Scala Tympani Research Articles

Outer hair cells stir cochlear fluids.

We hypothesized that active outer hair cells drive cochlear fluid circulation. The hypothesis was tested by delivering the neurotoxin, kainic acid, to the intact round window of young gerbil cochleae while monitoring auditory responses in the cochlear nucleus. Sounds presented at a modest level significantly expedited kainic acid delivery. When outer-hair-cell motility was suppressed by salicylate, the facilitation effect was compromised. A low-frequency tone was more effective than broadband noise, especially for drug delivery to apical locations. Computational model simulations provided the physical basis for our observation, which incorporated solute diffusion, fluid advection, fluid-structure interaction, and outer-hair-cell motility. Active outer hair cells deformed the organ of Corti like a peristaltic tube to generate apically streaming flows along the tunnel of Corti and basally streaming flows along the scala tympani. Our measurements and simulations coherently suggest that active outer hair cells in the tail region of cochlear traveling waves drive cochlear fluid circulation.

Quantitative in-vitro assessment of a novel robot-assisted system for cochlear implant electrode insertion.

As an increasing number of cochlear implant candidates exhibit residual inner ear function, hearing preservation strategies during implant insertion are gaining importance. Manual implantation is known to induce traumatic force and pressure peaks. In this study, we use a validated in-vitro model to comprehensively evaluate a novel surgical tool that addresses these challenges through motorized movement of a forceps. Using lateral wall electrodes, we examined two subgroups of insertions: 30 insertions were performed manually by experienced surgeons, and another 30 insertions were conducted with a robot-assisted system under the same surgeons' supervision. We utilized a realistic, validated model of the temporal bone. This model accurately reproduces intracochlear frictional conditions and allows for the synchronous recording of forces on intracochlear structures, intracochlear pressure, and the position and deformation of the electrode array within the scala tympani. We identified a significant reduction in force variation during robot-assisted insertions compared to the conventional procedure, with average values of 12mN/s and 32mN/s, respectively. Robotic assistance was also associated with a significant reduction of strong pressure peaks and a 17dB reduction in intracochlear pressure levels. Furthermore, our study highlights that the release of the insertion tool represents a critical phase requiring surgical training. Robotic assistance demonstrated more consistent insertion speeds compared to manual techniques. Its use can significantly reduce factors associated with intracochlear trauma, highlighting its potential for improved hearing preservation. Finally, the system does not mitigate the impact of subsequent surgical steps like electrode cable routing and cochlear access sealing, pointing to areas in need of further research.

Cochlear implantation in otosclerosis: surgical and audiological outcomes between ossified and non-ossified cochlea.

To evaluate (1) Audiological and surgical outcomes in patients with otosclerosis following cochlear implantation. (2) surgical difficulties and outcomes between both groups. (3) Audiological outcomes between both groups. Retrospective study conducted at Otology and Skull Base Surgery Center. Data were analyzed from 111 patients with otosclerosis (114 ears) who underwent cochlear implant surgery using the cochlear implant database. Demographic characteristics (age, sex, and operated ear), auditory outcomes, and operative details (extent of cochlear ossification, surgical approach [posterior tympanotomy or subtotal petrosectomy], electrode insertion [partial/complete, scala tympani or vestibuli], and complications) were analyzed Auditory outcomes were assessed over at least one year follow-up period using pure tone audiometry and speech discrimination scores. Patients were divided into two groups (with and without cochlear ossification) to compare auditory outcomes and surgical outcomes. The mean age of patients with ossified and non-ossified cochlea was 60.04 and 62.22years respectively. Sixty-five of 114 ears had cochlear ossification, with complete round window involvement in 75.4% of these patients, while the rest had partial or complete basal turn ossification. Subtotal petrosectomy was performed in 63.1% and 28.6% of ossified and non-ossified cochlea respectively while the rest underwent cochlear implantation through posterior tympanotomy. Only one case had scala vestibuli insertion and four had incomplete electrode insertion. Six patients underwent re-implantation due to infection, device failure, and erosion of the posterior canal wall. Auditory outcomes among patients with ossified otosclerosis were slightly better than those without ossification but this difference was not statistically significant. Cochlear implantation for otosclerosis yields excellent auditory outcomes with a low rate of surgical complications, despite the high incidence of cochlear ossification.

