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1.  Diagnostic Utility of Laser-Doppler Vibrometry in Conductive Hearing Loss with Normal Tympanic Membrane 
Otology & Neurotology  2003;24(2):165-175.
Hypothesis
It was hypothesized that laser-Doppler vibrometry measurements of umbo velocity in aerated middle ears with conductive loss can differentiate ossicular interruptions, stapes fixations, and mallear fixations. More generally, we hypothesize that laser-Doppler vibrometry measurements of umbo velocity can give information about how differences in the impedance that the ossicles work against affect middle-ear function.
Background
Laser-Doppler vibrometry is a well-established research tool for exploring middle-ear function. The authors wished to investigate its potential as a clinical tool for differential diagnosis of the cause of conductive hearing loss.
Methods
Laser-Doppler vibrometry was used to investigate the relationship between the sound-induced velocity of the tympanic membrane at the umbo and the cause of conductive hearing loss when the tympanic membrane was normal and the middle ear was aerated. The results of measurements in 17 adult ears before exploratory tympanotomy were compared with the surgically determined cause of the hearing loss. The authors also measured the motion of the umbo in 10 patients who had undergone successful small-fenestra stapedectomy procedures. In all the studied ears, pure-tone audiograms were measured at the time of laser-Doppler vibrometry testing.
Results
There were clear statistical differences between the umbo velocity in normal ears and in ears with different ossicular pathologic conditions. There was also a clear separation of the results between ears with ossicular interruptions and ossicular fixation. The pattern of laser-Doppler vibrometry measurements in poststapedectomy ears approximated the pattern in ears with ossicular interruptions.
Conclusion
Comparison of laser-Doppler vibrometry results and audiometry may be a sensitive and selective indicator of ossicular pathologic conditions as well as a useful tool for investigating middle ear function.
PMCID: PMC1464085  PMID: 12621328
Laser-Doppler vibrometry; Conductive hearing loss; Middle ear function; Audiometry
2.  Investigation of the Mechanics of Type III Stapes Columella Tympanoplasty Using Laser-Doppler Vibrometry 
Objectives
To investigate the middle ear mechanics of Type III stapes columella tympanoplasty using laser-Doppler vibrometry (LDV) and to determine whether LDV was useful in the identification of structural factors responsible for poor hearing outcomes.
Background
The Type III stapes columella tympanoplasty procedure involves placing a tympanic membrane (TM) graft directly onto the stapes head. Postoperative hearing results vary widely, with air-bone gaps (ABGs) ranging from 10 to 60 dB.
Methods
Laser-Doppler vibrometry measurements were performed in 22 patients (23 ears) who underwent Type III stapes columella tympanoplasty. The measurements were made at three locations on the TM graft: over the stapes head, over the round window, and on the anterior TM. The LDV results were correlated with the clinical and audiologic findings.
Results
The 23 ears were divided into three groups: Nonaerated ears (n = 2). The ABGs were 30 to 60 dB. The TM velocities over all three locations were 20 to 40 dB lower than normal umbo velocity (in normally hearing subjects). Fixed stapes with aerated middle ear (n = 2). The ABGs were 40 to 60 dB, and TM velocities were equivalent to normal umbo velocity in one case and lower by 15 to 20 dB in another case. Mobile stapes and aerated middle ear (n = 19). There were two subgroups in this category: 1) small ABGs less than 25 dB (n = 7) and large gaps greater than or equal to 25 dB (n = 12). There were small differences in TM graft velocity at all three measurement locations between these two subgroups. However, these small differences did not explain the large difference in ABG between the two subgroups.
Conclusion
Nonaeration of the middle ear and stapes fixation lead to large residual conductive hearing losses after Type III tympanoplasty. Laser-Doppler vibrometry can aid in the diagnosis of nonaeration of the middle ear but does not readily diagnose stapes fixation. Postoperative results can vary even in cases of a mobile stapes and an aerated middle ear. We hypothesize that these variations may be the result of differences in the coupling between the TM graft and the stapes head. Measurements of TM velocities by means of LDV did not show clear differences between cases with good hearing and cases with poor hearing in ears with a mobile stapes and an aerated ear. Except for diagnosis of nonaeration of the middle ear, LDV seems to have limited clinical usefulness to identify causes of failure after Type III tympanoplasty.
doi:10.1097/MAO.0b013e31811f40fb
PMCID: PMC2586981  PMID: 17948356
Air-bone gap; Laser-Doppler vibrometry; Middle ear mechanics; Tympanoplasty
3.  Middle Ear Cavity Morphology Is Consistent with an Aquatic Origin for Testudines 
PLoS ONE  2013;8(1):e54086.
