Evaluation of a Slim Modiolar Electrode Array: A Temporal Bone Study.

HYPOTHESIS: Evaluation of the Slim Modiolar (SM) electrode in temporal bones (TB) will elucidate the electrode's insertion outcomes. BACKGROUND: The SM electrode was designed for atraumatic insertion into the scala tympani, for ideal perimodiolar positioning and with a smaller caliber to minimize interference with cochlear biological processes. METHODS: The SM electrode was inserted into TBs via a cochleostomy. First, the axial force of insertion was measured. Next, TBs were inserted under fluoroscopy to study insertion dynamics, followed by histologic evaluation of electrode placement and cochlear trauma. A subset of TBs were inserted with the Contour Advance (CA) electrode for comparison. RESULTS: Sixteen of 22 insertions performed to measure the axial force of insertion had flat or near zero insertion force profiles. Six insertions had increased insertion forces, which were attributed to improper sheath depth before electrode insertion. Under real-time fluoroscopy, 23 of 25 TBs had uneventful insertion and good perimodiolar placement. There was 1 scala vestibuli insertion due to suboptimal cochleostomy position and 1 tip roll over related to premature electrode deployment. When compared with the CA electrode, 14 of 15 insertions with the SM electrode resulted in a more perimodiolar electrode position. No evidence of trauma was found in histologic evaluation of the 24 TBs with scala tympani insertions. CONCLUSION: TB evaluation revealed that the SM electrode exerts minimal insertion forces on cochlear structures, produces no histologic evidence of trauma, and reliably assumes the perimodiolar position. Nonstandard cochleostomy location, improper sheath insertion depth, or premature deployment of the electrode may lead to suboptimal outcomes.

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 aµ-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 50µs.Main results. ANO thresholds are lower in ST (mean/std =µ/σ= 189/55µA) stimulation compared to SV (µ/σ= 323/119µA) stimulation. Contrary, CAT thresholds are higher for the ST array (µ/σ= 165/42µA) compared to the SV array (µ/σ= 122/46µA). 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.

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.

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 20 Hz and 1 kHz 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 140 eq. dB SPL at low frequencies ≤ 200 Hz to 90 eq. dB SPL at 1 kHz. 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.

Exploring Trauma Patterns and Contributing Factors With Slim Straight Electrode Array After Cochlear Implantation.

OBJECTIVE: To assess trauma patterns associated with the insertion of lateral wall electrode arrays. The study focused on 3 categories-scala tympani (ST), intermediate, and scala vestibuli (SV)-to identify traumatic patterns and contributing factors. STUDY DESIGN: Retrospective study. SETTING: Data from 106 cochlear implant recipients at a tertiary otologic center. METHODS: Demographic and surgical data were collected from recipients who underwent cochlear implantation manually and with RobOtol®. Measurements included cochlear dimensions, angular depth of insertion, and position of the first electrode. Three-dimensional reconstructions were used to analyze the electrode array location relative to the basilar membrane, categorized into ST, intermediate, and SV electrodes. Nontraumatic insertion was defined as all electrodes in the ST, while traumatic insertions had 1 or more electrodes in intermediate or SV locations. RESULTS: Out of 106 cases, 44% had nontraumatic and 56% had traumatic insertions. Demographic and surgical characteristics showed no association with traumatic insertions. A deeper position of the first electrode, relative to the round window, was associated with traumatic insertions (P = .03). Three trauma patterns were observed: distal (facing the apical electrodes), proximal (facing the middle electrodes around 180°), and distal/proximal. CONCLUSION: This study considers the intermediate position which could be associated with basilar membrane lesions. Risk zones for intracochlear trauma with lateral wall arrays were identified distally and proximally. Traumatic insertions were independently linked to deeper array placement. Future studies should explore whether gentler insertion, without insisting on further electrode array insertion depth, could reduce the trauma during cochlear implantation.

Cochlear aqueduct revisited: A histological study using human fetuses.

