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Ultrasound (US) can noninvasively activate intact brain circuits, making it a promising neuromodulation technique. However, little is known about the underlying mechanism. Here, we apply transcranial US and perform brain mapping studies in guinea pigs using extracellular electrophysiology. We find that US elicits extensive activation across cortical and subcortical brain regions. However, transection of the auditory nerves or removal of cochlear fluids eliminates the US-induced activity, revealing an indirect auditory mechanism for US neural activation. Our findings indicate that US activates the ascending auditory system through a cochlear pathway, which can activate other non-auditory regions through cross-modal projections. This cochlear pathway mechanism challenges the idea that US can directly activate neurons in the intact brain, suggesting that future US stimulation studies will need to control for this effect to reach reliable conclusions., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Optical neural stimulation in the cochlea has been presented as an alternative technique to the electrical stimulation due to its potential in spatially selectivity enhancement. So far, few studies have selected the near-infrared (NIR) laser in cochlear neural stimulation and limited optical parameter space has been examined. This paper focused on investigating the optical parameter effect on NIR stimulation of auditory neurons, especially under shorter pulse durations. The spiral ganglion neurons in the cochlea of deafened guinea pigs were stimulated with a pulsed 810-nm NIR laser in vivo. The laser radiation was delivered by an optical fiber and irradiated towards the modiolus. Optically evoked auditory brainstem responses (OABRs) with various optical parameters were recorded and investigated. The OABRs could be elicited with the cochlear deafened animals by using the 810-nm laser in a wide pulse duration ranged from 20 to 1000 μs. Results showed that the OABR intensity increased along with the increasing laser radiant exposure of limited range at each specific pulse duration. In addition, for the pulse durations from 20 to 300 μs, the OABR intensity increased monotonically along with the pulse duration broadening. While for pulse durations above 300 μs, the OABR intensity basically kept stable with the increasing pulse duration. The 810-nm NIR laser could be an effective stimulus in evoking the cochlear neuron response. Our experimental data provided evidence to optimize the pulse duration range, and the results suggested that the pulse durations from 20 to 300 μs could be the optimized range in cochlear neural activation with the 810-nm-wavelength laser.

Research on auditory neural triggering by optical stimulus has been developed as an emerging technique to elicit the auditory neural response, which may provide an alternative method to the cochlear implants. However, most previous studies have been focused on using longer-wavelength near-infrared (>1800 nm) laser. The effect comparison of different laser wavelengths in short-wavelength infrared (SWIR) range on the auditory neural stimulation has not been previously explored. In this study, the pulsed 980- and 810-nm SWIR lasers were applied as optical stimuli to irradiate the auditory neurons in the cochlea of five deafened guinea pigs and the neural response under the two laser wavelengths was compared by recording the evoked optical auditory brainstem responses (OABRs). In addition, the effect of radiant exposure, laser pulse width, and threshold with the two laser wavelengths was further investigated and compared. The one-way analysis of variance (ANOVA) was used to analyze those data. Results showed that the OABR amplitude with the 980-nm laser is higher than the amplitude with the 810-nm laser under the same radiant exposure from 10 to 102 mJ/cm 2 . And the laser stimulation of 980 nm wavelength has lower threshold radiant exposure than the 810 nm wavelength at varied pulse duration in 20-500 μs range. Moreover, the 810-nm laser has a wider optimized pulse duration range than the 980-nm laser for the auditory neural stimulation.

We evaluated the role of iron deficiency (ID) without anemia on hearing function and cochlear pathophysiology of young rats before and after noise exposure. We used rats at developmental stages as an animal model to induce ID without anemia by dietary iron restriction. We have established this dietary restriction model in the rat that should enable us to study the effects of iron deficiency in the absence of severe anemia on hearing and ribbon synapses. Hearing function was measured on Postnatal Day (PND) 21 after induction of ID using auditory brainstem response (ABR). Then, the young rats were exposed to loud noise on PND 21. After noise exposure, hearing function was again measured. We observed the morphology of ribbon synapses, hair cells and spiral ganglion cells (SGCs), and assessed the expression of myosin VIIa, vesicular glutamate transporter 3 and prestin in the cochlea. ID without anemia did not elevate ABR threshold shifts, but reduced ABR wave I peak amplitude of young rats. At 70, 80, and 90 dB SPL, amplitudes of wave I (3.11 ± 0.96 µV, 3.52 ± 1.31 µV, and 4.37 ± 1.08 µV, respectively) in pups from the ID group were decreased compared to the control (5.92 ± 1.67 µV, 6.53 ± 1.70 µV, and 6.90 ± 1.76 µV, respectively) (p < 0.05). Moreover, ID without anemia did not impair the morphology hair cells and SGCs, but decreased the number of ribbon synapses. Before noise exposure, the mean number of ribbon synapses per inner hair cell (IHC) was significantly lower in the ID group (8.44 ± 1.21) compared to that seen in the control (13.08 ± 1.36) (p < 0.05). In addition, the numbers of ribbon synapses per IHC of young rats in the control (ID group) were 6.61 ± 1.59, 3.07 ± 0.83, 5.85 ± 1.63 and 12.25 ± 1.97 (3.75 ± 1.45, 2.03 ± 1.08, 3.81 ± 1.70 and 4.01 ± 1.65) at 1, 4, 7 and 14 days after noise exposure, respectively. Moreover, ABR thresholds at 4 and 8 kHz in young rats from the ID group were significantly elevated at 7 and 14 days after noise exposure compared to control (p < 0.05). The average number of young rat SGCs from the ID group were significantly decreased in the basal turn of the cochlea compared to the control (p < 0.05). Therefore, ID without anemia delayed the recovery from noise-induced hearing loss and ribbon synapses damage, increased SGCs loss, and upregulated prestin after noise exposure. Thus, the cochleae in rat pups with ID without anemia were potentially susceptible to loud noise exposure, and this deficit may be attributed to the reduction of ribbon synapses and SGCs.

