Four-Point Impedance: A Potential Biomarker for Residual Hearing After Cochlear Implantation.

INTRODUCTION: Preservation of residual hearing after cochlear implantation allows for electroacoustic stimulation, which leads to better music appreciation, noise localization, and speech comprehension in noisy environments. Real-time intraoperative electrocochleography (rt-ECochG) monitoring has shown promise in improving residual hearing rates. Four-point impedance (4PI) is being explored as a potential biomarker in cochlear implantation that has been associated with fibrotic tissue response, hearing loss, and dizziness. In this study, we explore whether monitoring both rt-ECochG intraoperatively and postoperative 4PI improves predictions of the preservation of residual hearing. METHODS: This was a prospective cohort study. Adults with residual acoustic hearing underwent cochlear implantation with intraoperative intracochlear electrocochleography (ECochG) monitoring. The surgeon responded to a drop in ECochG signal amplitude of greater than 30% by a standardized manipulation of the electrode with the aim of restoring the ECochG. At the end of the procedure, the ECochG signal was categorized as being maintained or having dropped more than 30%. 4PI was measured on 1 day, 1 week, and 1 and 3 months after cochlear implantation. Residual hearing was measured by routine pure-tone audiogram at 3 months postoperatively. The ECochG category and 4PI impedance values were entered as factors in a multiple linear regression predicting the protection of residual hearing. RESULTS: Twenty-six patients were recruited. Rt-ECochG significantly predicted residual hearing at 3 months (t test; mean difference, 37.7%; p = 0.002). Inclusion of both 1-day or 3-month 4PI in a multiple linear regression with rt-ECochG markedly improved upon correlations with residual hearing compared with the rt-ECochG-only model (rt-ECochG and 1-d 4PI model, R2 = 0.67; rt-ECochG and 3-mo 4PI model, R2 = 0.72; rt-ECochG-only model, R2 = 0.33). CONCLUSIONS: Both rt-ECochG and 4PI predict preservation of residual hearing after cochlear implantation. These findings suggest that the biological response of the cochlea to implantation, as reflected in 4PI, is an important determinant of residual hearing, independent of the acute effects on hearing during implant surgery seen with rt-ECochG. We speculate that 4PI relates to inflammation 1 day after implantation and fibrosis at 3 months.

Efficient two-step excitation energy transfer in artificial light-harvesting antenna based on bacteriochlorophyll aggregates.

Chlorosomes of green photosynthetic bacteria are large light-harvesting complexes enabling these organisms to survive at extremely low-light conditions. Bacteriochlorophylls found in chlorosomes self-organize and are ideal candidates for use in biomimetic light-harvesting in artificial photosynthesis and other applications for solar energy utilization. Here we report on the construction and characterization of an artificial antenna consisting of bacteriochlorophyll c co-aggregated with ß-carotene, which is used to extend the light-harvesting spectral range, and bacteriochlorophyll a, which acts as a final acceptor for excitation energy. Efficient energy transfer between all three components was observed by means of fluorescence spectroscopy. The efficiency varies with the ß-carotene content, which increases the average distance between the donor and acceptor in both energy transfer steps. The efficiency ranges from 89 to 37% for the transfer from ß-carotene to bacteriochlorophyll c, and from 93 to 69% for the bacteriochlorophyll c to bacteriochlorophyll a step. A significant part of this study was dedicated to a development of methods for determination of energy transfer efficiency. These methods may be applied also for study of chlorosomes and other pigment complexes.

The Effect of Electrode Position on Behavioral and Electrophysiologic Measurements in Perimodiolar Cochlear Implants.

