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AUDIOLOGY·청능재활 ISSN 1738-9399 REVIEW PAPER 2013;9:95-112 Copyright ⓒ 2013 Korean Academy of Audilogy Diagnosis and Characterization of Middle-ear and Cochlear Functions Biomedical and Mechanical Engineering, University of Oklahoma, OK, USA Rong Z. Gan ABSTRACT Hearing impairment is one of the most common physical disabilities in the world. Conductive hearing loss results from dysfunction of the middle ear, and sensorineural hearing loss results from abnormalities within the cochlea or central nervous system. To improve the diagnosis of hearing loss and develop new technologies for restoration of hearing, changes of the middle ear and cochlear functions in relation to ear structural disorders in hearing impaired ears need to be characterized. This paper summarizes our biomedical engineering approach to characterize the middle ear and cochlear functions in normal and diseased ears. With the experimental measurements in human temporal bones and animal models and the finite element (FE) modeling of the human ear, a better understanding of biomechanics of the ear for sound transmission is achieved. The acoustic-mechanical vibration and energy transmission through the middle ear in normal and diseased ears can be visualized and quantified in a 3-dimensional FE model. Four novel model-derived “auditory test curves” named as the middle ear transfer function, energy absorbance, admittance tympanogram, and tympanic membrane holography are generated with clinically relevant applications. Keywords: Cochlea, Ear biomechanics, Finite element model, Hearing loss, Laser vibrometry, Middle ear, Middle ear disorder loss and the abnormalities within the cochlea or INTRODUCTION central nervous system results in sensorineural hearing The human middle ear, including tympanic loss. To improve diagnosis of hearing loss and membrane (TM) and three ossicules (i.e., malleus, develop new technologies for restoration of hearing, incus and stapes) suspended in an air-filled middle ear the changes of the middle ear and cochlear functions cavity by suspensory ligaments/muscles, constitutes a in relation to ear structural disorders in hearing mechanical system for sound transmission from the impaired ears need to be characterized. external ear canal to the inner ear or cochlea. The The first area for function characterization is the middle ear dysfunction results in conductive hearing middle ear transfer function. Sound entry to the middle ear through the TM initiates the transfer Received: Nov 28, 2013 Accepted: Nov 30, 2013 Corresponding Author: Rong Z. Gan, School of Aerospace and Mechanical Engineering, University of Oklahoma, 865 Asp Avenue, Room 200, Norman, OK 73019; E-mail: [email protected]; Tel: 1-405-325-1099 function. Output of the middle ear system is an acoustic-mechanical transmission by the states footplate, which sets into the oval window and transmits vibrations into cochlear fluid. Since the transfer 95 96 AUDIOLOGY·청능재활 2013;9:95-112 function of the middle ear cannot be measured readily middle ear pressure was varied from zero to positive in living humans, various experimental measures using or negative in human temporal bones (Dai et al., 2008a; the fresh human cadaveric temporal bones (Dirckx & Gan et al., 2006a; Ravicz et al., 2004). Decraemer, 1992; Gan et al., 1997, 2001, 2004a; Gyo In addition to studies in temporal bones, the et al., 1987; Merchant et al., 1997; Peake et al., 1992; diseased animal models provide a unique approach to Ravicz et al., 2004; Voss et al., 2000), animal models investigate the effects of changes of middle ear (Dai & Gan, 2008b, 2010; Guan & Gan, 2011, 2013; structure such as the tissue inflammation or infection Larsson et al., 2005; Lee & Rosowski, 2001; Qin et on METF. Animal models of otitis media have been al., 2010; Turcann et al., 2009; von Unge et al., reported in the literature, but the changes of TM 1995), and different theoretical modeling methods mobility and METF are recently reported by our group (Feng & Gan, 2004b; Gan et al., 2004, 2006b, 2010; in otitis media models of guinea pig and chinchilla Goode et al., 1994; Kringlebotn, 1988; Sun et al., (Dai & Gan, 2008b, 2010; Guan & Gan, 2011, 2013a; 2002a; Zhang & Gan, 2011a; Zwislocki, 1962) have Guan et al., 2013a, 2013b). The acoustic-mechanical been used