The impact of size on middle-ear sound transmission in elephants, the largest terrestrial mammal.

Elephants have a unique auditory system that is larger than any other terrestrial mammal. To quantify the impact of larger middle ear (ME) structures, we measured 3D ossicular motion and ME sound transmission in cadaveric temporal bones from both African and Asian elephants in response to air-conducted (AC) tonal pressure stimuli presented in the ear canal (PEC). Results were compared to similar measurements in humans. Velocities of the umbo (VU) and stapes (VST) were measured using a 3D laser Doppler vibrometer in the 7-13,000 Hz frequency range, stapes velocity serving as a measure of energy entering the cochlea-a proxy for hearing sensitivity. Below the elephant ME resonance frequency of about 300 Hz, the magnitude of VU/PEC was an order of magnitude greater than in human, and the magnitude of VST/PEC was 5x greater. Phase of VST/PEC above ME resonance indicated that the group delay in elephant was approximately double that of human, which may be related to the unexpectedly high magnitudes at high frequencies. A boost in sound transmission across the incus long process and stapes near 9 kHz was also observed. We discuss factors that contribute to differences in sound transmission between these two large mammals.

The impact of size on middle-ear sound transmission in elephants, the largest terrestrial mammal.

Elephants have a unique auditory system that is larger than any other terrestrial mammal. To quantify the impact of larger middle ear (ME) structures, we measured 3D ossicular motion and ME sound transmission in cadaveric temporal bones from both African and Asian elephants in response to air-conducted (AC) tonal pressure stimuli presented in the ear canal (P EC ). Results were compared to similar measurements in humans. Velocities of the umbo (V U ) and stapes (V ST ) were measured using a 3D laser Doppler vibrometer in the 7-13,000 Hz frequency range, stapes velocity serving as a measure of energy entering the cochlea-a proxy for hearing sensitivity. Below the elephant ME resonance frequency of about 300 Hz, the magnitude of V U /P EC was an order of magnitude greater than in human, and the magnitude of V ST /P EC was 5x greater. Phase of V ST /P EC above ME resonance indicated that the group delay in elephant was approximately double that of human, which may be related to the unexpectedly high magnitudes at high frequencies. A boost in sound transmission across the incus long process and stapes near 9 kHz was also observed. We discuss factors that contribute to differences in sound transmission between these two large mammals.

Bone-conduction hyperacusis induced by superior canal dehiscence in human: the underlying mechanism.

Our ability to hear through bone conduction (BC) has long been recognized, but the underlying mechanism is poorly understood. Why certain perturbations affect BC hearing is also unclear. An example is BC hyperacusis (hypersensitive BC hearing)-an unnerving symptom experienced by patients with superior canal dehiscence (SCD). We measured BC-evoked sound pressures in scala vestibuli (PSV) and scala tympani (PST) at the basal cochlea in cadaveric human ears, and estimated hearing by the cochlear input drive (PDIFF = PSV - PST) before and after creating an SCD. Consistent with clinical audiograms, SCD increased BC-driven PDIFF below 1 kHz. However, SCD affected the individual scalae pressures in unexpected ways: SCD increased PSV below 1 kHz, but had little effect on PST. These new findings are inconsistent with the inner-ear compression mechanism that some have used to explain BC hyperacusis. We developed a computational BC model based on the inner-ear fluid-inertia mechanism, and the simulated effects of SCD were similar to the experimental findings. This experimental-modeling study suggests that (1) inner-ear fluid inertia is an important mechanism for BC hearing, and (2) SCD facilitates the flow of sound volume velocity through the cochlear partition at low frequencies, resulting in BC hyperacusis.

Superior Canal Dehiscence Similarly Affects Cochlear Pressures in Temporal Bones and Audiograms in Patients.

