Middle Cranial Fossa Approach-Modules for Surgical Rehearsal and Education.

BACKGROUND: Virtual reality simulation has gained prominence as a valuable surgical rehearsal and education tool in neurosurgery. Approaches to the internal auditory canal, cerebellopontine angle, and ventral brainstem region using the middle cranial fossa are not well explored by simulation. OBJECTIVE: We hope to contribute to this paucity in simulation tools devoted to the lateral skull base, specifically the middle cranial fossa approach. METHODS: Eight high-resolution microcomputed tomography scans of human cadavers were used as volumetric data sets to construct a high-fidelity visual and haptic rendering of the middle cranial fossa using CardinalSim software. Critical neurovascular structures related to this region of the skull base were segmented and incorporated into the modules. RESULTS: The virtual models illustrate the 3-dimensional anatomic relationships of neurovascular structures in the middle cranial fossa and allow a realistic interactive drilling environment. This is facilitated by the ability to render bone opaque or transparent to reveal the proximity to critical anatomy allowing for practice of the virtual dissection in a graduated fashion. CONCLUSION: We have developed a virtual library of middle cranial fossa approach models, which integrate relevant neurovascular structures with aims to improve surgical training and education. A ready extension is the potential for patient-specific application and pathology.

Machine learning approaches used to analyze auditory evoked responses from the human auditory brainstem: A systematic review.

BACKGROUND: The application of machine learning algorithms for assessing the auditory brainstem response has gained interest over recent years with a considerable number of publications in the literature. In this systematic review, we explore how machine learning has been used to develop algorithms to assess auditory brainstem responses. A clear and comprehensive overview is provided to allow clinicians and researchers to explore the domain and the potential translation to clinical care. METHODS: The systematic review was performed based on PRISMA guidelines. A search was conducted of PubMed, IEEE-Xplore, and Scopus databases focusing on human studies that have used machine learning to assess auditory brainstem responses. The duration of the search was from January 1, 1990, to April 3, 2021. The Covidence systematic review platform (www.covidence.org) was used throughout the process. RESULTS: A total of 5812 studies were found through the database search and 451 duplicates were removed. The title and abstract screening process further reduced the article count to 89 and in the proceeding full-text screening, 34 articles met our full inclusion criteria. CONCLUSION: Three categories of applications were found, namely neurologic diagnosis, hearing threshold estimation, and other (does not relate to neurologic or hearing threshold estimation). Neural networks and support vector machines were the most commonly used machine learning algorithms in all three categories. Only one study had conducted a clinical trial to evaluate the algorithm after development. Challenges remain in the amount of data required to train machine learning models. Suggestions for future research avenues are mentioned with recommended reporting methods for researchers.

Unlocking the human inner ear for therapeutic intervention.

The human inner ear contains minute three-dimensional neurosensory structures that are deeply embedded within the skull base, rendering them relatively inaccessible to regenerative therapies for hearing loss. Here we provide a detailed characterisation of the functional architecture of the space that hosts the cell bodies of the auditory nerve to make them safely accessible for the first time for therapeutic intervention. We used synchrotron phase-contrast imaging which offers the required microscopic soft-tissue contrast definition while simultaneously displaying precise bony anatomic detail. Using volume-rendering software we constructed highly accurate 3-dimensional representations of the inner ear. The cell bodies are arranged in a bony helical canal that spirals from the base of the cochlea to its apex; the canal volume is 1.6 µL but with a diffusion potential of 15 µL. Modelling data from 10 temporal bones enabled definition of a safe trajectory for therapeutic access while preserving the cochlea's internal architecture. We validated the approach through surgical simulation, anatomical dissection and micro-radiographic analysis. These findings will facilitate future clinical trials of novel therapeutic interventions to restore hearing.

Three-Dimensional Modeling and Measurement of the Human Cochlear Hook Region: Considerations for Tonotopic Mapping.

HYPOTHESIS: Measuring the length of the basilar membrane (BM) in the cochlear hook region will result in improved accuracy of cochlear duct length (CDL) measurements. BACKGROUND: Cochlear implant pitch mapping is generally performed in a patient independent approach, which has been shown to result in place-pitch mismatches. In order to customize cochlear implant pitch maps, accurate CDL measurements must be obtained. CDL measurements generally begin at the center of the round window (RW) and ignore the basal-most portion of the BM in the hook region. Measuring the size and morphology of the BM in the hook region can improve CDL measurements and our understanding of cochlear tonotopy. METHODS: Ten cadaveric human cochleae underwent synchrotron radiation phase-contrast imaging. The length of the BM through the hook region and CDL were measured. Two different CDL measurements were obtained for each sample, with starting points at the center of the RW (CDLRW) and the basal-most tip of the BM (CDLHR). Regression analysis was performed to relate CDLRW to CDLHR. A three-dimensional polynomial model was determined to describe the average BM hook region morphology. RESULTS: The mean CDLRW value was 33.03 ±â€Š1.62 mm, and the mean CDLHR value was 34.68 ±â€Š1.72 mm. The following relationship was determined between CDLRW and CDLHR: CDLHR  = 1.06(CDLRW)-0.26 (R2  = 0.99). CONCLUSION: The length and morphology of the hook region was determined. Current measurements underestimate CDL in the hook region and can be corrected using the results herein.

Comparison of machine learning models to classify Auditory Brainstem Responses recorded from children with Auditory Processing Disorder.