The position of testudines in vertebrate phylogeny is being re-evaluated. At present, testudine morphological and molecular data conflict when reconstructing phylogenetic relationships. Complicating matters, the ecological niche of stem testudines is ambiguous. To understand how turtles have evolved to hear in different environments, we examined middle ear morphology and scaling in most extant families, as well as some extinct species, using 3-dimensional reconstructions from micro magnetic resonance (MR) and submillimeter computed tomography (CT) scans. All families of testudines exhibited a similar shape of the bony structure of the middle ear cavity, with the tympanic disk located on the rostrolateral edge of the cavity. Sea Turtles have additional soft tissue that fills the middle ear cavity to varying degrees. When the middle ear cavity is modeled as an air-filled sphere of the same volume resonating in an underwater sound field, the calculated resonances for the volumes of the middle ear cavities largely fell within testudine hearing ranges. Although there were some differences in morphology, there were no statistically significant differences in the scaling of the volume of the bony middle ear cavity with head size among groups when categorized by phylogeny and ecology. Because the cavity is predicted to resonate underwater within the testudine hearing range, the data support the hypothesis of an aquatic origin for testudines, and function of the middle ear cavity in underwater sound detection.
doi:10.1371/journal.pone.0054086
PMCID: PMC3544720  PMID: 23342082
4.  Hearing in the African lungfish (Protopterus annectens): pre-adaptation to pressure hearing in tetrapods? 
Biology Letters  2010;7(1):139-141.
Lungfishes are the closest living relatives of the tetrapods, and the ear of recent lungfishes resembles the tetrapod ear more than the ear of ray-finned fishes and is therefore of interest for understanding the evolution of hearing in the early tetrapods. The water-to-land transition resulted in major changes in the tetrapod ear associated with the detection of air-borne sound pressure, as evidenced by the late and independent origins of tympanic ears in all of the major tetrapod groups. To investigate lungfish pressure and vibration detection, we measured the sensitivity and frequency responses of five West African lungfish (Protopterus annectens) using brainstem potentials evoked by calibrated sound and vibration stimuli in air and water. We find that the lungfish ear has good low-frequency vibration sensitivity, like recent amphibians, but poor sensitivity to air-borne sound. The skull shows measurable vibrations above 100 Hz when stimulated by air-borne sound, but the ear is apparently insensitive at these frequencies, suggesting that the lungfish ear is neither adapted nor pre-adapted for aerial hearing. Thus, if the lungfish ear is a model of the ear of early tetrapods, their auditory sensitivity was limited to very low frequencies on land, mostly mediated by substrate-borne vibrations.
doi:10.1098/rsbl.2010.0636
PMCID: PMC3030901  PMID: 20826468
lungfish; hearing; vibration; tetrapod; sound; evolution
5.  The Auditory Anatomy of the Minke Whale (Balaenoptera acutorostrata): A Potential Fatty Sound Reception Pathway in a Baleen Whale 
Cetaceans possess highly derived auditory systems adapted for underwater hearing. Odontoceti (toothed whales) are thought to receive sound through specialized fat bodies that contact the tympanoperiotic complex, the bones housing the middle and inner ears. However, sound reception pathways remain unknown in Mysticeti (baleen whales), which have very different cranial anatomies compared to odontocetes. Here, we report a potential fatty sound reception pathway in the minke whale (Balaenoptera acutorostrata), a mysticete of the balaenopterid family. The cephalic anatomy of seven minke whales was investigated using computerized tomography and magnetic resonance imaging, verified through dissections. Findings include a large, well-formed fat body lateral, dorsal, and posterior to the mandibular ramus and lateral to the tympanoperiotic complex. This fat body inserts into the tympanoperiotic complex at the lateral aperture between the tympanic and periotic bones and is in contact with the ossicles. There is also a second, smaller body of fat found within the tympanic bone, which contacts the ossicles as well. This is the first analysis of these fatty tissues' association with the auditory structures in a mysticete, providing anatomical evidence that fatty sound reception pathways may not be a unique feature of odontocete cetaceans. Anat Rec, 2012. © 2012 Wiley Periodicals, Inc.
doi:10.1002/ar.22459
PMCID: PMC3488298  PMID: 22488847
cetacea; mysticete; hearing; ear; acoustic fat; imaging
6.  Measurement of Conductive Hearing Loss in Mice 
Hearing research  2009;263(1-2):93-103.
In order to discriminate conductive hearing loss from sensorineural impairment, quantitative measurements were used to evaluate the effect of artificial conductive pathology on distortion product otoacoustic emissions (DPOAEs), auditory brainstem responses (ABRs) and laser Doppler vibrometry (LDV) in mice. The conductive manipulations were created by perforating the pars flaccida of the tympanic membrane, filling or partially filling the middle-ear cavity with saline, fixing the ossicular chain, and interrupting the incudo-stapedial joint. In the saline-filled and ossicular-fixation groups, averaged DPOAE thresholds increased relative to the control state by 20 to 36 dB and 25 to 39 dB respectively with the largest threshold shifts occurring at frequencies less than 20 kHz, while averaged ABR thresholds increased 12 to 19 dB and 12 to 25 dB respectively without the predominant low-frequency effect. Both DPOAE and ABR thresholds were elevated by less than 10 dB in the half-filled saline condition; no significant change was observed after pars flaccida perforation. Conductive pathology generally produced a change in DPOAE threshold in dB that was 1.5 to 2.5 times larger than the ABR threshold change at frequencies less than 30 kHz; the changes in the two thresholds were nearly equal at the highest frequencies. While mild conductive pathology (ABR threshold shifts of < 10 dB) produced parallel shifts in DPOAE growth with level functions, manipulations that produced larger conductive hearing losses (ABR threshold shifts > 10 dB) were associated with significant deceases in DPOAE growth rate. Our LDV measurements are consistent with others and suggest that measurements of umbo velocity are not an accurate indicator of conductive hearing loss produced by ossicular lesions in mice.