OBJECTIVES: The diagnosis of superior canal dehiscence (SCD) is challenging and audiograms play an important role in raising clinical suspicion of SCD. The typical audiometric finding in SCD is the combination of increased air conduction (AC) thresholds and decreased bone conduction thresholds at low frequencies. However, this pattern is not always apparent in audiograms of patients with SCD, and some have hearing thresholds that are within the normal reference range despite subjective reports of hearing impairment. In this study, we used a human temporal bone model to measure the differential pressure across the cochlear partition (PDiff) before and after introduction of an SCD. PDiff estimates the cochlear input drive and provides a mechanical audiogram of the temporal bone. We measured PDiff across a wider frequency range than in previous studies and investigated whether the changes in PDiff in the temporal bone model and changes of audiometric thresholds in patients with SCD were similar, as both are thought to reflect the same physical phenomenon. DESIGN: We measured PDiff across the cochlear partition in fresh human cadaveric temporal bones before and after creating an SCD. Measurements were made for a wide frequency range (20 Hz to 10 kHz), which extends down to lower frequencies than in previous studies and audiograms. PDiff = PSV- PST is calculated from pressures measured simultaneously at the base of the cochlea in scala vestibuli (PSV) and scala tympani (PST) during sound stimulation. The change in PDiff after an SCD is created quantifies the effect of SCD on hearing. We further included an important experimental control-by patching the SCD, to confirm that PDiff was reversed back to the initial state. To provide a comparison of temporal bone data to clinical data, we analyzed AC audiograms (250 Hz to 8kHz) of patients with symptomatic unilateral SCD (radiographically confirmed). To achieve this, we used the unaffected ear to estimate the baseline hearing function for each patient, and determined the influence of SCD by referencing AC hearing thresholds of the SCD-affected ear with the unaffected contralateral ear. RESULTS: PDiff measured in temporal bones (n = 6) and AC thresholds in patients (n = 53) exhibited a similar pattern of SCD-related change. With decreasing frequency, SCD caused a progressive decrease in PDiff at low frequencies for all temporal bones and a progressive increase in AC thresholds at low frequencies. SCD decreases the cochlear input drive by approximately 6 dB per octave at frequencies below ~1 kHz for both PDiff and AC thresholds. Individual data varied in frequency and magnitude of this SCD effect, where some temporal-bone ears had noticeable effects only below 250 Hz. CONCLUSIONS: We found that with decrease in frequency the progressive decrease in low-frequency PDiff in our temporal bone experiments mirrors the progressive elevation in AC hearing thresholds observed in patients. This hypothesis remains to be tested in the clinical setting, but our findings suggest that that measuring AC thresholds at frequencies below 250 Hz would detect a larger change, thus improving audiograms as a diagnostic tool for SCD.

Intracochlear Sound Pressure Measurements in Normal Human Temporal Bones During Bone Conduction Stimulation.

Bone conduction (BC) is heavily relied upon in the diagnosis and treatment of hearing loss, but is poorly understood. For example, the relative importance and frequency dependence of various identified BC sound transmission mechanisms that contribute to activate the cochlear partition remain unknown. Recently, we have developed techniques in fresh human cadaveric specimens to directly measure scalae pressures with micro-fiberoptic sensors, enabling us to monitor the input pressure drive across the cochlear partition that triggers the cochlear traveling wave during air conduction (AC) and round-window stimulation. However, BC stimulation poses challenges that can result in inaccurate intracochlear pressure measurements. Therefore, we have developed a new technique described here that allows for precise measurements during BC. Using this new technique, we found that BC stimulation resulted in pressure in scala vestibuli that was significantly higher in magnitude than in scala tympani for most frequencies, such that the differential pressure across the partition-the input pressure drive-was similar to scala vestibuli pressure. BC (stimulated by a Bone Anchored Hearing Aid [Baha]) showed that the mechanisms of sound transmission in BC differ from AC, and also showed the limitations of the Baha bandwidth. Certain kinematic measurements were generally proportional to the cochlear pressure input drive: for AC, velocity of the stapes, and for BC, low-frequency acceleration and high-frequency velocity of the cochlear promontory. Therefore, our data show that to estimate cochlear input drive in normal ears during AC, stapes velocity is a good measure. During BC, cochlear input drive can be estimated for low frequencies by promontory acceleration (though variable across ears), and for high frequencies by promontory velocity.