INTRODUCTION: Auditory brainstem responses (ABRs) offer a unique opportunity to assess the neural integrity of the peripheral auditory nervous system in individuals presenting with listening difficulties. ABRs are typically recorded and analyzed by an audiologist who manually measures the timing and quality of the waveforms. The interpretation of ABRs requires considerable experience and training, and inappropriate interpretation can lead to incorrect judgments about the integrity of the system. Machine learning (ML) techniques may be a suitable approach to automate ABR interpretation and reduce human error. OBJECTIVES: The main objective of this paper was to identify a suitable ML technique to automate the analysis of ABR responses recorded as a part of the electrophysiological testing in the Auditory Processing Disorder clinical test battery. METHODS: ABR responses recorded during routine clinical assessment from 136 children being evaluated for auditory processing difficulties were analyzed using several common ML algorithms: Support Vector Machines (SVM), Random Forests (RF), Decision Trees (DT), Gradient Boosting (GB), Extreme Gradient Boosting (Xgboost), and Neural Networks (NN). A variety of signal feature extraction techniques were used to extract features from the ABR waveforms as inputs to the ML algorithms. Statistical significance testing and confusion matrices were used to identify the most robust model capable of accurately identifying neurological abnormalities present in ABRs. RESULTS: Clinically significant features in the time-frequency representation of the signal were identified. The ML model trained using the Xgboost algorithm was identified as the most robust model with an accuracy of 92% compared to other models. CONCLUSION: The findings of the present study demonstrate that it is possible to develop accurate ML models to automate the process of analyzing ABR waveforms recorded at suprathreshold levels. There is currently no ML-based application to screen children with listening difficulties. Therefore, it is expected that this work will be translated into an evaluation tool that can be used by audiologists in the clinic. Furthermore, this work may aid future researchers in exploring ML paradigms to improve clinical test batteries used by audiologists in achieving accurate diagnoses.

Aeration of the Human Prussak's Space: A 3D Synchrotron Imaging Study.

OBJECTIVES: Prussak's space (PS) is an intricate middle ear region which may play an essential role in the development of middle ear disease. The three-dimensional (3D) anatomy of the human PS and its drainage routes remain relatively unknown. Earlier studies have histologically analyzed PS, by micro-dissection and endoscopy. Here, we used synchrotron-radiation phase-contrast imaging (SR-PCI), 3D reconstructions, and modeling to study the framework of the human PS, including aeration pathways. It may lead to increased understanding of development of middle ear pathology. DESIGN: Nine human temporal bone specimens underwent in-line SR-PCI at the Canadian Light Source in Saskatoon, Saskatchewan, Canada. Data were processed with volume-rendering software to create 3D reconstructions using scalar opacity mapping and segmentations to visualize its walls in fixed, undecalcified human temporal bones. RESULTS: The PS was found to be an irregular, variably shaped chamber with different aeration systems. Three different drainage pathways were found: 1) via the posterior malleolar pouch of von Tröltsch in seven of nine ears; 2) directly posterior-inferior into the mesotympanum medial to the posterior malleolar pouch in one ear; and 3) anteriorly in another. The posterior-inferior communications depended on the anatomy of the posterior malleolar fold. In one bilateral case, the aeration differed between the ears. Earlier descriptions of upper ventilation routes between the PS and the epitympanic spaces could not be substantiated. CONCLUSIONS: The 3D anatomy of the membrane folds organizing the PS in humans was demonstrated for the first time using in-line SR-PCI. The PS was always aerated into the mesotympanum, suggesting its relative independence of attic ventilation. The impact of its various drainage routes on middle ear ventilation and disease were discussed.

A Synchrotron and Micro-CT Study of the Human Endolymphatic Duct System: Is Meniere's Disease Caused by an Acute Endolymph Backflow?

Background: The etiology of Meniere's disease (MD) and endolymphatic hydrops believed to underlie its symptoms remain unknown. One reason may be the exceptional complexity of the human inner ear, its vulnerability, and surrounding hard bone. The vestibular organ contains an endolymphatic duct system (EDS) bridging the different fluid reservoirs. It may be essential for monitoring hydraulic equilibrium, and a dysregulation may result in distension of the fluid spaces or endolymphatic hydrops. Material and Methods: We studied the EDS using high-resolution synchrotron phase contrast non-invasive imaging (SR-PCI), and micro-computed tomography (micro-CT). Ten fresh human temporal bones underwent SR-PCI. One bone underwent micro-CT after fixation and staining with Lugol's iodine solution (I2KI) to increase tissue resolution. Data were processed using volume-rendering software to create 3D reconstructions allowing orthogonal sectioning, cropping, and tissue segmentation. Results: Combined imaging techniques with segmentation and tissue modeling demonstrated the 3D anatomy of the human saccule, utricle, endolymphatic duct, and sac together with connecting pathways. The utricular duct (UD) and utriculo-endolymphatic valve (UEV or Bast's valve) were demonstrated three-dimensionally for the first time. The reunion duct was displayed with micro-CT. It may serve as a safety valve to maintain cochlear endolymph homeostasis under certain conditions. Discussion: The thin reunion duct seems to play a minor role in the exchange of endolymph between the cochlea and vestibule under normal conditions. The saccule wall appears highly flexible, which may explain occult hydrops occasionally preceding symptoms in MD on magnetic resonance imaging (MRI). The design of the UEV and connecting ducts suggests that there is a reciprocal exchange of fluid among the utricle, semicircular canals, and the EDS. Based on the anatomic framework and previous experimental data, we speculate that precipitous vestibular symptoms in MD arise from a sudden increase in endolymph pressure caused by an uncontrolled endolymphatic sac secretion. A rapid rise in UD pressure, mediated along the fairly wide UEV, may underlie the acute vertigo attack, refuting the rupture/K+-intoxication theory.