C-Phycocyanin Attenuates Noise-Induced Cochlear Synaptopathy via the Inhibition of Oxidative Stress and Intercellular Adhesion Molecule-1 in the Cochlea.

The synapses between inner hair cells (IHCs) and spiral ganglion neurons (SGNs) are the most vulnerable structures in the noise-exposed cochlea. Cochlear synaptopathy results from the disruption of these synapses following noise exposure and is considered the main cause of poor speech understanding in noisy environments, even when audiogram results are normal. Cochlear synaptopathy leads to the degeneration of SGNs if damaged IHC-SGN synapses are not promptly recovered. Oxidative stress plays a central role in the pathogenesis of cochlear synaptopathy. C-Phycocyanin (C-PC) has antioxidant and anti-inflammatory activities and is widely utilized in the food and drug industry. However, the effect of the C-PC on noise-induced cochlear damage is unknown. We first investigated the therapeutic effect of C-PC on noise-induced cochlear synaptopathy. In vitro experiments revealed that C-PC reduced the H2O2-induced generation of reactive oxygen species in HEI-OC1 auditory cells. H2O2-induced cytotoxicity in HEI-OC1 cells was reduced with C-PC treatment. After white noise exposure for 3 h at a sound pressure of 118 dB, the guinea pigs intratympanically administered 5 µg/mL C-PC exhibited greater wave I amplitudes in the auditory brainstem response, more IHC synaptic ribbons and more IHC-SGN synapses according to microscopic analysis than the saline-treated guinea pigs. Furthermore, the group treated with C-PC had less intense 4-hydroxynonenal and intercellular adhesion molecule-1 staining in the cochlea compared with the saline group. Our results suggest that C-PC improves cochlear synaptopathy by inhibiting noise-induced oxidative stress and the inflammatory response in the cochlea.

A Guinea Pig Model Suggests That Objective Assessment of Acoustic Hearing Preservation in Human Ears With Cochlear Implants Is Confounded by Shifts in the Spatial Origin of Acoustically Evoked Potential Measurements Along the Cochlear Length.

OBJECTIVES: Our recent empirical findings have shown that the auditory nerve compound action potential (CAP) evoked by a low-level tone burst originates from a narrow cochlear region tuned to the tone burst frequency. At moderate to high sound levels, the origins shift to the most sensitive audiometric regions rather than the extended high-frequency regions of the cochlear base. This means that measurements evoked from extended high-frequency sound stimuli can shift toward the apex with increasing level. Here we translate this study to understand the spatial origin of acoustically evoked responses from ears that receive cochlear implants, an emerging area of research and clinical practice that is not completely understood. An essential step is to first understand the influence of the cochlear implant in otherwise naive ears. Our objective was to understand how function of the high-frequency cochlear base, which can be excited by the intense low-frequency sounds that are frequently used for objective intra- and postoperative monitoring, can be influenced by the presence of the cochlear implant. DESIGN: We acoustically evoked responses and made measurements with an electrode placed near the guinea pig round window. The cochlear implant was not utilized for either electrical stimulation or recording purposes. With the cochlear implant in situ, CAPs were acoustically evoked from 2 to 16 kHz tone bursts of various levels while utilizing the slow perfusion of a kainic acid solution from the cochlear apex to the cochlear aqueduct in the base, which sequentially reduced neural responses from finely spaced cochlear frequency regions. This cochlear perfusion technique reveals the spatial origin of evoked potential measurements and provides insight on what influence the presence of an implant has on acoustical hearing. RESULTS: Threshold measurements at 3 to 11 kHz were elevated by implantation. In an individual ear, thresholds were elevated and lowered as cochlear implant was respectively inserted and removed, indicative of "conductive hearing loss" induced by the implant. The maximum threshold elevation occurred at most sensitive region of the naive guinea pig ear (33.66 dB at 8 kHz), making 11 kHz the most sensitive region to acoustic sounds for guinea pig ears with cochlear implants. Conversely, the acute implantation did not affect the low-frequency, 500 Hz thresholds and suprathreshold function, as shown by the auditory nerve overlapped waveform. As the sound pressure level of the tone bursts increased, mean data show that the spatial origin of CAPs along the cochlear length shifted toward the most sensitive cochlear region of implanted ears, not the extended high-frequency cochlear regions. However, data from individual ears showed that after implantation, measurements from moderate to high sound pressure levels originate in places that are unique to each ear. CONCLUSIONS: Alterations to function of the cochlear base from the in situ cochlear implant may influence objective measurements of implanted ears that are frequently made with intense low-frequency sound stimuli. Our results from guinea pigs advance the interpretation of measurements used to understand how and when residual acoustic hearing is lost in human ears receiving a cochlear implant.