Impedances of the inner and middle ear estimated from intracochlear sound pressures in normal human temporal bones.

For almost a decade, we have measured intracochlear sound pressures evoked by air conducted (AC) sound presented to the ear canal in many fresh human cadaveric specimens. Similar measurements were also obtained during round window (RW) mechanical stimulation in multiple specimens. In the present study, we use our accumulated data of intracochlear pressures and simultaneous velocity measurements of the stapes or RW to determine acoustic impedances of the cochlear partition, RW, and the leakage paths from scala vestibuli and scala tympani, as well as the reverse middle ear impedance. With these impedances, we develop a computational lumped-element model of the normal ear that illuminates fundamental mechanisms of sound transmission. To calculate the impedances for our model, we use data that passes strict inclusion criteria of: (a) normal middle-ear transfer function defined as the ratio of stapes velocity to ear-canal sound pressure, (b) no evidence of air within the inner ear, and (c) tight control of the pressure sensor sensitivity. After this strict screening, updated normal means, as well as individual representative data, of ossicular velocities and intracochlear pressures for AC and RW stimulation are used to calculate impedances. This work demonstrates the existence and the value of physiological acoustic leak impedances that can sometimes contribute significantly to sound transmission for some stimulation modalities. This model allows understanding of human sound transmission mechanisms for various sound stimulation methods such as AC, RW, and bone conduction, as well as sound transmission related to otoacoustic emissions.

PVDF-Based Piezoelectric Microphone for Sound Detection Inside the Cochlea: Toward Totally Implantable Cochlear Implants.

We report the fabrication and characterization of a prototype polyvinylidene fluoride polymer-based implantable microphone for detecting sound inside gerbil and human cochleae. With the current configuration and amplification, the signal-to-noise ratios were sufficiently high for normally occurring sound pressures and frequencies (ear canal pressures >50-60 dB SPL and 0.1-10 kHz), though 10 to 20 dB poorer than for some hearing aid microphones. These results demonstrate the feasibility of the prototype devices as implantable microphones for the development of totally implantable cochlear implants. For patients, this will improve sound reception by utilizing the outer ear and will improve the use of cochlear implants.

Factors affecting sound energy absorbance in acute otitis media model of chinchilla.

Acute otitis media (AOM) is a rapid-onset infection of the middle ear which results in middle ear pressure (MEP), middle ear effusion (MEE), and structural changes in middle ear tissues. Previous studies from our laboratory have identified that MEP, MEE, and middle ear structural changes are three factors affecting tympanic membrane (TM) mobility and hearing levels (Guan et al., 2014, 2013). Sound energy reflectance or absorbance (EA) is a diagnostic tool increasingly used in clinical settings for the identification of middle ear diseases. However, it is unclear whether EA can differentiate these three factors in an AOM ear. Here we report wideband EA measurements in the AOM model of chinchilla at three experimental stages: unopened, pressure released, and effusion removed. These correspond to the combined and individual effects of the three factors on sound energy transmission. AOM was produced by transbullar injection of Haemophilus influenzae in two treatment groups: 4 days (4D) and 8 days (8D) post inoculation. These time points represent the relatively early and later phase of AOM. In each group of chinchillas, EA at 250-8000 Hz was measured using a wideband tympanometer at three experimental stages. Results show that the effects of MEP, MEE, and tissue structural changes over the frequency range varied with the disease time course. MEP was the primary contributor to reduction of EA in 4D AOM ears and had a smaller effect in 8D ears. MEE reduced the EA at 6-8 kHz in 4D ears and 2-8 kHz in 8D ears and was responsible for the EA peak in both 4D and 8D ears. The residual EA loss due to structural changes was observed over the frequency range in 8D ears and only at high frequencies in 4D ears. The EA measurements were also compared with the published TM mobility loss in chinchilla AOM ears.

An Intracochlear Pressure Sensor as a Microphone for a Fully Implantable Cochlear Implant.