doi:10.1016/j.heares.2009.10.002
PMCID: PMC2866764  PMID: 19835942
Middle ear pathology; Distortion product otoacoustic emissions; Auditory brainstem responses; Umbo velocity; Mouse
7.  Evolution of a sensory novelty: Tympanic ears and the associated neural processing 
Brain Research Bulletin  2007;75(2-4):365-370.
Tympanic hearing is a true evolutionary novelty that appears to have developed independently in at least five major tetrapod groups—the anurans, turtles, lepidosaurs, archosaurs and mammals. The emergence of a tympanic ear would have increased the frequency range and sensitivity of hearing. Furthermore, tympana were acoustically coupled through the mouth cavity and therefore inherently directional in a certain frequency range, acting as pressure difference receivers. In some lizard species, this acoustical coupling generates a 50-fold directional difference, usually at relatively high frequencies (2–4 kHz).
In ancestral atympanate tetrapods, we hypothesize that low-frequency sound may have been processed by non-tympanic mechanisms like those in extant amphibians. The subsequent emergence of tympanic hearing would have led to changes in the central auditory processing of both high-frequency sound and directional hearing. These changes should reflect the independent origin of the tympanic ears in the major tetrapod groups. The processing of low-frequency sound, however, may have been more conserved, since the acoustical coupling of the ancestral tympanate ear probably produced little sensitivity and directionality at low frequencies. Therefore, tetrapod auditory processing may originally have been organized into low- and high-frequency streams, where only the high-frequency processing was mediated by tympanic input.
The closure of the middle ear cavity in mammals and some birds is a derived condition, and may have profoundly changed the operation of the ear by decoupling the tympana, improving the low-frequency response of the tympanum, and leading to a requirement for additional neural computation of directionality in the central nervous system. We propose that these specializations transformed the low- and high-frequency streams into time and intensity pathways, respectively.
doi:10.1016/j.brainresbull.2007.10.044
PMCID: PMC3269633  PMID: 18331899
Middle ear; Tympanum; Lizard; Frog; Hearing; Auditory; Brain stem
8.  STRUCTURE AND FUNCTION OF THE MIDDLE EAR APPARATUS OF THE AQUATIC FROG, XENOPUS LAEVIS 
We report the results of anatomical and vibrometric studies of the middle ear of the African clawed frog, Xenopus laevis. The cartilaginous tympanic disk of Xenopus shows pronounced sexual dimorphism, that of male frogs being much larger than that of females, relative to body size. The stapes footplate, however, is not enlarged in males. The cucullaris muscle was found to insert on the stapes in frogs of both sexes. Using laser interferometry to examine the response of middle ear structures to airborne sound, the stapes footplate was found to vibrate close to 180° out-of-phase with the tympanic disk across a range of frequencies, this resembling the relationship between tympanic membrane and footplate movement previously described in ranid frogs. By contrast, whereas there is a pronounced difference in vibration velocity between tympanic membrane and footplate in ranids, the footplate vibration velocity in Xenopus was found to be similar to that of the tympanic disk. This may be interpreted as an adaptation to improve the detection of sound underwater.
PMCID: PMC2953823  PMID: 20953303
9.  Clinical Utility of Laser-Doppler Vibrometer Measurements in Live Normal and Pathologic Human Ears 
Ear and hearing  2008;29(1):3-19.
The laser-Doppler vibrometer (LDV) is a research tool that can be used to quickly measure the sound-induced velocity of the tympanic membrane near the umbo (the inferior tip of the malleus) in live human subjects and patients. In this manuscript we demonstrate the LDV to be a sensitive and selective tool for the diagnosis and differentiation of various ossicular disorders in patients with intact tympanic membranes and aerated middle ears. Patients with partial or total ossicular interruption or malleus fixation are readily separated from normal-hearing subjects with the LDV. The combination of LDV measurements and air-bone gap can distinguish patients with fixed stapes from those with normal ears. LDV measurements can also help differentiate air-bone gaps produced by ossicular pathologies from those associated with pathologies of inner-ear sound conduction such as a superior semicircular canal dehiscence.
doi:10.1097/AUD.0b013e31815d63a5
PMCID: PMC2572196  PMID: 18091103
10.  Combined Effect of Fluid and Pressure on Middle Ear Function 
Hearing research  2007;236(1-2):22-32.