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.

Estimating vibration artifacts in preclinical experimental assessment of actuator efficiency in bone-conduction hearing devices.

OBJECTIVES: Test feasibility of a means to distinguish artifact from relevant signal in an experimental method for pre-clinical assessment of bone conduction (BC) stimulation efficiency based on measurement of intracochlear pressure (ICP). METHODS: Experiments were performed on fresh-frozen human temporal bones and cadaver heads. In a first step, fiber optic pressure sensors inserted into the cochlea through cochleostomies were intentionally vibrated to generate relative motion versus the stationary specimen, and the resulting ICP artifact recorded, before and after attaching the sensor fiber to the bone with glue. In a second step, BC stimulation was applied in the conventional location for a commercial bone anchored implant, as well as two alternative locations closer to the otic capsule. Again, ICP was recorded and compared with an estimated artifact, calculated from the previous measurements with intentional vibration of the fiber. RESULTS: Intentional vibration of the sensor fiber creates relative motion between fiber and bone, as intended, and causes an ICP signal. The stimulus does not create substantial promontory vibration, indicating that the measured ICP is all artifact, i.e. would not occur if the sensor were not in place. Fixating the sensor fiber to the bone with glue reduces the ICP artifact by at least 20 dB. BC stimulation also creates relative motion between sensor fiber and bone, as expected, from which an estimated ICP artifact level can be calculated. The ICP signal measured during BC stimulation is well above the estimated artifact, at least in some specimens and at some frequencies, indicating "real" cochlear stimulation, which would result in an auditory percept in a live subject. Stimulation at the alternative locations closer to the otic capsule appear to result in higher ICP (no statistical analysis performed), indicating a trend towards more efficient stimulation than at the conventional location. CONCLUSIONS: Intentional vibration of the fiber optic sensor for measurement of ICP can be used to derive an estimate of the artifact to be expected when measuring ICP during BC stimulation, and to characterize the effectiveness of glues or other means of reducing the artifact caused by relative motion of fiber and bone.

Modified Experimental Conditions for Noise-Induced Hearing Loss in Mice and Assessment of Hearing Function and Outer Hair Cell Damage.

An animal model of noise-induced hearing loss (NIHL) is useful for pathologists, therapists, pharmacologists, and hearing researchers to thoroughly understand the mechanism of NIHL, and subsequently optimize the corresponding treatment strategies. This study aims to create an improved protocol for developing a mouse model of NIHL. Male C57BL/6J mice were used in this study. Unanesthetized mice were exposed to loud noises (1 and 6 kHz, presented simultaneously at 115-125 dB SPL-A) continuously for 6 h per day for 5 consecutive days. Auditory function was assessed 1 day and 1 week after noise exposure, using auditory brainstem response (ABR). After the ABR measurement, the mice were sacrificed, and their organs of Corti were collected for immunofluorescence staining. From the auditory brainstem response (ABR) measurements, significant hearing loss was observed 1 day after noise exposure. After 1 week, the hearing thresholds of the experimental mice decreased to ~80 dB SPL, which was still a significantly higher level than the control mice (~40 dB SPL). From the results of immunofluorescence imaging, outer hair cells (OHCs) were shown to be damaged. In summary, we created a model of NIHL using male C57BL/6J mice. A new and simple device for generating and delivering pure-tone noise was developed and then employed. Quantitative measurements of hearing thresholds and morphological confirmation of OHC damage both demonstrated that the applied noise successfully induced an expected hearing loss.

Labyrinthine Fluid Signal Intensity on T2-Weighted MR Imaging in Patients With Vestibular Schwannomas Undergoing Proton Radiotherapy: A Longitudinal Assessment.