BACKGROUND AND AIM: The cochlear aqueduct (CA) connects between the perilymphatic space of the cochlea and the subarachnoid space in the posterior cranial fossa. The study aimed to examine 1) whether cavitation of the CA occurs on the subarachnoid side or the cochlear side and 2) the growth and/or degeneration of the CA and its concomitant vein. METHODS: We examined paraffin-embedded histological sections from human fetuses: 15 midterm fetuses (crown-rump length or CRL, 39-115 mm) and 12 near-term fetuses (CRL, 225-328 mm). RESULTS: A linear mesenchymal condensation, i.e., a likely candidate of the CA anlage, was observed without the accompanying vein at 9-10 weeks. The vein appeared until 15 weeks, but it was sometimes distant from the CA. At 10-12 weeks, the subarachnoid space (or the epidural space) near the glossopharyngeal nerve rapidly protruded into the CA anlage and reached the scala tympani, in which cavitation was gradually on-going but without epithelial lining. However, CA cavitation did not to occur in the anlage. At the opening to the scala, the epithelial-like lining of the CA lost its meningeal structure. At near-term, the CA was often narrowed and obliterated. CONCLUSION: The CA develops from meningeal tissues when the cavitation of the scala begins. The latter cavitation seemed to reduce tissue stiffness leading, to meningeal protrusion. The so-called anlage of CA might be a phylogenetic remnant of the glossopharyngeal nerve branch. A course of cochlear veins appears to be determined by a rule different from the CA development.

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

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

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.

Evaluation of insertion quality of a slim perimodiolar electrode array.

OBJECTIVES: The influence of cochlear morphology and electrode array design on scalar position and dislocation rates is of great interest in CI surgery. The aim of this study is to evaluate scalar position and specific points of dislocation in relation to cochlear morphology in patients implanted with a new slim perimodiolar electrode array. MATERIALS AND METHODS: Patients were implanted using the slim modiolar electrode array (= SMA) (= 532/632 electrode array of Cochlear™). Postoperative imaging was performed via cone beam computed tomography (CBCT) and the scans were analyzed regarding cochlear morphology (distances A and B and cochlear height), scalar location of the electrode array, basal insertion depth and apical insertion angle. Furthermore, electrode array design and surgical protocols were evaluated. RESULTS: 81 ears implanted with the SMA were retrospectively included. We evaluated 3 electrode array tip fold over intraoperatively via X-ray imaging and performed revision during the same surgery. The CBCT scans showed 76 initial scala tympani (ST) insertions without dislocation. Two ears showed a dislocated array, one at 77° and the other at 163°. Three arrays were inserted into scala vestibuli (SV) via cochleostomy. These patients showed no signs of obliteration. Cochlear morphology showed no influence on angular insertion depth and scalar position. CONCLUSIONS: The SMA showed a very low rate of scalar dislocations due to its slim electrode array design (2.7%). We could find a learning curve regarding the handling and the risk of dislocation and tip fold over with this electrode array. The rate of intraoperative tip fold over detection via X-ray imaging was 3.7%. Therefore, we highly recommend X-ray imaging and transimpedance matrix measurements within the surgery protocol. Scala vestibuli insertions happened in patients with cochleostomy only. We could identify two specific points of dislocation depending on electrode array design.

Development of Automated Tool for Electrode Array Insertion and its Study on Intracochlear Pressure.

Cochlear implantation is the most successful approach for people with profound sensorineural hearing loss. Manual insertion of the electrode array may result in damaging the soft tissue structures and basilar membrane. An automated electrode array insertion device is reported to be less traumatic in cochlear implant surgery. OBJECTIVES: The present work develops a simple, reliable, and compact device for automatically inserting the electrode array during cochlear implantation and test the device to observe intracochlear pressure during simulated electrode insertion. METHODS: The device actuates the electrode array by a roller mechanism. For testing the automated device, a straight cochlea having the dimension of the scala tympani and a model electrode is developed using a 3D printer. A pressure sensor is utilized to observe the pressure change at different insertional conditions. RESULTS: The electrode is inserted into a prototype cochlea at different speeds without any pause, and it is noticed that the pressure is increased with the depth of insertion of the electrode irrespective of the speed of electrode insertion. The rate of pressure change is observed to be increased exponentially with the speed of insertion. CONCLUSION: At an insertion speed of 0.15 mm/s, the peak pressure is observed to be 133 Pa, which can be further evaluated in anatomical models for clinical scenarios. LEVEL OF EVIDENCE: N/A Laryngoscope, 134:1388-1395, 2024.

[Insertion of a second electrode array-a rare complication of CI reimplantation. German version]. / Insertion eines zweiten Elektrodenträgers ­ eine seltene Komplikation bei CI-Reimplantation.

Due to a technical defect or a medical indication, it may be necessary to explant a cochlear implant. This case report shows that there is the risk of encountering a nonremovable electrode array-as described here from the scala tympani-during cochlear reimplantation. In the present case, insertion of a second electrode array into the free and nonobstructed scala vestibuli was successful. Nonetheless, the indication for reimplantation must be carefully considered, especially in patients with tolerable limitations with little or no loss of speech understanding. Furthermore, surgery should not be performed solely because an implant upgrade is desired.

