Scala Vestibuli Research Articles

Flat-Panel Volume Computed Tomography for Cochlear Implant Electrode Array Examination in Isolated Temporal Bone Specimens

Flat-panel based volume computed tomography could improve cochlear implant electrode evaluation in comparison with multislice computed tomography. Flat-panel based volume computed tomography offers higher spatial resolution and less metal artifacts than multislice computed tomography. Both characteristics could improve the evaluation of challenging but important questions in cochlear implantation assessment, such as an exact imaging of cochlea, osseous spiral lamina, electrode array position, and single electrode contacts. These questions are not currently fully answered by multislice computed tomography. Four isolated temporal bone specimens were scanned in a current multislice computed tomography scanner and in two experimental flat-panel based volume computed tomography scanners before and after cochlea implantation. To compare flat-panel based volume computed tomography and multislice computed tomography, four features were rated according to the following criteria: 1) visibility of the cochlea; 2) visibility of the osseous spiral lamina; 3) discernibility of individual electrode contacts; and 4) the ability to determine the electrode array position relative to scala tympani and scala vestibuli. Layer-by-layer microgrinding pictures were used as the ground truth for verification of imaging findings. Flat-panel based volume computed tomography was superior to multislice computed tomography in all four features rated. The cochlea and facial nerve canal were much better delineated in flat-panel based volume computed tomography. The osseous spiral lamina and single electrode contacts were only visible in flat-panel based volume computed tomography. Assessment of implant position with regard to the cochlear spaces was considerably improved by flat-panel based volume computed tomography. Cochlear implantation assessment could be improved by flat-panel based volume computed tomography and, therefore, would be highly beneficial for cochlea implantation research and for clinical evaluation. However, these first results were shown by scanning isolated temporal bone specimens; scanning whole human skull bases might be more challenging.

Cochlear transducer operating point adaptation

The operating point (OP) of outer hair cell (OHC) mechanotransduction can be defined as any shift away from the center position on the transduction function. It is a dc offset that can be described by percentage of the maximum transduction current or as an equivalent dc pressure in the ear canal. The change of OP can be determined from the changes of the second and third harmonics of the cochlear microphonic (CM) following a calibration of its initial value. We found that the initial OP was dependent on sound level and cochlear sensitivity. From CM generated by a lower sound level at 74 dB SPL to avoid saturation and suppression of basal turn cochlear amplification, the OHC OP was at constant 57% of the maximum transduction current (an ear canal pressure of -0.1 Pa). To perturb the OP, a constant force was applied to the bony shell of the cochlea at the 18 kHz best frequency location using a blunt probe. The force applied over the scala tympani induced an OP change as if the organ of Corti moved toward the scala vestibuli (SV) direction. During an application of the constant force, the second harmonic of the CM partially recovered toward the initial level, which could be described by two time constants. Removing the force induced recovery of the second harmonic to its normal level described by a single time constant. The force applied over the SV caused an opposite result. These data indicate an active mechanism for OHC transduction OP.

Middle Ear Forward and Reverse Transmission in Gerbil

The middle ear transmits environmental sound to the inner ear. It also transmits acoustic energy sourced within the inner ear out to the ear canal, where it can be detected with a sensitive microphone as an otoacoustic emission. Otoacoustic emissions are an important noninvasive measure of the condition of sensory hair cells and to use them most effectively one must know how they are shaped by the middle ear. In this contribution, forward and reverse transmissions through the middle ear were studied by simultaneously measuring intracochlear pressure in scala vestibuli near the stapes and ear canal pressure. Measurements were made in gerbil, in vivo, with acoustic two-tone stimuli. The forward transmission pressure gain was about 20-25 dB, with a phase-frequency relationship that could be fit by a straight line, and was thus characteristic of a delay, over a wide frequency range. The forward delay was about 32 micros. The reverse transmission pressure loss was on average about 35 dB, and the phase-frequency relationship was again delaylike with a delay of about 38 mus. Therefore to a first approximation the middle ear operates similarly in the forward and reverse directions. The observation that the amount of pressure reduction in reverse transmission was greater than the amount of pressure gain in forward transmission suggests that complex motions of the tympanic membrane and ossicles affect reverse more than forward transmission.