OBJECTIVE: In vestibular schwannoma patients, a loss of signal intensity (SI) on T2-weighted magnetic resonance imaging (MRI) has been reported within the ipsilateral labyrinth. The purpose of this study was to quantitatively evaluate the occurrence and course of this intensity loss in relation to proton radiotherapy and its possible association with hearing loss. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary referral center. PATIENTS: Patients who received proton therapy for a vestibular schwannoma and underwent at least two high-resolution T2-weighted cisternographic sequence (constructive interference in steady state/fast imaging employing steady-state acquisition/DRIVE) MRIs and audiometry assessments. MAIN OUTCOME MEASURES: Relative T2 SIs from the vestibules and basal/apical cochlear turns of the labyrinth, bilaterally. RESULTS: Ninety-five MRI scans from 34 patients were included. The apical turn of the ipsilateral cochlea showed a lower mean cochlear SI than on the contralateral side (±3.5 versus 5.0). The mean relative cochlear SI did not significantly change after proton radiotherapy. The ipsilateral vestibule showed a higher SI than the cochlea. The relative mean cochlear SI was not directly correlated to (the degree of) hearing loss before or after proton radiotherapy, nor did it predict future hearing loss. CONCLUSION: The relative mean cochlear SI on cisternographic T2-MRI in vestibular schwannoma patients is diminished on the treated side, when compared with the ipsilateral vestibule and the contralateral cochlea/vestibule. The SI of the ipsilateral cochlea does not further decrease after proton radiotherapy and seems to be related to the tumor rather than the therapy. The diminished cochlear SI does not correlate with subsequent loss of hearing.

Volumetry improves the assessment of the vestibular aqueduct size in inner ear malformation.

OBJECTIVES: Enlarged vestibular aqueduct (EVA) is a common finding associated with inner ear malformations (IEM). However, uniform radiologic definitions for EVA are missing and various 2D-measurement methods to define EVA have been reported. This study evaluates VA volume in different types of IEM and compares 3D-reconstructed VA volume to 2D-measurements. METHODS: A total of 98 high-resolution CT (HRCT) data sets from temporal bones were analyzed (56 with IEM; [cochlear hypoplasia (CH; n = 18), incomplete partition type I (IPI; n = 12) and type II (IPII; n = 11) and EVA (n = 15)]; 42 controls). VA diameter was measured in axial images. VA volume was analyzed by software-based, semi-automatic segmentation and 3D-reconstruction. Differences in VA volume between the groups and associations between VA volume and VA diameter were assessed. Inter-rater-reliability (IRR) was assessed using the intra-class-correlation-coefficient (ICC). RESULTS: Larger VA volumes were found in IEM compared to controls. Significant differences in VA volume between patients with EVA and controls (p < 0.001) as well as between IPII and controls (p < 0.001) were found. VA diameter at the midpoint (VA midpoint) and at the operculum (VA operculum) correlated to VA volume in IPI (VA midpoint: r = 0.78, VA operculum: r = 0.91), in CH (VA midpoint: r = 0.59, VA operculum: r = 0.61), in EVA (VA midpoint: r = 0.55, VA operculum: r = 0.66) and in controls (VA midpoint: r = 0.36, VA operculum: r = 0.42). The highest IRR was found for VA volume (ICC = 0.90). CONCLUSIONS: The VA diameter may be an insufficient estimate of VA volume, since (1) measurement of VA diameter does not reliably correlate with VA volume and (2) VA diameter shows a lower IRR than VA volume. 3D-reconstruction and VA volumetry may add information in diagnosing EVA in cases with or without additional IEM.

Monitoring Cochlear Health With Intracochlear Electrocochleography During Cochlear Implantation: Findings From an International Clinical Investigation.

