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.

Comprehension of Cochlear Duct Length for Incomplete Partition Types.

OBJECTIVE: Preoperative assessment of the cochlear duct length (CDL) and cochlear dimensions allows the selection of optimized implants. We aimed to evaluate the CDL measurements in incomplete partition (IP) defect patients and to create a reference to the literature. METHODS: Forty-one patients with IP (13 IP I, 23 IP II, and 5 IP III) and 30 controls were included in the study. The standardized cochlear image showing the basal turn in the most expansive plane was reconstructed from temporal high-resolution computed tomography images. Cochlear duct length measured manually (CDL-M) was measured by points placed consecutively on the lateral wall of the cochlea. The defined equations for estimating CDL (CDL measured according to Schurzig et al formula [CDL-Ɵ], CDL measured according to Escudé et al formula [CDL-E], CDL measured according to Alexiades et al formula [CDL-A]) were calculated from the same images. Cochlear duct length mean values obtained by each method were compared for each IP type. RESULTS: The longest CDL value was found in the control group, irrespective of the calculation method. Incomplete partition II cases had the most extended mean CDL among IP types. Incomplete partition III had the shortest CDL among all groups' CDL-M values. However, the mean CDL-M values of IP types I and III showed close results. There was no significant difference between the CDL-E and CDL-M values of the control group. Similarly, no significant difference was found between CDL-Ɵ and CDL-M values in IP type III cases. However, the results of other estimating formulations of all groups differed significantly from CDL-M values. CONCLUSION: Cochlear duct length differences were detected between the control group and IP subtypes. These differences should be considered when choosing the appropriate electrode length. Because the results of formulas estimating CDL may differ from CDL-M in both control and IP cases, it would be more appropriate to use manual measurements in clinical practice.

Interobserver variability of cochlear duct measurements in pediatric cochlear implant candidates.

PURPOSE: The objective of the study was to evaluate the proposed cochlear duct length estimation based on the cochlear 'A value'. Furthermore, we assessed the interobserver variability between radiology and otolaryngology attending physicians and otolaryngology trainees. METHODS: Thirteen pediatric cochlear implant candidates were retrospectively analyzed by three otolaryngology physicians (attending physician, second year, and fourth year trainees) and a radiology attending. The cochlear duct length was calculated based on the formula of Grover et al. The differences in acquired measurements between observers were compared using the Wilcoxon matched signed-rank test. RESULTS: The differences in measurements between the attending otolaryngologist and radiologist were not statistically different, while several significant differences were observed with regard to measurements of attending doctors compared to both residents. In particular, a significant difference between the second year otolaryngology resident and otolaryngology and radiology attending was observed for one side (right ear p = 0.034 and p = 0.012, respectively). Moreover, the fourth year resident calculated significantly different cochlear duct measurements when compared to the attending otolaryngologist (left ear p = 0.014) and radiologist (right ear p = 0.047). Interestingly, differently experienced otolaryngology residents provided significantly different measurements for both ears. CONCLUSIONS: Based on these results, cochlear duct length measurement according to the proposed method may be a reliable and cost-effective method. Indeed, otolaryngology training may be sufficient to provide measurements comparable to radiologists. On the other hand, additional efforts should be invested during otolaryngology training in terms of the evaluation of radiological imaging which may increase the capabilities of otolaryngology residents in this regard.

CT imaging-based approaches to cochlear duct length estimation-a human temporal bone study.