Combining perimodiolar electrode placement and atraumatic insertion properties in cochlear implantation – fact or fantasy?

Conclusions. Except for basal cochlear traumatization, all specimens implanted into scala tympani showed atraumatic insertion properties and good perimodiolar electrode positioning. Cochleostomy preparation and placement can have a significant impact on levels of basal cochlear trauma. Objective. In the past, perimodiolar cochlear implant electrodes increased the risk for intracochlear traumatization when compared to free-fitting arrays. Recently, however, clinical evidence for atraumatic perimodiolar implantations with preservation of residual hearing has been described. The aim of this paper was to histologically evaluate a perimodiolar cochlear implant array for its insertion properties in cadaver human temporal bones. Surgical and electrode factors, as well as preparation artifacts influencing intracochlear trauma, were considered in the evaluation. Materials and methods. Sixteen human temporal bones were harvested up to 24 hours post mortem and implanted immediately with the Nucleus 24 Contour Advance cochlear implant electrode array. Implantations were either performed using a regular caudal approach cochleostomy or through the round window membrane. After implantation, all bones underwent special histological processing, which allowed sectioning of undecalcified bone. Insertion properties were evaluated according to a grading system. Results. Fourteen specimens were implanted into scala tympani and only two exhibited basal trauma attributable to electrode insertion characteristics. Two bones were implanted into scala vestibuli after causing trauma in the region of the cochleostomy. Insertion depths ranged from 180° to 400°. All bones showed good perimodiolar electrode positioning. Basal trauma due to surgical issues and histological artifacts was present in 10 of 16 bones.

Letter to the Editor

In order to find out whether it is possible to visualize experimental endolymphatic hydrops in the cochlea with magnetic resonance imaging (MRI) at 4.7 T, we used 11 guinea pigs. Five normal guinea pigs were used as controls. Early manifestation of endolymphatic hydrops was evaluated in endolymphatic sac (ES)-intact animals (n = 6), and advanced manifestation in ES-damaged animals (n = 5) by means of MRI with gadolinium-diethylenetriaminepentaacetate-bismethylamide (Gd-DTPA-BMA) contrast agent. Hearing was tested with electrocochleography. The surface area of 3 partitions of the cochlea was used to quantify endolymphatic hydrops. The fine structure of the 3 partitions of the cochlea was visualized with MRI in all animals, as Gd-DTPA-BMA appeared mainly in the scala tympani and scala vestibuli. As early as 5 days after endolymphatic sac surgery, endolymphatic hydrops started to appear as visualized by MRI and also verified with histology. Severe damage to the inner ear barrier with Gd-DTPA-BMA leakage into the scala media was detected with MRI in 1 ES-damaged animal that had a 60-dB hearing loss. To conclude, endolymphatic hydrops can be visualized with high-resolution MRI by means of Gd-DTPA-BMA, and it is possible to quantify the extent of endolymphatic hydrops. Damage to the inner ear barrier or possible rupture of membranes can be shown with the assistance of Gd-DTPA-BMA.

Phase of neural excitation relative to basilar membrane motion in the organ of Corti: Theoretical considerations

Although the auditory transduction process is dependent on neural excitation of the auditory nerve in relation to motion of the basilar membrane (BM) in the organ of Corti (OC), specifics of this process are unclear. In this study, therefore, an attempt was made to estimate the phase of the neural excitation relative to the BM motion using a finite-element model of the OC at the basal turn of the gerbil, including the fluid-structure interaction with the lymph fluid. It was found that neural excitation occurs when the BM exhibits a maximum velocity toward the scala vestibuli at 10 Hz and shows a phase delay relative to the BM motion with increasing frequency up to 800 Hz. It then shows a phase advance until the frequency reaches 2 kHz. From 2 kHz, neural excitation again shows a phase delay with increasing frequency. From 800 Hz up to 2 kHz, the phase advances because the dominant force exerted on the hair bundle shifts from a velocity-dependent Couette flow-induced force to a displacement-dependent force induced by the pressure difference. The phase delay that occurs from 2 kHz is caused by the resonance process of the hair bundle of the IHC.