to describe middle ear mechanics in normal, transmissions in otitis media ears are revealed through diseased, and reconstructed ears. those studies with a close relation to structural variations The magnitude of stapes vibration is about 0.1 nm in the middle ear. at the threshold of hearing. To measure such small Moreover, the auditory testing curves of sound vibrations in human temporal bones, laser Doppler energy transduction from the ear canal to middle ear vibrometry (LDV) provides a critical technique for are frequently measured in clinics (Dirks & Morgan, accurately measuring any moving middle ear structures 2000; Feeny et al., 2003, 2009; Keefe et al., 1993; such as the TM, ossicles, and round window membrane Keefe & Simmons, 2003). The wideband acoustic without contact (Dai et al., 2007a, 2007b, 2008a; Gan admittance (tympanogram), middle ear energy absorbance, et al., 2001, 2004a, 2006a, 2009; Hato et al., 2003; and auditory brainstem response (ABR) are also Murakami et al., 1997; Nuttall & Dolan, 1996; Rosowski obtained from animal models of otitis media (Dai & & Lee, 2002). Based LDV measurements of the ear Gan, 2008b; Guan & Gan, 2011). The experimental components in response to sound stimuli in the ear results provide a correlation between the mechanical canal, the middle ear transfer function (METF), defined measurements and hearing level in normal and diseased as the relationship between vibration of the stapes ears. This is the second area of middle ear function footplate and sound pressure level (SPL) in the ear characterization: sound energy transduction through canal or the vibration ratio of the stapes footplate to the ear. the TM, can be characterized over the auditory To better understand the acoustic-mechanical frequency range (Dai et al., 2007b, 2008a; Gan et al., transmission from the ear canal to middle ear and 2004a, 2006a; Guan & Gan, 2011). To further investigate cochlea, different theoretical models have been changes of METF in diseased ears such as otitis developed to simulate the function of the ear. Early media with effusion diagnosed with fluid in the middle modeling of middle ear function used a transformer ear cavity and middle ear pressure different from analogy with circuit models or lumped parameter models ambient pressure, the movements of the TM and reported by Hudde & Weistenhöfer(1997), Kringlebotn stapes footplate are measured while saline or silicone & Gundersen(1985), and Zwislocki(1960). We also fluid was introduced into the middle ear and the published a lumped parametric model of the human ear R Gan : Diagnosis and Characterization of Middle-ear and Cochlear Functions 97 to study the METF (Feng & Gan, 2004). However, METF, energy absorbance (EA), admittance tympanogram the circuit model has the limitation in simulating the (AT), and TM holography are generated with clinically- realistic acoustic-mechanical response in the ear relevant applications. involving complex geometry and an array of material compositions. The finite element (FE) model as a computer-based numerical procedure has distinct advantages in modeling complex biological system such as the ear. FE method is always capable of modeling the MATERIALS AND METHODS 1. Measurement of acoustic-mechanical vibrations with laser Doppler vibrometry complex geometry, ultrastructural characteristics, and As one of few groups in 1990s using LDV to non-homogenous and anisotropic material properties of measure vibrations in the ear, the LDV (Polytec, biological systems. FE models can also determine the Model OFV-501) was first used for measuring the detailed vibration modes, stress distributions, and movement of stapes footplate at the frequencies of 200 dynamic behaviors at any locations in a system, which ~ 8,000 Hz to determine the normal middle ear is not possible with analytical solutions and experimental function and the effect of implant mass on stapes measures (Gan et al., 2004b, 2006b; Koike & Wade, movement (Gan et al., 1997, 2001). The input sound 2002; Lee et al., 2006; Qi et al., 2008; Sun et al, level in the ear canal at 2 mm from the TM (umbo) 2002a, 2002b). A systematic literature search on was increased from 80 to 90 dB and 100 dB. The middle ear FE model and analysis with a focus on FE increase of footplate displacement for every 10 dB modeling of the middle ear transfer