In our previous studies, the effects of effusion and pressure on sound transmission were investigated separately. The aim of this study is to investigate the combined effect of fluid and pressure on middle ear function. An otitis media with effusion model was created by injecting saline solution and air pressure simultaneously into the middle ear of human temporal bones. Tympanic membrane displacement in response to 90 dB SPL sound input was measured by a laser vibrometer and the compliance of the middle ear was measured by a tympanometer. The movement of the tympanic membrane at the umbo was reduced up to 17 dB by the combination of fluid and pressure in the middle ear over the auditory frequency range. The fluid and pressure effects on the umbo movement in the fluid-pressure combination are not additive. The combined effect of fluid and pressure on the umbo movement is different compared with that of only fluid or pressure change in the middle ear. Negative pressure in fluid-pressure combination had more effect on middle ear function than positive pressure. Tympanometry can detect the middle ear pressure of the fluid-pressure combination. This study provides quantitative information for analysis of the combined effect of fluid and pressure on tympanic membrane movement.
doi:10.1016/j.heares.2007.11.005
PMCID: PMC2346543  PMID: 18162348
laser vibrometer; middle ear mechanics; otitis media; temporal bone; tympanometry
11.  Effect of Middle Ear Fluid on Sound Transmission and Auditory Brainstem Response in Guinea Pigs 
Hearing research  2011;277(1-2):96-106.
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.
doi:10.1016/j.heares.2011.03.003
PMCID: PMC3137689  PMID: 21414396
middle ear effusion; middle ear transfer function; laser vibrometer; auditory brainstem response
12.  Analysis of chick (Gallus gallus) middle ear columella formation 
Background
The chick middle ear bone, the columella, provides an accessible model in which to study the tissue and molecular interactions necessary for induction and patterning of the columella, as well as associated multiple aspects of endochondral ossification. These include mesenchymal condensation, chondrogenesis, ossification of the medial footplate and shaft, and joint formation between the persistent cartilage of the extracolumella and ossified columella. Middle and external ear defects are responsible for approximately 10% of congenital hearing defects. Thus, understanding the morphogenesis and the molecular mechanisms of the formation of the middle ear is important to understanding normal and abnormal development of this essential component of the hearing apparatus.
Results
The columella, which arises from proximal ectomesenchyme of the second pharyngeal arch, is induced and patterned in a dynamic multi-step process. From the footplate, which inserts into the inner ear oval window, the shaft spans the pneumatic middle ear cavity, and the extracolumella inserts into the tympanic membrane. Through marker gene and immunolabeling analysis, we have determined the onset of each stage in the columella's development, from condensation to ossification. Significantly, a single condensation with the putative shaft and extracolumella arms already distinguishable is observed shortly before initiation of five separate chondrogenic centers within these structures. Ossification begins later, with periosteum formation in the shaft and, unexpectedly, a separate periosteum in the footplate.
Conclusions
The data presented in this study document the spatiotemporal events leading to morphogenesis of the columella and middle ear structures and provide the first gene expression data for this region. These data identify candidate genes and facilitate future functional studies and elucidation of the molecular mechanisms of columella formation.
doi:10.1186/1471-213X-10-16
PMCID: PMC2834582  PMID: 20158901
13.  Discovery of a Lipid Synthesising Organ in the Auditory System of an Insect 
PLoS ONE  2012;7(12):e51486.
Weta possess typical Ensifera ears. Each ear comprises three functional parts: two equally sized tympanal membranes, an underlying system of modified tracheal chambers, and the auditory sensory organ, the crista acustica. This organ sits within an enclosed fluid-filled channel–previously presumed to be hemolymph. The role this channel plays in insect hearing is unknown. We discovered that the fluid within the channel is not actually hemolymph, but a medium composed principally of lipid from a new class. Three-dimensional imaging of this lipid channel revealed a previously undescribed tissue structure within the channel, which we refer to as the olivarius organ. Investigations into the function of the olivarius reveal de novo lipid synthesis indicating that it is producing these lipids in situ from acetate. The auditory role of this lipid channel was investigated using Laser Doppler vibrometry of the tympanal membrane, which shows that the displacement of the membrane is significantly increased when the lipid is removed from the auditory system. Neural sensitivity of the system, however, decreased upon removal of the lipid–a surprising result considering that in a typical auditory system both the mechanical and auditory sensitivity are positively correlated. These two results coupled with 3D modelling of the auditory system lead us to hypothesize a model for weta audition, relying strongly on the presence of the lipid channel. This is the first instance of lipids being associated with an auditory system outside of the Odentocete cetaceans, demonstrating convergence for the use of lipids in hearing.
doi:10.1371/journal.pone.0051486
PMCID: PMC3520794  PMID: 23251553
14.  Measurements of Human Middle- and Inner-Ear Mechanics With Dehiscence of the Superior Semicircular Canal 
Objectives
(1) To develop a cadaveric temporal-bone preparation to study the mechanism of hearing loss resulting from superior semicircular canal dehiscence (SCD) and (2) to assess the potential usefulness of clinical measurements of umbo velocity for the diagnosis of SCD.
