Cochlear Turn Research Articles

Clinico-Radiological Manifestations of Cochlear Schwannomas.

Cochlear schwannomas, which are categorized into intracochlear and intravestibulocochlear schwannomas (ICs and IVCs, respectively) are rare and may cause hearing loss (HL). The affected region is invariably correlated with tumor location, which can be detected on magnetic resonance imaging (MRI). We describe the cochleovestibular manifestations of ICs and IVCs. The study included 31 patients with ICs or IVCs. Tumor extent and exact locations were delineated using MRI. Types of HL were subcategorized into the low-to-mid frequency (250 Hz to 1 kHz), mid-to-high frequency (>1 kHz), and all-frequency (universal) HL groups. The tumors involved the entire cochlear turn (two ICs) or extended beyond the cochleae (nine IVCs) in 11 patients, and 20 ICs were located in specific locations as follows: 14 in the basal, 3 in the middle, and 3 in the middle and apical turns. No patient showed tumor invasion of the internal auditory canal or middle ear. The pattern of HL usually reflects the location or extent of a tumor. We observed HL at all frequencies, at low-to-mid frequencies, and at mid-to-high frequencies in 13, 4, and 14 patients, respectively. Dizziness or tinnitus was observed in >50% of patients. Surgical tumor removal was performed in 10 patients, and the remaining patients are undergoing annual monitoring. Cochlear schwannomas may be associated with HL, which may worsen over time and reflect tumor location. Therefore, these lesions should be considered in the differential diagnosis in patients who present with idiopathic, fluctuating, progressive or sudden HL.

The characteristics of three-dimensional real inversion recovery MRI sequence in delayed Meniere’s disease

Background Delayed Meniere’s disease (DMD) is characterized by episodic vertigo occurring after a significant delay following longstanding sensorineural hearing loss. However, its pathogenesis and characteristics remain unclear. Objectives To explore the characteristics of endolymphatic hydrops (EH) in DMD and investigate its pathology using MRI. Materials and methods 17 patients diagnosed with DMD were included in this study. A 3D-real-IR MRI sequence was utilized to visualize and grade EH. The signal intensity of the basal cochlear turn was compared to that of the cerebellar white matter to calculate the CC ratio. A paired t-test was employed to assess the differences in the CC ratio between the affected and unaffected sides in patients with unilateral DMD. Results EH was present in 100% of cases on the affected side. Unilateral EH was seen in 82.4%, and bilateral EH in 23.5%. Vestibular EH without cochlear involvement occurred in 29.4%, and cochlear EH without vestibular involvement in 5.9%. The CC ratio was significantly higher on the affected side (p < 0.01). Conclusions and significance A significant grade of vestibular EH was observed in DMD, with bilateral EH being relatively common. The increased contrast on the affected side may reflect the underlying pathology in DMD patients.

Comparative Histopathologic Analysis of Inner Ear Damage in Meningitis: Otogenic Versus Meningogenic Routes.

To distinguish the patterns of inner ear changes between meningogenic and otogenic routes in meningitis cases. Our hypothesis is that pinpointing distinct patterns linked to each route could aid in the development of diagnostic strategies and targeted therapies. Temporal bones (TBs) from patients with a history of meningitis and histopathological evidence of labyrinthitis were divided into two groups (otogenic and meningogenic). Inner ear histopathological examination was performed to identify qualitative and semi-quantitative changes. This assessment encompassed inflammation patterns, indications of early ossification, hair cell loss, and alterations in the lateral wall, round window membrane, cochlear aqueduct and vestibular aqueduct. Thirty-six TBs were included in the study (otogenic, 21; meningogenic, 15). Generalized labyrinthitis was more common in otogenic cases (100% vs. 53%, p < 0.001). Early signs of cochlear ossification were exclusively observed in otogenic cases (9 TBs). The spiral ligament of otogenic cases has shown a uniform loss of fibrocytes across all cochlear turns, while meningogenic cases showed more severe loss in the apical turn. Otogenic cases exhibited a higher prevalence of severe inflammation of the cochlear aqueduct and endolymphatic sac. Meningogenic cases showed more severe loss of vestibular hair cells in the otolithic organs. Otogenic cases displayed a higher prevalence of changes in the spiral ligament and signs of early ossification, whereas meningogenic cases were associated with a higher degree of vestibular damage. Our findings emphasize the importance of considering the infection route and its implications for timely diagnosis and development of pathology-oriented treatment strategies. NA Laryngoscope, 2024.