OBJECTIVE: To validate an intracochlear piezoelectric sensor for its ability to detect intracochlear pressure and function as a microphone for a fully implantable cochlear implant. METHODS: A polyvinylidene fluoride (PVDF) piezoelectric pressure sensor was inserted into a human fresh cadaveric round window at varying depths. An external sound pressure stimulus was applied to the external auditory canal (EAC). EAC pressure, stapes velocity, and piezoelectric sensor voltage output were recorded. RESULTS: The PVDF sensor was able to detect the intracochlear sound pressure response to an acoustic input to the EAC. The frequency response of the pressure measured with the intracochlear sensor was similar to that of the pressure at the EAC, with the expected phase delay of the middle ear transmission. The magnitude of the response increased and smoothened with respect to frequency as the sensor was inserted more deeply into the scala tympani. Artifact measurements, made with the sensor in air near the round window, showed flat frequency response in both magnitude and phase, which were distinct from those measured when the sensor was inserted in the round window. CONCLUSION: This study describes a novel method of measuring intracochlear pressure for an otologic microphone composed of a piezoelectric polymer, and demonstrates feasibility. Our next goal is to improve device sensitivity and bandwidth. Our long-term objective is to imbed the piezoelectric sensor within a conventional cochlear implant electrode, to enable a device to both measure intracochlear sound pressure and deliver electrical stimulus to the cochlea, for a fully implantable cochlear implant.

Motion of tympanic membrane in guinea pig otitis media model measured by scanning laser Doppler vibrometry.

Otitis media (OM) is an inflammatory or infectious disease of the middle ear. Acute otitis media (AOM) and otitis media with effusion (OME) are the two major types of OM. However, the tympanic membrane (TM) motion differences induced by AOM and OME have not been quantified in animal models in the literature. In this study, the guinea pig AOM and OME models were created by transbullar injection of Streptococcus pneumoniae type 3 and lipopolysaccharide, respectively. To explore the effects of OM on the entire TM vibration, the measurements of full-field TM motions were performed in the AOM, OME and untreated control ears by using scanning laser Doppler vibrometry (SLDV). The results showed that both AOM and OME generally reduced the displacement peak and produced the traveling-wave-like motions at relatively low frequencies. Compared with the normal ear, OME resulted in a significant change of the TM displacement mainly in the inferior portion of the TM, and AOM significantly affected the surface motion across four quadrants. The SLDV measurements provide more insight into sound-induced TM vibration in diseased ears.

Morphological changes in the tympanic membrane associated with Haemophilus influenzae-induced acute otitis media in the chinchilla.

OBJECTIVE: The tympanic membrane (TM) couples sound waves entering the outer ear canal to mechanical vibrations of the ossicular chain in the middle ear. During acute otitis media (AOM), dynamic structural changes in the TM can occur, which potentially affect sound transmission. It has remained unclear whether TM changes contribute significantly to the conductive hearing loss associated with human AOM. Studies that systematically and quantitatively assess the impact of morphological and mechanical characteristics of the TM on hearing in animal models of AOM have been few in number and lack detail. Our current study focused on the identification of quantitative morphological changes in the TM of the adult chinchilla. METHOD: AOM was produced by transbullar injection of the nontypeable (acapsular) Haemophilus influenzae strain 86-028NP into two treatment groups of chinchillas: one 4 days (4D) post bacterial challenge, and a second treatment group after 8 days (8D) post challenge. Structure and thickness were examined histologically at nine locations over the TM in untreated controls and in animals from both AOM treatment groups. RESULTS: TM thickness was found to have increased significantly (110-150%) at all measured locations of H. influenzae-infected ears when compared with uninfected (normal) TMs at 4D post bacterial challenge. Cellular proliferation and infiltration in the outer epithelial layer were primary contributors to this thickening. In ears infected for 8D, the TM was substantially thicker, a 200-300% increase from uninfected control values, due to edema and cell proliferation in both the outer and inner epithelial layers. In both 4D and 8D ears, thickening of the TM was more prominent in the superior-anterior quadrant. CONCLUSION: This study provides unequivocal structural evidence that significant TM thickness increases are associated with AOM induced by a well characterized H. influenzae human clinical isolate of low passage number. These and additional thickness data from early and later stages in middle ear infection will be used to derive the mechanical properties of the TM in a future study from our laboratory.