functions and SPL change was equal to 10 dB over the whole related pathologies was conducted by Zhao et al. frequency range. The results showed the linearity of (2009). This review paper indicated that the FE model normal METF as the frequency response curves of the of human ear developed by our group was the most stapes footplate displacement in response to sound comprehensive model to date (2009), which was based input level at the TM. When the implant mass was on a complete set of histological section images of the applied at the incus-stapes joint (ISJ), this linearity did temporal bone. not change. The present paper summarizes our biomedical Two LDVs (Polytec, Models CLV-700 and OFV- engineering approach to characterize the middle ear 501) were then used to measure vibrations of the TM, and cochlear functions in normal and diseased ears. stapes, and ISJ. One laser beam (CLV-700) was The experimental measurements of METF in human focused on the TM at the umbo through the ear canal temporal bones and animal models, the measurements and the second laser (OFV-501) was used to measure of mechanical properties of ear tissues, and the finite movement of the stapes footplate or ISJ caused by element modeling of human ear are presented, which acoustic vibration of the TM. Distribution of the provide basic understanding of biomechanics of the ear vibration along ossicular chain was revealed through for sound transmission. The acoustic-mechanical vibration the experiments (Gan et al., 2004a). Stapes and TM and energy transmission through the middle ear in displacement transfer functions were determined using normal and diseased ears are visualized and quantified dual LDV, provided accurate amplitude and phase in a 3-dimensional (3D) FE model of the ear. Four relationships from stapes footplate, ISJ, and TM. novel model-derived “auditory test curves” named as the After the normal function of the middle ear was 98 AUDIOLOGY·청능재활 2013;9:95-112 characterized in temporal bones, the middle ear disease middle ear pressure and fluid levels in the cavity such as otitis media with effusion (OME) was with a correction factor for cochlear load. The results simulated in temporal bones by injecting fluid (saline) demonstrated that the middle ear pressure (positive and into the middle ear cavity and adjusting pressure in negative) reduced the TM motion at frequencies below the middle ear. Two LDVs were used to detect the 1.5 kHz; fluid in the middle ear cavity reduced the change of METF in OME model of temporal bones. TM motion at frequencies over 1 kHz; a combination The experimental setup displayed in Figure 1 is from of fluid and pressure reduced the movement of the Gan et al.(2006a). A hearing laser vibrometer TM at all frequencies (Dai et al., 2008a; Gan et al., (Polytec, CLV-700) was used to measure the vibration 2006a). In addition to a single point LDV, we have of the TM (umbo) and the second LDV (OFV-501) used a scanning laser Doppler vibrometer (Polytec, was used to measure the movement of stapes from the PSV-400) to measure and image the full-field surface medial side of the footplate. The experiment began motion of the TM in temporal bones (Zhang et al, with one laser only to measure the TM displacement 2013). The external ear canal was surgically removed in bones with intact cochlea. The METF, which is until about 90% of the TM surface was visible under defined as the displacement transmission ratio (DTR) the microscope. of the TM to footplate, was derived under different Figure 1. Schematic diagram of the experimental setup in human temporal bones with two laser vibrometers for measuring vibrations at the TM and stapes footplate. One laser was aimed on the TM at the umbo and another laser was aimed on the medial site of the stapes footplate with open cochlea. From Gan et al. (2006a) R Gan : Diagnosis and Characterization of Middle-ear and Cochlear Functions 99 TM displacements were measured under normal (no following LPS injections. The change of the DTR fluid in the middle ear cavity) and diseased conditions from the TM to the round window occurred mainly in (OME, fluid in the cavity) with different fluid levels over chronic (e.g., 14 days post LPS injection) OME ears. frequencies ranging from 0.2 to 8 kHz. The results from To further investigate cochlear function in OME experiments showed