Background
The syndrome of dehiscence of the superior semicircular canal is a clinical condition encompassing a variety of vestibular and auditory symptoms, including an air-bone gap at low frequencies. It has been hypothesized that the dehiscence acts as a “third window” into the inner ear that shunts acoustic energy away from the cochlea at low frequencies, causing hearing loss.
Methods
Sound-induced stapes, umbo, and round-window velocities were measured in prepared temporal bones (n = 8) using laser-Doppler vibrometry (1) with the superior semicircular canal intact, (2) after creation of a dehiscence in the superior canal, and (3) with the dehiscence patched. Clinical measurements of umbo velocity in live SCD ears (n = 29) were compared with similar data from our cadaveric temporal-bone preparations.
Results
An SCD caused a significant reduction in sound-induced round-window velocity at low frequencies, small but significant increases in sound-induced stapes and umbo velocities, and a measurable fluid velocity inside the dehiscence. The increase in sound-induced umbo velocity in temporal bones was also found to be similar to that measured in the 29 live ears with SCD.
Conclusion
Findings from the cadaveric temporal-bone preparation were consistent with the third-window hypothesis. In addition, measurement of umbo velocity in live ears is helpful in distinguishing SCD from other otologic pathologies presenting with an air-bone gap (e.g., otosclerosis).
doi:10.1097/01.mao.0000244370.47320.9a
PMCID: PMC2585995  PMID: 17255894
Air-bone gap; Conductive hearing loss; Semicircular canal dehiscence; Superior semicircular canal dehiscence
15.  Acoustic communication and the evolution of hearing in fishes. 
Fishes have evolved a diversity of sound-generating organs and acoustic signals of various temporal and spectral content. Additionally, representatives of many teleost families such as otophysines, anabantoids, mormyrids and holocentrids possess accessory structures that enhance hearing abilities by acoustically coupling air-filled cavities to the inner ear. Contrary to the accessory hearing structures such as Weberian ossicles in otophysines and suprabranchial chambers in anabantoids, sonic organs do not occur in all members of these taxa. Comparison of audiograms among nine representatives of seven otophysan families from four orders revealed major differences in auditory sensitivity, especially at higher frequencies (> 1 kHz) where thresholds differed by up to 50 dB. These differences showed no apparent correspondence to the ability to produce sounds (vocal versus non-vocal species) or to the spectral content of species-specific sounds. In anabantoids, the lowest auditory thresholds were found in the blue gourami Trichogaster trichopterus, a species not thought to be vocal. Dominant frequencies of sounds corresponded with optimal hearing bandwidth in two out of three vocalizing species. Based on these results, it is concluded that the selective pressures involved in the evolution of accessory hearing structures and in the design of vocal signals were other than those serving to optimize acoustic communication.
PMCID: PMC1692861  PMID: 11079416
16.  Clinical Investigation and Mechanism of Air-Bone Gaps in LargeVestibular Aqueduct Syndrome 
Objectives
Patients with large vestibular aqueduct syndrome (LVAS) often demonstrate an air-bone gap at the low frequencies on audiometric testing. The mechanism causing such a gap has not been well elucidated. We investigated middle ear sound transmission in patients with LVAS, and present a hypothesis to explain the air-bone gap.
Methods
Observations were made on 8 ears from 5 individuals with LVAS. The diagnosis of LVAS was made by computed tomography in all cases. Investigations included standard audiometry and measurements of umbo velocity by laser Doppler vibrometry (LDV) in all cases, as well as tympanometry, acoustic reflex testing, vestibular evoked myogenic potential (VEMP) testing, distortion product otoacoustic emission (DPOAE) testing, and middle ear exploration in some ears.
Results
One ear with LVAS had anacusis. The other 7 ears demonstrated air-bone gaps at the low frequencies, with mean gaps of 51 dB at 250 Hz, 31 dB at 500 Hz, and 12 dB at 1,000 Hz. In these 7 ears with air-bone gaps, LDV showed the umbo velocity to be normal or high normal in all 7; tympanometry was normal in all 6 ears tested; acoustic reflexes were present in 3 of the 4 ears tested; VEMP responses were present in all 3 ears tested; DPOAEs were present in 1 of the 2 ears tested, and exploratory tympanotomy in 1 case showed a normal middle ear. The above data suggest that an air-bone gap in LVAS is not due to disease in the middle ear. The data are consistent with the hypothesis that a large vestibular aqueduct introduces a third mobile window into the inner ear, which can produce an air-bone gap by 1) shunting air-conducted sound away from the cochlea, thus elevating air conduction thresholds, and 2) increasing the difference in impedance between the scala vestibuli side and the scala tympani side of the cochlear partition during bone conduction testing, thus improving thresholds for bone-conducted sound.
Conclusions
We conclude that LVAS can present with an air-bone gap that can mimic middle ear disease. Diagnostic testing using acoustic reflexes, VEMPs, DPOAEs, and LDV can help to identify a non–middle ear source for such a gap, thereby avoiding negative middle ear exploration. A large vestibular aqueduct may act as a third mobile window in the inner ear, resulting in an air-bone gap at low frequencies.