Cochlear lateral wall changes secondary to hypercholesterolemia and noise exposure in the chinchilla model

Objective: To investigate the effects of hypercholesterolemia on the cochlear lateral wall structures in chinchillas and its impact on the susceptibility of the inner ear structures to noise exposure. Materials and Methods: Fifteen chinchilla temporal bones were selected from the Animal Temporal Bone Collection of the Paparella Otopathology and Pathogenesis Laboratory at the University of Minnesota. The experimental group was subjected to 3-month 1% cholesterol diet, while the control group maintained a standard diet. After 3 months, the experimental group's left ears exposed to noise trauma for 10 minutes while right ears did not. One month later the animals were euthanized, and the temporal bones harvested from the animals underwent histopathological examination with morphometric assessments of stria vascularis (SV) and spiral ligament (SL). Results: Histopathological analysis revealed no significant differences (p &gt; 0.05) in total SL area across cochlear turns between the experimental and control groups. However, distinct variations were observed in SV area within the lower basal (p

The cochlear hook region detects harmonics beyond the canonical hearing range.

Ultrasound, or sound at frequencies exceeding the conventional range of human hearing, is not only audible to mice, microbats, and dolphins, but also creates an auditory sensation when delivered through bone conduction in humans. Although ultrasound is utilized for brain activation and in hearing aids, the physiological mechanism of ultrasonic hearing remains unknown. In guinea pigs, we found that ultrasound above the hearing range delivered through ossicles of the middle ear evokes an auditory brainstem response and a mechano-electrical transduction current through hair cells, as shown by the local field potential called the cochlear microphonic potential (CM). The CM synchronizes with ultrasound, and like the response to audible sounds is actively and nonlinearly amplified. In vivo optical nano-vibration analysis revealed that the sensory epithelium in the hook region, the basal extreme of the cochlear turns, resonates in response both to ultrasound within the hearing range and to harmonics beyond the hearing range. The results indicate that hair cells can respond to stimulation at the optimal frequency and its harmonics, and the hook region detects ultrasound stimuli with frequencies more than two octaves higher than the upper limit of the ordinary hearing range.

Age-related alterations in efferent medial olivocochlear-outer hair cell and primary auditory ribbon synapses in CBA/J mice.

Hearing decline stands as the most prevalent single sensory deficit associated with the aging process. Giving compelling evidence suggesting a protective effect associated with the efferent auditory system, the goal of our study was to characterize the age-related changes in the number of efferent medial olivocochlear (MOC) synapses regulating outer hair cell (OHC) activity compared with the number of afferent inner hair cell ribbon synapses in CBA/J mice over their lifespan. Organs of Corti of 3-month-old CBA/J mice were compared with mice aged between 10 and 20 months, grouped at 2-month intervals. For each animal, one ear was used to characterize the synapses between the efferent MOC fibers and the outer hair cells (OHCs), while the contralateral ear was used to analyze the ribbon synapses between inner hair cells (IHCs) and type I afferent nerve fibers of spiral ganglion neurons (SGNs). Each cochlea was separated in apical, middle, and basal turns, respectively. The first significant age-related decline in afferent IHC-SGN ribbon synapses was observed in the basal cochlear turn at 14 months, the middle turn at 16 months, and the apical turn at 18 months of age. In contrast, efferent MOC-OHC synapses in CBA/J mice exhibited a less pronounced loss due to aging which only became significant in the basal and middle turns of the cochlea by 20 months of age. This study illustrates an age-related reduction on efferent MOC innervation of OHCs in CBA/J mice starting at 20 months of age. Our findings indicate that the morphological decline of efferent MOC-OHC synapses due to aging occurs notably later than the decline observed in afferent IHC-SGN ribbon synapses.

Electrocochleography-Based Tonotopic Map: II. Frequency-to-Place Mismatch Impacts Speech-Perception Outcomes in Cochlear Implant Recipients.