OBJECTIVES: Knowledge about cochlear duct length (CDL) may assist electrode choice in cochlear implantation (CI). However, no gold standard for clinical applicable estimation of CDL exists. The aim of this study is (1) to determine the most reliable radiological imaging method and imaging processing software for measuring CDL from clinical routine imaging and (2) to accurately predict the insertion depth of the CI electrode. METHODS: Twenty human temporal bones were examined using different sectional imaging techniques (high-resolution computed tomography [HRCT] and cone beam computed tomography [CBCT]). CDL was measured using three methods: length estimation using (1) a dedicated preclinical 3D reconstruction software, (2) the established A-value method, and (3) a clinically approved otosurgical planning software. Temporal bones were implanted with a 31.5-mm CI electrode and measurements were compared to a reference based on the CI electrode insertion angle measured by radiographs in Stenvers projection (CDLreference). RESULTS: A mean cochlear coverage of 74% (SD 7.4%) was found. The CDLreference showed significant differences to each other method (p < 0.001). The strongest correlation to the CDLreference was found for the otosurgical planning software-based method obtained from HRCT (CDLSW-HRCT; r = 0.87, p < 0.001) and from CBCT (CDLSW-CBCT; r = 0.76, p < 0.001). Overall, CDL was underestimated by each applied method. The inter-rater reliability was fair for the CDL estimation based on 3D reconstruction from CBCT (CDL3D-CBCT; intra-class correlation coefficient [ICC] = 0.43), good for CDL estimation based on 3D reconstruction from HRCT (CDL3D-HRCT; ICC = 0.71), poor for CDL estimation based on the A-value method from HRCT (CDLA-HRCT; ICC = 0.29), and excellent for CDL estimation based on the A-value method from CBCT (CDLA-CBCT; ICC = 0.87) as well as for the CDLSW-HRCT (ICC = 0.94), CDLSW-CBCT (ICC = 0.94) and CDLreference (ICC = 0.87). CONCLUSIONS: All approaches would have led to an electrode choice of rather too short electrodes. Concerning treatment decisions based on CDL measurements, the otosurgical planning software-based method has to be recommended. The best inter-rater reliability was found for CDLA-CBCT, for CDLSW-HRCT, for CDLSW-CBCT, and for CDLreference. KEY POINTS: • Clinically applicable calculations using high-resolution CT and cone beam CT underestimate the cochlear size. • Ten percent of cochlear duct length need to be added to current calculations in order to predict the postoperative CI electrode position. • The clinically approved otosurgical planning software-based method software is the most suitable to estimate the cochlear duct length and shows an excellent inter-rater reliability.

Implementation of secondary reconstructions of flat-panel volume computed tomography (fpVCT) and otological planning software for anatomically based cochlear implantation.

PURPOSE: For further improvements in cochlear implantation, the measurement of the cochlear duct length (CDL) and the determination of the electrode contact position (ECP) are increasingly in the focus of clinical research. Usually, these items were investigated by multislice computed tomography (MSCT). The determination of ECP was only possible by research programs so far. Flat-panel volume computed tomography (fpVCT) and its secondary reconstructions (fpVCTSECO) allow for high spatial resolution for the visualization of the temporal bone structures. Using a newly developed surgical planning software that enables the evaluation of CDL and the determination of postoperative ECP, this study aimed to investigate the combination of fpVCT and otological planning software to improve the implementation of an anatomically based cochlear implantation. METHODS: Cochlear measurements were performed utilizing surgical planning software in imaging data (MSCT, fpVCT and fpVCTSECO) of patients with and without implanted electrodes. RESULTS: Measurement of the CDL by the use of an otological planning software was highly reliable using fpVCTSECO with a lower variance between the respective measurements compared to MSCT. The determination of the inter-electrode-distance (IED) between the ECP was improved in fpVCTSECO compared to MSCT. CONCLUSION: The combination of fpVCTSECO and otological planning software permits a simplified and more reliable analysis of the cochlea in the pre- and postoperative setting. The combination of both systems will enable further progress in the development of an anatomically based cochlear implantation.

Variation of the cochlear anatomy and cochlea duct length: analysis with a new tablet-based software.

PURPOSE: In cochlear implantation, thorough preoperative planning together with measurement of the cochlear duct length (CDL) assists in choosing the correct electrode length. For measuring the CDL, different techniques have been introduced in the past century along with the then available technology. A tablet-based software offers an easy and intuitive way to visualize and analyze the anatomy of the temporal bone, its proportions and measure the CDL. Therefore, we investigated the calculation technique of the CDL via a tablet-based software on our own cohort retrospectively. METHODS: One hundred and eight preoperative computed tomography scans of the temporal bone (slice thickness < 0.7 mm) of already implanted FLEX28™ and FLEXSOFT™ patients were found eligible for analysis with the OTOPLAN software. Measurements were performed by two trained investigators independently. CDL, angular insertion depth (AID), and cochlear coverage were calculated and compared between groups of electrode types, sex, sides, and age. RESULTS: Mean CDL was 36.2 ± 1.8 mm with significant differences between sex (female: 35.8 ± 0.3 mm; male: 36.5 ± 0.2 mm; p = 0.037), but none concerning side or age. Differences in mean AID (FLEX28: 525.4 ± 46.4°; FLEXSOFT: 615.4 ± 47.6°), and cochlear coverage (FLEX28: 63.9 ± 5.6%; FLEXSOFT: 75.8 ± 4.3%) were significant (p < 0.001). CONCLUSION: A broad range of CDL was observed with significant larger values in male, but no significant differences concerning side or age. Almost every cochlea was measured longer than 31.0 mm. Preoperative assessment aids in prevention of complications (incomplete insertion, kinking, tipfoldover), attempt of atraumatic insertion, and addressing individual necessities (hearing preservation, cochlear malformation). The preferred AID of 720° (two turns of the cochlea) was never reached, opening the discussion for the requirement of longer CI-electrodes versus a debatable audiological benefit for the patient in his/her everyday life.