that in normal TM a simple ears, displacement of the basilar membrane (BM) in deflection shape with one or two major displacement guinea pig ears with OME (3 and 14 days after LPS peak regions was observed at low frequencies (1 kHz and injection) were measured at the basal turn and the below) while complicated ring-like pattern of the apex (Dai & Gan, 2010). The measurement of BM deflection shapes appeared at higher frequencies (4 kHz movement was conducted in guinea pig temporal and above). The middle ear fluid mainly affected TM bones and all vibration measurements were completed deflection shapes at the frequencies higher than 1 kHz. within 2 h of the guinea pigs’ deaths. The results showed that the displacement sensitivity of the BM at the apex and the basal turn to sound pressure in the 2. Animal models of otitis media for function characterization Otitis media with effusion and acute otitis media (AOM) are two main types of otitis media. OME ear canal was reduced up to 25 dB at their characteristic frequencies, respectively. Cochlear gain with respect to umbo movement was also changed in ears with OME in both groups. describes the symptoms of middle ear effusion without Combined measurements of METF and ABR infection, and AOM is an acute infection of the threshold in live guinea pigs with middle ear effusion middle ear and caused by bacteria in about 70% of (MEE) were reported by Guan & Gan(2011). The MEE cases (Gould & Matz, 2010). With the long term goal was created by injecting saline into the middle ear of evaluating middle ear function with otitis media, cavity from zero (control) to 0.1 and 0.2 ml (full fill of animal models of OME and AOM were created in the cavity). Vibrations of the TM (umbo), the tip of the which middle ear transfer functions could be measured. incus, and the round window membrane were measured OME was created by injecting lipopolysaccharide with a laser vibrometer (Polytec, HLV 1000) at (LPS) into the middle ear in guinea pigs (Dai & Gan, frequencies of 0.2 ~ 40 kHz when the middle ear fluid 2008b, 2010). The experimental animals were divided increased from 0 to 0.2 ml. ABR waveform was into 3 groups based on survival time after LPS recorded as the middle ear fluid increased using the injection (3, 7, or 14 days). These times reflect early, TDT system III (TDT, FL). Repeated click stimuli and medium, and chronic stages, respectively, of OME tone burst stimuli with alternating polarity were after LPS injection. Evidence of OME was assessed delivered by the speaker (CF1, TDT) with the sound by otoscopy, tympanograms, histological sections of delivery tube placed 4 mm away from the umbo. In this the TM, and by measuring the volume of fluid study, the METF was represented by DTR of the TM (effusion) in the middle ear. Vibrations of the umbo to the incus tip, which varied with frequency and fluid and round window membrane were measured with a level. The MEE reduced the displacement of TM, incus LDV (Polytec, Model HLV 1000) at the frequency tip, and round window membrane mainly at high range of 0.2 ~ 40 kHz in control and three groups of frequencies and the reduction was related to the OME ears. Displacement of both the umbo and round volume of fluid in the cavity. window membrane was reduced at all time-points 100 AUDIOLOGY·청능재활 2013;9:95-112 Figure 2. Observations of the TM and ossicles in control and diseased guinea pig ears after 3 days of inoculation. Upper panel: otoscopic photographs of TM in control (A), OME (B), and AOM ear (C). Lower panel: microscopic photographs of middle ear ossicles in control (D), OME (E), and AOM ear (F). From Guan et al. (2013ae) (Color in online) Acute otitis media was created in both guinea pig behind the TM. In AOM ear (Figure 2C), purulent and chinchilla by using two most common bacterial effusion was observed in the middle ear and the TM pathogens: Streptococcus pneumonia and Haemophilus showed distinct redness resulting from dilation of blood influenza reported by Guan & Gan(2013) and Guan et vessels. Figures 2D ~ 2F display the typical ossicular al.