Frequency dependence and harmonic distortion of stapes displacement and intracochlear pressure in response to very high level sounds

Previous reports have suggested that intracochlear pressures (PIC) measured at the base of the cochlea increase directly proportionally with stapes displacement (DStap) in response to moderately high (<130 dB SPL) level sounds. Consistent with this assumption, we have reported that for low frequency sounds (<1 kHz), stapes displacement and intracochlear pressures increase linearly with sound pressure level (SPL) for moderately high levels (<130 dB SPL), but saturate at higher exposure levels (>130 dB SPL). However, the magnitudes of each response were found to be frequency dependent, thus the relationship between DStap and PIC may vary at higher frequencies or higher levels.In order to further examine this frequency and level dependence, measurements of DStap and PIC were made in cadaveric human temporal bones prepared with a mastoidectomy and extended facial recess to expose the ossicular chain. PIC was measured in scala vestibuli (PSV) and scala tympani (PST) simultaneously with SPL in the external auditory canal (PEAC) and laser Doppler vibrometry (LDV) measurements of stapes velocity (VStap). Consistent with prior reports, DStap and PSV increased proportionally with sound pressure level in the ear canal up to a frequency-dependent saturation point, above which both DStap and PSV showed a distinct deviation from proportionality with PEAC, suggesting that their relationship may remain constant at these high frequencies. Likewise, while the asymptotic value, and SPL at which saturation occurred were frequency dependent in both DStap and PSV, the reduction in gain with increasing SPL above this level was constant above this level at all frequencies, and the magnitude of responses at harmonics of the driving frequency increased with increasing level, consistent with harmonic distortion via peak clipping. Importantly, this nonlinear distortion shifts the energy arriving at the inner ear to higher frequencies than are present in incident stimulus, thus exposing the high frequency sensitive components of the auditory system to more noise than would be expected from measurement of that stimulus on its own. Overall, responses suggest that the cochlear representation of very high-level air conducted stimuli is limited by nonlinearities in the middle ear, and that this peak limiting leads to increased high frequency cochlear exposures than are present in the driving stimulus.

Tracking Lymphatic Drainage Pathways Through Inner Ear Channels: A Systematic Review.

The search for potential lymphatic routes through the cochlea, or membranous portions of the inner ear labyrinth, remains a significant challenge. Researchers often focus on lower mammals rather than humans to uncover these pathways. This review aims to delineate the speculated lymphatic routes within the inner ear to date. It follows the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, conducting a comprehensive search of PubMed, Scopus, Crossref, and Google databases using the terms "inner ear" and "lymph." The problem, intervention, comparison, outcome (PICO) search strategy was employed, and analysis was performed using equation and scope metrics. Articles were screened and filtered using the CADIMA automation tool, resulting in 33 articles being reviewed, of which 23 were selected. Potential lymphatic drainage routes identified include the round window, oval window, scala tympani, spiral limbus, and lateral wall of the cochlea. The vestibular side of Reissner's membrane was noted as a key nodal point for lymphocytes within the inner ear. This review maps the proposed lymphatic networks in the inner ear and highlights existing gaps. It systematically gathers, evaluates, and synthesizes available evidence on the lymphatic pathways of the inner ear, offering valuable insights into their presence, structure, function, and clinical significance.

The role of pressure and friction forces in automated insertion of cochlear implants.

Despite the success of cochlear implant (CI) surgery for hearing restoration, reducing CI electrode insertion forces is an ongoing challenge with the goal to further reduce post-implantation hearing loss. While research in this field shows that both friction and quasistatic pressure forces occur during CI insertion, there is a lack of studies distinguishing between these origins. The present study was conducted to analyze the contribution of both force phenomena during automated CI insertion. Five MED-EL FLEX28 CI electrode arrays were inserted into both a regular and uncoiled version of the same average scala tympani (ST). Both ST models had a pressure release hole at the apical end, which was kept open or closed to quantify pressure forces. ST models were filled with different sodium dodecyl sulfate (SDS) lubricants (1, 5, and 10% SDS, water). The viscosity of lubricants was determined using a rheometer. Insertions were conducted with velocities ranging from v= 0.125 mm/s to 2.0 mm/s. Viscosity of SDS lubricants at 20°C was 1.28, 1.96, and 2.51 mPas for 1, 5, and 10% SDS, respectively, which lies within the values reported for human perilymph. In the uncoiled ST model, forces remained within the noise floor (maximum: 0.049 × 10-3 N ± 1.5 × 10-3 N), indicating minimal contribution from quasistatic pressure. Conversely, forces using the regular, coiled ST model were at least an order of magnitude larger (minimum: Fmax = 28.95 × 10-3 N, v = 1 mm/s, 10% SDS), confirming that friction forces are the main contributor to total insertion forces. An N-way ANOVA revealed that both lubricant viscosity and insertion speed significantly reduce insertion forces (p < 0.001). For the first time, this study demonstrates that at realistic perilymph viscosities, quasistatic pressure forces minimally affect the total insertion force profile during insertion. Mixed friction is the main determinant, and significantly decreases with increaseing insertion speeds. This suggests that in clinical settings with similar ST geometries and surgical preparation, quasistatic pressure plays a subordinate role. Moreover, the findings indicate that managing the hydrodynamics of the cochlear environment, possibly through pre-surgical preparation or the use of specific lubricants, could effectively reduce insertion forces.