[Measuring the cochlea using a tablet-based software package: influence of imaging modality and rater background]. / Vermessung der Cochlea mittels eines Tablet-basierten Softwarepakets: Einfluss der Bildgebungsmodalität und des Untersucherhintergrunds.

BACKGROUND: Cochlear duct length (CDL) is subject to significant individual variation. In the context of cochlear implantation, adapting the electrode array length to the CDL is of potential interest, as it has been associated with improvements in both speech recognition and sound quality. Using a tablet-based software package, it is possible to measure CDL at the level of the organ of Corti (CDLOC) to select appropriate electrode array lengths based on individual cochlear anatomy. OBJECTIVE: To identify effects of imaging modality and rater background on CDL estimates. METHODS: Magnetic resonance imaging (MRI) and flat-panel volume CT (fpVCT) scans of 10 patients (20 cochleae) were analyzed using the OTOPLAN software package (MED-EL, Innsbruck, Austria). Raters were an otorhinolaryngology (ORL) specialist, an ORL resident, and an audiologist. To analyze effects of rater background and imaging modality on CDL measurements, linear mixed models were constructed. RESULTS: Measurements showed mean CDLOC(fpVCT) = 36.69 ± 1.78 mm and CDLOC(MRI) = 36.81 ± 1.87 mm. Analyses indicated no significant effect of rater background (F(2, 105) = 0.84; p = 0.437) on CDL estimates. Imaging modality, on the other hand, significantly affected CDL (F (1, 105) = 20.70; p < 0.001), whereby estimates obtained using MRI were 0.89 mm larger than those obtained using fpVCT. CONCLUSION: No effect of rater background on CDL estimates could be identified, suggesting that comparable measurements could be obtained by personnel other than specially trained neurootologists. While imaging modality (fpVCT vs. MRI) did impact CDL results, the difference was small and of questionable clinical significance.

[Cochlear Implantation: Evaluation of Cochlear Duct Length (CDL)]. / Cochlea-Implantation: Bestimmung der Cochlear Duct Length (CDL).

Personalized care in the context of cochlear implantation is becoming increasingly important. Choosing the right electrode could improve speech understanding. The measurement of the cochlear length plays an important role: preoperatively, in order to select a suitable electrode length; postoperatively, on the one hand to check the correct electrode position, on the other hand to enable anatomically based fitting of the electrode contacts. Of the various possible localizations of the CDL measurements within the cochlear turns, the one on the organ of Corti (CDLOC) is the most frequently used and clinically most important. In the CDL measurement, a direct and indirect evaluation can be distinguished. There is also the possibility of reconstructing and measuring the CDL in 3D and calculating it mathematically, e.g. using spiral equations. In this context, measurements based on radiological imaging are gaining increasing importance. Therefore, if there is the possibility of performing higher-resolution imaging, this should be strived preoperatively in order to enable the most precise possible procedure and thus a good outcome. Otological planning software can help to create an interface between new findings regarding CDL measurement and higher-resolution imaging for an individualized cochlear implantation.

Cochlear duct length and cochlear distance on preoperative CT: imaging markers for estimating insertion depth angle of cochlear implant electrode.

