A post-processing protocol for three-dimensional visualization of the inner ear using the volume-rendering technique based on a standard magnetic resonance imaging protocol.

A superior diagnostic quality compared to other post-processing (PP) techniques for three-dimensional (3D) inner ear imaging has been attributed to volume rendering (VR). We defined and assessed a VR protocol for 3D visualization of the inner ear in a routine imaging setting. Following definition of a VR protocol by using lower threshold values, surface shading, perspective views and related parameters, standardized 3D views of the inner ear were generated and evaluated in 32 patients suffering from sensorineural or combined hearing loss. Comprehensive inner ear visualization was achieved in 28 patients by means of two 3D shaded-surface views. Incomplete data acquisition (1/32), motion and pulsation artefacts (2/32) and interposed fluid-retaining mastoid cells (1/32) were responsible for non-diagnostic image quality in 4/32 patients. In 5/32 patients modifications of the PP protocol involving the threshold value and depth-cueing parameters helped to establish diagnostic image quality. Mean post-processing time amounted to 5.8 min per site. 3D imaging with the VR technique is suitable for routine inner ear assessment if direct VR, predefined PP protocols and standardized labyrinthine views are used.     

Virtual endoscopy of the middle and inner ear with spiral computed tomography

OBJECTIVE: To evaluate the inner anatomy of the auditory apparatus by means of virtual endoscopy of spiral computed tomography (CT) data sets. BACKGROUND: Virtual endoscopy permits simulation of the fiberoptic endoscopy perspective by processing CT or magnetic resonance images. METHODS: Seven formalin-fixed specimens of human mastoid were scanned with spiral CT with the following protocol: beam collimation 1 mm, pitch ratio 1, reconstruction spacing 0.2 to 0.5 mm, field of view 90 mm. For the generation of endoscopic views of the auditory spaces, the axial images were processed with Navigator software 2.0 running on UltraSparc I workstation. RESULTS: Virtual endoscopy allowed the demonstration of the external auditory canal, the head and handle of the malleus, the stapes and incudostapedial articulation, the corpus, the long process of the incus with its lenticular process and the short limb, the malleoincudal articulation, the rounded promontory, the round and oval windows, and Prussak's space. From inside the basal turn of the cochlea, virtual endoscopy showed the orifices of the fenestrae cochlea and vestibuli, the origin of the lateral and the anterior semicircular canals, and the basal turn of cochlea. The optimal perspectives that allowed demonstration of the anatomical details of the middle and inner ear are described. CONCLUSION: Virtual endoscopy allows the generation of inner views of the auditory spaces. This new method of image processing can be proposed as an integrative tool of spiral CT imaging.     

Symposium: new data for noise standards. 3. Organ culture of the mammalian inner ear: a tool to study inner ear deafness

Twelfth gestation day kreisler otocysts were explanted into an organ culture system and allowed to develop for nine days. The homozygotic (kr/kr) kreisler otocysts showed significant developmental differences when compared to the development that occurred in the organ culture specimens of the otocysts of its heterozygotic (+ /kr) litter mates. The differences in development observed in vitro were the same major developmental differences that had been observed in vivo. The phenotypic expression of the kreisler genome has expressed itself in vitro in the homozygotic kreisler otocyst.     

The low temperature vacuum embedding technique for X-ray microanalysis of the developing inner ear

The method of low-temperature embedding in vacuo using methacrylate resins, was tested for X-ray microanalysis of the embryonic inner ear of the CBA/CBA mouse. Fetal inner ears were examined on gestational days 16 and 18. The technique was evaluated in comparison with earlier used preparation techniques for X-ray microanalysis. With plastic embedding, an improvement of the morphological resolution was achieved, which allows reliable structural identification on the subcellular level. Furthermore, the possibility of orientating of the specimen prior to sectioning provides a better controlled and less time-consuming sectioning.     

经水平半规管开窗充填前庭池治疗脑脊液耳漏一例

患者女,55岁,因左耳听力下降40余年,于2006年6月人院.患者40余年前发现左耳听力下降,未进一步诊治.半年前无明显诱因出现左鼻流清水样涕,当地医院诊断为变应性鼻炎,给予对症治疗.2个月前出现头痛、头晕、恶心、呕吐,当地医院诊断为化脓性脑膜炎,经治疗后痊愈,但左鼻仍间断流清涕,当地医院颞骨CT显示左中耳乳突炎.体格检查:神志清楚,智力正常,头面部无畸形,神经系统检查阴性.     

Technical note on microcatheter implantation for local inner ear drug delivery: surgical technique and safety aspects.