Experimental and modeling study of human tympanic membrane motion in the presence of middle ear liquid.

Vibration of the tympanic membrane (TM) has been measured at the umbo using laser Doppler vibrometry and analyzed with finite element (FE) models of the human ear. Recently, full-field TM surface motion has been reported using scanning laser Doppler vibrometry, holographic interferometry, and optical coherence tomography. Technologies for imaging human TM motion have the potential to lead to using a dedicated clinical diagnosis tool for identification of middle ear diseases. However, the effect of middle ear fluid (liquid) on TM surface motion is still not clear. In this study, a scanning laser Doppler vibrometer was used to measure the full-field surface motion of the TM from four human temporal bones. TM displacements were measured under normal and disease-mimicking conditions with different middle ear liquid levels over frequencies ranging from 0.2 to 8 kHz. An FE model of the human ear, including the ear canal, middle ear, and spiral cochlea was used to simulate the motion of the TM in normal and disease-mimicking conditions. The results from both experiments and FE model show that a simple deflection shape with one or two major displacement peak regions of the TM in normal ear was observed at low frequencies (1 kHz and below) while complicated ring-like pattern of the deflection shapes appeared at higher frequencies (4 kHz and above). The liquid in middle ear mainly affected TM deflection shapes at the frequencies higher than 1 kHz.

Measurement of basilar membrane motion during round window stimulation in guinea pigs.

Driving the cochlea in reverse via the round window membrane (RWM) is an alternative treatment option for the hearing rehabilitation of a nonfunctional or malformed middle ear. However, cochlear stimulation from the RWM side is not a normal sound transmission pathway. The basilar membrane (BM) motion elicited by mechanical stimulation of the RWM is unknown. In this study, the BM movement at the basal turn was investigated in both reverse via RWM drive and acoustic stimulation in the ear canal or forward drive in postmortem isolated temporal bone preparations of guinea pigs. During reverse drive, a magnet-coil was coupled on RWM, and the BM vibration at the basal turn and the movement of the incus tip were measured with laser Doppler vibrometry. During forward drive, the vibration of the incus tip induced by sound pressure in the ear canal resulted in BM vibration and the BM movement at the same location as that in the reverse stimulation was measured. The displacement ratio of the BM to RWM in reverse drive and the ratio of the BM to incus in forward drive were compared. The results demonstrated that the BM response measured in both situations was similar in nature between forward and reverse drives. This study provides new knowledge for an understanding of BM movement induced by reverse drive via the RWM stimulation.

Factors affecting loss of tympanic membrane mobility in acute otitis media model of chinchilla.

Recently we reported that middle ear pressure (MEP), middle ear effusion (MEE), and ossicular changes each contribute to the loss of tympanic membrane (TM) mobility in a guinea pig model of acute otitis media (AOM) induced by Streptococcus pneumoniae (Guan and Gan, 2013). However, it is not clear how those factors vary along the course of the disease and whether those effects are reproducible in different species. In this study, a chinchilla AOM model was produced by transbullar injection of Haemophilus influenzae. Mobility of the TM at the umbo was measured by laser vibrometry in two treatment groups: 4 days (4D) and 8 days (8D) post inoculation. These time points represent relatively early and later phases of AOM. In each group, the vibration of the umbo was measured at three experimental stages: unopened, pressure-released, and effusion-removed ears. The effects of MEP and MEE and middle ear structural changes were quantified in each group by comparing the TM mobility at one stage with that of the previous stage. Our findings show that the factors affecting TM mobility do change with the disease time course. The MEP was the dominant contributor to reduction of TM mobility in 4D AOM ears, but showed little effect in 8D ears when MEE filled the tympanic cavity. MEE was the primary factor affecting TM mobility loss in 8D ears, but affected the 4D ears only at high frequencies. After the release of MEP and removal of MEE, residual loss of TM mobility was seen mainly at low frequencies in both 4D and 8D ears, and was associated with middle ear structural changes. Our findings establish that the factors contributing to TM mobility loss in the chinchilla ear were similar to those we reported previously for the guinea pig ears with AOM. Outcomes did not appear to differ between the two major bacterial species causing AOM in these animal models.