OBJECTIVES: Electrocochleography (ECochG) is emerging as a tool for monitoring cochlear function during cochlear implant (CI) surgery. ECochG may be recorded directly from electrodes on the implant array intraoperatively. For low-frequency stimulation, its amplitude tends to rise or may plateau as the electrode is inserted. The aim of this study was to explore whether compromise of the ECochG signal, defined as a fall in its amplitude of 30% or more during insertion, whether transient or permanent, is associated with poorer postoperative acoustic hearing, and to examine how preoperative hearing levels may influence the ability to record ECochG. The specific hypotheses tested were threefold: (a) deterioration in the pure-tone average of low-frequency hearing at the first postoperative follow-up interval (follow-up visit 1 [FUV1], 4 to 6 weeks) will be associated with compromise of the cochlear microphonic (CM) amplitude during electrode insertion (primary hypothesis); (b) an association is observed at the second postoperative follow-up interval (FUV2, 3 months) (secondary hypothesis 1); and (c) the CM response will be recorded earlier during electrode array insertion when the preoperative high-frequency hearing is better (secondary hypothesis 2). DESIGN: International, multi-site prospective, observational, between groups design, targeting 41 adult participants in each of two groups, (compromised CM versus preserved CM). Adult CI candidates who were scheduled to receive a Cochlear Nucleus CI with a Slim Straight or a Slim Modiolar electrode array and had a preoperative audiometric low-frequency average thresholds of ≤80 dB HL at 500, 750, and 1000 Hz in the ear to be implanted, were recruited from eight international implant sites. Pure tone audiometry was measured preoperatively and at postoperative visits (FUV1 and follow-up visit 2 [FUV2]). ECochG was measured during and immediately after the implantation of the array. RESULTS: From a total of 78 enrolled individuals (80 ears), 77 participants (79 ears) underwent surgery. Due to protocol deviations, 18 ears (23%) were excluded. Of the 61 ears with ECochG responses, amplitudes were < 1 µV throughout implantation for 18 ears (23%) and deemed "unclear" for classification. EcochG responses >1 µV in 43 ears (55%) were stable throughout implantation for 8 ears and compromised in 35 ears. For the primary endpoint at FUV1, 7/41 ears (17%) with preserved CM had a median hearing loss of 12.6 dB versus 34/41 ears (83%) with compromised CM and a median hearing loss of 26.9 dB ( p < 0.014). In assessing the practicalities of measuring intraoperative ECochG, the presence of a measurable CM (>1 µV) during implantation was dependent on preoperative, low-frequency thresholds, particularly at the stimulus frequency (0.5 kHz). High-frequency, preoperative thresholds were also associated with a measurable CM > 1 µV during surgery. CONCLUSIONS: Our data shows that CM drops occurring during electrode insertion were correlated with significantly poorer hearing preservation postoperatively compared to CMs that remained stable throughout the electrode insertion. The practicality of measuring ECochG in a large cohort is discussed, regarding the suggested optimal preoperative low-frequency hearing levels ( < 80 dB HL) considered necessary to obtain a CM signal >1 µV.

Novel Multiportal Approach to the Internal Auditory Canal for Hearing-Preserving Surgery: Feasibility Assessment in Dissections.

OBJECTIVE: State-of-the-art, minimally invasive endoscopic transcanal surgery of the internal auditory canal (IAC) sacrifices the cochlea with complete hearing loss. With a combination of the transcanal infracochlear and transmastoid retrolabyrinthine approaches, we aim to preserve hearing and enable minimally invasive surgical treatment of vestibular schwannoma. In this study, we investigate the anatomical indications and the feasibility of both approaches in dissections, in human whole head specimens. METHODS: We operated whole head anatomical specimens with a four-handed technique, using the retrolabyrinthine approach as the main surgical corridor and the infracochlear approach for endoscopic visualization. We tested 4 different powered surgical systems. We collected intraoperative data on the size of the access windows, the surgical freedom, and the exposed area of the IAC. Finally, we evaluated the outcome in postoperative computed tomography scans. RESULTS: Six out of 14 sides were anatomically suitable and qualified for the surgery based on preoperative computed tomography. In all attempted sides, the IAC could be reached and opened, leaving the ossicular chain and the labyrinth intact. 51%-75% of the length and 22%-40% of the circumference of the IAC could be exposed. All tested instruments were beneficial at different stages of the surgery. The four-handed technique enabled good maneuverability of the instruments. CONCLUSIONS: The combined multiportal approach to the IAC is feasible with a good surgical exposure and full anatomical preservation of hearing. State-of-the-art surgical instruments in specimens with suitable anatomy are sufficient to perform this approach.