Force on inner hair cell cilia

The cochlea of the inner ear transforms the incoming sound pressure into neural excitation. Despite extensive experiments and modeling for the past century, understanding the behavior of the cochlea is far from complete. With an efficient program (Fast4) for shell of revolution structures, all mechanical (elastic) details of the curved cochlear cross-section and the organ of Corti can be computed. Based on the known values for the elastic moduli of the protein fibers and estimates for the geometry, the responses to point and pressure loads have been calculated which are reasonably close to the direct measurements. In the present work, the details of the inner hair cell are included, with a fluid gap between the tip of the cilia and the Hensen stripe of the tectorial membrane. A simple model for the near contact indicates nonlinear response similar to the intracellular recordings. This near contact is included into a more complete elastic model for the organ of Corti that includes three rows of cilia and tip links. The phase of the maximum tension of the tip link, which causes excitation of the cell, is computed for low frequencies for comparison to measurements. For low frequencies the fluid motion in the organ of Corti is approximately two-dimensional. The phase is found to be affected by: (1) geometrical difference between basal and upper turns of the cochlea, (2) initial gap spacing between the tip of the cilium and the Hensen stripe, (3) initial gap spacing between the tip of the cilium and the tectorial membrane, (4) presence of an electrode probe constraint on the motion of the inner hair cell, and (5) the stiffness of the tectorial membrane. The latter is the most significant. For a soft tectorial membrane, the excitation is generally between maximum velocity and displacement of the basilar membrane toward scala vestibuli. However, for a stiff tectorial membrane, the phase changes to an excitation with velocity and displacement toward scala tympani. Thus a possible mechanical reason is offered for the auditory nerve excitation in the base of the chinchilla cochlea for basilar membrane velocity toward scala tympani and in the middle and upper turns of the guinea pig cochlea, excitation for velocity toward scala vestibuli.

Communication between the Perilymphatic Scalae and Spiral Ligament Visualized by in vivo MRI

We evaluated the transport of Gadolinium-diethylenetriaminepentaacetate-bismethylamide (Gd-DTPA-BMA) through the round window (RW) membrane into the perilymphatic space with 4.7-T MRI in an animal study and 1.5-T MRI in humans. After administration of Gd-DTPA-BMA onto the intact RW membrane of guinea pig, Gd-DTPA-BMA uptake was observed in the basal turn and part of the second turn within 40 min. The scala tympani, scala vestibuli, the fibrous part of the spiral ligament and semicircular canal all showed uptake of Gd-DTPA-BMA. All turns of the cochlea were filled with Gd within 10 min in the perforated RW membrane administration group and within 30 min in the intravenous administration group. In patients who accepted middle ear injection of Gd-DTPA-BMA, uptake was observed within 2 h in the basal turn and semicircular canal. After 12 h the apex did still not show any uptake. Gd-DTPA-BMA is transported from the RW to the semicircular canal, the scala tympani and scala vestibuli without passing the helicotrema.

Predicting the effect of post-implant cochlear fibrosis on residual hearing

Intracochlear scarring is a well-described sequela of cochlear implantation. We developed a mathematical model of passive cochlear mechanics to predict the impact that this might have upon residual acoustical hearing after implantation. The cochlea was modeled using lumped impedance terms for scala vestibuli (SV), scala tympani (ST), and the cochlear partition (CP). The damping of ST and CP was increased in the basal one half of the cochlea to simulate the effect of scar tissue. We found that increasing the damping of the ST predominantly reduced basilar membrane vibrations in the apex of the cochlea while increasing the damping of the CP predominantly reduced basilar membrane vibrations in the base of the cochlea. As long as intracochlear scarring continues to occur with cochlear implantation, there will be limitations on hearing preservation. Newer surgical techniques and electrode technologies that do not result in as much scar tissue formation will permit improved hearing preservation.