(2013a, 2013b). The AOM model of guinea pig was chain and the round window niche in normal, OME, and created by intrabullar injection of Streptococcus AOM ears. In control ear (Figure 2D), there were no pneumonia type 3 (Guan & Gan, 2013; Guan et al., signs of middle ear inflammation, and the middle ear 2013a) and the AOM model of chinchilla was created ossicles were clearly identified. In OME ear (Figure 2E), by injection of Haemophilus influenza (Guan et al., the ossicular chain appeared normal. In AOM ear (Figure 2013b). The microscopic observations and histological 2F), the purulent adhesions were formed between the section images of the TM, middle ear cavity, and ossicles and the middle ear bony wall and commonly ossicles showed the morphological or middle ear observed between the manubrium and promontory, and structural changes in AOM ears. Figure 2 displays the around the oval window and round window niche. microscopic observations of the TM and middle ear in The displacement of the TM at the umbo in control, OME, and AOM ears of guinea pigs (Guan et response to 80 dB SPL sound in the ear canal was al., 2013a). In normal ear (Figure 2A), the TM was measured in AOM ears using LDV and compared translucent and no fluid was visible behind the TM. with those obtained from control and OME ears. It In OME ear (Figure 2B), serous effusion was present was found that the TM mobility in AOM ears was R Gan : Diagnosis and Characterization of Middle-ear and Cochlear Functions 101 lower than that in experimental OME ears at low along our three models: from the TM and middle ear frequencies, and the difference was mainly caused by ossicular chain only (Model #1) to the complete the middle ear ossicular structure changes during the middle ear with the cavity and external ear canal bacterial infection in AOM (Guan et al., 2013a). (Model #2) and to the entire ear with the spiral cochlea (Model #3). All the models have the accurate 3. 3D FE model of the human ear Using the combined technologies of FE analysis geometric configurations of the ear components and the capability to analyze the transmission of sound pressure-induced vibrations through the ear. and 3D reconstruction, we have published three FE Model #3 (male, age 52, left ear) was first reported models of the human ear based on the complete sets by Gan & Wang(2007) without cochlea attached to the of histological section images of three adult temporal oval window or stapes. This preliminary model provided bones (Gan & Wang, 2007; Gan et al., 2002, 2004b, insight into simulation of middle ear effusion and the 2006b, 2007; Gan et al., 2009, 2010; Sun et al., 2002a, acoustic-structure-fluid coupled FE analysis. The model 2002b; Wang et al., 2007; Zhang & Gan, 2011a, 2013a). included the external ear canal, middle ear ossicles The 3D solid model was first constructed based on with attached ligaments and muscle tendons, and histological section images using the 3D geometry middle ear cavity. By introducing saline or silicon reconstruction software such as SolidWorks. Then, the fluid into the middle ear cavity, Gan & Wang model was meshed into a number of elements using quantitatively evaluated how fluid level and viscosity HyperMesh software. Finally, the meshed model was affected the middle ear transfer function. Recently, this input into ANSYS for FE analysis. Our long-term goal model has been improved by adding the spiral cochlea for modeling of the ear is to develop a comprehensive with three chambers of the scala vestibule (ST), scala 3D model of the human ear with clinically-relevant media (SM) and scala tympani (ST) separated by applications. cochlear basilar membrane and Reissner’s membrane as The complexity of FE model was gradually increased shown in Figure 3 (Zhang & Gan, 2011a, 2013a). Figure 3. (A) FE model of the human ear in anterior-medial view. The model consists of external ear canal, TM, 3 ossicles, 2 joints, 6 ligaments and muscle tendons, stapedial annual ligament, middle ear cavity, and cochlea. (B) FE model of cochlea with the BM (SV, SM and RM are shown transparently). (C) Cross section of cochlea model showing three chambers and two membranes. From Zhang & Gan (2011a) (Color in online) 102 AUDIOLOGY·청능재활 2013;9:95-112 The basilar membrane has two and half turns from 2012a, 2012b). Compared with the adult model, the ear the base to the apex. Helicotrema is the place where canal volume and middle ear cavity volume of the the SV and ST chambers are connected with each pediatric model are smaller than those in the adult other. This is the most comprehensive ear model up model. However, dimensions