A new method of preoperative assessment of correct electrode array alignment based on post-operative measurements in a cochlear implanted cohort.

PURPOSE: During cochlear implantation surgery, a range of complications may occur such as tip fold-over. We recently developed a method to estimate the insertion orientation of the electrode array. The aim of the study was to determine the optimal angle of orientation in a cohort of cochlear implanted patients. METHODS: On eighty-five CT scans (80 uncomplicated insertions and 5 cases with tip fold-over), location of the electrode array's Insertion Guide (IG), Orientation marker (OM) and two easily identifiable landmarks (the round window (RW) and the incus short process (ISP)) were manually marked. The angle enclosed by ISP-RW line and the Cochlear™ Slim Modiolar electrode array's OM line determined the electrode array insertion angle. RESULTS: The average insertion angle was 45.0-47.2° ± 10.4-12° SD and was validated with 98% confidence interval. Based on the measurements obtained, patients' sex and age had no impact on the size of this angle. Although the angles of the tip fold-over cases (44.9°, 46.9°, 34.2°, 54.3°, 55.9°) fell within this average range, the further it diverted from the average it increased the likelihood for tip fold-over. CONCLUSION: Electrode array insertion in the individually calculated angle relative to the visible incus short process provides a useful guide for the surgeon when aiming for the optimal angle, and potentially enhances good surgical outcomes. Our results show that factors other than the orientation angle may additionally contribute to failures in implantation when the Slim Modiolar electrode is used.

Postoperative radiological assessment of the mastoid facial canal in cochlear implant patients in correlation with facial nerve stimulation.

OBJECTIVES: To correlate the radiological assessment of the mastoid facial canal in postoperative cochlear implant (CI) cone-beam CT (CBCT) and other possible contributing clinical or implant-related factors with postoperative facial nerve stimulation (FNS) occurrence. METHODS: Two experienced radiologists evaluated retrospectively 215 postoperative post-CI CBCT examinations. The mastoid facial canal diameter, wall thickness, distance between the electrode cable and mastoid facial canal, and facial-chorda tympani angle were assessed. Additionally, the intracochlear position and the insertion angle and depth of electrodes were evaluated. Clinical data were analyzed for postoperative FNS within 1.5-year follow-up, CI type, onset, and causes for hearing loss such as otosclerosis, meningitis, and history of previous ear surgeries. Postoperative FNS was correlated with the measurements and clinical data using logistic regression. RESULTS: Within the study population (mean age: 56 ± 18 years), ten patients presented with FNS. The correlations between FNS and facial canal diameter (p = 0.09), wall thickness (p = 0.27), distance to CI cable (p = 0.44), and angle with chorda tympani (p = 0.75) were statistically non-significant. There were statistical significances for previous history of meningitis/encephalitis (p = 0.001), extracochlear-electrode-contacts (p = 0.002), scala-vestibuli position (p = 0.02), younger patients' age (p = 0.03), lateral-wall-electrode type (p = 0.04), and early/childhood onset hearing loss (p = 0.04). Histories of meningitis/encephalitis and extracochlear-electrode-contacts were included in the first two steps of the multivariate logistic regression. CONCLUSION: The mastoid-facial canal radiological assessment and the positional relationship with the CI electrode provide no predictor of postoperative FNS. Histories of meningitis/encephalitis and extracochlear-electrode-contacts are important risk factors. KEY POINTS: • Post-operative radiological assessment of the mastoid facial canal and the positional relationship with the CI electrode provide no predictor of post-cochlear implant facial nerve stimulation. • Radiological detection of extracochlear electrode contacts and the previous clinical history of meningitis/encephalitis are two important risk factors for postoperative facial nerve stimulation in cochlear implant patients. • The presence of scala vestibuli electrode insertion as well as the lateral wall electrode type, the younger patient's age, and early onset of SNHL can play important role in the prediction of post-cochlear implant facial nerve stimulation.

Assessment of cochlear electrophysiology in typically developing children and children with auditory processing disorder.