Insertion of a second electrode array-a rare complication of CI reimplantation.

Due to a technical defect or a medical indication, it may be necessary to explant a cochlear implant. This case report shows that there is the risk of encountering a nonremovable electrode array-as described here from the scala tympani-during cochlear reimplantation. In the present case, insertion of a second electrode array into the free and nonobstructed scala vestibuli was successful. Nonetheless, the indication for reimplantation must be carefully considered, especially in patients with tolerable limitations with little or no loss of speech understanding. Furthermore, surgery should not be performed solely because an implant upgrade is desired.

Auditory outcomes after scala vestibuli array insertion are similar to those after scala tympani insertion 1 year after cochlear implantation.

PURPOSE: In cochlear implantation, a scala vestibuli (SV) insertion of an electrode array is a rare occurrence and is reported to be linked to poor hearing outcomes. Using the same electrode array, the auditory performance of patients with a complete SV location was compared with that of patients having a complete scala tympani (ST) location 1 year after implantation. METHODS: Thirty-three patients were included in this retrospective case-control study (SV, n = 12; ST, n = 21). The matching criteria were electrode array type, age at implantation, and duration of severe or profound deafness. The array location was analyzed using 3D reconstruction of postoperative CT scans. Postoperative audiological evaluation of the implanted ear was performed using pure-tone audiometry, speech recognition of monosyllabic words in quiet, and words and sentences in noise. RESULTS: On the preoperative CT scan, six patients in the SV group presented with both round window (RW) and ST ossification, three with RW ossification alone, and three with no RW ossification. Auditory performance did not differ between SV and ST groups 1 year after cochlear implantation. Speech recognition of words was 49 ± 7.6% and 56 ± 5.0% in quiet and 75 ± 9.5% and 66 ± 6.0% in noise in SV and ST groups, respectively. CONCLUSION: ST insertion is the gold standard that allows the three cochlear scalae to preserve scalar cochlear integrity. However, 1 year after implantation, a planned or unexpected SV insertion is not detrimental to hearing outcomes, providing similar auditory performance in quiet and noise to ST insertion.

Assessing the manufacturable 32-channel cochlear electrode array: evaluation results for clinical trials.

Reliability evaluation results of a manufacturable 32-channel cochlear electrode array are reported in this paper. Applying automated laser micro-machining process and a layer-by-layer silicone deposition scheme, authors developed the manufacturing methods of the electrode array for fine patterning and mass production. The developed electrode array has been verified through the requirements specified by the ISO Standard 14708-7. And the insertion trauma of the electrode array has been evaluated based on human temporal bone studies. According to the specified requirements, the electrode array was assessed through elongation & insulation, flexural, and fatigue tests. In addition, Temporal bone study was performed using eight fresh-frozen cadaver temporal bones with the electrode arrays inserted via the round window. Following soaking in saline condition, the impedances between conducting wires of the electrode array were measured over 100 kΩ (the pass/fail criterion). After each required test, it was shown that the electrode array maintained the electrical continuity and insulation condition. The average insertion angle of the electrode array inside the scala tympani was 399.7°. The human temporal bone studies exhibited atraumatic insertion rate of 60.3% (grade 0 or 1). The reliability of the manufacturable electrode array is successfully verified in mechanical, electrical, and histological aspects. Following the completion of a 32-channel cochlear implant system, the performance and stability of the 32-channel electrode array will be evaluated in clinical trials.

Incomplete Partition Type II Cochlear Malformations: Delineating the Three-Dimensional Structure from Digitized Human Histopathological Specimens.

HYPOTHESIS: There are clinically relevant differences in scalae anatomy and spiral ganglion neuron (SGN) quantity between incomplete partition type II (IP-II) and normal cochleae. BACKGROUND: IP-II is a commonly implanted cochlear malformation. Detailed knowledge of intracochlear three-dimensional (3D) morphology may assist with cochlear implant (CI) electrode selection/design and enable optimization of audiologic programming based on SGN maps. METHODS: IP-II (n = 11) human temporal bone histological specimens were identified from the National Institute on Deafness and Other Communication Disorders National Temporal Bone Registry and digitized. The cochlear duct, scalae, and surgically relevant anatomy were reconstructed in 3D. A machine learning algorithm was applied to map the location and number of SGNs. RESULTS: 3D scalae morphology of the basal turn was normal. Scala tympani (ST) remained isolated for 540 degrees before fusing with scala vestibuli. Mean ST volume reduced below 1 mm 2 after the first 340 degrees. Scala media was a distinct endolymphatic compartment throughout; mean ± standard deviation cochlear duct length was 28 ± 3 mm. SGNs were reduced compared with age-matched norms (mean, 48%; range, 5-90%). In some cases, SGNs failed to ascend Rosenthal's canal, remaining in an abnormal basalward modiolar location. Two forms of IP-II were seen: type A and type B. A majority (98-100%) of SGNs were located in the basal modiolus in type B IP-II, compared with 76 to 85% in type A. CONCLUSION: Hallmark features of IP-II cochleae include the following: 1) fusion of the ST and scala vestibuli at a mean of 540 degrees, 2) highly variable and overall reduced SGN quantity compared with normative controls, and 3) abnormal SGN distribution with cell bodies failing to ascend Rosenthal's canal.