of cochlea in pediatric to date and is capable to analyze middle ear and model are similar to that of the adult model. The cochlear functions and the interactions between the validation process for the pediatric model is currently middle ear and cochlea. under investigation with a focus on identifying In addition to the importance of anatomic structure mechanical properties of soft tissues for young subjects. for an ear model, the accuracy of FE model for function analysis also depends on material properties of model components such as the mechanical RESULTS properties of middle ear soft tissues. In the previously published models (Gan & Wang, 2007; Gan et al., 2002, 2004b, 2006b, 2007, 2009; Sun et al., 2002a), 1. Validation of the FE model in simulating middle ear and cochlea functions the TM, suspensory ligaments and muscle tendons To validate the FE model of human ear, 90 dB were all assumed as elastic materials. In fact, the SPL pure tones were applied in the ear canal with 2 human ear works at the auditory frequency range from mm away from the TM. Harmonic structure-acoustic 20 Hz to 20 kHz and the ear tissues show viscoelastic -fluid coupled analysis was conducted over the auditory or frequency-dependent dynamic properties which were frequency range from 0.2 to 10 kHz. The METF measured and confirmed in our lab (Gan et al., 2013; defined as the displacement of the TM and stapes Luo et al., 2009a, 2009b; Zhang & Gan, 2010, 2013b, footplate (FP) were derived from the FE model and 2013c). Thus, the dynamic properties of middle ear compared with the published experimental measurements tissues should be included in FE model to achieve the (Figure 4A). The sound pressure gain defined as the accurate analysis for acoustic-mechanical transmission. ratio between fluid pressure at the base of cochlear SV In our comprehensive FE model of the human ear, the and sound pressure at the ear canal was derived from viscoelastic material properties are applied to the the model and compared with the published experimental middle ear soft tissues and the model has resulted in data (Zhang & Gan, 2011a) (Figure 4B). a better simulation of METF over the auditory The model was further validated for middle ear frequency range from 0.2 to 10 kHz (Zhang & Gan, input impedance and energy absorbance in comparison 2011a, 2013a). with the experimental results in Figure 5. Figures 5A Considering otitis media is the most frequently and 5B show the magnitude and phase of the model- diagnosed illness in young children, a pediatric model derived middle ear impedance at the TM compared is needed for investigating the mechanisms of otitis with the experimental results measured on human media in pediatric population. Based on the histological temporal bones by Rabinowitz(1981), Stepp & Voss section images of a temporal bone (male, 4-year old, (2005), and Voss et al.(2000). left ear), a pediatric model is constructed in our lab. A general agreement between the model and This model consists of the ear canal, TM, middle ear experimental results was observed over the frequency ossicles with suspensory ligaments and muscle tendons, range of 0.2 to 4 kHz. middle ear cavity, and spiral cochlea (Zhang & Gan, R Gan : Diagnosis and Characterization of Middle-ear and Cochlear Functions 103 Figure 4. (A) Displacement of the TM and stapes footplate (FP) derived from the FE model compared with the experimental measurements in human temporal bones. (B) Sound pressure gain derived from FE model compared with published experimental data. From Zhang & Gan(2011a) Figure 5C shows the model-derived EA curve compared with the clinical measurements in patients’ ears of normal hearing at frequencies of 0.2 to 8 kHz. The model-derived EA was generally consistent with those reported by Feeney et al.(2003), Keefe et al. (2003), Margolis et al.(1999), and Voss & Allen(1994). The model-derived EA values were slightly higher than the mean values of the published results from 3 to 5 kHz. However, it was still in the 5% to 95% Figure 5. (A) and (B): The FE model-derived middle ear (ME) input impedance at TM (thick solid line) compared with the published experimental data in magnitude (A) and phase (B). (C): The FE model- derived energy absorbance (EA) (thick solid line) compared with the published measurement data on human ears. The thin dot lines represent the 5-95% range of EA measured on 75 normal-hearing adults by Feeney et al. (2003). From Zhang & Gan (2013a) (Color in online) range of EA measured on 75 normal-hearing adults by Feeney et al.