HYPOTHESIS: Despite its invasiveness, the temporary implantation of a microcatheter into the middle ear cavity is an appropriately safe method for providing continuous drug delivery to the inner ear. BACKGROUND: For the application of drugs to the inner ear, different delivery strategies are available ranging from intratympanic injections to temporarily implanted microcatheters. It has recently been demonstrated that the choice of the drug delivery system influences the pharmacokinetics in the inner ear. If a continuous drug application over several weeks is required, a secure placement of the delivery device (i.e., the microcatheter) is necessary to guarantee efficient drug delivery and to avoid unwanted side effects. STUDY DESIGN: Retrospective chart review. MATERIALS AND METHODS: During 2000 to 2005, 25 patients with acute unilateral severe-to-profound hearing loss or anacusis and failure of systemic high-dose glucocorticoid and rheological therapy were offered an intratympanic delivery of glucocorticoids via a temporarily implanted catheter and an external pump for up to 4 weeks as a salvage treatment option. The standardized surgical implantation and fixation technique developed for the microcatheter were characterized by six elements: 1) a medial and a lateral tunnel connected by a groove in the posterior wall of the bony ear canal, 2) stabilization of the catheter with bone wax and soft tissue plugs in the tunnels, 3) an ear canal packing, 4) a series of fixating sutures along the catheter, 5) an adhesive dressing, and 6) additional tapes at the connecting line between pump and catheter. At the end of the implantation period, the catheter was removed by a second surgical procedure allowing for evaluation of the catheter position and the condition of the middle ear space. RESULTS: Adverse events included catheter dislocation, catheter obstruction, formation of mild granulation tissue in the middle ear cavity, tympanic membrane defects, and ear canal skin defects. With introduction of an improved implantation and fixation technique, the number of catheter dislocations could be significantly reduced. No complications were observed on long-term follow-up. CONCLUSION: If the pharmacokinetics or pharmacodynamics of a specific local inner ear therapy approach requires a continuous intratympanic drug application (e.g., to restore hearing in patients with severe or profound hearing loss), the temporary implantation of a microcatheter by a standardized surgical technique is a feasible and appropriately safe method for providing continuous drug delivery to the inner ear.     

KHRI-3 monoclonal antibody-induced damage to the inner ear: antibody staining of nascent scars

Intracochlear infusion of the KHRI-3 monoclonal antibody results in in vivo binding to guinea pig inner ear supporting cells, loss of hair cells and hearing loss. To further characterize the basis for KHRI-3-induced hearing loss, antibody was produced in a bioreactor in serum-free medium, affinity purified, and compared to conventionally prepared antibody by infusion into the scala tympani using mini-osmotic pumps. In vivo antibody binding was observed in 10 of 11 guinea pigs. A previously unreported pattern of KHRI-3 antibody binding to cells involved in scar formation was noted in five guinea pigs. All but one of the KHRI-3-infused animals demonstrated a hearing loss of > 10 dB in the treated ear. In five of 11 animals the threshold shift was 30 dB or more, and all had hair cell losses. In one guinea pig infused with 2 mg/ml of antibody, the organ of Corti was absent in the basal turn of the infused ear. This ear had a 45-50 dB threshold shift but, curiously, no detectable antibody binding in the residual organ of Corti. Organ of Corti tissue was fragile in antibody-infused ears. Breaks within the outer hair cell region occurred in 5/11 infused ears. The contralateral ears were normal except for one noise-exposed animal that demonstrated hair cell loss in the uninfused ear. Three animals were exposed to 6 kHz noise (108 dB) for 30 min on day 7. Antibody access to the organ of Corti may be increased in animals exposed to noise, since the strongest in vivo binding was observed in noise-exposed animals. Loss of integrity of the organ of Corti seems to be the primary mechanism of inner ear damage by KHRI-3 antibody. The binding of KHRI-3 antibody in new scars suggests a role of the antigen in scar formation. Antibodies with binding properties similar to KHRI-3 have been detected in 51% of patients diagnosed with autoimmune sensorineural hearing loss; thus, it seems likely that such autoantibodies also may have pathologic effects resulting in hearing loss in humans.     

New approach for 3D imaging and geometry modeling of the human inner ear.