OBJECTIVE: Children with auditory processing disorder (APD) are reported to have abnormal auditory brainstem responses (ABR) but little is understood about their cochlear integrity. Poor cochlear integrity can affect neural responses. In this study, cochlear and auditory brainstem integrity was investigated in children with APD. METHOD: Twenty children with APD, sixteen typically developing children and twenty adults participated in this study. Click evoked electrocochleography (ECochG) and ABRs were recorded from all the participants. Cochlear responses were analyzed using a) latency and amplitude of summating potential; action potential, b) transmission time between summating potential and action potential, c) summating potential/action potential amplitude ratio and d) action potential latency difference to condensation and rarefaction polarity. Amplitude in the ABR components was examined. RESULTS: Children with APD showed similar cochlear function to the typically developing children. There were no significant differences in wave I amplitude between children with APD and typically developing children. However, wave V amplitude was significantly reduced in children with APD compared to typically developing children. CONCLUSION: In the absence of any functional differences in the cochlea, children with APD can show poor amplitude in the later components of the ABR. The ABR anomalies observed in children with APD arise due to poor neural processing, possibly after the first auditory synapse.

Practicable assessment of cochlear size and shape from clinical CT images.

There is considerable interpersonal variation in the size and shape of the human cochlea, with evident consequences for cochlear implantation. The ability to characterize a specific cochlea, from preoperative computed tomography (CT) images, would allow the clinician to personalize the choice of electrode, surgical approach and postoperative programming. In this study, we present a fast, practicable and freely available method for estimating cochlear size and shape from clinical CT. The approach taken is to fit a template surface to the CT data, using either a statistical shape model or a locally affine deformation (LAD). After fitting, we measure cochlear size, duct length and a novel measure of basal turn non-planarity, which we suggest might correlate with the risk of insertion trauma. Gold-standard measurements from a convenience sample of 18 micro-CT scans are compared with the same quantities estimated from low-resolution, noisy, pseudo-clinical data synthesized from the same micro-CT scans. The best results were obtained using the LAD method, with an expected error of 8-17% of the gold-standard sample range for non-planarity, cochlear size and duct length.

Assessment of cochlear toxicity in response to chronic 3,3'-iminodipropionitrile in mice reveals early and reversible functional loss that precedes overt histopathology.

The peripheral auditory and vestibular systems rely on sensorineural structures that are vulnerable to ototoxic agents that cause hearing loss and/or equilibrium deficits. Although attention has focused on hair cell loss as the primary pathology underlying ototoxicity, evidence from the peripheral vestibular system indicates that hair cell loss during chronic exposure is preceded by synaptic uncoupling from the neurons and is potentially reversible. To determine if synaptic pathology also occurs in the peripheral auditory system, we examined the extent, time course, and reversibility of functional and morphological alterations in cochleae from mice exposed to 3,3'-iminodipropionitrile (IDPN) in drinking water for 2, 4 or 6 weeks. Functionally, IDPN exposure caused progressive high- to low-frequency hearing loss assessed by measurement of auditory brainstem response wave I absolute thresholds and amplitudes. The extent of hearing loss scaled with the magnitude of vestibular dysfunction assessed behaviorally. Morphologically, IDPN exposure caused progressive loss of outer hair cells (OHCs) and synapses between the inner hair cells (IHCs) and primary auditory neurons. In contrast, IHCs were spared from ototoxic damage. Importantly, hearing loss consistent with cochlear synaptopathy preceded loss of OHCs and synapses and, moreover, recovered if IDPN exposure was stopped before morphological pathology occurred. Our observations suggest that synaptic uncoupling, perhaps as an early phase of cochlear synaptopathy, also occurs in the peripheral auditory system in response to IDPN exposure. These findings identify novel mechanisms that contribute to the earliest stages of hearing loss in response to ototoxic agents and possibly other forms of acquired hearing loss.

Utility and value of pre-operative CT and MRI for cochlear implantation in the elderly.

