In vivo dynamic characterization of the human tympanic membrane using pneumatic optical coherence tomography

Decreased mobility of the human eardrum, the tympanic membrane (TM), is an essential indicator of a prevalent middle ear infection. The current diagnostic method to assess TM mobility is via pneumatic otoscopy, which provides subjective and qualitative information of subtle motion. In this study, a handheld spectral-domain pneumatic optical coherence tomography system was developed to simultaneously measure the displacement of the TM, air pressure inputs applied to a sealed ear canal, and to perform digital pneumatic otoscopy. A novel approach based on quantitative parameters is presented to characterize spatial and temporal variations of the dynamic TM motion. Furthermore, the TM motions of normal middle ears are compared with those of ears with middle ear infections. The capability of noninvasively measuring the rapid motion of the TM is beneficial to understand the complex dynamics of the human TM, and can ultimately lead to improved diagnosis and management of middle ear infections.     

Smartphone‐based spectral imaging otoscope: System development and preliminary study for evaluation of its potential as a mobile diagnostic tool

We develop a novel smartphone‐based spectral imaging otoscope for telemedicine and examine its capability for the mobile diagnosis of middle ear diseases. The device was applied to perform spectral imaging and analysis of an ear‐mimicking phantom and a normal and abnormal tympanic membrane for evaluation of its potential for the mobile diagnosis. Spectral classified images were obtained via online spectral analysis in a remote server. The phantom experimental results showed that it allowed us to distinguish four different fluids located behind a semitransparent membrane. Also, in the spectral classified images of normal ears (n = 3) and an ear with chronic otitis media (n = 1), the normal and abnormal regions in each ear could be quantitatively distinguished with high contrast. These preliminary results thus suggested that it might have the potentials for providing quantitative information for the mobile diagnosis of various middle ear diseases.     

3D finite element model of the chinchilla ear for characterizing middle ear functions

Chinchilla is a commonly used animal model for research of sound transmission through the ear. Experimental measurements of the middle ear transfer function in chinchillas have shown that the middle ear cavity greatly affects the tympanic membrane (TM) and stapes footplate (FP) displacements. However, there is no finite element (FE) model of the chinchilla ear available in the literature to characterize the middle ear functions with the anatomical features of the chinchilla ear. This paper reports a recently completed 3D FE model of the chinchilla ear based on X-ray micro-computed tomography images of a chinchilla bulla. The model consisted of the ear canal, TM, middle ear ossicles and suspensory ligaments, and the middle ear cavity. Two boundary conditions of the middle ear cavity wall were simulated in the model as the rigid structure and the partially flexible surface, and the acoustic-mechanical coupled analysis was conducted with these two conditions to characterize the middle ear function. The model results were compared with experimental measurements reported in the literature including the TM and FP displacements and the middle ear input admittance in chinchilla ear. An application of this model was presented to identify the acoustic role of the middle ear septa—a unique feature of chinchilla middle ear cavity. This study provides the first 3D FE model of the chinchilla ear for characterizing the middle ear functions through the acoustic-mechanical coupled FE analysis.     