BACKGROUND: The shape and position of cochlear implant electrodes could potentially influence speech perception, as this determines the proximity of implant electrodes to the spiral ganglion. However, the literature to date reveals no consistent association between speech perception and either the proximity of electrode to the medial cochlear wall or the depth of insertion. These relationships were explored in a group of implant recipients receiving the same precurved electrode. METHODS: This was a retrospective study of adults who underwent cochlear implantation with Cochlear Ltd.'s Slim Perimodiolar electrode at the Royal Victorian Eye and Ear Hospital between 2015 and 2018 (n = 52). Postoperative images were obtained using cone beam computed tomography (CBCT) and analyzed by multi-planar reconstruction to identify the position of the electrode contacts within the cochlea, including estimates of the proximity of the electrodes to the medial cochlear wall or modiolus and the angular depth of insertion. Consonant-vowel-consonant (CVC) monosyllabic phonemes were determined preoperatively, and at 3 and 12 months postoperatively. Electrically evoked compound action potential (ECAP) thresholds and impedance were measured from the implant array immediately after implantation. The relationships between electrode position and speech perception, electrode impedance, and ECAP threshold were an analyzed by Pearson correlation. RESULTS: Age had a negative impact on speech perception at 3 months but not 12 months. None of the electrode-wide measures of proximity between electrode contacts and the modiolus, nor measures of proximity to the medial cochlear wall, nor the angular depth of insertion of the most apical electrode correlated with speech perception. However, there was a moderate correlation between speech perception and the position of the most basal electrode contacts; poorer speech perception was associated with a greater distance to the modiolus. ECAP thresholds were inversely related to the distance between electrode contacts and the modiolus, but there was no clear association between this distance and impedance. CONCLUSIONS: Speech perception was significantly affected by the proximity of the most basal electrodes to the modiolus, suggesting that positioning of these electrodes may be important for optimizing speech perception. ECAP thresholds might provide an indication of this proximity, allowing for its optimization during surgery.

Intra-cochlear Flushing Reduces Tissue Response to Cochlear Implantation.

INTRODUCTION: Intraoperative trauma leading to bleeding during cochlear implantation negatively impacts residual hearing of cochlear implant recipients. There are no clinical protocols for the removal of blood during implantation, to reduce the consequential effects such as inflammation and fibrosis which adversely affect cochlear health and residual hearing. This preclinical study investigated the implementation of an intra-cochlear flushing protocol for the removal of blood. METHODS: Three groups of guinea pigs were studied for 28 days after cochlear implantation; cochlear implant-only (control group); cochlear implant with blood injected into the cochlea (blood group); and cochlear implant, blood injection, and flushing of the blood from the cochlea intraoperatively (flush group). Auditory brainstem responses (ABRs) in addition to tissue response volumes were analyzed and compared between groups. RESULTS: After implantation, the blood group exhibited the highest ABR thresholds when compared to the control and flush group, particularly in the high frequencies. On the final day, the control and blood group had similar ABR thresholds across all frequencies tested, whereas the flush group had the lowest thresholds, significantly lower at 24 kHz than the blood and control group. Analysis of the tissue response showed the flush group had significantly lower tissue responses in the basal half of the array when compared with the blood and control group. CONCLUSIONS: Flushing intra-cochlear blood during surgery resulted in better auditory function and reduced subsequent fibrosis in the basal region of the cochlea. This finding prompts the implementation of a flushing protocol in clinical cochlear implantation. LEVEL OF EVIDENCE: N/A Laryngoscope, 134:1410-1416, 2024.

Using Four-Point Impedance to Detect and Locate Blood during Cochlear Implantation.

Biosensing technologies are emerging as an important consideration when designing implantable medical devices. For cochlear implants, biosensors may help preserve the natural hearing a patient has prior to implantation by detecting blood in the cochlea during insertion. If blood enters the cochlea, it creates a hostile environment leading to further hearing loss and reduced device function. Here we present four-point impedance, measured directly from a commercial cochlear implant, as a biosensor for real-time detection of blood in the cochlea. The four-point impedance of different concentrations of whole blood in saline were measured using the impedance-measuring capabilities of a cochlear implant with a square-wave stimulation. Impedance derived from a cochlear implant succeeded in differentiating concentrations of blood in saline with results from a sensitivity analysis showing the lowest concentration the system could detect was between 12 % to 21 % of whole blood. In a subsequent in-vitro study, continuous four-point impedance was measured from a cochlear implant while it was inserted into a 3D printed cochlear model, followed by an injection of blood to emulate surgical events. These results demonstrated four-point impedance from a cochlear implant can instantaneously detect the addition of blood within the cochlea and localize it along the electrode array. The adaptation of a biosensing tool using a cochlear implant provides more information that can be relayed to the surgeon intraoperatively to potentially enhance hearing outcomes with the implant.Clinical Relevance - Using the cochlear implant itself to detect intra-cochlear bleeding may open therapeutic avenues to prevent further hearing loss.