Evaluating cochlear implant trauma to the scala vestibuli

Placement of cochlear implant electrodes into the scala vestibuli may be intentional, e.g. in case of blocked scala tympani or unintentional as a result of trauma to the basilar membrane or erroneous location of the cochieostomy. The aim of this study was to evaluate the morphological consequences and cochlear trauma after implantation of different cochlear implant electrode arrays in the scala vestibuli. Human temporal bone study with histological and radiological evaluation. Twelve human cadaver temporal bones were implanted with different cochlear implant electrodes. Implanted bones were processed using a special method to section undecalcified bone. Cochlear trauma and intracochlear positions. All implanted electrodes were implanted into the scala vestibuli using a special approach that allows direct scala vestibuli insertions. Fractures of the osseous spiral lamina were evaluated in some bones in the basal cochlear regions. In most electrodes, delicate structures of the organ of Corti were left intact, however, Reissner's membrane was destroyed in all specimens and the electrode lay upon the tectorial membrane. In some bones the organ of Corti was destroyed. Scala vestibuli insertions did not cause severe trauma to osseous or neural structures, thus preserving the basis for electrostimulation of the cochlea. However, destruction of Reissner's membrane and impact on the Organ of Corti can be assumed to destroy residual hearing.

High-resolution MRI of the Labyrinth: Optimization of Scan Parameters with 3D-FSE

The aim of our study was to optimize the parameters of high-resolution MRI of the labyrinth with a 3D-FSE sequence. We investigated TR, TE, Matrix, FOV, and coil selection in terms of CNR (contrast-to-noise ratio) and SNR (signal-to-noise ratio) by comparing axial images and/or three-dimensional images. The optimal 3D-FSE sequence parameters were as follows: 1.5 Tesla MR unit (Signa LX, GE Medical Systems), 3D-FSE sequence, dual 3-inch surface coil, acquisition time=12.08 min., TR=5000 msec, TE=300 msec, 3 NEX, FOV=12 cm, matrix=256 x 256, slice thickness=0.5 mm/0.0 sp, echo train=64, bandwidth=+/-31.5 kHz. High-resolution MRI of the labyrinth using the optimized 3D-FSE sequence parameters permits visualization of important anatomic details (such as scala tympani and scala vestibuli), making it possible to determine inner ear anomalies and the patency of cochlear turns. To obtain excellent heavily T2-weighted axial and three-dimensional images in the labyrinth, high CNR, SNR, and spatial resolution are significant factors at the present time. Furthermore, it is important not only to optimize the scan parameters of 3D-FSE but also to select an appropriate coil for high-resolution MRI of the labyrinth.

Cochlear Microperfusion: Experimental Evaluation of a Potential New Therapy for Severe Hearing Loss Caused by Inflammation

Cochlear microperfusion will be a useful treatment of severe sensorineural hearing loss caused by inflammation. Viruses, bacteria, and autoimmunity can initiate inflammation in the inner ear. The acute phase is associated with elevations in cytokines, nitrous oxide, and cellular infiltrates and the breakdown of the blood-labyrinthine barrier. The chronic phase leads to irreversible ossification of the labyrinth. The authors developed cochlear microperfusion to facilitate removal of inflammatory cells and their byproducts during the acute phase of inflammation. Using a ventral approach to the guinea pig cochlea, the authors displaced resident perilymph by delivering perfusate into the scala vestibuli and collecting the effluent from the scala tympani. The authors evaluated the benefit of the procedure in an animal model of severe hearing loss caused by inflammation. Healthy controls undergoing cochlear microperfusion with phosphate-buffered saline incurred a mean hearing loss of 16 dB (n=4). This hearing loss was associated with the creation of two cochleostomies and not the perfusion itself. Sterile labyrinthitis (n=5) generated by perfusion of the cochlea with antigen consistently produced severe hearing loss over the initial 48 hours, and this hearing loss persisted for the subsequent 7 days. Therapeutic cochlear microperfusion, performed within the first 24 hours of developing severe hearing loss (n=9), immediately restored on average 24 dB (p <0.007) of hearing. Cochlear microperfusion is a promising new technique for treating severe deafness caused by inflammation. The benefit may be sustained when combined with local delivery of immunosuppressive agents to the inner ear.