PURPOSE: To determine the utility and value of pre-operative imaging among the elderly population ≥70 y.o. with bilateral progressive sensorineural hearing loss undergoing cochlear implantation. MATERIALS AND METHODS: A retrospective, cross-sectional review was performed at a tertiary referral center between 2010 and 2018 including patients ≥70 y.o. with bilateral presbycusis who underwent preoperative imaging and cochlear implantation. Primary outcome was whether pre-operative imaging changed the surgeon's surgical plan such as side of implant or abort procedure entirely. Patient characteristics including age, sex, side of implant, imaging modality, whether imaging changed surgical plan, and surgical complications were reviewed. One-way analysis of variance with post-hoc tests using the Bonferroni and Fisher's exact test were used to examine differences between groups. Secondary outcome was cost of preoperative imaging. RESULTS: One hundred thirty-three patients (mean age 79.38 [5.51 SD]) who underwent a total of 142 surgical cases and 147 total scans. There were 92, 27, and 14 patients who underwent CT, MRI, or both, respectfully (n=133). Of the 142 implants that were placed, preoperative imaging did not reveal a contraindication to placing implant on one side over another. Total cost of imaging was $29,694. Estimated cost if 20% of cochlear implant eligible patients ≥70 y.o. underwent imaging is $7,763,490. CONCLUSION: Decreasing unnecessary preoperative imaging can potentially decrease cost in cochlear implantation. In this sample, preoperative imaging did not affect the surgeon's choice of which side to operate on. However, imaging may provide an anatomic roadmap and contribute to either surgical confidence or caution. With the increasing amount of cochlear implant eligible elderly adults, preoperative imaging needs to be more clearly defined in this unique population.

Quantitative assessment of cochlear and vestibular ganglion neurons in temporal bones with chronic otitis media.

PURPOSE: In this study, we aimed to determine whether or not COM leads to loss of spiral and Scarpa ganglion neurons. METHODS: From the human temporal bone (HTB) collection at the University of Minnesota we selected human temporal bones with COM, defined as the presence of clinically intractable tissue abnormalities in the middle ear (cholesteatoma, perforation of the eardrum, granulation tissue, fibrosis, tympanosclerosis, and cholesterol granuloma). We also selected HTBs from donors with no ear diseases as controls. We quantitatively analyzed the number of spiral and Scarpa ganglion cells and compared the results obtained in the control and study groups. RESULTS: In both COM and control groups we observed a significant negative correlation between age and number of both spiral (R = -0.632; P < 0.001; 95% CI - 0.766 to - 0.434) and Scarpa ganglion (R = - 0.404; P = 0.008; 95% CI - 0.636 to - 0.051) cells. We did not find any significant differences in the number of spiral ganglion cells (in total or per segment) or in the density of Scarpa ganglion cells (in each vestibular nerve or both) in the COM group as compared with controls (P > 0.05). CONCLUSIONS AND RELEVANCE: Our results did not demonstrate significant loss of cochlear or vestibular peripheral ganglion neuron loss in HTBs with COM as compared with controls.

Use of the auditory brainstem response for assessment of cochlear synaptopathy in humans.

Although clinical use of the auditory brainstem response (ABR) to detect retrocochlear disorders has been largely replaced by imaging in recent years, the discovery of cochlear synaptopathy has thrown this foundational measure of auditory function back into the spotlight. Whereas modern imaging now allows for the noninvasive detection of vestibular schwannomas, imaging technology is not currently capable of detecting cochlear synaptopathy, the loss of the synaptic connections between the inner hair cells and afferent auditory nerve fibers. However, animal models indicate that the amplitude of the first wave of the ABR, a far-field evoked potential generated by the synchronous firing of auditory nerve fibers, is highly correlated with synaptic integrity. This has led to many studies investigating the use of the ABR as a metric of synaptopathy in humans. However, these studies have yielded mixed results, leading to a lack of consensus about the utility of the ABR as an indicator of synaptopathy. This review summarizes the animal and human studies that have investigated the ABR as a measure of cochlear synaptic function, discusses factors that may have contributed to the mixed findings and the lessons learned, and provides recommendations for future use of this metric in the research and clinical settings.

Towards effective assessment of normal hearing function from ABR using a time-variant sweep-tone stimulus approach.