Auditory nerve fiber excitability for alternative electrode placement in the obstructed human cochlea: electrode insertion in scala vestibuli versus scala tympani

Objective. The cochlear implant (CI) belongs to the most successful neuro-prostheses. Traditionally, the stimulating electrode arrays are inserted into the scala tympani (ST), the lower cochlear cavity, which enables simple surgical access. However, often deep insertion is blocked, e.g. by ossification, and the auditory nerve fibers (ANFs) of lower frequency regions cannot be stimulated causing severe restrictions in speech understanding. As an alternative, the CI can be inserted into the scala vestibuli (SV), the other upper cochlear cavity. Approach. In this computational study, the excitability of 25 ANFs are compared for stimulation with ST and SV implants. We employed a 3-dimensional realistic human cochlear model with lateral wall electrodes based on a μ-CT dataset and manually traced fibers. A finite element approach in combination with a compartment model of a spiral ganglion cell was used to simulate monophasic stimulation with anodic (ANO) and cathodic (CAT) pulses of 50 μs. Main results. ANO thresholds are lower in ST (mean/std = μ/σ = 189/55 μA) stimulation compared to SV (μ/σ = 323/119 μA) stimulation. Contrary, CAT thresholds are higher for the ST array (μ/σ = 165/42 μA) compared to the SV array (μ/σ = 122/46 μA). The threshold amplitude depends on the specific fiber-electrode spatial relationship, such as lateral distance from the cochlear axis, the angle between electrode and target ANF, and the curvature of the peripheral process. For CAT stimulation the SV electrodes show a higher selectivity leading to less cross-stimulation of additional fibers from different cochlear areas. Significance. We present a first simulation study with a human cochlear model that investigates an additional CI placement into the SV and its impact on the excitation behavior. Results predict comparable outcomes to ST electrodes which confirms that SV implantation might be an alternative for patients with a highly obstructed ST.

Intra-Cochlear Electrode Position Impacts the Preservation of Residual Hearing in an Animal Model of Cochlear Implant Surgery.

Preservation of residual hearing after cochlear implantation remains challenging. There are several approaches to preserve residual hearing, but the configuration of the implant electrode array seems to play a major role. Lateral wall electrode arrays are seemingly more favorable in this context. To date, there are no experimental data available which correlate the spatial electrode position in the scala tympani with the extent of hearing preservation. Based on micro-computed tomography (µCT) imaging data, this study analyses the exact position of a pure silicone electrode array inserted into the cochlea of four guinea pigs. Array position data were correlated with the extent of hearing loss after implantation, measured using auditory brainstem measurements in the frequency range of the area occupied by the electrode array area as well as apical to the array. The use of pure silicone arrays without electrodes resulted in artifact-free, high-resolution µCT images that allowed precise determination of the arrays' positions within the scala tympani. The electrode arrays' locations ranged from peri-modiolar to an anti-modiolar. These revealed a correlation of a lower postoperative hearing loss with a higher spatial proximity to the lateral wall. This correlation was found in the low-frequency range only. A significant correlation between the inter-individual differences in the diameter of the scala tympani and the postoperative hearing loss could not be observed. This study demonstrates the importance of the intra-cochlear electrode array's position for the preservation of residual hearing. The advantage of such an electrode array's position approximated to the lateral wall suggests, at least for this type of electrode array applied in the guinea pig, it would be advantageous in the preservation of residual hearing for the apical part of the cochlea, beyond the area occupied by the electrode array.

Endoscopic-Assisted Cochlear Implantation in Far Advanced Otosclerosis.