Bilateral cochlear implant user with a right ear scala vestibuli insertion and left ear scala tympani insertion: case report

A young man became totally deaf as a consequence of a posttraumatic intrahospital meningitis. A high-resolution CT scan showed partial ossification in both ears. As total ossification of the right scala tympani was found the right scala vestibuli was selected to insert a MED-EL system, Combi 40+ Short. A basal medial insertion was achieved, with 12 active electrodes. The patient was able to understand speech with the speech processor along in about 2 months. Six months later, the same system, Combi 40+ Short was implanted in the left ear (LE) which presented ossification at the level of the third portion of the inferior part of the basal turn. In this case, the 12 electrodes where positioned in a medial apex portion of the scala tympani. In spite the fact that the arrays of electrodes were located in totally different regions of the cochlea, he was able to match the pitch between some electrodes. Speech tests in quite and noise with a SNR of 0, 5, 10 and 15 dB were performed with the right ear (RE) alone, left ear alone and both ears. The speech material was made up of consonant identification, vowel transition identification and everyday sentence recognition. The results showed that discrimination in noise was better using both implants despite the fact that he already had poor discrimination with the left ear alone.

Permeability of the blood-labyrinth barrier in mice following acoustic injury

Problem: The blood-brain barrier is a well-described structure that excludes the transport of molecules from the blood stream into the brain. The cochlea has been demonstrated to maintain a similar barrier with the intravascular space, termed the blood-labyrinth barrier (BLB). Its presence has been established with the use of radio-labeled proteins and ions, showing that a gradient exists between the serum and the perilymph. However, an anatomic study of the permeability gradients in different regions of the cochlea has not been performed. The purpose of this study is, therefore (1) to assess the presence of a BLB in the cochlea using Evans blue (EB), and (2) to investigate the effects of acoustic injury on the integrity of such a barrier. Methods: Normal control and noise-exposed mice were intravascularly injected with EB and after 20 minutes, brain and cochlea were harvested. EB staining was viewed under fluorescence microscopy. Results: In the cochlea, EB fluorescence demonstrated areas of high permeability including the bone marrow and blood vessels within the stria vascularis. There were also areas of moderate permeability such as the intra-strial compartment of the stria vascularis. Finally there were areas of relative impermeability found in the cochlear duct, spiral ligament, spiral limbus, scala vestibuli, and scala tympani. In this experiment we demonstrated that acoustic injury can change the permeability characteristics of the cochlea and causes leakiness of the BLB in the spiral ligament. Conclusion: The EB dye test is a technique that can be applied to assess the integrity of the BLB. Within the inner ear, there are specific regions that demonstrate high permeability, moderate permeability, and relative impermeability to EB. Significance: Acoustic trauma causes changes in the intrinsic properties of the BLB and results in leakiness of the BLB in the spiral ligament, precisely in the location where inflammatory cells migrate in response to acoustic injury. Support: This study was funded by the American Academy of Otolaryngology-Head and Neck Surgery resident research grant award.