PMCID: PMC2585521  PMID: 17727085
air-bone gap; audiometry; conductive hearing loss; large vestibular aqueduct syndrome
17.  Bone Anchored Hearing Aid 
Executive Summary
Objective
The objective of this health technology policy assessment was to determine the effectiveness and cost-effectiveness of bone-anchored hearing aid (BAHA) in improving the hearing of people with conduction or mixed hearing loss.
The Technology
The (BAHA) is a bone conduction hearing device that includes a titanium fixture permanently implanted into the mastoid bone of the skull and an external percutaneous sound processor. The sound processor is attached to the fixture by means of a skin penetrating abutment. Because the device bypasses the middle ear and directly stimulates the cochlea, it has been recommended for individuals with conduction hearing loss or discharging middle ear infection.
The titanium implant is expected to last a lifetime while the external sound processor is expected to last 5 years. The total initial device cost is approximately $5,300 and the external sound processor costs approximately $3,500.
Review of BAHA by the Medical Advisory Secretariat
The Medical Advisory Secretariat’s review is a descriptive synthesis of findings from 36 research articles published between January 1990 and May 2002.
Summary of Findings
No randomized controlled studies were found. The evidence was derived from level 4 case series with relative small sample sizes (ranging from 30-188). The majority of the studies have follow-up periods of eight years or longer. All except one study were based on monaural BAHA implant on the side with the best bone conduction threshold.
Safety
Level 4 evidence showed that BAHA has been be implanted safely in adults and children with success rates of 90% or higher in most studies. No mortality or life threatening morbidity has been reported. Revision rates for tissue reduction or resiting were generally under 10% for adults but have been reported to be as high as 25% in pediatric studies.
Adverse skin reaction around the skin penetration site was the most common complication reported. Most of these conditions were successfully treated with antibiotics, and only 1% to 2% required surgical revision. Less than 1% required removal of the fixture.
Other complications included failure to osseointegrate and loss of fixture and/or abutment due to trauma or infection.
Effectiveness
Studies showed that BAHAs were implanted in people who have conduction or mixed hearing loss, congenital atresia or suppurative otitis media who were not candidates for surgical repair, and who cannot use conventional bone conduction hearing aids. The need for BAHA is not age- related. Objective audiometric measures and subjective patient satisfaction surveys showed that BAHA significantly improved the unaided and aided free field and sound field thresholds as well as speech discrimination in quiet and in noise for former users of conventional bone conduction hearing aids. The outcomes were ambiguous for former users of air conduction hearing aids.
BAHA has been shown to reduce the frequency of ear infection and reduce the discharge particularly among patients with suppurative otitis media.
Patients have reported that BAHA improved their quality of life. Reported benefits were improved speech intelligibility, better sound comfort, less pressure on the head, less skin irritation, greater cosmetic acceptance and increase in confidence. Main reported shortcomings were wind noise, feedback and difficulty in using the telephone.
Experts and the BAHA manufacturer recommended that recipients of a BAHA implant be at least 5 years old. Challenges associated with the implantation of BAHA in pediatric patients include thin bone, soft bone, higher rates of fixture loss due to trauma, psychological problems, and higher revision rates due to rapid bone growth. The overall outcomes are comparable to adult BAHA. The benefits of pediatric BAHA (e.g. on speech development) appear to outweigh the disadvantages.
Screening according to strict eligibility criteria, preoperative counselling, close monitoring by a physician with BAHA expertise and on-going follow-up were identified as critical factors for long-term implant survival. Examples of eligibility criteria were provided.
Cost-effectiveness
No literature on cost-effectiveness of BAHA was found.
PMCID: PMC3387772  PMID: 23074440
18.  When signal meets noise: Immunity of the frog ear to interference 
Die Naturwissenschaften  2009;96(7):835-843.
Sound stimulates the tympanic membrane (TM) of anuran amphibians through multiple, poorly understood pathways. It is conceivable that interactions between the internal and external inputs to the TM contribute to the non-linear effects that noise is known to produce at higher levels of the auditory pathway. To explore this issue we conducted measurements of TM vibration in response to tones in the presence of noise in the frog Eupsophus calcaratus. Laser vibrometry revealed that the power spectra (n=16) of the TM velocity in response to pure tones at a constant level of 80 dB SPL had a maximum centered at an average frequency of 2344 Hz (range 1700–2990 Hz) and a maximum velocity of 61.1 dB re 1 μm/s (range 42.9–66.6 dB re 1 μm/s). These TM vibration velocity response profiles in the presence of increasing levels of 4-kHz band-pass noise were unaltered up to noise levels of 90 dB SPL. For the relatively low spectral densities of the noise used, the TM remains in its linear range. Such vibration patterns facilitate the detection of tonal signals in noise at the tympanic membrane, and may underlie the remarkable vocal responsiveness maintained by males of E. calcaratus under noise interference.
doi:10.1007/s00114-009-0542-9
PMCID: PMC2900188  PMID: 19404599
Anurans; Noise exposure; Tympanic membrane
19.  Mouse Middle Ear Ion Homeostasis Channels and Intercellular Junctions 
PLoS ONE  2012;7(6):e39004.