Four-Point Impedance and Utricular Dysfunction Is Associated with Postoperative Dizziness after Cochlear Implantation.

INTRODUCTION: Postimplantation dizziness is common, affecting approximately 50% of patients. Theories for dizziness include utricular inflammation, endolymphatic hydrops, and loss of perilymph. Four-point impedance (4PI) is a novel impedance measurement in cochlear implantation that shows potential to predict hearing loss, inflammation, and fibrotic tissue response. Here, we associate 4PI with dizziness after implantation and explore the link with utricular function. METHODS: Subjective visual vertical (SVV) as a measure of utricular function was recorded preoperatively as a baseline. 4PI was measured immediately postinsertion. Ongoing follow-up was performed at 1 day, 1 week, and 1 month, postoperatively. At each follow-up, 4PI, SVV, and the patients' subjective experience of dizziness were assessed. DISCUSSION: Thirty-eight adults were recruited. One-day 4PI was significantly higher in patients dizzy within the next week (254 Ω vs 171 Ω, p = 0.015). The optimum threshold on receiver operating characteristic curve was 190 Ω, above which patients had 10 times greater odds of developing dizziness (Fisher exact test, OR = 9.95, p = 0.0092). This suggests that 4PI varies with changes in the intracochlear environment resulting in dizziness, such as inflammation or hydrops. SVV significantly deviated away from the operated ear at 1 day (fixed effect estimate = 2.6°, p ≤ 0.0001) and 1 week (fixed effect estimate 2.7°, p ≤ 0.001). CONCLUSION: One-day 4PI is a potentially useful marker for detecting postoperative dizziness after cochlear implantation. Of the current theories for postoperative dizziness, inflammation might explain the findings seen here, as would changes in hydrostatic pressure. Future research should focus on detecting and exploring these labyrinthine changes in further detail.

Developing an Evidence-Based Surgical Curriculum: Learning from a Randomized Controlled Trial of Surgical Rehearsal in Virtual Reality.

BACKGROUND: Surgical rehearsal - patient-specific preoperative surgical practice - can be provided by virtual reality simulation. This study investigated the effect of surgical rehearsal on cortical mastoidectomy performance and procedure duration. METHODS: University students (n=40) were randomized evenly into a rehearsal and control group. After watching a video tutorial on cortical mastoidectomy, participants completed the procedure on a virtual reality simulator as a pre-test. Participants completed a further 8 cortical mastoidectomies on the virtual reality simulator as training before drilling two 3-dimensional (3D) printed temporal bones. The rehearsal group received 3D printed bones they had previously operated on in virtual reality, while the control group received 2 new bones. Cortical mastoidectomy was assessed by 3 blinded graders using the Melbourne Mastoidectomy Scale. RESULTS: There was high interrater reliability between the 3 graders (intraclass correlation coefficient, r=0.8533, P < .0001). There was no difference in the mean surgical performance on the two 3D printed bones between the control and rehearsal groups (P=.2791). There was no significant difference in the mean procedure duration between the control and rehearsal groups for both 3D printed bones (P=.8709). However, there was a significant decrease in procedure duration between the first and second 3D printed bones (P < .0001). CONCLUSION: In this study, patient-specific virtual reality rehearsal provided no additional advantage to cortical mastoidectomy performance by novice operators compared to generic practice on a virtual reality simulator. Further, virtual reality training did not improve cortical mastoidectomy performance on 3D printed bones, highlighting the impact of anatomical diversity and changing operating modalities on the acquisition of new surgical skills.