Imaging procedures in cochlear implant patients – evaluation of different radiological techniques

The purpose of this study was to evaluate the feasibility and usability of different radiologic methods (single-slice computed tomography (CT), multi-slice CT and rotational tomography (RT)) for assessment of the position of cochlear implant electrodes. Cochlear implants in an isolated human temporal bone and in a complete formalin-fixed cadaver head were examined and the electrode position was determined. Subsequently, the labyrinth bone was isolated out of the cadaver head and histologically examined to compare the results of histology with imaging. Single-slice CT reliably identifies the electrode inside the human cochlea; however, due to the technically based large electrode artifact its position inside the cochlear spaces (e.g. electrode position in scala tympani or scala vestibuli) cannot be detected. Multi-slice CT of the cadaver head also showed artifacts that complicate the assessment of electrode position. Using RT the electrode artifact is small and therefore the electrode position within the cochlear spaces, scala tympani versus scala vestibuli, can be assessed. This technique was also applicable in a complete cadaver head, which is in contrast with former studies. In conclusion, CT allows the identification of electrode arrays inside the human cochlea. Multi-slice CT permits a much more precise depiction of the electrode inside the cochlea. RT alone has minimized electrode artifacts to a high extent and permits the assessment of the electrode position within the scala tympani or scala vestibuli. As RT was performed successfully in a complete cadaver head, further studies for evaluation of the intracochlear electrode position can now be performed in patients.

Surgical techniques for cell transplantation into the mouse cochlea.

This study investigated surgical procedures for cell transplantation into the mouse inner ear. Female C57BL/6 mice were used as recipient animals. Fetal mouse neural stem cells expressing green fluorescence were used as donor cells. Two methods, an injection of transplants from the lateral semicircular canal (LSCC) and from the cochlear lateral wall (CLW), were examined. Two weeks after transplantation, the distribution of transplant-derived cells in the cochlea was examined. Effects on auditory function were assessed by measurement of auditory brain stem responses (ABRs). Cochleae receiving cell transplantation from the LSCC exhibited robust survival of transplant-derived cells mainly in the scala vestibuli and scala tympani. Transplantation from the LSCC caused elevation of ABR thresholds by less than 10 dB SPL. However, transplantation from the CLW resulted in considerable hearing loss, even though transplant-derived cells settled in the scala media. These findings demonstrate that an approach from the LSCC can be utilized for cell transplantation into the perilymph without causing apparent auditory disorder, while an approach from the CLW delivers cells to the endolymph but appears to cause auditory dysfunction.

In vivo visualization of endolymphatic hydrops in guinea pigs: magnetic resonance imaging evaluation at 4.7 tesla.

In order to find out whether it is possible to visualize experimental endolymphatic hydrops in the cochlea with magnetic resonance imaging (MRI) at 4.7 T, we used 11 guinea pigs. Five normal guinea pigs were used as controls. Early manifestation of endolymphatic hydrops was evaluated in endolymphatic sac (ES)-intact animals (n = 6), and advanced manifestation in ES-damaged animals (n = 5) by means of MRI with gadolinium-diethylenetriaminepentaacetate-bismethylamide (Gd-DTPA-BMA) contrast agent. Hearing was tested with electrocochleography. The surface area of 3 partitions of the cochlea was used to quantify endolymphatic hydrops. The fine structure of the 3 partitions of the cochlea was visualized with MRI in all animals, as Gd-DTPA-BMA appeared mainly in the scala tympani and scala vestibuli. As early as 5 days after endolymphatic sac surgery, endolymphatic hydrops started to appear as visualized by MRI and also verified with histology. Severe damage to the inner ear barrier with Gd-DTPA-BMA leakage into the scala media was detected with MRI in 1 ES-damaged animal that had a 60-dB hearing loss. To conclude, endolymphatic hydrops can be visualized with high-resolution MRI by means of Gd-DTPA-BMA, and it is possible to quantify the extent of endolymphatic hydrops. Damage to the inner ear barrier or possible rupture of membranes can be shown with the assistance of Gd-DTPA-BMA.