Obtaining high-resolution three-dimensional (3D) geometry data performs a necessary assumption for modeling cochlear mechanics. Preferably this procedure has to be done noninvasively to preserve the original morphology. Depending on the actual application, various levels of spatial resolution and tissue differentiation should be reached. Here a new approach is presented which allows 3D imaging of temporal bone specimens with intact regions of interest and spatial resolution currently in the 10-microm range, but providing capabilities for future enhancements down to the submicron level. The technique is based on microtomography by X-rays or synchrotron radiation respectively. The structural data are reconstructed and converted to geometry data by 3D image processing, and eventually transferred into simulation environments, e.g., Finite Element Analysis, but may also be used for general visualization tasks in research, clinics, and education.     

The new classification system for inner ear malformations: the INCAV system

Conclusions: The proposed INCAV system standardizes reporting of inner ear malformations; gives adequate information about the structures of inner ear; defines the ears which could not be classified before; and helps in the selection of the ear as the cochlear implant candidate. Also it is easy-to-use for radiologists, and useful to the referring otolaryngologists.

Objective: This study was conducted to explore a more specific, definitive classification system which was based on radiological criteria for inner ear malformations.

Method: This study found 43 patients who had inner ear malformations, magnetic resonance (MR), and computed tomography (CT) imaging, together with the retrospective evaluation of the medical records between August 2010 and February 2015. It analyzed inner ear structures by dividing five sub-groups and each sub-group was given a letter: internal acoustic canal (I), cochlear nerve (N), cochlea (C), vestibular aqueduct (A) and vestibule (V). Based on their malformations, these anatomical structures have been assigned grades and have been classified by using increasing numbers which were dependent to increasing order of severity of the malformation.

Results: Among these 43 patients, there were six normal (I₀N₀C₀A₀V₀) and 80 inner ear malformations. All of the ears were defined successfully by the INCAV system.     

Local treatment of the inner ear: A study of three different polymers aimed for middle ear administration

Conclusion: A formulation based on sodium hyaluronate (NaHYA) was the most promising candidate vehicle for intra-tympanic drug administration regarding conductive hearing loss, inflammatory reactions, and elimination. Objectives: Recent advances in inner ear research support the idea of using the middle ear cavity for drug administration to target the inner ear. This paper presents rheological and safety assessments of three candidate polymer formulations for intra-tympanic drug administration. Method: The formulations were based on sodium carboxymethyl cellulose (NaCMC), sodium hyaluronate (NaHYA), and poloxamer 407 (POL). Rheological studies were performed with a controlled rate instrument of the couette type. Safety studies were performed in guinea pigs subjected to an intra-tympanic injection of the formulations. Hearing function was explored with ABR before and 1, 2, and 3 weeks after the injection. Elimination of the formulations marked with coal was explored with an endoscopic digital camera 1, 2, and 3 weeks after injection. Middle and inner ear morphology was examined with light microscopy 6 days after injection. Results: The results speak in favor of NaHYA, since it did not cause prolonged hearing threshold elevations. The results of the elimination and morphological investigations support the conclusion of NaHYA being the most promising candidate for intra-tympanic administration.     

A perspective from magnetic resonance imaging findings of the inner ear: Relationships among cerebrospinal, ocular and inner ear fluids

Visualization of endolymphatic hydrops has been performed using magnetic resonance imaging (MRI) after intratympanic or intravenous gadolinium (Gd) injection. Our recent findings indicate that just as the prevalence of asymptomatic glaucoma is greater than that of symptomatic glaucoma, there are also many cases of asymptomatic endolymphatic hydrops. It is assumed that the asymptomatic endolymphatic hydrops that precedes Ménière's disease is found more frequently using MRI than with other techniques. Gd in the inner ear moves into the cerebrospinal fluid (CSF) via the internal auditory meatus. Gd enhancement is also recognized in the ocular fluid after the intravenous Gd administration. In this paper, the relationships between CSF, ocular fluid and inner ear fluid are reviewed. The central nervous system, eye and inner ear contain specialized extracellular fluids that are essential for maintaining their function: CSF, ocular fluid consisting of vitreous humor and aqueous humor, and inner ear fluid consisting of perilymph and endolymph. Abnormal accumulation of or pressure elevation in these fluids is associated with hydrocephalus, glaucoma and Ménière's disease, respectively. The dura mater and the arachnoid membrane of the optic nerve canal and inner ear meatus are very close to the eye and the inner ear, respectively. It has been reported that low CSF pressure is associated with glaucoma and endolymphatic hydrops. In glaucoma and Ménière's disease, nerve damage to ganglion cells rather than damage of the sensory cells is directly associated with progression of the disease. Retinal ganglion cells in glaucoma and spiral ganglion cells in Ménière's disease are targets of the abnormal accumulation of, or increased pressure in, the extracellular fluid, just as neurons are damaged in hydrocephalus. Studies on hydrocephalus, glaucoma and Ménière's disease as a group may deepen our understanding of each disease.     