Objective. The auditory brainstem response (ABR) audiometry is a means of assessing the functional status of the auditory neural pathway in the clinic. The conventional click ABR test lacks good neural synchrony and it mainly evaluates high-frequency hearing while the common tone-burst ABR test only detects hearing loss of a certain frequency at a time. Additionally, the existing chirp stimuli are designed based on average data of cochlear characteristics, ignoring individual differences amongst subjects.Approach. Therefore, this study designed a new stimulus approach based on a sweep-tone concept with a time variant and spectrum characteristics that could be customized based on an individual's cochlear characteristics. To validate the efficiency of the proposed method, we compared its performance with the click and tone-bursts using ABR recordings from 11 normal-hearing adults.Main results. Experimental results showed that the proposed sweep-tone ABR achieved a higher amplitude compared with those elicited by the click and tone-bursts. When the stimulus level or rate was varied, the sweep-tone ABR consistently elicited a larger response than the corresponding click ABR. Moreover, the sweep-tone ABR appeared earlier than the click ABR under the same conditions. Specifically, the mean wave V peak-to-peak amplitude of the sweep-tone ABR was 1.3 times that of the click ABR at 70 dB nHL (normal hearing level) and a rate of 20 s-1, in which the former saved 40% of test time.Significance. In summary, the proposed sweep-tone approach is found to be more efficient than the traditional click and tone-burst in eliciting ABR.

Assessment of Angular Insertion-Depth of Bilateral Cochlear Implants Using Plain X-ray Scans.

OBJECTIVE: To evaluate in cochlear implant patients, the feasibility and reliability of angular depth of insertion (aDOI) measurements using plain x-ray scans. STUDY DESIGN: Retrospective study where three observers independently evaluated and compared intraoperative anterior-posterior and oblique x-ray scans. SETTING: A tertiary pediatric medical center. PATIENTS: Included were 50 children (100 ears) who underwent bilateral simultaneous cochlear implantation during 2008 to 2015. MAIN OUTCOME MEASURES: Inter-rater agreement of aDOI measured in plain x-ray scans; effect of head position on measured aDOI; and symmetry of aDOI between patients' ears in bilateral simultaneous cochlear implantations. RESULTS: Differences in the average aDOI measurements among the three observers ranged between 2 and 7 degrees. There was high inter-rater agreement (R = 0.99, p < 0.01) among all observers, and strong correlations between each pair of observers (0.92-0.99). Head rotation of 45 degrees (between the two views) resulted in a median difference in aDOI of 14 degrees, with excellent correlation among the observers. The rate of asymmetry was high, with a median difference of 39 degrees and up to 220 degrees between ears. CONCLUSIONS: Assessment of aDOI using intraoperative plain x-rays is efficient and reliable. The effect of head positioning on measurement is small. Further studies are needed to evaluate the effect of aDOI and insertion symmetry on functional outcomes.

Comparison between high-resolution 3D-IR with real reconstruction and 3D-flair sequences in the assessment of endolymphatic hydrops in 3 tesla.

BACKGROUND: The main sequences used to assess degree of endolymphatic hydrops (EH) are the 3D- inversion-recovery (IR) with real reconstruction and the 3D- fluid-attenuated inversion recovery (FLAIR). OBJECTIVES: The purpose of this study is to describe and compare both sequences. MATERIAL AND METHODS: Forty-two consecutive patients diagnosed with probable or definite Ménièr´s disease were referred for hydrops MR examination. Vestibular and cochlear EH in both sequences were read by two independent radiologists, unaware of the patient's clinical status. The primary study endpoint was the concordance in the hydrops detection and severity with both imaging sequences. This was assessed using the Cohen's kappa Κ statistic for disease grading and Pearson Χ2 test to test the difference in detection rates of hydrops. Statistical significance was defined as two-sided p < .05. RESULTS: We obtained an excellent overall concordance, with a kappa of 0.821, (p < .001) when comparing hydrops detection. The degree of concordance is higher in vestibular hydrops than in cochlear hydrops. The 3D-IR sequence detected more hydrops than the 3D FLAIR, (62 vs. 39.5%, p < .03). CONCLUSION: The 3D-IR sequence seems to be superior to the 3D-FLAIR for the assessment of EH. Significance: The 3D-IR sequence should be considered as a standalone parameter for a shorter and optimized EH magnetic resonance imaging protocol.