OBJECTIVES: Preoperative estimation of the insertion depth angle of cochlear implant (CI) electrodes is essential for surgical planning. The purpose of this study was to determine the cochlear size using preoperative CT and to investigate the correlation between cochlear size and insertion depth angle in morphologically normal cochlea. METHODS: Thirty-five children who underwent CI were included in this study. Cochlear duct length (CDL) and the diameter of the cochlear basal turn (distance A/B) on preoperative CT and the insertion depth angle of the CI electrode on postoperative radiographs were independently measured by two readers. Correlation between cochlear size and insertion depth angle was evaluated. Interobserver agreement was calculated using the intraclass correlation coefficient (ICC). RESULTS: The mean CDL, distance A, and distance B of 70 ears were 36.20 ± 1.57 mm, 8.67 ± 0.42 mm, and 5.73 ± 0.32 mm, respectively. The mean insertion depth angle was 431.45 ± 38.42°. Interobserver agreements of CDL, distance A/B, and insertion depth angle were fair to excellent (ICC 0.864, 0.862, 0.529, and 0.958, respectively). Distance A (r = - 0.7643) and distance B (r = - 0.7118) showed a negative correlation with insertion depth angle, respectively (p < 0.0001). However, the correlation between CDL and insertion depth angle was not statistically significant (r = - 0.2333, p > 0.05). CONCLUSIONS: The CDL and cochlear distance can be reliably obtained from preoperative CT. Distance A can be used as a predictive marker for estimating insertion depth angle during CI surgery.

Modiolar Proximity of Slim Modiolar Electrodes and Cochlear Duct Length: Correlation for Potential Basis of Customized Cochlear Implantation With Perimodiolar Electrodes.

OBJECTIVES: Recent studies have shown that cochlear duct length (CDL) varies among individuals and could significantly influence the final position of the electrode and its trajectory in the cochlea. Given this, we hypothesized that the degree of modiolar proximity of novel slim modiolar electrodes, such as CI532 and CI632, can also be affected by CDL. To test this hypothesis, we retrospectively evaluated individual CDL to determine if there is any significant correlation of CDL with degree of modiolar proximity. METHODS: Fifty-one ears from 38 subjects implanted with slim modiolar electrodes by a single surgeon through the round window approach using the pull-back technique were included. Our cohort was classified according to the deafness onset (congenital versus postlingual) and the degree of modiolar proximity (less versus tight) with reference to the spiral diameter made by the slim modiolar electrodes in situ on transorbital x ray. We then analyzed the CDL and its metrics using a readily available surgical preplanning tool (OTOPLAN) to obtain comparable data. RESULTS: Among 30 ears associated with congenital deafness, 9 ears (30%) showed less modiolar proximity, while none of the 21 ears from 19 subjects with postlingual deafness exhibited "less modiolar proximity" based on our criteria. In this study, CDL showed significant variation among subjects. Importantly, a significant inverse correlation between spiral diameter and CDL (ρ = -0.581, p < 0.001) was found, showing that shorter CDLs have longer spiral diameter and less modiolar proximity. Moreover, further pull-back technique characterized by pulling out the electrode a little bit more in cases with shorter CDL, if not always, exhibited tighter modiolar proximity. CONCLUSION: A preponderance of less modiolar proximity of the electrode was observed exclusively among congenital deafness cases, demonstrated by a less tight spiral configuration even under the pull-back technique. Our data suggest that shorter CDL is associated with a less tight spiral configuration of slim modiolar electrodes postoperatively. Depending on the insertion technique, the differential degree of modiolar proximity of slim modiolar electrodes can be alleviated in cases with short CDL, which justifies cochlear duct length-based customized insertion of slim modiolar electrodes.

Computed Tomography-Based Measurements of the Cochlear Duct: Implications for Cochlear Implant Pitch Tuning.

OBJECTIVES: To determine the sources of variability for cochlear duct length (CDL) measurements for the purposes of fine-tuning cochlear implants (CI) and to propose a set of standardized landmarks for computed tomography (CT) pitch mapping. DESIGN: This was a retrospective cohort study involving 21 CI users at a tertiary referral center. The intervention involved flat-panel CT image acquisition and secondary reconstructions of CIs in vivo. The main outcome measures were CDL measurements, CI electrode localization measurements, and frequency calculations. RESULTS: Direct CT-based measurements of CI and intracochlear landmarks are methodologically valid, with a percentage of error of 1.0% ± 0.9%. Round window (RW) position markers (anterior edge, center, or posterior edge) and bony canal wall localization markers (medial edge, duct center, or lateral edge) significantly impact CDL calculations [F(2, 78) = 9.9, p < 0.001 and F(2, 78) = 1806, p < 0.001, respectively]. These pitch distortions could be as large as 11 semitones. When using predefined anatomical landmarks, there was still a difference between researchers [F(2, 78) = 12.5; p < 0.001], but the average variability of electrode location was reduced to differences of 1.6 semitones (from 11 semitones. CONCLUSIONS: A lack of standardization regarding RW and bony canal wall landmarks results in great CDL measurement variability and distorted pitch map calculations. We propose using the posterior edge of the RW and lateral bony wall as standardized anatomical parameters for CDL calculations in CI users to improve pitch map calculations. More accurate and precise pitch maps may improve CI-associated pitch outcomes.