Comparison of eardrum mobility in acute otitis media and otitis media with effusion models.

OBJECTIVE: To investigate the eardrum mobility difference between acute otitis media (AOM) and experimental otitis media with effusion (OME). ANIMAL MODELS: Thirty-three Hartley guinea pigs were included in this study. The AOM and OME were created by transbullar injection of Streptococcus pneumoniae and lipopolysaccharide into the middle ear, respectively. MAIN OUTCOME MEASURES: Three days after inoculation, the morphologic changes of the middle ear were assessed with otoscopy and histologic sections. Vibrations of the tympanic membrane (TM) at umbo in response to pure tone sound were measured using laser Doppler vibrometry. RESULTS: The purulent effusion, ossicular adhesion, and thickened TM and middle ear mucosa were observed in the AOM ears, and the OME ears had serous effusion and less thickened TM and mucosa in the middle ear. The displacement of TM in AOM was lower than that in OME ears, especially at 0.2 to 4 kHz. CONCLUSION: The TM mobility difference between the AOM and OME ears were mainly caused by the middle ear ossicular structure changes during the bacterial infection in AOM.

Mechanisms of tympanic membrane and incus mobility loss in acute otitis media model of guinea pig.

Acute otitis media (AOM) is a rapid infection of middle ear due to bacterial or viral invasion. The infection commonly leads to negative pressure and purulent effusion in the middle ear. To identify how these changes affect tympanic membrane (TM) mobility or sound transmission through the middle ear, we hypothesize that pressure, effusion, and structural changes of the middle ear are the main mechanisms of conductive hearing loss in AOM. To test the hypothesis, a guinea pig AOM model was created by injection of Streptococcus pneumoniae. Three days post inoculation, vibration of the TM at umbo in response to input sound in the ear canal was measured at three experimental stages: intact, pressure-released, and effusion-drained AOM ears. The vibration of the incus tip was also measured after the effusion was removed. Results demonstrate that displacement of the TM increased mainly at low frequencies when pressure was released. As the effusion was removed, the TM mobility increased further but did not reach the level of the normal ear at low frequencies. This was caused by middle ear structural changes or adhesions on ossicles in AOM. The structural changes also affected movement of the incus at low and high frequencies. The results provide new evidence for understanding the mechanism of conductive hearing loss in AOM.

Effect of middle ear fluid on sound transmission and auditory brainstem response in guinea pigs.

Combined measurements of middle ear transfer function and auditory brainstem response (ABR) in live guinea pigs with middle ear effusion (MEE) are reported in this paper. The MEE model was created by injecting saline into the middle ear cavity. Vibrations of the tympanic membrane (TM), the tip of the incus, and the round window membrane (RWM) were measured with a laser vibrometer at frequencies of 0.2-40 kHz when the middle ear fluid increased from 0 to 0.2 ml (i.e., full fill of the cavity). The click and pure tone ABRs were recorded as the middle ear fluid increased. Fluid introduction reduced mobility of the TM, incus and RWM mainly at high frequencies (f > 1 kHz). The magnitude of this reduction was related to the volume of fluid. The displacement transmission ratio of the TM to incus varied with frequency and fluid level. The volume displacement ratio of the oval window to round window was approximately 1.0 over most frequencies. Elevation of ABR thresholds and prolongation of ABR latencies were observed as fluid level increased. Reduction of TM displacement correlated well with elevation of ABR threshold at 0.5-8 kHz. Alterations in the ratio of ossicular displacements before and after fluid induction are consistent with fluid-induced changes in complex ossicular motions.