Modern cochlear implants (CIs) use varying-length electrode arrays inserted at varying insertion angles within variably sized cochleae. Thus, there exists an opportunity to enhance CI performance, particularly in postlinguistic adults, by optimizing the frequency-to-place allocation for electrical stimulation, thereby minimizing the need for central adaptation and plasticity. There has been interest in applying Greenwood or Stakhovskaya et al. function (describing the tonotopic map) to postoperative imaging of electrodes to improve frequency allocation and place coding. Acoustically-evoked electrocochleography (ECochG) allows for electrophysiologic best-frequency (BF) determination of CI electrodes and the potential for creating a personalized frequency allocation function. The objective of this study was to investigate the correlation between early speech-perception performance and frequency-to-place mismatch. This retrospective study included 50 patients who received a slim perimodiolar electrode array. Following electrode insertion, five acoustic pure-tone stimuli ranging from 0.25 to 2 kHz were presented, and electrophysiological measurements were collected across all 22 electrode contacts. Cochlear microphonic tuning curves were subsequently generated for each stimulus frequency to ascertain the BF electrode or the location corresponding to the maximum response amplitude. Subsequently, we calculated the difference between the stimulus frequency and the patient's CI map's actual frequency allocation at each BF electrode, reflecting the frequency-to-place mismatch. BF electrocochleography-total response (BF-ECochG-TR), a measure of cochlear health, was also evaluated for each subject to control for the known impact of this measure on performance. Our findings showed a moderate correlation (r = 0.51; 95% confidence interval: 0.23 to 0.76) between the cumulative frequency-to-place mismatch, as determined using the ECochG-derived BF map (utilizing 500, 1000, and 2000 Hz), and 3-month performance on consonant-nucleus-consonant words (N = 38). Larger positive mismatches, shifted basal from the BF map, led to enhanced speech perception. Incorporating BF-ECochG-TR, total mismatch, and their interaction in a multivariate model explained 62% of the variance in consonant-nucleus-consonant word scores at 3 months. BF-ECochG-TR as a standalone predictor tended to overestimate performance for subjects with larger negative total mismatches and underestimated the performance for those with larger positive total mismatches. Neither cochlear diameter, number of cochlear turns, nor apical insertion angle accounted for the variability in total mismatch. Comparison of ECochG-BF derived tonotopic electrode maps to the frequency allocation tables reveals substantial mismatch, explaining 26.0% of the variability in CI performance in quiet. Closer examination of the mismatch shows that basally shifted maps at high frequencies demonstrate superior performance at 3 months compared with those with apically shifted maps (toward Greenwood and Stakhovskaya et al.). The implications of these results suggest that electrophysiological-based frequency reallocation might lead to enhanced speech-perception performance, especially when compared with conventional manufacturer maps or anatomic-based mapping strategies. Future research, exploring the prospective use of ECochG-based mapping techniques for frequency allocation is underway.

Insertion trauma of a novel inner ear catheter for intracochlear drug delivery.

Even with recent research advances, effective delivery of a compound to its target cells inside the inner ear remains a challenging endeavor due to anatomical and physiological barriers. Direct intracochlear drug administration with an inner ear catheter (IEC) aims to overcome this obstacle and strives to provide a safe and efficient way for inner ear pharmacotherapy. The goal of this study was to histologically and audiologically evaluate the traumatic properties of a novel IEC for intracochlear drug delivery in a large animal model. Seven inner ears of piglets that had undergone intracochlear fluorescein isothiocyanate dextran application via an IEC (n = 4) or round window membrane (RWM) puncture with a needle (n = 3) followed by sequential apical perilymph sampling were histologically analyzed. Additionally, obtained objective auditory compound action potential and cochlear microphonic measurements were compared. Cochlear cryosections were stained using hematoxylin and eosin, and preservation of inner ear structures was investigated. Moreover, one cochlea was methylmethacrylate-embedded and analyzed with the IEC in situ. Histological evaluation revealed an atraumatic insertion and subsequent compound application in a majority of IEC-inserted inner ears. Click cochlear compound action potential (CAP) shifts in the IEC groups reached a maximum of 5 dB (1.25 ± 2.5 dB) post administration and prior to perilymph sampling. In comparison, application by RWM puncture generated a maximum click CAP hearing threshold shift of 50 dB (23.3 ± 23.1 dB) coinciding with coagulated blood in the basal cochlear turn in one specimen of the latter group. Furthermore, in situ histology showed an atraumatic insertion of the IEC demonstrating preserved intracochlear structures. The IEC appears to be a promising and efficient way for inner ear drug delivery. The similarities between the porcine and human inner ear enhance the clinical translation of our findings and increase confidence regarding the safe applicability of the IEC in human subjects.