耳内镜与显微镜下Ⅰ型鼓室成形术治疗慢性化脓性中耳炎的疗效比较及术后短期内听力恢复效果的影响因素分析

摘要 目的：比较耳内镜与显微镜下Ⅰ型鼓室成形术治疗慢性化脓性中耳炎的疗效,并分析术后短期内听力恢复效果的影响因素。方法：选取2019年3月~2022年2月期间我院收治的158例慢性化脓性中耳炎患者,均接受Ⅰ型鼓室成形术治疗,根据手术方式不同分为耳内镜组（81例）和显微镜组（77例）,比较两组临床疗效及术后6个月的听力恢复不良发生率。收集相关资料,采用多因素Logistic回归分析术后短期内听力恢复效果的影响因素。结果：两组鼓膜穿孔发生例数组间对比无统计学差异（P>0.05）。耳内镜组的手术时间、住院时间短于显微镜组,术中出血量、医疗费用、干耳时间>1个月例数、耳廓麻木发生例数少于显微镜组（P<0.05）。耳内镜组、显微镜组术后6个月的听力恢复不良发生率组间对比无统计学差异（P>0.05）。单因素分析结果显示,慢性化脓性中耳炎患者术后6个月听力恢复效果与鼓室黏膜、鼓膜张肌腱、咽鼓管情况、是否鼓室硬化、听小骨周围是否肉芽包裹、术前鼓室内是否有脓性分泌物有关（P<0.05）。多因素Logistic回归分析显示,鼓膜张肌腱缺损、咽鼓管不通、鼓室硬化、听小骨周围肉芽包裹、术前鼓室内有脓性分泌物是慢性化脓性中耳炎患者术后短期内听力恢复不良的危险因素（P<0.05）。结论：与显微镜下Ⅰ型鼓室成形术治疗慢性化脓性中耳炎相比,耳内镜下进行手术可缩短手术时间、住院时间,减少术中出血量和住院费用,降低并发症发生率。此外,患者术后短期内听力恢复效果受到鼓膜张肌腱、咽鼓管、鼓室硬化、听小骨周围肉芽包裹、术前鼓室内脓性分泌物等多种因素的影响。     

化脓性中耳炎病原菌感染的研究进展

化脓性中耳炎是耳鼻喉科临床常见疾病,可导致听力下降、鼓膜充血、鼓膜穿孔、耳鸣、耳痛及流脓等。化脓性中耳炎主要由微生物进入中耳引起感染,使中耳黏膜发生化脓性病变,且不同患者感染的病原菌不同。本文从化脓性中耳炎的发病机制、病原菌及其耐药性和治疗方法等几个方面进行综述,以期为临床化脓性中耳炎的诊断及合理用药提供参考。     

Non‐invasive optical assessment of viscosity of middle ear effusions in otitis media

Eustachian tube dysfunction can cause fluid to collect within the middle ear cavity and form a middle ear effusion (MEE). MEEs can persist for weeks or months and cause hearing loss as well as speech and learning delays in young children. The ability of a physician to accurately identify and characterize the middle ear for signs of fluid and/or infection is crucial to provide the most appropriate treatment for the patient. Currently, middle ear infections are assessed with otoscopy, which provides limited and only qualitative diagnostic information. In this study, we propose a method utilizing cross‐sectional depth‐resolved optical coherence tomography to noninvasively measure the diffusion coefficient and viscosity of colloid suspensions, such as a MEE. Experimental validation of the proposed technique on simulated MEE phantoms with varying viscosity and particulate characteristics is presented, along with some preliminary results from in vivo and ex vivo samples of human MEEs.

In vivo Optical Coherence Tomography (OCT) image of a human tympanic membrane and Middle Ear Effusion (MEE) (top), with a CCD image of the tympanic membrane surface (inset). Below is the corresponding time‐lapse M‐mode OCT data acquired along the white dotted line over time, which can be analyzed to determine the Stokes–Einstein diffusion coefficient of the effusion.     

Biomechanics of the tympanic membrane

The tympanic membrane is a key component of the human auditory apparatus which is a complex biomechanical system, devoted to sound reception and perception. Over the past 30 years, various bioengineering approaches have been applied to the ear modeling and particularly to the middle part. The tympanic membrane, included in the middle ear, transfers sound waves into mechanical vibration from the ear canal into the middle ear. Changes in structure and mechanical properties of the tympanic membrane due to middle ear diseases or damages can deteriorate sound transmission. An accurate model of the tympanic membrane, which simulates the acoustic-mechanical transmission, could improve clinical surgical intervention. In this paper a detailed survey of the biomechanics and the modeling of the tympanic membrane focusing on the finite element method is conduced. Eight selected models are evaluated and compared deducing the main features and most design parameters from published models, mainly focusing on geometric, constraint and material aspects. Non-specified parameters are replaced with the most commonly employed values. Our simulation results (in terms of modal frequencies and umbo displacement), compared with published numerical and experimental results, show a good agreement even if some scattering appears to indicate the need of further investigation and experimental validation.     