(2003). the model was used to investigate the efficiency of After validation with the experimental measurements the forward and reverse mechanical driving with middle obtained in human temporal bones and the clinical data, ear implant and the passive vibration of basilar 104 AUDIOLOGY·청능재활 2013;9:95-112 membrane with cochlear implant placed in the cochlear (AT), and TM holography. Among these 4 curves, scala tympani. The middle ear transfer function and METF represents equivalent conductive hearing loss as the cochlear function of the basilar membrane vibration the displacement of stapes footplate per sound pressure were derived from the model. This comprehensive ear in the ear canal; AT represents the compliance of the model provides a novel computational tool to visualize middle ear as the ratio of volume velocity of the TM and compute the implantable hearing devices and to pressure; EA shows the ratio of energy absorbed by surgical procedures (Gan et al., 2010; Zhang & Gan, the middle ear; TM holography (time-average) 2011a). illustrates a full-field view of TM motion with displacement of each point on the TM. Each curve is 2. FE model-derived auditory test curves - auditory test modeling system (ATMS) correlated to patient age (adult or young children) and disease with defined parameters of the middle ear structure and tissue mechanical properties. ATMS software is built based on two 3D FE Users can input the patient information and models of the human ear: the adult and pediatric clinical observations into ATMS and select the models and some preliminary results are reported function they want to check, such as the METF, EA, recently by Gan et al.(2014) and Ji et al.(2013). ATMS AT, or TM holography. For example, for observations allows audiologists and physicians to input the patient of “TM stiffness increase”, the stiffness change of information and their observations during the hearing the TM (pars tensa and flaccida), or incus-stapes test. The software package includes two normal joint, or stapedial annular ligament can be selected models and two diseased models named as “general separately or together. Figures 6 ~ 8 show a few middle ear disorders” and “otitis media” for both adult examples of the auditory curves under “general and pediatric ears. The outputs from ATMS are 4 middle ear disorders” directory in ATMS database. novel model-derived “auditory test curves”: the middle The curves reflect the effects of stiffness changes ear transfer function (METF), wideband energy of the middle ear on METF, AT, and EA. absorbance (EA), wideband admittance tympanogram Figure 6. (A) The METF curves in response to stiffness changes of IS joint in ATMS database (B) The AT curves over ear canal pressure level from -300 to 300 daPa in response to TM stiffness changes in ATMS database (Color in online) R Gan : Diagnosis and Characterization of Middle-ear and Cochlear Functions 105 Figure 6A shows the METF (stapes footplate not linearly related to the change of TM stiffness. At displacement) vary with the IS joint stiffness. As can frequencies above 4 kHz, there was no significant be seen in this figure, the METF is not sensitive to change of EA as TM stiffness varied. Figure 7B stiffness increasing between 1.5 and 4 times the shows the EA in response to the ossicular chain normal value. However, when the stiffness increased to stiffness changing into 0.2, 5, 25, and 100 times the 8 times the normal value, the stapes footplate normal value. When the ossicular chain became stiffer displacement was increased by 10 ~ 20 dB over the (×5, ×25 or ×100), the EA decreased at frequencies entire frequency range. The decrease of stiffness (×0.5) below 4 kHz, while it increased above 4 kHz. When resulted in decreasing of footplate displacement at the ossicular chain stiffness increased more than 25 frequencies below 2 kHz. Figure 6B shows the AT–ear times the normal value, there was only a minor canal pressure curves at any frequency (e.g., 226 Hz) change of EA. In that situation, the EA was dominated as the TM stiffness varies. The admittance increases as by the properties of the TM. As shown in Figure the