To evaluate the effectiveness of cochlear implantation (CI) in case of far advanced otosclerosis and to evaluate the value of using intraoperative otoendoscopy to facilitate the identification of the round window membrane and the scala tympani without the need to remove the posterior canal wall or to perform a subtotal petrosectomy. Retrospective case-series study. Tertiary academic CI center. This study was conducted on patients with far advanced otosclerosis who underwent endoscopic-assisted CI between January 2010 and June 2020 at the same CI center. The minimum follow-up period was 2 years after surgery. Fourteen patients were included in the study. Ten patients had undergone a previous stapedotomy. Electrode insertion in the scala tympani was successfully accomplished in all cases included in the study. There was a statistically significant improvement in pure-tone average and speech discrimination scores in all cases of the study group (p < 0.0001). There were no statistically significant differences in postoperative pure-tone average or speech discrimination scores between cases with and without cochlear ossification or between cases with and without a previous stapedotomy (p > 0.05). Endoscopic-assisted CI is an effective option for hearing restoration in patients with far advanced otosclerosis. Otoendoscopy can facilitate visualization and access to the scala tympani without the need to remove the posterior canal wall or to perform a subtotal petrosectomy.

The impact of round window reinforcement on middle and inner ear mechanics with air and bone conduction stimulation

The round window (RW) membrane plays an important role in normal inner ear mechanics. Occlusion or reinforcement of the RW has been described in the context of congenital anomalies or after cochlear implantation and is applied as a surgical treatment for hyperacusis. Multiple lumped and finite element models predict a low-frequency hearing loss with air conduction of up to 20 dB after RW reinforcement and limited to no effect on hearing with bone conduction stimulation. Experimental verification of these results, however, remains limited.Here, we present an experimental study measuring the impact of RW reinforcement on the middle and inner ear mechanics with air and bone conduction stimulation. In a within-specimen repeated measures design with human cadaveric specimens (n = 6), we compared the intracochlear pressures in scala vestibuli (PSV) and scala tympani (PST) before and after RW reinforcement with soft tissue, cartilage, and bone cement. The differential pressure (PDIFF) across the basilar membrane – known to be closely related to the hearing sensation - was calculated as the complex difference between PSV and PST.With air conduction stimulation, both PSV and PSTincreased on average up to 22 dB at frequencies below 1500 Hz with larger effect sizes for PST compared to PSV. The PDIFF, in contrast, decreased up to 11 dB at frequencies between 700 and 800 Hz after reinforcement with bone cement.With bone conduction, the average within-specimen effects were less than 5 dB for either PSV, PST, or PDIFF. The inter-specimen variability with bone conduction, however, was considerably larger than with air conduction.This experimental study shows that RW reinforcement impacts air conduction stimulation at low frequencies. Bone conduction stimulation seems to be largely unaffected. From a clinical point of view, these results support the hypothesis that delayed loss of air conduction hearing after cochlear implantation could be partially explained by the impact of RW reinforcement.

Optical method to preserve residual hearing in patients receiving a cochlear implant

IntroductionWorldwide, thousands of patients with severe to profound hearing loss restore their hearing with cochlear implant (CI) devices. Newer developments in electrode design and manufacturing and a better understanding of cochlear mechanics allow for conserving critical structures, often translating into serviceable residual hearing and improving device performance. Monitoring insertion speed and intraluminal pressure helps mitigate some of these challenges. However, the information becomes available after irreparable damage has occurred.MethodsWe developed and tested a high-resolution optical system to navigate the intricate anatomy of the cochlea during electrode insertion. The miniaturized optical system was integrated in conventional cochlear implants electrode arrays and custom-made cochlear probes. Electrode insertion were conducted in eight cadaveric human temporal bones and video recordings were acquired. Micro-computed tomography (μCT) scans were performed to evaluate the position of the modified electrode arrays.ResultsFull insertions of the modified CI electrode were successfully conducted and verified by μCT scans. Video recordings of the cochlear structures visible in scala tympani were acquired, and no scala migration was detected.DiscussionSurgeons can now follow the CI electrode's path during its insertion and reduce cochlear damage through early interventions and steering of the CI electrode. Our device will be compatible with robotic platforms that are already available to insert these electrodes.

Hampshire Sheep as a Large-Animal Model for Cochlear Implantation.