Static versus dynamic gerbil tympanic membrane elasticity: derivation of the complex modulus

An accurate estimation of tympanic membrane stiffness is important for realistic modelling of middle ear mechanics. Tympanic membrane stiffness has been investigated extensively under either quasi-static or dynamic loading conditions. It is known that biological tissues are sensitive to strain rate. Therefore, in this work, the mechanical behaviour of the tympanic membrane was studied under both quasi-static and dynamic loading conditions. Experiments were performed on the pars tensa of four gerbil tympanic membranes. A custom-built indentation apparatus was used to perform in situ tissue indentations and testing was done applying both quasi-static and dynamic sinusoidal indentations up to 8.2?Hz. The unloaded shape of the tympanic membrane was measured and used to create specimen-specific finite element models to simulate the experiments. The frequency dependent Young's modulus of each specimen was then estimated by an inverse analysis in which the error between experimental and simulated indentation data was optimised for each indentation frequency separately. Using an 8?μm central region thickness, we found Young's moduli between 71 and 106?MPa (n = 4) at 0.2?Hz indentation frequency. A standard linear viscoelastic model and a viscoelastic model with a continuous relaxation spectrum were used to derive a complex modulus in the frequency domain. Due to experimental limitations, the indentation frequency upper limit was 8.2?Hz. The average relative modulus increase in this domain was 14% and the increase was the strongest below 6?Hz.     

Viscoelastic properties of gerbil tympanic membrane at very low frequencies

The tympanic membrane transfers sound waves in the ear canal to mechanical vibrations in the middle ear and cochlea. Good estimates of the mechanical properties of the tympanic membrane are important to obtain realistic models. Up till now, only limited resources about tympanic membrane viscoelastic properties are available in the literature. This study aimed to quantify the viscoelastic properties of gerbil tympanic membrane. Step indentations were applied with a custom indenter on four fresh, intact tympanic membranes and the resulting force relaxation was measured. The reduced relaxation functions were then fitted with two viscoelastic model representations: a 5-parameter Maxwell model and a model with a continuous relaxation spectrum. The average relaxation function is described by an initial rapid decrease of 6.5% with characteristic time 0.77 s, followed by a long term decrease with characteristic time 46 s that gradually tends stable till a total relaxation of 15%. The relaxation curves in the time domain were transformed to complex moduli in the frequency domain. It was found that these transformations yield information on strain-rate dependence only from quasi-static to the very lowest acoustic frequencies. Finally, relaxation and hysteresis were simulated in a finite element model with viscoelastic material properties.     

A mathematical model of the primary visual cortex and hypercolumn

A mathematical model of the primary visual cortex is presented. Basically, the model comprises two features. Firstly, in analogy with the principle of the computerized tomography (CT), it assumes that simple cells in each hypercolumn are not merely detecting line segments in images as features, but rather that they are as a whole representing the local image with a certain representation. Secondly, it assumes that each hypercolumn is performing spatial frequency analyses of local images using that representation, and that the resultant spectra are represented by complex cells. The model is analyzed using numerical simulations and its advantages are discussed from the viewpoint of visual information processing. It is shown that 1) the proposed processing is tolerant to shifts in position of input images, and that 2) spatial frequency filtering operations can be easily performed in the model.     

A novel multi-head CNN design to identify plant diseases using the fusion of RGB images

Plant diseases and insect pests cause a significant threat to agricultural production. Early detection and diagnosis of these diseases are critical and can reduce economic losses. The recent development of deep learning (DL) benefits various fields, such as image processing, remote sensing, medical diagnosis, and agriculture. This work proposed a novel approach based on DL for plant disease detection by fusing RGB and segmented images. A multi-headed DenseNet-based architecture was developed, considering two images as input. We evaluated the model on a public dataset, PlantVillage, consisting of 54183 images with 38 classes. The fivefold cross-validation technique achieved an average accuracy, recall, precision, and f1-score of 98.17%, 98.17%, 98.16%, and 98.12%, respectively. The proposed approach can distinguish various plant diseases with different characteristics by image fusion. The high success rate with low standard deviation proves the robustness of the model, and the model can be integrated into plant disease detection and early warning system.     