Objective: The purpose of this study was to evaluate the effects of fiberoptic collimation technique on auditory neural stimulation in the cochlea with 808 nm wavelength lasers., Background Data: Recently, the pulsed near-infrared lasers in the 800-1000 nm wavelength range have been investigated as an emerging technique to trigger auditory neural response in the cochlea. A laser beam divergence in the optical stimulation pathway exists, which may affect stimulation efficiency and spatial selectivity., Methods: The fiberoptic collimation technique was proposed for cochlear neuron stimulation, and the C-lens element was designed as the collimation structure. The spiral ganglion cells in deafened guinea pigs' cochlea were irradiated with collimated and uncollimated near-infrared lasers. Optically evoked auditory brainstem response (OABR) under the two laser output modes were recorded., Results: Laser with the collimation technique evoked an average 58% higher OABR amplitude than the uncollimated laser output. In addition, the collimated laser setup consumed on average 35.2% of laser energy compared with the uncollimated laser when evoking the same OABR amplitude., Conclusions: The fiberoptic collimation technique improved stimulation efficiency and reduced stimulating energy consumption in near-infrared neural stimulation in cochlea. The positive effects of laser collimation technique could benefit further research in optically based cochlear implants.

The discovery that a pulsed laser could trigger an auditory neural response inspired ongoing research on cochlear implants activated by optical stimulus rather than by electrical current. However, most studies to date have used visible light (532 nm) or long-wavelength near-infrared (>1840  nm ) and involved making a hole in the cochlea. This paper investigates the effect of optical parameters on the optically evoked compound action potentials (oCAPs) from the guinea pig cochlea, using a pulsed semiconductor near-infrared laser (980 nm) without making a hole in the cochlea. Synchronous trigger laser pulses were used to stimulate the cochlea, before and after deafening, upon varying the pulse duration (30–1000  μs ) and an amount of radiant energy (0–53.2  mJ/cm 2 ). oCAPs were successfully recorded after deafening. The amplitude of the oCAPs increased as the infrared radiant energy was increased at a fixed 50  μs pulse duration, and decreased with a longer pulse duration at a fixed 37.1  mJ/cm 2 radiant energy. The latency of the oCAPs shortened with increasing radiant energy at a fixed pulse duration. With a higher stimulation rate, the amplitude of the oCAPs’ amplitude decreased.

Pulsed near-infrared radiation has been proposed as an alternative stimulus for auditory nerve stimulation and could be potentially used in the design of cochlear implant. Although the infrared with high absorption coefficient of water (i.e., wavelength ranged from 1.8 to 2.2 μm) has been widely investigated, the lymph in the cochlea absorbs most of the infrared energies, and only a small part can arrive at the target auditory nerves. The present study is aimed to test whether the short-wavelength near-infrared irradiation with lower absorption coefficients can penetrate the lymph fluid to stimulate the auditory nerves. An 808-nm near-infrared laser was chosen to stimulate the auditory nerve in the guinea pig cochlea. The infrared pulse was delivered by an optical fiber that was surgically inserted near the round window membrane and oriented toward the spiral ganglion cells in the basal turn of the cochlea. The 2-Hz infrared pulses were used to stimulate the cochlea before and after the deafness with different pulse durations (100-1,000 μs). Optically evoked compound action potentials (oCAPs) were recorded during the infrared radiation. We successfully recorded oCAPs from both normal hearing animals and deafened animals. The oCAP amplitude increased with the infrared radiation energy. The preliminary experiment suggests that the near-infrared with lower absorption coefficients can effectively pass through the lymph filled in the cochlea and stimulate the auditory nerve. Further studies will optimize the deafness animal model and determine the optimal stimulation parameters.