Interpreting electrically evoked emissions using a finite-element model of the cochlea

Electrically evoked otoacoustic emissions (EEOAEs) are used to investigate in vivo cochlear electromechanical function. Electrical stimulation through bipolar electrodes placed very close to the basilar membrane (in the scala vestibuli and scala tympani) gives rise to a narrow frequency range of EEOAEs, limited to around 20 kHz when the electrodes are placed near the 18-kHz best frequency place. Model predictions using a three-dimensional inviscid fluid model in conjunction with a middle ear model [S. Puria and J. B. Allen, J. Acoust. Soc. Am. 104, 3463–3481 (1998)] and a simple model for outer hair cell activity [S. Neely and D. Kim, J. Acoust. Soc. Am. 94, 137–146 (1993)] are used to interpret the experimental results. To estimate effect of viscosity, model results are compared with those obtained for a viscous fluid. The models are solved using a 2.5-D finite-element formulation. Predictions show that the high frequency limit of the excitation is determined by the spatial extent of the current stimulus. The global peaks in the EEOAE spectra are interpreted as constructive interference between electrically evoked backward traveling waves and forward traveling waves reflected from the stapes. Steady state response predictions of the model are presented.

Cochlear implantation and Cogan syndrome.

To evaluate outcomes and issues pertaining to cochlear implantation in a group of subjects affected by Cogan syndrome. Prospective cohort. Department of Ophthalmology and Otorhinolaryngology, University of Parma. Five postlingually deafened adults suffering from a typical form of Cogan syndrome who underwent cochlear implantation. Benefit from cochlear implantation as measured by word and everyday sentence recognition tests. Surgical issues and postoperative complications were also evaluated. In two cases, intracochlear electrodes were inserted into the scala vestibuli because of the ossification of the scala tympani. Two patients experienced a recurrence of keratitis the day after surgery. To date, with a follow-up of 1 to 4 years, no patient has experienced flap complications or other local or systemic complications. At the 12-month postoperative evaluation, all patients had gained useful open-set speech perception, achieving a mean score of 91% and 95% on word and everyday sentence recognition tests, respectively. Patients deafened by Cogan syndrome demonstrated high levels of speech understanding after undergoing cochlear implantation. Obliteration of the cochlea may complicate electrode implantation, requiring modifications of the surgical technique. Stress consequent to the surgical procedure may instigate an acute phase of the basic illness.

High Variability of Perilymphatic Entry of Neutral Molecules Through the Round Window

Objective—To improve the efficacy of intratympanic therapy using perilymphatic entry through the round window membrane.Material and Methods—The perilymphatic entry characteristics of 2 neutral molecules, mannitol (182.2 Da) and inulin (7,000 Da), were studied. A polyethylene catheter was placed in contact with the guinea pig round window membrane and sealed with cyanoacrylate glue. This catheter was linked to an osmotic minipump that delivered 100 μl portions of 3H-mannitol or 3H-inulin solutions over a 7-day period at a constant rate (0.5 μl/h). Perilymph in the scala vestibuli and scala tympani, cerebrospinal fluid (CSF) and plasma were sampled after 4–7 days of delivery.Results—Despite the constant rate of infusion, perilymphatic radioactivity varied widely from one animal to the other, probably as a function of the position of the microcatheter within the round window niche and/or the permeability of the round window. Even a large molecule such as inulin entered the perilymphatic space. Seven days after the beginning of 3H-mannitol administration, the radioactivity was higher in the perilymph of the scala tympani than in that of the scala vestibuli. The perilymphatic radioactivity on Day 7 was ≈50% lower than that measured on Day 4 (p=NS). Finally, round window membrane delivery did not preclude distant spread of the molecules into the blood and CSF.Conclusions—Using round window membrane delivery, the perilymphatic entry of mannitol and inulin depended on their molecular weight. Intratympanic delivery induced a high inter-individual heterogeneity of the drug concentration within the inner ear, with subsequent variability of the therapeutic effects.