Fine structure of the noctuid moth ear. I. The transducer area and connections to the tympanic membrane in Feltia subgothica haworth

The sensillum of the ear of Feltia subgothica contains two ciliated receptor cells, the A cells. The cilium of each is enclosed within a well developed scolops consisting of a cap, a set of scolopalial rods and a collar, an unusual structure contained within the dendrite. The tip of the cilium is inserted in a channel in the scolopalial cap. The cap is linked to the tympanic membrane by a series of three structures: a cap cell, a microtubular shaft and a microfibrillar plug. The two latter structures are heavily reinforced by cytoskeletal elements and the microfibrillar plug is actually continuous with the tympanic membrane. These three structures transmit the vibration of the tympanic membrane to the scolops. The simplicity and accessibility of the ear suggests that it might be a good system in which to investigate cellular events associated with transduction of sound in these receptors.     

Formation of the middle ear: recent progress on the developmental and molecular mechanisms

The middle ear allows animals to hear while moving in an aerial medium. It is composed of a cavity harbouring a chain of three ossicles that transmit vibrations produced by airborne sound in the tympanic membrane into the inner ear, where they are converted into neural impulses. The middle ear develops in the branchial arches, and this requires sequential interactions between the epithelia and the underlying mesenchyme. Gene-inactivation experiments have identified genes required for the formation of different middle ear components. Some encode for signalling molecules, including Endothelin1 and Fgf8, probable mediators of epithelial-mesenchymal interactions. Other genes, including Eya1, Prx1, Hoxa1, Hoxa2, Dlx1, Dlx2, Dlx5, and Gsc, are most likely involved in patterning and morphogenetic processes in the neural crest-derived mesenchyme. Mechanisms controlling formation of a functional tympanic membrane are also discussed. Basically, the tympanic ring, which serves as support for the tympanic membrane, directs invagination of the first pharyngeal cleft ectoderm to form the external acoustic meatus (EAM), which provides the outer layer of the membrane. Gsc and Prx1 are essential for tympanic ring development. While invaginating, the EAM controls skeletogenesis in the underlying mesenchyme to form the manubrium of the malleus, the link between the membrane and the middle ear ossicles.     

Assembling a functional tympanic membrane: signals from the external acoustic meatus coordinate development of the malleal manubrium

In terrestrial mammals, hearing starts with the perception of acoustic pressure by the tympanic membrane. Vibrations in this membrane are then transduced into the inner ear by the ossicle chain of the middle ear, composed of the malleus, incus and stapes. The proper connection of the ossicle chain with the tympanic membrane, provided by the insertion of the manubrium of the malleus into the eardrum, is essential for the functionality of the hearing apparatus. We describe here the mechanisms regulating the development of the manubrium and its integration into the tympanic membrane. We show that the external acoustic meatus (EAM), which eventually forms the outer epithelium of the tympanic membrane, plays an essential role in this developmental process. Histological and expression analyses indicate that the manubrium develops close to the EAM with a similar temporal sequence. In addition, when the middle ear ossicles are allowed to develop in vitro under conditions that do not support further EAM development, the manubrium develops only up to the stage of its induction at the time of explantation. Moreover, genetically or teratogenically derived alterations in the EAM also have an effect on manubrial development. Finally, we show that the EAM is the source of two quite opposite activities, one that induces chondrogenesis and another that represses it. The combination of these two activities results in the proper positioning of the manubrium.     

Rotation of middle ear ossicles during cetacean development

Cetacean middle ears are unique among mammals in that they have an elongated tympanic membrane, a greatly reduced manubrium mallei, and an incudal crus longum that is shorter than the crus breve. Elongation of the tympanic membrane and reduction of the manubrium is thought to be related to an evolutionary rotation of the incus and malleus out of the plane of the tympanic membrane. We examined if rotation also occurs during ontogeny by comparing the middle ears of two species of dolphins (Delphinus delphis, Stenella attenuata) at different stages of development. We observed that: the incus has the body and crural proportions as in terrestrial mammals early in development; the incudomallear complex rotates approximately 90 degrees following ossification; the tympanic membrane is not elongated until relatively late in development. Therefore, some of the unique characteristics of the cetacean middle ear develop as modifications of an initially terrestrial-like morphology.     