Sheep have been proposed as a large-animal model for studying cochlear implantation. However, prior sheep studies report that the facial nerve (FN) obscures the round window membrane (RWM), requiring FN sacrifice or a retrofacial opening to access the middle-ear cavity posterior to the FN for cochlear implantation. We investigated surgical access to the RWM in Hampshire sheep compared to Suffolk-Dorset sheep and the feasibility of Hampshire sheep for cochlear implantation via a facial recess approach. Sixteen temporal bones from cadaveric sheep heads (ten Hampshire and six Suffolk-Dorset) were dissected to gain surgical access to the RWM via an extended facial recess approach. RWM visibility was graded using St. Thomas' Hospital (STH) classification. Cochlear implant (CI) electrode array insertion was performed in two Hampshire specimens. Micro-CT scans were obtained for each temporal bone, with confirmation of appropriate electrode array placement and segmentation of the inner ear structures. Visibility of the RWM on average was 83% in Hampshire specimens and 59% in Suffolk-Dorset specimens (p = 0.0262). Hampshire RWM visibility was Type I (100% visibility) for three specimens and Type IIa (> 50% visibility) for seven specimens. Suffolk-Dorset RWM visibility was Type IIa for four specimens and Type IIb (< 50% visibility) for two specimens. FN appeared to course more anterolaterally in Suffolk-Dorset specimens. Micro-CT confirmed appropriate CI electrode array placement in the scala tympani without apparent basilar membrane rupture. Hampshire sheep appear to be a suitable large-animal model for CI electrode insertion via an extended facial recess approach without sacrificing the FN. In this small sample, Hampshire specimens had improved RWM visibility compared to Suffolk-Dorset. Thus, Hampshire sheep may be superior to other breeds for ease of cochlear implantation, with FN and facial recess anatomy more similar to humans.

Acoustic stimulation of the human round window by laser-induced nonlinear optoacoustics.

The feasibility of low frequency pure tone generation in the inner ear by laser-induced nonlinear optoacoustic effect at the round window was demonstrated in three human cadaveric temporal bones (TB) using an integral pulse density modulation (IPDM). Nanosecond laser pulses with a wavelength in the near-infrared (NIR) region were delivered to the round window niche by an optical fiber with two spherical lenses glued to the end and a viscous gel at the site of the laser focus. Using IPDM, acoustic tones with frequencies between 20Hz and 1kHz were generated in the inner ear. The sound pressures in scala tympani and vestibuli were recorded and the intracochlear pressure difference (ICPD) was used to calculate the equivalent sound pressure level (eq. dB SPL) as an equivalent for perceived loudness. The results demonstrate that the optoacoustic effect produced sound pressure levels ranging from 140eq. dB SPL at low frequencies ≤ 200Hz to 90eq. dB SPL at 1kHz. Therefore, the produced sound pressure level is potentially sufficient for patients requiring acoustic low frequency stimulation. Hence, the presented method offers a potentially viable solution in the future to provide the acoustic stimulus component in combined electro-acoustic stimulation with a cochlear implant.

Effects of Cochlear Implantation and Steroids on the Aging Guinea Pig Cochlea.

The objective was to determine the effects of older age on hearing preservation after cochlear implantation (CI), and whether steroids improve hearing preservation in older animals. We hypothesized greater hearing preservation would be observed in (1) young animals compared to older animals and (2) older animals receiving steroids compared to no steroids. The secondary objective was to assess levels of fibrosis utilizing optical coherence tomography (OCT). Experimental Animal Study. Laboratory. Three groups of guinea pigs: young (YCI; 8.5 ± 0.5 weeks; n = 10), old (OCI; 19.1 ± 1.0 months; n = 9) and old + steroids (OCI+S; 19.1 ± 1.0 months; n = 9) underwent CI. The OCI+S group received a steroid taper over 7 days starting 2 days before surgery to 4 days after. Auditory brainstem response (ABR) measurements were performed preoperatively and postoperatively. OCT imaging was performed to assess cochleae for extent of fibrotic tissue growth in the scala tympani. The YCI group had significantly better hearing preservation as measured by smaller increases in ABR thresholds [mean shift: 2.79 ± 0.66] compared to the OCI group [mean shift = 12.44 ± 5.6]. The OCI+S group had significantly better hearing preservation [2.66 ± 1.50] compared to the OCI group. No significant differences was seen in fibrosis across groups. Young animals and older animals that received steroids had better hearing after CI than older animals not given steroids, but hearing preservation was not correlated with the level of fibrosis assessed using OCT. This work is the first to investigate differences in hearing preservation by age in an animal model, and supports the protective effects of steroids on hearing preservation in older individuals.