Waveguides for neurostimulation in the cochlea

IntroductionOptical stimulation has been suggested for neural stimulation to improve cochlear implants. Light allows for more spatially selective activation of neuron populations than electrical current, offering more independent frequency bands along the spiral ganglion. These bands are available to encode acoustic information with anticipated better frequency resolution, improving cochlear implant user performance in noisy listening environments, tonal languages, and music perception.MethodsOptical cochlear implants (oCIs) can deliver light either directly via small emitters within the cochlea or via waveguides from external optical sources. We investigated three waveguide designs made from OrmoComp®, a polymer that cures through ultraviolet (UV) radiation. Waveguides were fabricated via injection molding and coated using dip-coating or thermal reflow, or through aspiration of OrmoComp® into polyimide tubing that served as the cladding of the waveguide. The choice of fabrication technique directly determined the waveguides' total diameter: thermal reflow yielded ≈940 μm, dip-coating produced ≈306 μm, and aspiration resulted in ≈132 μm core diameter waveguides. Given the human cochlea's small size, we focused on analyzing the 306-μm and 132-μm waveguides, evaluating their optical performance (propagation and bending losses) and mechanical properties (bending stiffness and insertion forces). Furthermore, we evaluated some of these designs in in-vivo guinea pigs experiments.ResultsFor the 100-μm core diameter waveguides, the propagation losses were 12.34 ± 1.26, 1.18 ± 0.88, 1.49 ± 0.58, and 3.43 ± 0.68 dB/cm at 534, 1,375, 1,460, and 1,550 nm, respectively. The respective bending losses at a 2 mm radius of curvature were 5.50 ± 1.32, 0.56 ± 0.26, 0.79 ± 0.18, and 0.64 ± 0.23 dB, and at 1 mm 8.54 ± 1.30, 2.05 ± 0.84, 2.11 ± 0.50, and 1.44 ± 0.37 dB. The bending stiffness of a 1 mm segment of the 100-μm-diameter waveguides was 18.9 ± 2.2 N/m. Insertion forces for the 100-μm-diameter waveguides into an acrylic human-size scala tympani model were &amp;lt; 25 mN. For the waveguides with 306 and 940 μm total diameter, the propagation losses ranged between 0.43 and 2.40 dB/cm at 534, 680, 1,375, and 1,550 nm, between 2.19 and 3.78 dB/cm at 450 and 1,460 nm. Bending losses for 360 degrees at 1,375 nm were 5.0, 2.4, and 0.46 for a bending radius of 2.5-, 3-, and 4-mm.DiscussionOur study demonstrated that the polymer OrmoComp® is suitable for fabricating waveguides to transmit near-infrared radiation. In-vivo experiments showed optically evoked auditory responses originating from optical stimulation in the guinea pigs' first cochlear turn while radiation was delivered. Incoming experiments will focus on evaluating long-term performance of these waveguides in guinea pigs and cats. This study will be designed to provide insights into the waveguides' performance and biocompatibility over extended periods, essential for their potential clinical application in future oCIs.

Cochlear Implantation: Small Cochlear Diameter May Indicate Degree of Abnormality.

Cochlear size variation was first reported in 1884, and since then, there have been various reports confirming the same. Yet, there is no single report that has displayed the wide variations in the cochlear size in a single layout capturing the cochlea in the oblique coronal view/ cochlear view. Basal turn diameter (A-value) was measured in the oblique coronal plane using the OTOPLAN® otological preplanning tool in 104 computed tomography (CT) scans of the temporal bones of cochlear implant (CI) recipients in a tertiary CI center. All CT scans with an image resolution of at least 0.5 mm and identified as having cochleae with normal anatomy were included in this study. A 3-dimensional (3D) segmentation was performed using the 3D slicer and visualized to evaluate the impact of cochlear size on the number of turns studied. The A-value was found to vary between 7.3 mm and 10.4 mm among the studied patients. Three-dimensional segmentation of the inner ear revealed only 2 turns of the cochlea in 4 ears, with A-values of 7.3, 8.8, 7.8, and 7.7 mm. One ear had only 11 /2 turns of the cochlea, with an A-value of 7.9 mm. As a further advancement in the assessment of cochlear size as determined by the A-value, 3D segmentation of the complete inner ear provides a full picture of the number of cochlear turns. Three-dimensional segmentation of the entire inner ear could help improve the preoperative planning of CI surgery and have implications for electrode array selection. Cochlear size could be a predictor of the number of cochlear turns, even in cases that look normal from the radiological findings. The findings of this study could help in improving the preoperative planning for a more successful CI surgery by differentiating between the normal and abnormal cochlea.