Microvascular networks in tympanic membrane, malleus periosteum, and annulus perichondrium of neonatal mongrel dog: a vasculoanatomic model for surgical considerations

India-ink-imaged blood-vessel networks in cleared tympanic membranes and adnexa from ten neonatal dogs were examined microscopically and photographed. The major significance of the study lies in documentation of a dual source of arterial supply, a bilaminar relationship of arterial and venous plexuses intrinsic to the tympanic membrane, and a consistent major venous pathway relative to a definite locus (pars flaccida of the membrane). Illustration of all three types of blood pathways (arteries, veins, and capillaries) provides new vasculoanatomic data that are essential to ear surgery, specifically--to myringotomies and myringoplasties. A comparison was made between dog and human tympanic membrane structures and their arterial supplies. Close similarities suggested that dog tympanic membrane might serve as a suitable model for development of innovative surgical procedures and as a model for rehearsal of difficult techniques. The results of this investigation provide a valuable caveat to otologists.     

Investigation of the human tympanic membrane oscillation ex vivo by Doppler optical coherence tomography

Investigations of the tympanic membrane (TM) can have an important impact on understanding the sound conduction in the ear and can therefore support the diagnosis and treatment of diseases in the middle ear. High‐speed Doppler optical coherence tomography (OCT) has the potential to describe the oscillatory behaviour of the TM surface in a phase‐sensitive manner and additionally allows acquiring a three‐dimensional image of the underlying structure. With repeated sound stimuli from 0.4 kHz to 6.4 kHz, the whole TM can be set in vibration and the spatially resolved frequency response functions (FRFs) of the tympanic membrane can be recorded. Typical points, such as the umbo or the manubrium of malleus, can be studied separately as well as the TM surface with all stationary and wave‐like vibrations. Thus, the OCT methodology can be a promising technique to distinguish between normal and pathological TMs and support the differentiation between ossicular and membrane diseases. (© 2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

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.     

Middle-ear development

Laser interferometry was used to measure umbo velocity in the developing BALB/c mouse middle ear at 133 pure-tone frequencies between 2.0 kHz and 40.0 kHz, all at a constant 100 dB sound pressure level. Umbo velocities increased with age across the entire frequency range, and reached adult-like levels by about 19 days between 2.0 and 22.0 kHz. Velocities at 28.0 and 34.0 kHz took 27 and 52 days respectively to reach adult-like levels.A simple middle-ear model utilizing compliance, resistance, and inertia elements matched the general trends of our velocity results and provided an indication of the anatomical basis for the growth in umbo velocity. The model suggested that velocity development at the lowest frequencies may be attributed to increases in tympanic membrane compliance. The model also indicated that both the frictional resistance of the middle ear and the inertia of the tympanic membrane and ossicles decreased during the growth period.At frequencies below 20.0 kHz, age-related increases in umbo velocity coincided with improvements in Nj₁ thresholds recorded from the round window and evoked potential thresholds obtained from the cochlear nucleus. These results indicated that the functional development of the middle-ear plays a major role in the development of hearing in the mouse.Portions of this work were presented at the Fifteenth Meeting of the Association for Research in Otolaryngology     

Mechanisms of Hearing Loss after Blast Injury to the Ear

Given the frequent use of improvised explosive devices (IEDs) around the world, the study of traumatic blast injuries is of increasing interest. The ear is the most common organ affected by blast injury because it is the body’s most sensitive pressure transducer. We fabricated a blast chamber to re-create blast profiles similar to that of IEDs and used it to develop a reproducible mouse model to study blast-induced hearing loss. The tympanic membrane was perforated in all mice after blast exposure and found to heal spontaneously. Micro-computed tomography demonstrated no evidence for middle ear or otic capsule injuries; however, the healed tympanic membrane was thickened. Auditory brainstem response and distortion product otoacoustic emission threshold shifts were found to be correlated with blast intensity. As well, these threshold shifts were larger than those found in control mice that underwent surgical perforation of their tympanic membranes, indicating cochlear trauma. Histological studies one week and three months after the blast demonstrated no disruption or damage to the intra-cochlear membranes. However, there was loss of outer hair cells (OHCs) within the basal turn of the cochlea and decreased spiral ganglion neurons (SGNs) and afferent nerve synapses. Using our mouse model that recapitulates human IED exposure, our results identify that the mechanisms underlying blast-induced hearing loss does not include gross membranous rupture as is commonly believed. Instead, there is both OHC and SGN loss that produce auditory dysfunction.