Hypothesis
The middle ear contains homeostatic mechanisms that control the movement of ions and fluids similar to those present in the inner ear, and are altered during inflammation.
Background
The normal middle ear cavity is fluid-free and air-filled to allow for effective sound transmission. Within the inner ear, the regulation of fluid and ion movement is essential for normal auditory and vestibular function. The same ion and fluid channels active in the inner ear may have similar roles with fluid regulation in the middle ear.
Methods
Middle and inner ears from BALB/c mice were processed for immunohistochemistry of 10 specific ion homeostasis factors to determine if similar transport and barrier mechanisms are present in the tympanic cavity. Examination also was made of BALB/c mice middle ears after transtympanic injection with heat-killed Haemophilus influenza to determine if these channels are impacted by inflammation.
Results
The most prominent ion channels in the middle ear included aquaporins 1, 4 and 5, claudin 3, ENaC and Na+,K+-ATPase. Moderate staining was found for GJB2, KCNJ10 and KCNQ1. The inflamed middle ear epithelium showed increased staining due to expected cellular hypertrophy. Localization of ion channels was preserved within the inflamed middle ear epithelium.
Conclusions
The middle ear epithelium is a dynamic environment with intrinsic mechanisms for the control of ion and water transport to keep the middle ear clear of fluids. Compromise of these processes during middle ear disease may underlie the accumulation of effusions and suggests they may be a therapeutic target for effusion control.
doi:10.1371/journal.pone.0039004
PMCID: PMC3376096  PMID: 22720014
20.  Structures that Contribute to Middle-Ear Admittance in Chinchilla 
We describe measurements of middle-ear input admittance in chinchillas (Chinchilla lanigera) before and after various manipulations that define the contributions of different middle-ear components to function. The chinchilla’s middle-ear air spaces have a large effect on the low-frequency compliance of the middle ear, and removing the influences of these spaces reveals a highly admittant tympanic membrane and ossicular chain. Measurements of the admittance of the air spaces reveal that the high-degree of segmentation of these spaces has only a small effect on the admittance. Draining the cochlea further increases the middle-ear admittance at low frequencies and removes a low-frequency (less than 300 Hz) level dependence in the admittance. Spontaneous or sound-driven contractions of the middle-ear muscles in deeply anesthetized animals were associated with significant changes in middle-ear admittance.
doi:10.1007/s00359-006-0159-9
PMCID: PMC2729694  PMID: 16944166
Middle-ear structure-function; Comparative Auditory Function
21.  Underwater audiogram of the California sea lion by the conditioned vocalization technique1 
Conditioning techniques were developed demonstrating that pure tone frequencies under water can exert nearly perfect control over the underwater click vocalizations of the California sea lion (Zalophus californianus). Conditioned vocalizations proved to be a reliable way of obtaining underwater sound detection thresholds in Zalophus at 13 different frequencies, covering a frequency range of 250 to 64,000 Hz. The audiogram generated by these threshold measurements suggests that under water, the range of maximal sensitivity for Zalophus lies between one and 28 kHz with best sensitivity at 16 kHz. Between 28 and 36 kHz there is a loss in sensitivity of 60 dB/octave. However, with relatively intense acoustic signals (> 38 dB re 1 μb underwater), Zalophus will respond to frequencies at least as high as 192 kHz. These results are compared with the underwater hearing of other marine mammals.
Images
doi:10.1901/jeab.1972.17-339
PMCID: PMC1333909  PMID: 5033891
22.  Middle-Ear Pressure Gain and Cochlear Partition Differential Pressure in Chinchilla 
Hearing research  2009;263(1-2):16-25.
An important step to describe the effects of inner-ear impedance and pathologies on middle- and inner-ear mechanics is to quantify middle- and inner-ear function in the normal ear. We present middle-ear pressure gain GMEP and trans-cochlear-partition differential sound pressure ΔPCP in chinchilla from 100 Hz to 30 kHz derived from measurements of intracochlear sound pressures in scala vestibuli PSV and scala tympani PST and ear-canal sound pressure near the tympanic membrane PTM. These measurements span the chinchilla's auditory range. GMEP had constant magnitude of about 20 dB between 300 Hz and 20 kHz and phase that implies a 40-μs delay, values with some similarities to previous measurements in chinchilla and other species. ΔPCP was similar to GMEP below about 10 kHz and lower in magnitude at higher frequencies, decreasing to 0 dB at 20 kHz. The high-frequency rolloff correlates with the audiogram and supports the idea that middle-ear transmission limits high-frequency hearing, providing a stronger link between inner-ear macromechanics and hearing. We estimate the cochlear partition impedance ZCP from these and previous data. The chinchilla may be a useful animal model for exploring the effects of nonacoustic inner-ear stimulation such as “bone conduction” on cochlear mechanics.
doi:10.1016/j.heares.2009.11.014
PMCID: PMC2866808  PMID: 19945521
Middle-ear sound transmission; introcochlear sound pressure; middle-ear gain; cochlear impedance; chinchilla
23.  Experimental Investigation of Rotational Tomography in Reconstructed Middle Ears with Clinical Implications 
Hearing research  2009;263(1-2):191-197.