Electrocochleographic Patterns Predicting Increased Impedances and Hearing Loss after Cochlear Implantation.

OBJECTIVES: Different patterns of electrocochleographic responses along the electrode array after insertion of the cochlear implant electrode array have been described. However, the implications of these patterns remain unclear. Therefore, the aim of the study was to correlate different peri- and postoperative electrocochleographic patterns with four-point impedance measurements and preservation of residual hearing. DESIGN: Thirty-nine subjects with residual low-frequency hearing which were implanted with a slim-straight electrode array could prospectively be included. Intracochlear electrocochleographic recordings and four-point impedance measurements along the 22 electrodes of the array (EL, most apical EL22) were conducted immediately after complete insertion and 3 months after surgery. Hearing preservation was assessed after 3 months. RESULTS: In perioperative electrocochleographic recordings, 22 subjects (56%) showed the largest amplitude around the tip of the electrode array (apical-peak, AP, EL20 or EL22), whereas 17 subjects (44%) exhibited a maximum amplitude in more basal regions (mid-peak, MP, EL18 or lower). At 3 months, in six subjects with an AP pattern perioperatively, the location of the largest electrocochleographic response had shifted basally (apical-to-mid-peak, AP-MP). Latency was analyzed along the electrode array when this could be discerned. This was the case in 68 peri- and postoperative recordings (87% of all recordings, n = 78). The latency increased with increasing insertion depth in AP recordings (n = 38, median of EL with maximum latency shift = EL21). In MP recordings (n = 30), the maximum latency shift was detectable more basally (median EL12, p < 0.001). Four-point impedance measurements were available at both time points in 90% (n = 35) of all subjects. At the 3-month time point, recordings revealed lower impedances in the AP group (n = 15, mean = 222 Ω, SD = 63) than in the MP (n = 14, mean = 295 Ω, SD= 7 6) and AP-MP groups (n = 6, mean = 234 Ω, SD = 129; AP versus MP p = 0.026, AP versus AP-MP p = 0.023, MP versus AP-MP p > 0.999). The amplitudes of perioperative AP recordings showed a correlation with preoperative hearing thresholds ( r2 =0.351, p = 0.004). No such correlation was detectable in MP recordings ( r2 = 0.033, p = 0.484). Audiograms were available at both time points in 97% (n = 38) of all subjects. The mean postoperative hearing loss in the AP group was 13 dB (n = 16, SD = 9). A significantly larger hearing loss was detectable in the MP and AP-MP groups with 28 (n = 17, SD = 10) and 35 dB (n = 6, SD = 13), respectively (AP versus MP p = 0.002, AP versus AP-MP p = 0.002, MP versus AP-MP p = 0.926). CONCLUSION: MP and AP-MP response patterns of the electrocochleographic responses along the electrode array after cochlear implantation are correlated with higher four-point impedances and poorer postoperative hearing compared to AP response patterns. The higher impedances suggest that MP and AP-MP patterns are associated with increased intracochlear fibrosis.

Four-Point Impedance Changes After Cochlear Implantation for Lateral Wall and Perimodiolar Implants.

OBJECTIVE: Monitor four-point impedance in cochlear implant recipients over time and determine if implant type, surgical approach, and electrode positioning affected impedance measurements. STUDY DESIGN: Prospective observational. SETTING: Hospital. PATIENTS: Adult cochlear implant recipients implanted with a perimodiolar or lateral wall cochlear implant. MAIN OUTCOME MEASURES: Mean values for four-point impedances were calculated for all electrode contacts at perioperative and 3 months after surgery. Linear mixed models were applied to the impedance data to compare between implant types and time points. The angular insertion depth and electrode position relative to the medial and lateral wall, commonly termed the Intracochlear Position Index (ICPI), were collected and compared with impedance measurements. RESULTS: Perioperatively, the four-point impedance was similar between implant types, with perimodiolar implants having marginally higher impedance values in the basal region. At 3 months after surgery, impedances significantly increased in the basal half of the electrode array for both implants, with higher impedance values for CI532 implants. There were no significant differences in insertion angle depth between implant types. The ICPI values for the seven most basal electrodes were similar for both implants; however, CI532 arrays were significantly more medially placed along the remaining apical portion of the array, which is expected. ICPI values did not correlate with impedance measurements for either implant. CONCLUSIONS: Four-point impedance increases at 3 months after surgery may reflect fibrous tissue formation after cochlear implantation. The higher impedance values in perimodiolar implants may reflect a more extensive fibrosis formation as a result of surgical approaches used, requiring drilling of the cochlea bone.