内耳免疫反应中细胞凋亡及Caspase-3动态表达的研究

目的:研究内耳免疫反应过程中是否存在细胞凋亡,以及细胞凋亡是否与Caspase3信号转导有关。方法:选用雌性白色豚鼠45只,随机分为实验组29只,对照组16只,以钥孔虫戚血蓝蛋白(KLH)全身免疫后,实验组以相同抗原进行内耳免疫,对照组内耳注射等量的磷酸盐缓冲生理盐水(PBS),分别在内耳免疫术后1、3、5、7d和14d后处死动物,于免疫前及处死前行双侧听性脑干反应(ABR)测试。取内耳免疫侧耳蜗做石蜡切片。通过DNA末端转移酶介导的缺口末端标记法(TUNEL)检测内耳凋亡细胞,免疫组织化学检测内耳Caspase3的表达。结果:实验组豚鼠内耳免疫前、后反应阈比较有统计学意义(P<0.05或P<0.01);对照组给药前、后比较反应阈无明显变化。实验组豚鼠内耳均存在TUNEL染色阳性细胞,并且TUNEL染色阳性细胞具有凋亡细胞的典型形态学特征,而对照组仅在支持细胞、血管纹和螺旋神经节细胞中发现极少数TUNEL染色阳性细胞。Caspase3免疫组织化学染色实验组内耳从内耳免疫后5d开始出现阳性表达,而对照组表达阴性。结论:内耳免疫反应可以诱导细胞凋亡的发生;内耳免疫反应诱导细胞凋亡的发生中有Caspase3的激活。     

Mouse models for deafness: lessons for the human inner ear and hearing loss

In the field of hearing research, recent advances using the mouse as a model for human hearing loss have brought exciting insights into the molecular pathways that lead to normal hearing, and into the mechanisms that are disrupted once a mutation occurs in one of the critical genes. Inaccessible for most procedures other than high-resolution computed tomography (CT) scanning or invasive surgery, most studies on the ear in humans can only be performed postmortem. A major goal in hearing research is to gain a full understanding of how a sound is heard at the molecular level, so that diagnostic and eventually therapeutic interventions can be developed that can treat the diseased inner ear before permanent damage has occurred, such as hair cell loss. The mouse, with its advantages of short gestation time, ease of selective matings, and similarity of the genome and inner ear to humans, is truly a remarkable resource for attaining this goal and investigating the intrigues of the human ear.     

Stem cell therapy for the inner ear: recent advances and future directions

In vertebrates, perception of sound, motion, and balance is mediated through mechanosensory hair cells located within the inner ear. In mammals, hair cells are only generated during a short period of embryonic development. As a result, loss of hair cells as a consequence of injury, disease, or genetic mutation, leads to permanent sensory deficits. At present, cochlear implantation is the only option for profound hearing loss. However, outcomes are still variable and even the best implant cannot provide the acuity of a biological ear. The recent emergence of stem cell technology has the potential to open new approaches for hair cell regeneration. The goal of this review is to summarize the current state of inner ear stem cell research from a viewpoint of its clinical application for inner ear disorders to illustrate how complementary studies have the potential to promote and refine stem cell therapies for inner ear diseases. The review initially discusses our current understanding of the genetic pathways that regulate hair cell formation from inner ear progenitors during normal development. Subsequent sections discuss the possible use of endogenous inner ear stem cells to induce repair as well as the initial studies aimed at transplanting stem cells into the ear.     

Immune response and immunopathology of the inner ear: an update

Immune-mediated inner-ear disease includes clinical conditions associated with unilateral or bilateral rapidly progressive forms of sensorineural hearing loss. A systemic autoimmune disorder can be present in less than one-third of cases. Because of the lack of well defined detection methods to identify immune-mediated processes within the inner ear, and the fact that the human inner ear is not amenable to diagnostic biopsy, there has been great interest in developing animal models. Experimental models of sterile and virus-induced labyrinthitis support the participation of the immune system in the aetiopathogenesis of inner-ear disorders: interleukin-2 emanates from the endolymphatic sac and assists in changing the spiral modiolar vein, as in the expression of intercellular adhesion molecule 1, which allows the egrees of immune cells from the circulation. The formation of a fibro-osseous matrix ultimately results in degeneration of the inner ear. These investigations have allowed us to alter the immune response for the purpose of regulating its intensity and the subsequent damage to patients.