A large air-bone-gap after ossiculoplasty may be due to a malpositioned or displaced prosthesis. Rotational Tomography (RT) has the potential to provide high-resolution images of implants without artifacts and with less radiation dosage than CT scan.
Twenty-seven temporal bone specimens underwent measurements of middle ear transfer function using Laser-Doppler-Vibrometry (LDV) before and after placement of ossicular replacement prostheses (PORPs, TORPs) made of titanium. RT was performed on all specimens.
RT allowed 3-dimensional viewing of the temporal bone, accurate localization of implants within the reconstructed middle ear and determination of angles between the inserted prostheses and the tympanic membrane (TM) and/or the malleus handle (MH). Presence or absence of contact between the implant and the TM, malleus or stapes could be clearly visualized. Displaced prostheses were readily identified. The functional LDV measurements for TORPs showed a trend favoring coupling to the malleus handle, while for PORPs, coupling to the TM was favored. For PORPs, sound transmission was worse with increasing angles between the PORP and stapes superstructure (p<0.05). Following our experimental results RT is an innovative, relevant and useful imaging technique to obtain immediate postoperative feedback after ossicular reconstruction and to precisely determine the position of middle ear implants.
doi:10.1016/j.heares.2009.12.003
PMCID: PMC2866829  PMID: 19969056
Rotational tomography; middle ear; transfer function; prostheses; imaging; inclination angle
24.  Determinants of Hearing Loss in Perforations of the Tympanic Membrane 
Background
Although tympanic membrane perforations are common, there have been few systematic studies of the structural features determining the magnitude of the resulting conductive hearing loss. Our recent experimental and modeling studies predicted that the conductive hearing loss will increase with increasing perforation size, be independent of perforation location (contrary to popular otologic belief), and increase with decreasing size of the middle-ear and mastoid air space (an idea new to otology).
Objective
To test our predictions regarding determinants of conductive hearing loss in tympanic membrane perforations against clinical data gathered from patients.
Study Design
Prospective clinical study.
Setting
Tertiary referral center.
Inclusion Criteria
Patients with tympanic membrane perforations without other middle-ear disease.
Main Outcome Measures
Size and location of perforation; air-bone gap at 250, 500, 1,000, 2,000, and 4,000 Hz; and tympanometric estimate of volume of the middle-ear air spaces.
Results
Isolated tympanic membrane perforations in 62 ears from 56 patients met inclusion criteria. Air-bone gaps were largest at the lower frequencies and decreased as frequency increased. Air-bone gaps increased with perforation size at each frequency. Ears with small middle-ear volumes, ≤4.3 ml (n = 23), had significantly larger air-bone gaps than ears with large middle-ear volumes, >4.3 ml (n = 39), except at 2,000 Hz. The mean air-bone gaps in ears with small volumes were 10 to 20 dB larger than in ears with large volumes. Perforations in anterior versus posterior quadrants showed no significant differences in air-bone gaps at any frequency, although anterior perforations had, on average, air-bone gaps that were smaller by 1 to 8 dB at lower frequencies.
Conclusion
The conductive hearing loss resulting from a tympanic membrane perforation is frequency-dependent, with the largest losses occurring at the lowest sound frequencies; increases as size of the perforation increases; varies inversely with volume of the middle-ear and mastoid air space (losses are larger in ears with small volumes); and does not vary appreciably with location of the perforation. Effects of location, if any, are small.
doi:10.1097/01.mao.0000176177.17636.53
PMCID: PMC2918411  PMID: 16436981
Audiometry; Conductive hearing loss; Perforation; Tympanic membrane; Tympanometry
25.  Auditory sensitivity and the outer hair cell system in the CBA mouse model of age-related hearing loss 
Age-related hearing loss is a highly prevalent sensory disorder, from both the clinical and animal model perspectives. Understanding of the neurophysiologic, structural, and molecular biologic bases of age-related hearing loss will facilitate development of biomedical therapeutic interventions to prevent, slow, or reverse its progression. Thus, increased understanding of relationships between aging of the cochlear (auditory portion of the inner ear) hair cell system and decline in overall hearing ability is necessary. The goal of the present investigation was to test the hypothesis that there would be correlations between physiologic measures of outer hair cell function (otoacoustic emission levels) and hearing sensitivity (auditory brainstem response thresholds), starting in middle age. For the CBA mouse, a useful animal model of age-related hearing loss, it was found that correlations between these two hearing measures occurred only for high sound frequencies in middle age. However, in old age, a correlation was observed across the entire mouse range of hearing. These findings have implications for improved early detection of progression of age-related hearing loss in middle-aged mammals, including mice and humans, and distinguishing peripheral etiologies from central auditory system decline.
doi:10.2147/OAAP.S7202
PMCID: PMC3159169  PMID: 21866215
presbycusis; hearing loss; hair cells; auditory brainstem response; otoacoustic emissions; mouse hearing

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