Photobiomodulation with a wavelength > 800 nm induces morphological changes in stem cells within otic organoids and scala media of the cochlea.

Photobiomodulation (PBM) is a therapeutic approach to certain diseases based on light energy. Currently, stem cells (SCs) are being considered as putative treatments for previously untreatable diseases. One medical condition that could be treated using SCs is sensorineural hearing loss. Theoretically, if properly delivered and differentiated, SCs could replace lost hair cells in the cochlea. However, this is not currently possible due to the structural complexity and limited survival of SCs within the cochlea. PBM facilitates SC differentiation into other target cells in multiple lineages. Using light with a wavelength > 800 nm, which can penetrate the inner ear through the tympanic membrane, we assessed morphological changes of mouse embryonic stem cells (mESCs) during "otic organoid" generation, and within the scala media (SM) of the cochlea, after light energy stimulation. We observed enhanced differentiation, which was confirmed by an increased number of otic vesicles and increased cell attachment inside the SM. These results suggest that > 800-nm light affected the morphology of mESCs within otic organoids and SM of the cochlea. Based on our results, light energy could be used to enhance otic sensory differentiation, despite the structural complexity of the inner ear and limited survival time of SCs within the cochleae. Additional studies to refine the light energy delivery technology and maximize the effect on otic differentiation are required.

CT-scan contouring technique allows for direct and reliable measurements of the cochlear duct length: implication in cochlear implantation with straight electrode-arrays.

OBJECTIVES: The advent of hybrid electro-acoustic implants requires precise positioning of the electrode-array (EA) within the cochlea. The cochlea size, that is, the length of the cochlear scala tympani, is often indirectly estimated from distance A by Escudé's method. This technique has been confirmed by anatomical studies, in a bunch of cadaveric specimens, but it is not yet widely established in the field of computed tomography (CT). We compared cochlear duct length obtained by Escudé's method to those directly acquired on CT images. MATERIALS AND METHODS: The lengths of cochlear scala tympani were directly measured on CT scans by contouring the external cochlear wall (contouring technique-CoT). In fifteen patients implanted with a straight EA, the length of the EA and the measured length of the cochlea by the CoT were compared, to check the reliability of the CoT. Then, in 200 CT-scans, the length of the cochlear duct was measured by the CoT then compared to Escudé's method. RESULTS: In the 200 CT-scans which served for cochlear length measurements, a significant variability between the cochleae were observed, as expected. At 360°, the correlation between the measurements of the length of the cochlear scala tympani between the two techniques differed, with a difference of 0.2 ± 0.7 mm at 360° (extreme: 2 mm; p < 0.001) and 2.2 ± 1.2 mm at 540° (extreme: 5.6 mm; p < 0.001). CONCLUSION: The CoT can predict with accuracy the length of EA-insertion depth, more precisely than estimation methods such as Escudé's.

Five-year outcomes following hypofractionated stereotactic radiotherapy delivered in five fractions for acoustic neuromas: the mean cochlear dose may impact hearing preservation.

BACKGROUND: The aim of this study was to assess the clinical outcomes of acoustic neuromas (ANs) treated with hypofractionated stereotactic radiotherapy (hypo-FSRT) prescribed at a uniform dose. METHODS: Forty-seven patients with a unilateral AN were treated consecutively with hypo-FSRT between February 2007 and March 2012. Nineteen patients maintained a serviceable hearing status at the beginning of hypo-FSRT. The prescribed dose was 25 Gy delivered in five fractions per week to the isocenter, and the planning target volume was covered by the 80% isodose line. RESULTS: The median follow-up and audiometric follow-up periods were 61 and 52 months, respectively. The estimated tumor control rate at 5 years was 90% (95% CI 76-96). The existence of the cystic component before hypo-FSRT had a significantly worse impact on tumor control (p = 0.02). The estimated hearing preservation rates at 1, 3 and 5 years were 68% (95% CI 42-84), 41% (95% CI 20-62) and 36% (95% CI 15-57), respectively. A borderline significant difference was identified in the mean biological effective dose with an α/ß value of 3 Gy (BED3) to the ipsilateral cochlea between the preserved hearing and hearing loss groups (19 Gy vs. 28 Gy) (p = 0.08). CONCLUSIONS: Hypo-FSRT delivered in five fractions for unilateral ANs may achieve excellent tumor control with no severe facial or trigeminal complications. The mean BED3 in the cochlea may impact the hearing preservation rate. Therefore, the cochlear dose should be as low as possible.