stiffness decreased and decreases as the stiffness 7B, the softer ossicular chain (0.2 times normal increased. stiffness) resulted in a second peak at 1 kHz, similar Figure 7A shows the wideband EA presented as 2D to the EA with disarticulated ossicular chain (Zhang EA-frequency curves in response to the TM stiffness & Gan, 2013a). The 3D EA-frequency-ear canal changing into 0.5, 1.5, 2, 4, and 8 times the normal pressure curves of the ear with the normal and stiffer value. As can be seen in Figure 7A, the TM stiffness TM (×4 times the normal value) are displayed in has a significant effect on EA at frequencies below 4 Figure 8. The 3D curves visualize the change of EA kHz. The increasing of TM stiffness resulted in the with respect to both the ear canal pressure and decreasing of EA. However, the reduction of EA was frequency. Figure 7. The EA curves over the frequency range from 200 to 8,000 Hz in response to TM stiffness changes (A) and middle ear ossicular stiffness changes (B) in ATMS database (Color in online) 106 AUDIOLOGY·청능재활 2013;9:95-112 Figure 8. The 3D EA curves varying with frequency and ear canal pressure: (A) normal ear, (B) the ear with TM stiffness increased by 4 times the normal value (Color in online) Examples of auditory curves under “otitis media” 0.3 ml. When fluid was 0.1 ml, the pressure dominantly directory in ATMS database are shown in Figure 9. affected EA, especially at the frequencies lower than Figure 9A shows the EA-frequency curves in 4 kHz. When fluid increased to 0.3 ml, EA was response to negative middle ear pressure (MEP) critically affected by the fluid. The low MEE with levels: -50, -100, -150, and -200 daPa. As the MEP high MEP mainly affected EA at low frequencies, was reduced from 0 (normal) to -200 daPa, the while the high MEE with low MEP significantly slope of the EA curve at low frequencies (below 2 changed EA at high frequencies. kHz) decreased. The EA curve became flatter under larger MEP. EA reached its maximum value around 4 kHz, which did not change with the MEP level. DISCUSSIONS AND Figure 9B shows the change of EA-frequency curves CONCLUSIONS when middle ear effusion (MEE) levels reached 0.1, 0.3, 0.4, and 0.6 ml at zero MEP. When MEE Auditory test tools commonly used in clinics increased to 0.3 ml (up to the umbo), the EA was include the measurements of audiogram, tympanogram, significantly reduced at frequencies above 600 Hz. energy absorbance or reflectance, and ABR. To exam When MEE further increased to 0.6 ml (middle ear the ear or structural changes of the ear, physicians cavity filled), the EA-frequency curve was flat over routinely check patient’s otoscopy and occasionally the entire frequency range of 200 Hz to 8 kHz. check the CT or MRI images to identify the status of There was almost no EA predicted when the middle ear disorders. However, the exact cause of hearing ear cavity was filled with fluid, which means no loss in the tested ear may not be visible on physical acoustic energy was transferred into the middle ear. or radiological examination. The anatomic constrains Figure 9C shows EA curves at four combinations of provide challenges for audiologists or physicians to MEP and MEE levels: -50 daPa & 0.1 ml, -50 daPa explain the diagnosis results and the treatment options & 0.3 ml, -100 daPa & 0.1 ml, and -100 daPa & for hearing impairment. R Gan : Diagnosis and Characterization of Middle-ear and Cochlear Functions Figure 9. The EA curves of otitis media ear over the frequency range from 200 to 8,000 Hz in response to negative middle ear pressure (A), middle ear fluid volume (B), and combined negative pressure and fluid (C) 107 108 AUDIOLOGY·청능재활 2013;9:95-112 As reported in this paper, the comprehensive FE Acknowledgements model of the human ear developed by our group through a series of stages has demonstrated the The work was supported by NIH R01DC006632 advantages of this model in simulating the anatomy and R01DC011585. The author thanks her all former and function of the ear. This model can assist and current students, postdocs, and research collaborators audiologists and physicians to interpret the diagnosis of for their contributions to the work reported in this ear function changes in relation to its structural paper. variations in diseased or disordered ears. 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