Four-point Impedance Changes in the Early Post-Operative Period After Cochlear Implantation.

OBJECTIVE: Monitoring four-point impedance changes after cochlear implantation with comparison to conventional impedance measurements. Four-point impedance provides information regarding the bulk biological environment surrounding the electrode array, which is not discernible with conventional impedances. STUDY DESIGN: Prospective observational. SETTING: Hospital. PATIENTS: Adult cochlear implant recipients with no measurable hearing before implantation and implanted with a perimodiolar cochlear implant. MAIN OUTCOME MEASURES: Mean values for four-point and common ground impedances were calculated for all electrode contacts at intra-operative, 1 day, 1 week, 4 to 6 weeks, and 3 months post implantation. Linear mixed models were applied to the impedance data to compare between impedances and time points. Furthermore, patients were divided into groups dependent on the normalized change in four-point impedance from intra-operative to 1 day post-operative. The normalized change was then calculated for all other time points and compared across the two groups. RESULTS: Significant increases in four-point impedance occurred 1 day and 3 months after surgery, particularly in the basal half of the array. Four-point impedance at 1 day was highly predictive of four-point impedance at 3 months. Four-point impedance at the other time points showed marginal or no increases from intra-operative. Patients with an average increase higher than 10% in four-point impedance from intra-operative to 1 day, had significantly higher values at 3 months ( p = 0.012). These patterns were not observed in common ground impedance. CONCLUSION: This is the first study to report increases in four-point impedance within 24 hours of cochlear implantation. The increases at 1 day and 3 months align with the natural timeline of an acute and chronic inflammatory responses.

Automatic analysis of cochlear response using electrocochleography signals during cochlear implant surgery.

Cochlear implants (CIs) provide an opportunity for the hearing impaired to perceive sound through electrical stimulation of the hearing (cochlear) nerve. However, there is a high risk of losing a patient's natural hearing during CI surgery, which has been shown to reduce speech perception in noisy environments as well as music appreciation. This is a major barrier to the adoption of CIs by the hearing impaired. Electrocochleography (ECochG) has been used to detect intra-operative trauma that may lead to loss of natural hearing. There is early evidence that ECochG can enable early intervention to save natural hearing of the patient. However, detection of trauma by observing changes in the ECochG response is typically carried out by a human expert. Here, we discuss a method of automating the analysis of cochlear responses during CI surgery. We establish, using historical patient data, that the proposed method is highly accurate (∼94% and ∼95% for sensitivity and specificity respectively) when compared to a human expert. The automation of real-time cochlear response analysis is expected to improve the scalability of ECochG and improve patient safety.

Electrocochleography triggered intervention successfully preserves residual hearing during cochlear implantation: Results of a randomised clinical trial.