On the accuracy of cochlear duct length measurement in computed tomographic images.

PURPOSE: Patient specific selection of cochlear implants would benefit from pre-operative knowledge of cochlear length. Several methods for its measurement or estimation have been described in literature. This study focused on the achievable accuracy in clinically available imaging. METHODS: Five simplified cochlea models milled into porcine bone were scanned in water using clinical cone beam computed tomography. Due to their well-known dimensions these phantoms served as gold standard for the length measurements. Each phantom was measured ten times using the custom software Comet. In addition, cochleae in ten image datasets taken indiscriminately from clinical routine were measured ten times each to test the precision under realistic conditions. The results were also compared to estimations based on the diameter of the basal turn (A value) as described in literature. RESULTS: Measurement accuracy of the phantoms' lengths was high (average error: - 0.2 mm; standard deviation: 0.3 mm). The pooled standard deviation for the measurements in clinical datasets was 0.6 mm. Errors resulted mainly from problems locating the helicotrema. The estimations differed on average - 1.7 to + 0.4 mm from the manual measurements and had standard deviations between 0.5 and 0.6 mm depending on the algorithm. CONCLUSIONS: The program Comet was successfully used to accurately measure the length of the cochlea models in clinically available imaging. The lower image quality of patient scans reduced the precision of the measurement. Estimations using the A value are a quicker alternative for averagely sized cochleae in cases where the lack of accuracy is tolerable.

Measuring cochlear duct length in Asian population: worth giving a thought!

INTRODUCTION: The anatomy of the cochlea forms the basis for a successful cochlear implantation. Cochlear duct length (CDL) is defined as the length of the scala media as measured from the middle of the round window to helicotrema. Preoperative measurement of CDL is particularly important when precise intracochlear electrode array placement is desired. It can be done both histologically and radiologically. Preoperative high-resolution computed tomography (HRCT) scan which forms an integral part of cochlear implant workup is a useful tool to calculate CDL using 3D reconstructions. METHOD: This study was done in SMS Medical College and Hospital, Jaipur, India, which is a tertiary care hospital and referral centre for cochlear implants. HRCT temporal bones of all children less than 6 years of age, with congenital bilateral severe-to-profound SNHL who were being worked up for cochlear implant were studied and analysed. 124 patients (56 females and 68 males) with hearing loss were evaluated for cochlear implantation. HRCT temporal bone of these patients was analysed and a variable A was measured which is defined as the linear measurement from the round window to the farthest point on the opposite wall of the cochlea on a reformatted CT scan slice. RESULTS: Mean of distance A for right ear of these patients was 8.10 mm (range 7.7-9.2 mm). Mean for the same in left ear of these patients was 8.14 mm (range 7.7-9.0 mm), giving an overall average of 8.12 mm. Using the formula, CDL = 4.16A-3.98, we calculated the length of cochlear duct. Mean cochlear duct length was 29.8 mm with a range from 28 to 34.3 mm. CONCLUSION: To the best of our knowledge, this is the first large sample study of cochlear length in population of this part of the world. A smaller cochlear length in this part of the world as compared to the Caucasian cochlear duct is a significant finding in understanding of the cochlear anatomy and physiology. It would also have great implications on the insertion depth in cochlear implantation.

Intracochlear Scala Media Pressure Measurement: Implications for Models of Cochlear Mechanics.