Automatic electrode scalar location assessment after cochlear implantation using a novel imaging software.

As of today, image-based assessment of cochlear implant electrode array location is not part of the clinical routine. Low resolution and contrast of computer tomography (CT) imaging, as well as electrode array artefacts, prevent visibility of intracochlear structures and result in low accuracy in determining location of the electrode array. Further, trauma assessment based on clinical-CT images requires a uniform image-based trauma scaling. Goal of this study was to evaluate the accuracy of a novel imaging software to detect electrode scalar location. Six cadaveric temporal bones were implanted with Advanced Bionics SlimJ and Mid-Scala electrode arrays. Clinical-CT scans were taken pre- and postoperatively. In addition, micro-CTs were taken post-operatively for validation. The electrode scalar location rating done by the software was compared to the rating of two experienced otosurgeons and the micro-CT images. A 3-step electrode scalar location grading scale (0 = electrode in scala tympani, 1 = interaction of electrode with basilar membrane/osseous spiral lamina, 2 = translocation of electrode into scala vestibuli) was introduced for the assessment. The software showed a high sensitivity of 100% and a specificity of 98.7% for rating the electrode location. The correlation between rating methods was strong (kappa > 0.890). The software gives a fast and reliable method of evaluating electrode scalar location for cone beam CT scans. The introduced electrode location grading scale was adapted for assessing clinical CT images.

Effects of the Number of Channels and Channel Stimulation Rate on Speech Recognition and Sound Quality Using Precurved Electrode Arrays.

PURPOSE: This study investigated the relationship between the number of active electrodes, channel stimulation rate, and their interaction on speech recognition and sound quality measures while controlling for electrode placement. Cochlear implant (CI) recipients with precurved electrode arrays placed entirely within scala tympani and closer to the modiolus were hypothesized to be able to utilize more channels and possibly higher stimulation rates to achieve better speech recognition performance and sound quality ratings than recipients in previous studies. METHOD: Participants included seven postlingually deafened adult CI recipients with Advanced Bionics Mid-Scala electrode arrays confirmed to be entirely within scala tympani using postoperative computerized tomography. Twelve conditions were tested using four, eight, 12, and 16 electrodes and channel stimulation rates of 600 pulse per second (pps), 1,200 pps, and each participant's maximum allowable rate (1,245-4,800 pps). Measures of speech recognition and sound quality were acutely assessed. RESULTS: For the effect of channels, results showed no significant improvements beyond eight channels for all measures. For the effect of channel stimulation rate, results showed no significant improvements with higher rates, suggesting that 600 pps was sufficient for maximum speech recognition performance and sound quality ratings. However, across all conditions, there was a significant relationship between mean electrode-to-modiolus distance and all measures, suggesting that a lower mean electrode-to-modiolus distance was correlated with higher speech recognition scores and sound quality ratings. CONCLUSION: These findings suggest that even well-placed precurved electrode array recipients may not be able to take advantage of more than eight channels or higher channel stimulation rates (> 600 pps), but that closer electrode array placement to the modiolus correlates with better outcomes for these recipients.

Spread of the intracochlear electrical field: Implications for assessing electrode array location in cochlear implantation.