BACKGROUND: Preservation of natural hearing during cochlear implantation is associated with improved speech outcomes, however more than half of implant recipients lose this hearing. Real-time electrophysiological monitoring of cochlear output during implantation, made possible by recording electrocochleography using the electrodes on the cochlear implant, has shown promise in predicting hearing preservation. Sudden drops in the amplitude of the cochlear microphonic (CM) have been shown to predict more severe hearing losses. Here, we report on a randomized clinical trial investigating whether immediate surgical intervention triggered by these drops can save residual hearing. METHODS: A single-blinded placebo-controlled trial of surgical intervention triggered when CM amplitude dropped by at least 30% of a prior maximum amplitude during cochlear implantation. Intraoperative electrocochleography was recorded in 60 adults implanted with Cochlear Ltd's Thin Straight Electrode, half randomly assigned to a control group and half to an interventional group. The surgical intervention was to withdraw the electrode in ½-mm steps to recover CM amplitude. The primary outcome was hearing preservation 3 months following implantation, with secondary outcomes of speech-in-noise reception thresholds by group or CM outcome, and depth of implantation. RESULTS: Sixty patients were recruited; neither pre-operative audiometry nor speech reception thresholds were significantly different between groups. Post-operatively, hearing preservation was significantly better in the interventional group. This was the case in absolute difference (median of 30 dB for control, 20 dB for interventional, χ² = 6.2, p = .013), as well as for relative difference (medians of 66% for the control, 31% for the interventional, χ² = 5.9, p = .015). Speech-in-noise reception thresholds were significantly better in patients with no CM drop at any point during insertion compared with patients with a CM drop; however, those with successfully recovered CMs after an initial drop were not significantly different (median gain required for speech reception score of 50% above noise of 6.9 dB for no drop, 8.6 for recovered CM, and 9.8 for CM drop, χ² = 6.8, p = .032). Angular insertion depth was not significantly different between control and interventional groups. CONCLUSIONS: This is the first demonstration that surgical intervention in response to intraoperative hearing monitoring can save residual hearing during cochlear implantation.

The Effect of Different Round Window Sealants on Cochlear Mechanics Over Time.

BACKGROUND: This project investigated the effects of round window membrane (RWM) sealants after surgical incision, with a focus on audiological thresholds, ossicular mechanics, and the impact upon cochlear function and pathology. METHODS: Twenty-eight guinea pigs were randomly allocated to one of three sealant groups (muscle, n = 7; fascia, n = 7, Tisseel, n = 8) or an unsealed control group (n = 6). Preoperative hearing was measured using auditory brainstem responses (ABRs). The ossicular chain and RWM were exposed surgically, and Laser Doppler Vibrometry (LDV) measurements were obtained from the long process of the incus. The RWM was incised then sealed (or left unsealed) according to group. ABR testing and LDV measurements were repeated 4 and 12 weeks after surgery. At 12 weeks all cochleae were harvested. RESULTS: ABR thresholds deteriorated over time in all groups. Overall, group was not statistically significant (p = 0.064). There was no significant effect by group on LDV measurements (p = 0.798). Histopathological analyses of the RWM showed that the fascia group had more extensive fibrosis than other groups (Independent-Samples Median Test, p = 0.001). However, there were minimal differences in the outer hair cell counts between the different intervention groups. CONCLUSIONS: All the interventions appeared to be safe while none affected the cochlear mechanics or hearing thresholds in a statistically significant manner.

Real Time Monitoring During Cochlear Implantation: Increasing the Accuracy of Predicting Residual Hearing Outcomes.

OBJECTIVES: Real-time electrocochleography (rt-ECochG) is a method to detect intracochlear potential changes during cochlear implantation (CI). Steep amplitude drops of the cochlear microphonic (CM) signal (so called "ECochG events") have been correlated with worse residual hearing outcomes. However, the sensitivity and specificity of monitoring CM amplitude on its own are too low to use it as a biomarker. The aim of this article was to establish if additional signal components would help to better predict postoperative hearing outcomes. DESIGN AND SETTING: Single-center, prospective cohort study at a tertiary referral hospital. PARTICIPANTS AND INTERVENTIONS: Between 2017 and 2020, we included 73 adult patients receiving a lateral wall cochlear implant electrode. During electrode insertion, rt-ECochG measurements were performed. MAIN OUTCOMES: We calculated a multiple regression analysis for patients with one ECochG event. The dependant variable was the relative acoustic hearing result 4 weeks after surgery. Independent variables were CM latency, a ratio of the auditory nerve neurophonic to the CM (the ANN/CM index) as well as CM signal recovery. RESULTS: The change of the ANN/CM index linearly correlated with acoustic hearing outcomes 4 weeks after surgery. Adding this factor led to a statistically significant increase in the variance accounted for by the regression model. CONCLUSIONS: When monitoring the implantation process with rt-ECochG, prediction of postoperative hearing thresholds is improved by addition of the ANN/CM index to a model that includes CM amplitude fluctuation.