Models of the active cochlea build upon the underlying passive mechanics. Passive cochlear mechanics is based on physical and geometrical properties of the cochlea and the fluid-tissue interaction between the cochlear partition and the surrounding fluid. Although the fluid-tissue interaction between the basilar membrane and the fluid in scala tympani (ST) has been explored in both active and passive cochleae, there was no experimental data on the fluid-tissue interaction on the scala media (SM) side of the partition. To this aim, we measured sound-evoked intracochlear pressure in SM close to the partition using micropressure sensors. All the SM pressure data are from passive cochleae, likely because the SM cochleostomy led to loss of endocochlear potential. Thus, these experiments are studies of passive cochlear mechanics. SM pressure close to the tissue showed a pattern of peaks and notches, which could be explained as an interaction between fast and slow (i.e., traveling wave) pressure modes. In several animals SM and ST pressure were measured in the same cochlea. Similar to previous studies, ST-pressure was dominated by a slow, traveling wave mode at stimulus frequencies in the vicinity of the best frequency of the measurement location, and by a fast mode above best frequency. Antisymmetric pressure between SM and ST supported the classic single-partition cochlear models, or a dual-partition model with tight coupling between partitions. From the SM and ST pressure we calculated slow and fast modes, and from active ST pressure we extrapolated the passive findings to the active case. The passive slow mode estimated from SM and ST data was low-pass in nature, as predicted by cochlear models.

Making connections in the inner ear: recent insights into the development of spiral ganglion neurons and their connectivity with sensory hair cells.

In mammals, auditory information is processed by the hair cells (HCs) located in the cochlea and then rapidly transmitted to the CNS via a specialized cluster of bipolar afferent connections known as the spiral ganglion neurons (SGNs). Although many anatomical aspects of SGNs are well described, the molecular and cellular mechanisms underlying their genesis, how they are precisely arranged along the cochlear duct, and the guidance mechanisms that promote the innervation of their hair cell targets are only now being understood. Building upon foundational studies of neurogenesis and neurotrophins, we review here new concepts and technologies that are helping to enrich our understanding of the development of the nervous system within the inner ear.

Canonical Wnt signaling regulates the proliferative expansion and differentiation of fibrocytes in the murine inner ear.

Otic fibrocytes tether the cochlear duct to the surrounding otic capsule but are also critically involved in maintenance of ion homeostasis in the cochlea, thus, perception of sound. The molecular pathways that regulate the development of this heterogenous group of cells from mesenchymal precursors are poorly understood. Here, we identified epithelial Wnt7a and Wnt7b as possible ligands of Fzd-mediated ß-catenin (Ctnnb1)-dependent (canonical) Wnt signaling in the adjacent undifferentiated periotic mesenchyme (POM). Mice with a conditional deletion of Ctnnb1 in the POM exhibited a complete failure of fibrocyte differentiation, a severe reduction of mesenchymal cells surrounding the cochlear duct, loss of pericochlear spaces, a thickening and partial loss of the bony capsule and a secondary disturbance of cochlear duct coiling shortly before birth. Analysis at earlier stages revealed that radial patterning of the POM in two domains with highly condensed cartilaginous precursors and more loosely arranged inner mesenchymal cells occurred normally but that proliferation in the inner domain was reduced and cytodifferentiation failed. Cells with mis/overexpression of a stabilized form of Ctnnb1 in the entire POM mesenchyme sorted to the inner mesenchymal compartment and exhibited increased proliferation. Our analysis suggests that Wnt signals from the cochlear duct epithelium are crucial to induce differentiation and expansion of fibrocyte precursor cells. Our findings emphasize the importance of epithelial-mesenchymal signaling in inner ear development.

GATA3 controls the specification of prosensory domain and neuronal survival in the mouse cochlea.

HDR syndrome (also known as Barakat syndrome) is a developmental disorder characterized by hypoparathyroidism, sensorineural deafness and renal disease. Although genetic mapping and subsequent functional studies indicate that GATA3 haplo-insufficiency causes human HDR syndrome, the role of Gata3 in sensorineural deafness and auditory system development is largely unknown. In this study, we show that Gata3 is continuously expressed in the developing mouse inner ear. Conditional knockout of Gata3 in the developing inner ear disrupts the morphogenesis of mouse inner ear, resulting in a disorganized and shortened cochlear duct with significant fewer hair cells and supporting cells. Loss of Gata3 function leads to the failure in the specification of prosensory domain and subsequently, to increased cell death in the cochlear duct. Moreover, though the initial generation of cochleovestibular ganglion (CVG) cells is not affected in Gata3-null mice, spiral ganglion neurons (SGNs) are nearly depleted due to apoptosis. Our results demonstrate the essential role of Gata3 in specifying the prosensory domain in the cochlea and in regulating the survival of SGNs, thus identifying a molecular mechanism underlying human HDR syndrome.