Evaluation of cochlear and auditory brainstem functions in COVID-19 patients; a case control study

BackgroundMany viral infections can cause hearing loss due to affection of cochlear hair cells or neurogenic pathway. Although, the damage secondary to viral infections is mainly cochlear affection; auditory brainstem can be affected as well. It was predicted that SARS-COV-2 infection can similarly affect the auditory system. This study aimed to detect affection in auditory system and if present investigate the possible site of lesion (up to the level of the brain stem) in relation to COVID-19 infection.MethodsThis is a case control study, where the study group constituted of thirty adults, diagnosed with COVID-19 at least 2 weeks prior to testing and up to 6 months, without previous auditory complaints pre-COVID-19 or other risk factors that could affect the auditory pathway. Fifteen adult participants that were age and gender matched to the study group with no previous history of covid-19 infection constituted the control group. Audiological evaluations done to all participants were pure-tone and speech audiometry, tympanometry, transient-evoked otoacoustic emission with and without contralateral suppression and auditory brainstem response measurements.ResultsThe study group showed significantly worse pure tone thresholds at high frequencies 4 and 8 kHz (p < 0.01), significantly worse transient-evoked otoacoustic emission signal to noise ratio at 2800 Hz and 4000 Hz (p < 0.05) and significantly lower total suppression index (p<0.05). On the other hand, there was no significant difference between both groups in auditory brainstem response wave latencies (p > 0.05).ConclusionCOVID-19 had subtle effect on cochlear basal turn, and it is shown that the auditory efferent system may also be affected, while the auditory nerve and afferent brainstem pathways seems to be spared. Moreover, the absence of the symptoms of auditory dysfunction postcovid-19 does not guarantee normal auditory functions.

Landmark-based registration of a cochlear model to a human cochlea using conventional CT scans

Cochlear implants can provide an advanced treatment option to restore hearing. In standard pre-implant procedures, many factors are already considered, but it seems that not all underlying factors have been identified yet. One reason is the low quality of the conventional computed tomography images taken before implantation, making it difficult to assess these parameters. A novel method is presented that uses the Pietsch Model, a well-established model of the human cochlea, as well as landmark-based registration to address these challenges. Different landmark numbers and placements are investigated by visually comparing the mean error per landmark and the registrations’ results. The landmarks on the first cochlear turn and the apex are difficult to discern on a low-resolution CT scan. It was possible to achieve a mean error markedly smaller than the image resolution while achieving a good visual fit on a cochlear segment and directly in the conventional computed tomography image. The employed cochlear model adjusts image resolution problems, while the effort of setting landmarks is markedly less than the segmentation of the whole cochlea. As a next step, the specific parameters of the patient could be extracted from the adapted model, which enables a more personalized implantation with a presumably better outcome.

The impact of the size and angle of the cochlear basal turn on translocation of a pre-curved mid-scala cochlear implant electrode

Scalar translocation is a severe form of intra-cochlear trauma during cochlear implant (CI) electrode insertion. This study explored the hypothesis that the dimensions of the cochlear basal turn and orientation of its inferior segment relative to surgically relevant anatomical structures influence the scalar translocation rates of a pre-curved CI electrode. In a cohort of 40 patients implanted with the Advanced Bionics Mid-Scala electrode array, the scalar translocation group (40%) had a significantly smaller mean distance A of the cochlear basal turn (p < 0.001) and wider horizontal angle between the inferior segment of the cochlear basal turn and the mastoid facial nerve (p = 0.040). A logistic regression model incorporating distance A (p = 0.003) and horizontal facial nerve angle (p = 0.017) explained 44.0–59.9% of the variance in scalar translocation and correctly classified 82.5% of cases. Every 1mm decrease in distance A was associated with a 99.2% increase in odds of translocation [95% confidence interval 80.3%, 100%], whilst every 1-degree increase in the horizontal facial nerve angle was associated with an 18.1% increase in odds of translocation [95% CI 3.0%, 35.5%]. The study findings provide an evidence-based argument for the development of a navigation system for optimal angulation of electrode insertion during CI surgery to reduce intra-cochlear trauma.