Toward a Better Understanding of Electrocochleography: Analysis of Real-Time Recordings.

OBJECTIVES: Real-time electrocochleography (ECochG) has been used as a monitoring tool during cochlear implantation (CI), whereby, amplitude drops have been correlated with postoperative acoustic hearing results. However, no consensus has been reached as to how a single event of an amplitude drop should be characterized. The aim of this study was to identify ECochG events that predict loss of hearing 1 month after surgery. DESIGN: Fifty-five patients were included in this prospective cohort study. Real-time ECochG measurements were performed during CI electrode insertion. Single ECochG events were characterized according to their amplitude loss and slope steepness. RESULTS: Using receiver operating characteristic analyses, the most efficient cut-off criterion for a relative hearing loss of 25% was an amplitude loss of 61% at a fixed slope steepness of 0.2 µV/sec. Three-quarters of our population had at least one such event during implantation. Most events occurred shortly before full insertion. With increasing number of events, median residual hearing thresholds deteriorated for all frequencies. Larger amplitude drops trended toward worse hearing preservation. Signal recovery after an ECochG event could not be correlated to acoustic hearing outcomes. CONCLUSIONS: Our data suggest that amplitude drops exceeding 61% of the ongoing signal at a slope steepness of 0.2 µV/sec are correlated with worse acoustic hearing preservation. Clearly defined ECochG events have the potential to guide surgeons during CI in the future. This is essential if a fully automated data analysis is to be employed or benchmarking undertaken.

Cochlear microphonic latency predicts outer hair cell function in animal models and clinical populations.

As recently reported, electrocochleography recorded in cochlear implant recipients showed reduced amplitude and shorter latency in patients with more severe high-frequency hearing loss compared with those with some residual hearing. As the response is generated primarily by receptor currents in outer hair cells, these variations in amplitude and latency may indicate outer hair cell function after cochlear implantation. We propose that an absence of latency shift when the cochlear microphonic is measured on two adjacent electrodes indicates an absence or dysfunction of outer hair cells between these electrodes. We test this preclinically in noise deafened guinea pigs (2 h of a 124 dB HL, 16-24 kHz narrow-band noise), and clinically, in electrocochleographic recordings made in cochlear implant recipients immediately after implantation. We found that normal hearing guinea pigs showed a progressive increase in latency from basal to apical electrodes. In contrast, guinea pigs with significantly elevated high-frequency hearing thresholds showed no change in cochlear microphonic latency measured on basal electrodes (located approximately at the 16-24 kHz location in the cochlea).. In the clinical cohort, a significant negative correlation existed between cochlear microphonic latency shifts and hearing thresholds at 1-, 2-, & 4 kHz when tested on electrodes located at the relevant cochlear tonotopic place. This reduction in latency shift was such that patients with no measurable hearing also had no detectable latency shift (place assessed by CT scan, r's of -.70 to -.83). These findings suggest that electrocochleography can be used as a diagnostic tool to detect cochlear regions with functioning hair cells, which may be important for defining cross-over point for electro-acoustic stimulation.

Four-point impedance as a biomarker for bleeding during cochlear implantation.

Cochlear implantation has successfully restored the perception of hearing for nearly 200 thousand profoundly deaf adults and children. More recently, implant candidature has expanded to include those with considerable natural hearing which, when preserved, provides an improved hearing experience in noisy environments. But more than half of these patients lose this natural hearing soon after implantation. To reduce this burden, biosensing technologies are emerging that provide feedback on the quality of surgery. Here we report clinical findings on a new intra-operative measurement of electrical impedance (4-point impedance) which, when elevated, is associated with high rates of post-operative hearing loss and vestibular dysfunction. In vivo and in vitro data presented suggest that elevated 4-point impedance is likely due to the presence of blood within the cochlea rather than its geometry. Four-point impedance is a new marker for the detection of cochlear injury causing bleeding, that may be incorporated into intraoperative monitoring protocols during CI surgery.