Influence of inner ear impedance on middle ear sound transfer functions

IntroductionFor experimental studies on sound transfer in the middle ear, it may be advantageous to perform the measurements without the inner ear. In this case, it is important to know the influence of inner ear impedance on the middle ear transfer function (METF). Previous studies provide contradictory results in this regard. With the current study, we investigate the influence of inner ear impedance in more detail and find possible reasons for deviations in the previous studies. Methods11 fresh frozen temporal bones were prepared in our study. The factors related to inner ear impedance, including round window membrane stiffness, cochleostomy, cochlea fluid and cochlea destruction were involved in the experimental design. After measuring in the intact specimen as a reference (step 1), the round window membrane was punctured (step 2), then completely removed (step 3). The cochleostomy was performed (step 4) before the cochlear fluid was carefully suctioned through scala tympani (step 5) and scala vestibuli (step 6). Finally, cochlea was destroyed by drilling (step 7). Translational and rotational movement of the stapes footplate were measured and calculated at each step. The results of the steps were compared to quantify the effect of inner ear impedance changing related to the process of cochlear drainage. ResultsAs the inner ear impedance decreases from step 1 to 7, the amplitudes of the METF curves at each frequency gradually increase in general. From step 6 on, the measured METF are significantly different with respect to the intact group at high frequencies above 3 kHz. The differences are frequency dependent. However, the significant decrement of rotational motion appears at the frequencies above 4.5 kHz from the step 5. ConclusionThis study confirms the influence of inner ear impedance on METF only at higher frequencies (≥3 kHz). The rotational motions are more sensitive to the drainage of fluid at the higher frequency. Study results that found no influence of cochlea impedance may be due to incomplete drainage of the cochlea.

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

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. 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. 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. 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. N/A. Laryngoscope, 134:2889-2897, 2024.

EBF1 Limits the Numbers of Cochlear Hair and Supporting Cells and Forms the Scala Tympani and Spiral Limbus during Inner Ear Development.

Early B-cell factor 1 (EBF1) is a basic helix-loop-helix transcription factor essential for the differentiation of various tissues. Our single-cell RNA sequencing data suggest that Ebf1 is expressed in the sensory epithelium of the mouse inner ear. Here, we found that the murine Ebf1 gene and its protein are expressed in the prosensory domain of the inner ear, medial region of the cochlear duct floor, otic mesenchyme, and cochleovestibular ganglion. Ebf1 deletion in mice results in incomplete formation of the spiral limbus and scala tympani, increased number of cells in the organ of Corti and Kölliker's organ, and aberrant course of the spiral ganglion axons. Ebf1 deletion in the mouse cochlear epithelia caused the proliferation of SOX2-positive cochlear cells at E13.5, indicating that EBF1 suppresses the proliferation of the prosensory domain and cells of Kölliker's organ to facilitate the development of appropriate numbers of hair and supporting cells. Furthermore, mice with deletion of cochlear epithelium-specific Ebf1 showed poor postnatal hearing function. Our results suggest that Ebf1 is essential for normal auditory function in mammals.

Improved visualization of cochlear implant electrodes on photon counting detector CT

AbstractBackgroundCochlear implants (CIs) are used to rehabilitate moderate to profound sensorineural hearing loss and stimulate the auditory system via a multichannel electrode array positioned in the scala tympani. Imaging evaluation of CIs is substantially degraded by metallic artifacts. Photon‐counting detector (PCD)‐CT has the potential to minimize such artifacts, though this has not been convincingly established in prior studies. This study compared the visualization of CI electrodes on PCD‐CT to conventional energy integrating detector (EID)‐CT.Materials and MethodsFive patients with CIs were prospectively recruited to undergo temporal bone imaging on both EID‐CT and PCD‐CT scanners yielding 2D and 3D Volume Rendering Technique (VRT) images. Three nonblinded neuroradiologists reviewed 2D and 3D VRT images for the ability to resolve CI electrode leads using a Likert scale. The average Likert scores of PCD‐CT versus EID‐CT were calculated for each reader for both 2D and 3D VRT images. (Likert scores 1–5 based on inferior to superior rating of PCD‐CT compared to EID‐CT). Inter‐rater agreement was assessed using Krippendorff's alpha with ordinal weights. ResultsFive patients underwent temporal bone CT for CI array evaluation. As evidenced by 5‐point Likert scales that were independently used by the three reviewers, this study demonstrated superior resolution of CI electrode array using PCD‐CT as compared to EID‐CT with an average score of 4.2 ± 0.8 for 2D images and 4.9 ± 0.4 for 3D VRT images.ConclusionsPCD‐CT is superior to EID‐CT in the visualization of CI electrodes, particularly in 3D VRT imaging.