The association between high jugular bulb and mastoid pneumatization in adults.

The purpose of this study was to analyze the relationship between the degree of high jugular bulb (HJB) and mastoid pneumatization using high-resolution computed tomography (HRCT). Between April 2019 and June 2022, HRCT of the temporal bone was retrospectively analyzed in 1,025 patients. By excluding the other coexistent pathologies, 113 patients with HJBs were recruited for the study. The degree of the HJBs were defined as follows: Grade I, JB situated between inferior annulus of tympanic membrane and cochlear basal turn (CBT). Grade II, JB situated between CBT and lateral semicircular canal (LSC). Grade III, JB situated above LSC. The volume of mastoid pneumatization was based on HRCT images using a 3D reconstruction. There were 32 male and 81 female subjects (mean age, 41.2 ± 14.0 years; age range, 18-80 years). The male group included 16 Grade I, 28 Grade II and 6 Group III HJB subjects. The female group included 38 Grade I, 62 Grade II and 31 Group III HJB cases. In the different groups of HJB, the mastoid cell volume differences were also not statistically significant (p = 0.165). In the classification, Grade II was most common (90/181, 49.7%). This study found no correlation between mastoid air cell volume and HJB, suggesting that HJB may not affect the mastoid air cell development and disease occurrence. These data must be considered exploratory, requiring more extensive cross-sectional studies.

Immuno-surveillance and protection of the human cochlea.

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. 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. 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. 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.

Blood-labyrinth barrier breakdown in Meniere's disease.

We compared the signal intensity ratio (SIR) of the cochlear basal turn between Meniere's disease and healthy controls to investigate potential damage of the blood-labyrinth barrier in Meniere's disease. Thirty patients diagnosed with unilateral definite Meniere's disease and 24 healthy controls were enrolled. 3D-FLAIR scan was conducted to assess the grades of endolymphatic hydrops in Meniere's patients while measuring the SIR of cochlear basal turns in both groups. The differences of bilateral SIR between Meniere's disease and healthy control were compared, and the correlation between the SIR on affected ear in Meniere's disease and the grades of cochlear and vestibular hydrops were analyzed. SIR of affected ear in Meniere's disease exhibited significant increase compared to that of unaffected ear. No significant difference was observed in SIR between the two ears in the healthy control. Furthermore, the SIR of unaffected side in Meniere's disease was higher than that of both ears in healthy controls. The SIR in affected ear of Meniere's disease exhibited positive correlation with hydrops in both cochlea and vestibula. The permeability of blood-labyrinth barrier is increased in Meniere's disease, in combination with the typical criteria of Meniere's disease it may be a good biological marker. Destruction of blood-labyrinth barrier may be one of the causes of endolymphatic hydrops in Meniere's disease.

Applications of visualizing cochlear basal turn in cochlear implantation.

To report a reliable method in obtaining optimal cochlear basal turn and cross-section (c/s) of internal auditory canal (IAC) supporting Cochlear implantation (CI) procedure. Computer tomography (CT) and magnetic resonance image (MRI) scans of potential CI candidates from 2018 to 2022 from the tertiary center were considered for analysis. Slicer software was used in three-dimensional (3D) segmentation of inner ear and for capturing the cochlear basal turn. A total of 1932 head scans were made available for the analysis and out of which 1866 scans had normal anatomy (NA) inner ear. Incomplete partition (IP) type-I was identified in 19 ears, IP type-II in 27 ears, IP type-III in 6 ears, cochlear hypoplasia (CH) type-I in 6 ears, CH type-II in 1 ear, CH type-III in 3 ears, and CH type-IV is 3 ears, and enlarged vestibular aqueduct syndrome in 1 ear. 3D segmented inner ear helped in successfully obtaining the cochlear basal turn and the c/s of IAC in all anatomical types. Time taken to capture the cochlear basal turn with the help of 3D segmented inner ear was <1 min. Within the NA category, five cases showed scalar ossification, and its extent was identified in the cochlear basal turn. The identification and the extent of ossification in the scala tympani, shape of the basal turn, and the cochlear size measurement in cochlear basal turn has high clinical relevance as this helps in surgical planning and in choosing appropriate electrode length. Level of evidence: Level 2 to the best of our understanding.