Electrical Impedance as a Biomarker for Inner Ear Pathology Following Lateral Wall and Peri-modiolar Cochlear Implantation.

OBJECTIVES/HYPOTHESIS: Spikes in cochlear implant impedance are associated with inner ear pathology after implantation. Here, we correlate these spikes with episodes of hearing loss and/or vertigo, with a comparison between lateral wall and peri-modiolar electrode arrays. METHODS: Seven hundred seventy recipients of Cochlear's slim-straight, lateral wall electrode (CI422), or peri-modiolar (CI512) electrode were investigated for impedance spikes. Impedance fluctuations were defined as a median rise of ≥ 4 kΩ across all intracochlear electrodes from baseline measurements taken 2 weeks after switch-on. Medical records were analyzed from 189 of the 770 patients. RESULTS: The slim straight, lateral wall electrode was found to spike in impedance at a significantly higher rate than the peri-modiolar array (17% vs 12%). The peri-modiolar electrode tended to spike in impedance earlier than the slim-straight electrode. Impedance spikes were found to significantly correlate with medical events (hearing loss, vertigo, or tinnitus). Overall, in the "spike" group, 42 of 75 patients (56%) demonstrated a clinical event during the impedance spike, whereas 26 of 114 patients (22%) of the "non-spike" group had a clinical event. This significant difference existed with both implant types. CONCLUSION: These results demonstrate a small, but significant increase in impedance spikes in lateral wall electrodes, and support the relationship between spikes in cochlear implant impedances and postoperative inner-ear events, including the loss of residual hearing and vertigo. Monitoring cochlear implant impedance may be a method for early detection, and so the prevention, of these events in the future.

Magnetic Nanocomposites and Their Incorporation into Higher Order Biosynthetic Functional Architectures.

A magnetically active Fe3O4/poly(ethylene oxide)-block-poly(butadiene) (PEO-b-PBD) nanocomposite is formed by the encapsulation of magnetite nanoparticles with a short-chain amphiphilic block copolymer. This material is then incorporated into the self-assembly of higher order polymer architectures, along with an organic pigment, to yield biosynthetic, bifunctional optical and magnetically active Fe3O4/bacteriochlorophyll c/PEO-b-PBD polymeric chlorosomes.

Polymer-Chlorosome Nanocomposites Consisting of Non-Native Combinations of Self-Assembling Bacteriochlorophylls.

Chlorosomes are one of the characteristic light-harvesting antennas from green sulfur bacteria. These complexes represent a unique paradigm: self-assembly of bacteriochlorophyll pigments within a lipid monolayer without the influence of protein. Because of their large size and reduced complexity, they have been targeted as models for the development of bioinspired light-harvesting arrays. We report the production of biohybrid light-harvesting nanocomposites mimicking chlorosomes, composed of amphiphilic diblock copolymer membrane bodies that incorporate thousands of natural self-assembling bacteriochlorophyll molecules derived from green sulfur bacteria. The driving force behind the assembly of these polymer-chlorosome nanocomposites is the transfer of the mixed raw materials from the organic to the aqueous phase. We incorporated up to five different self-assembling pigment types into single nanocomposites that mimic chlorosome morphology. We establish that the copolymer-BChl self-assembly process works smoothly even when non-native combinations of BChl homologues are included. Spectroscopic characterization revealed that the different types of self-assembling pigments participate in ultrafast energy transfer, expanding beyond single chromophore constraints of the natural chlorosome system. This study further demonstrates the utility of flexible short-chain, diblock copolymers for building scalable, tunable light-harvesting arrays for technological use and allows for an in vitro analysis of the flexibility of natural self-assembling chromophores in unique and controlled combinations.