Optimization of pharmacological interventions in the guinea pig animal model-a new approach to calculate the perilymph volume of the scala tympani.

The guinea pig serves as a well-established animal model for inner ear research, offering valuable insights into the anatomy, physiology, and therapeutic interventions of the auditory system. However, the heterogeneity of results observed in both in-vivo experiments and clinical studies poses challenges in understanding and optimizing pharmacotherapy outcomes. This heterogeneity may be due to individual differences in the size of the guinea pig cochlea and thus in the volume of the scala tympani (ST), which can lead to different drug concentrations in the ST, a fact that has been largely overlooked thus far. To address this issue, we aimed to develop an approach for calculating the individual volume of perilymph within the ST before and after cochlear implant insertion. In this study, high-resolution μCT images of a total of n = 42 guinea pig temporal bones were used to determine the volume of the ST. We compared fresh, frozen, and fixed tissues from both colored and albino strains to evaluate the potential influence of tissue condition and strain on the results. Our findings demonstrate a variability in mean ST volume with a relative standard deviation (RSD) of 14.7%, comparable to studies conducted with humans (range RSD: 5 to 20%). This indicates that the guinea pig cochlea exhibits similar variability to that of the human cochlea. Consequently, it is crucial to consider this variability when designing and conducting studies utilizing the guinea pig as an animal model. Furthermore, we successfully developed a tool capable of estimating ST volume without the need for manual segmentation, employing two geometric parameters, basal diameter (A) and width (B) of the cochlea, corresponding to the cochlear footprint. The tool is available for free download and use on our website. This novel approach provides researchers with a valuable tool to calculate individual ST volume in guinea pigs, enabling more precise dosing strategies and optimization of drug concentrations for pharmacotherapy studies. Moreover, our study underscores the importance of acknowledging and accounting for inter-individual variability in animal models to enhance the translational relevance and applicability of research outcomes in the field of inner ear investigations.

Histological Reaction in the Round Window Membrane after Cochlear Implant Insertion in Nonhuman Primates

Introduction: The primary objective of this article was to determine if any histological alterations occur in the round window (RW) and adjacent anatomical structures of an animal model with normal hearing when a cochlear implant (CI) electrode array is inserted. Furthermore, this article aims to relate these histological alterations to the auditory changes generated. Methods: Cochlear implantation was performed, following the principles of minimally traumatic surgery (MTS), in 15 ears of nonhuman primates (Macaca fascicularis) (Mf) with normal hearing. Auditory brainstem-evoked potentials (ABR) using clicks and tones were used prior to surgery and during a 6-month follow-up period. Histological evaluation was carried out, analyzing the position of the electrode array with respect to the round window membrane (RWM), its percentage of occupation and integrity, the presence of intracochlear damage, and the tissue reaction provoked, the latter of which was quantified in the temporal bones. Results: Surgery was performed on all 15 ears without relevant incidences. Regarding histology, the electrode array in the RW of all ears presented a lateral position with respect to the modiolus. No lesions affecting the integrity of the RW were observed. The mean value of the array’s occupation in the RW was 25%. Tissue reaction, in the form of fibrosis, was observed in all ears and more intensely in the trans-RWM and post-RWM areas. In all ears, the electrodes remained on the scala tympani. No profound hearing impairment was recorded in any ear, being the mean loss of 25.4 dB when comparing presurgical thresholds with those collected 6 months after implantation in ABR click and 24.4 dB in ABR tone burst. Conclusions: The animal model and Hybrid L-14 (HL14) electrode array were optimal for implementing a surgical technique similar to that routinely performed on humans. Mild histological alterations were observed in the round window membrane and adjacent anatomical structures from the insertion of a cochlear implant electrode array. Following the minimally invasive technique, levels of hearing preservation were satisfactory, reaching a pre-post difference of 25.4 dB in the ABR click and 24.4 dB for a high-frequency tone burst. Complete hearing impairment was not observed in either ear. Correlation between the severity of histological alterations and hearing changes recorded in the ABR studies was observed.