The electrode-generated intracochlear electrical field (EF) spreads widely along the scala tympani surrounded by poorly-conducting tissue and it can be measured with monopolar transimpedance matrix (TIMmp). Bipolar TIM (TIMbp) allows estimations of local potential differences. With TIMmp, the correct alignment of the electrode array can be assessed, and TIMbp may be useful in more subtle evaluations of the electrode array's intracochlear location. In this temporal bone study, we investigated the effect of the cross-sectional scala area (SA) and the electrode-medial-wall distance (EMWD) on both TIMmp and TIMbp using three types of electrode arrays. Also, multiple linear regressions based on the TIMmp and TIMbp measurements were used to estimate the SA and EMWD. Six cadaver temporal bones were consecutively implanted with a lateral-wall electrode array (Slim Straight) and with two different precurved perimodiolar electrode arrays (Contour Advance and Slim Modiolar) for variation in EMWD. The bones were imaged with cone-beam computed tomography with simultaneous TIMmp and TIMbp measurements. The results from imaging and EF measurements were compared. SA increased from apical to basal direction (r = 0.96, p < 0.001). Intracochlear EF peak negatively correlated with SA (r = -0.55, p < 0.001) irrespective of the EMWD. The rate of the EF decay did not correlate with SA but it was faster in the proximity of the medial wall than in more lateral positions (r = 0.35, p < 0.001). For a linear comparison between the EF decaying proportionally to squared distance and anatomic dimensions, a square root of inverse TIMbp was applied and found to be affected by both SA and EMWD (r = 0.44 and r = 0.49, p < 0.001 for both). A regression model confirmed that together TIMmp and TIMbp can be used to estimate both SA and EMWD (R2 = 0.47 and R2 = 0.44, respectively, p < 0.001 for both). In TIMmp, EF peaks grow from basal to apical direction and EF decay is steeper in the proximity of the medial wall than in more lateral positions. Local potentials measured via TIMbp correlate with both SA and EMWD. Altogether, TIMmp and TIMbp can be used to assess the intracochlear and intrascalar position of the electrode array, and they may reduce the need for intra- and postoperative imaging in the future.

Growing human-scale scala tympani-likein vitrocell constructs.

Emerging materials and electrode technologies have potential to revolutionise development of higher resolution next-generation, bionic devices. However, barriers associated with the extended timescales, regulatory constraints, and opportunity costs of preclinical and clinical studies, can inhibit such innovation. Development ofin vitromodels that mimic human tissues would provide an enabling platform to overcome many of these barriers in the product development pathway. This research aimed to develop human-scale tissue engineered cochlea models for high throughput evaluation of cochlear implants on the bench. Novel mould-casting techniques and stereolithography three-dimensional (3D) printing approaches to template hydrogels into spiral-shaped structures resembling the scala tympani were compared. While hydrogels are typically exploited to support 3D tissue-like structures, the challenge lies in developing irregular morphologies like the scala tympani, in which the cochlear electrodes are commonly implanted. This study successfully developed human-scale scala tympani-like hydrogel structures that support viable cell adhesion and can accommodate cochlear implants for future device testing.

Microneedles Facilitate Small-Volume Intracochlear Delivery Without Physiologic Injury in Guinea Pigs.

HYPOTHESIS: Microneedle-mediated intracochlear injection through the round window membrane (RWM) will facilitate intracochlear delivery, not affect hearing, and allow for full reconstitution of the RWM within 48 hours. BACKGROUND: We have developed polymeric microneedles that allow for in vivo perforation of the guinea pig RWM and aspiration of perilymph for diagnostic analysis, with full reconstitution of the RWM within 48 to 72 hours. In this study, we investigate the ability of microneedles to deliver precise volumes of therapeutics into the cochlea and assess the subsequent consequences on hearing. METHODS: Volumes of 1.0, 2.5, or 5.0 µL of artificial perilymph were injected into the cochlea at a rate of 1 µL/min. Compound action potential (CAP) and distortion product otoacoustic emission were performed to assess for hearing loss (HL), and confocal microscopy was used to evaluate the RWM for residual scarring or inflammation. To evaluate the distribution of agents within the cochlea after microneedle-mediated injection, 1.0 µL of FM 1-43 FX was injected into the cochlea, followed by whole mount cochlear dissection and confocal microscopy. RESULTS: Direct intracochlear injection of 1.0 µL of artificial perilymph in vivo , corresponding to about 20% of the scala tympani volume, was safe and did not result in HL. However, injection of 2.5 or 5.0 µL of artificial perilymph into the cochlea produced statistically significant high-frequency HL persisting 48 hours postperforation. Assessment of RWMs 48 hours after perforation revealed no inflammatory changes or residual scarring. FM 1-43 FX injection resulted in distribution of the agent predominantly in the basal and middle turns. CONCLUSION: Microneedle-mediated intracochlear delivery of small volumes relative to the volume of the scala tympani is feasible, safe, and does not cause HL in guinea pigs; however, injection of large volumes induces high-frequency HL. Injection of small volumes of a fluorescent agent across the RWM resulted in significant distribution within the basal turn, less distribution in the middle turn, and almost none in the apical turn. Microneedle-mediated intracochlear injection, along with our previously developed intracochlear aspiration, opens the pathway for precision inner ear medicine.