Cochlea development shapes bat sensory system evolution.

Sensory organs must develop alongside the skull within which they are largely encased, and this relationship can manifest as the skull constraining the organs, organs constraining the skull, or organs constraining one another in relative size. How this interplay between sensory organs and the developing skull plays out during the evolution of sensory diversity; however, remains unknown. Here, we examine the developmental sequence of the cochlea, the organ responsible for hearing and echolocation, in species with distinct diet and echolocation types within the ecologically diverse bat super-family Noctilionoidea. We found the size and shape of the cochlea largely correlates with skull size, with exceptions of Pteronotus parnellii, whose high duty cycle echolocation (nearly constant emission of sound pulses during their echolocation process allowing for detailed information gathering, also called constant frequency echolocation) corresponds to a larger cochlear and basal turn, and Monophyllus redmani, a small-bodied nectarivorous bat, for which interactions with other sensory organs restrict cochlea size. Our findings support the existence of developmental constraints, suggesting that both developmental and anatomical factors may act synergistically during the development of sensory systems in noctilionoid bats.

Preclinical evaluation of the efficacy and safety of AAV1-hOTOF in mice and nonhuman primates

Pathogenic mutations in the OTOF gene cause autosomal recessive hearing loss (DFNB9), one of the most common forms of auditory neuropathy. There is no biological treatment for DFNB9. Here, we designed an OTOF gene therapy agent by dual AAV1 carrying human OTOF coding sequences with the expression driven by the hair cell-specific promoter Myo15, AAV1-hOTOF. To develop a clinical application of AAV1-hOTOF gene therapy, we evaluated its efficacy and safety in animal models by pharmacodynamics, behavior, and histopathology. AAV1-hOTOF inner ear delivery significantly improved hearing in Otof–/– mice without affecting normal hearing in wild-type mice. AAV1 was predominately distributed to the cochlea although it was detected in other organs such as the central nervous system and the liver, and no obvious toxic effects of AAV1-hOTOF were observed in mice. To further evaluate the safety of Myo15 promoter-driven AAV1-transgene, AAV1-GFP was delivered into the inner ear of Macaca fascicularis via the round window membrane. AAV1-GFP transduced 60–94% of the inner hair cells along the cochlear turns. AAV1-GFP was detected in isolated organs and no significant adverse effects were detected. These results suggest that AAV1-hOTOF is well tolerated and effective in animals, providing critical support for its clinical translation.

Evaluation of CI electrode position from imaging: comparison of an automated technique with the established manual method

BackgroundA manual evaluation of the CI electrode position from CT and DVT scans may be affected by diagnostic errors due to cognitive biases. The aim of this study was to compare the CI electrode localization using an automated method (image-guided cochlear implant programming, IGCIP) with the clinically established manual method.MethodsThis prospective experimental study was conducted on a dataset comprising N=50 subjects undergoing cochlear implantation with a Nucleus® CI532 or CI632 Slim Modiolar electrode. Scalar localization, electrode-to-modiolar axis distances (EMD) and angular insertion depth (aDOI) were compared between the automated IGCIP tool and the manual method. Two raters made the manual measurements, and the interrater reliability (±1.96·SD) was determined as the reference for the method comparison. The method comparison was performed using a correlation analysis and a Bland-Altman analysis.ResultsConcerning the scalar localization, all electrodes were localized both manually and automatically in the scala tympani. The interrater differences ranged between ±0.2 mm (EMD) and ±10° (aDOI). There was a bias between the automatic and manual method in measuring both localization parameters, which on the one hand was smaller than the interrater variations. On the other hand, this bias depended on the magnitude of the EMD respectively aDOI. A post-hoc analysis revealed that the deviations between the methods were likely due to a different selection of mid-modiolar axis.ConclusionsThe IGCIP is a promising tool for automated processing of CT and DVT scans and has useful functionality such as being able to segment the cochlear using post-operative scans. When measuring EMD, the IGCIP tool is superior to the manual method because the smallest possible distance to the axis is determined depending on the cochlear turn, whereas the manual method selects the helicotrema as the reference point rigidly. Functionality to deal with motion artifacts and measurements of aDOI according to the consensus approach are necessary, otherwise the IGCIP is not unrestrictedly ready for clinical use.