Background: The rapid spread of devices generating electromagnetic fields (EMF) has raised concerns as to the possible effects of this technology on humans. The auditory system is the neural organ most frequently and directly exposed to electromagnetic activity owing to the daily use of mobile phones. In recent publications, a possible correlation between mobile phone usage and central nervous system tumours has been detected. Very recently a deterioration in otoacoustic emissions and in the auditory middle latency responses after intensive and long-term magnetic field exposure in humans has been demonstrated., Methods: To determine with objective observations if exposure to mobile phone EMF affects acoustically evoked cochlear nerve compound action potentials, seven patients suffering from Ménière's disease and undergoing retrosigmoid vestibular neurectomy were exposed to the effects of mobile phone placed over the craniotomy for 5 min., Results: All patients showed a substantial decrease in amplitude and a significant increase in latency of cochlear nerve compound action potentials during the 5 min of exposure to EMF. These changes lasted for a period of around 5 min after exposure., Discussion: The possibility that EMF can produce relatively long-lasting effects on cochlear nerve conduction is discussed and analysed in light of contrasting previous literature obtained under non-surgical conditions. Limitations of this novel approach, including the effects of the anaesthetics, craniotomy and surgical procedure, are presented in detail.

We conducted a prospective study to identify prognostic factors of hearing preservation after gamma knife radiosurgery (GKRS) for vestibular schwannoma (VS). Twenty-seven patients with unilateral VS and serviceable hearing underwent GKRS. The mean lesion diameter was 17.3mm (range 6.1-30.0mm), the median marginal dose was 12 Gy (11-15 Gy), and the mean follow-up duration was 35.7 months (9-81 months). The probabilities of hearing preservation after GKRS were calculated using the Kaplan-Meier method. Tumor growth was controlled in 26 of the 27 patients (96.3%), and rates of hearing preservation were 85.1% and 68.1% at 2 and 3 years, respectively. A normal auditory brainstem response (ABR) (p = 0.008) and Gardner-Robertson class I hearing (p = 0.012) before GKRS were found to be significant prognostic factors of a favorable outcome. Our findings suggest that a normal pre GKRS ABR strongly predicts hearing preservation after GKRS. Accordingly, we advise that ABR should be considered with other prognostic factors when GKRS is considered in patients with VS., (Copyright 2009 Elsevier Ltd. All rights reserved.)

Objective: Management options for patients with vestibular schwannoma include observation, surgical resection, stereotactic radiosurgery (SRS), and stereotactic radiation therapy. In younger patients, resection is often advocated because of concern regarding the long-term effects of radiation. We studied tumor response and clinical outcomes after SRS in such patients., Methods: We reviewed long-term outcomes in 55 patients with vestibular schwannomas. Patients were 40 years of age or younger, underwent gamma knife (GK) SRS between 1987 and 2003, and were followed up for a minimum of 4 years. The median patient age was 35 years (range, 13-40 years). Forty-one patients had Gardner-Robertson class 1 to 4 hearing. Thirteen patients (24%) had undergone surgical removal. The median tumor volume was 1.7 mm. The median tumor margin dose was 13.0 Gy (range, 11-20 Gy)., Results: At a median of 5.3 years, (range, 4-20 years), 2 of 55 patients underwent GK SRS for a second time; 1 of these patients had had a recurrence after initial resection. The 5-year rate of freedom from additional management was 96%. Hearing preservation rates (i.e., remaining within the same Gardner-Robertson hearing class) were 93%, 87%, and 87% at 3, 5, and 10 years, respectively. In patients with serviceable hearing before SRS, it was maintained in 100%, 93%, and 93% of patients at 3, 5, and 10 years, respectively. Hearing preservation was related to a margin dose lower than 13 Gy (P = 0.017). At the last assessment, facial and trigeminal nerve function was preserved in 98.2% and 96.4% of patients, respectively; the only facial deficit (House-Brackmann grade III) occurred in a patient who received a tumor dose of 20 Gy early in our experience (1988). None of the patients treated with doses lower than 13 Gy experienced facial or trigeminal neuropathy. All patients continued their previous level of activity or employment after GK SRS. No patient developed a secondary radiation-related tumor., Conclusion: Our experience indicates that GK SRS is an effective management strategy for younger patients with vestibular schwannoma, most of whom have no additional cranial nerve dysfunction.

Radiosurgery has evolved into an effective alternative to microsurgical resection in the treatment of patients with vestibular schwannoma. We performed a systematic analysis of the literature in English on the radiosurgical treatment of vestibular schwannoma patients. A total of 254 published studies reported assessable and quantifiable outcome data of patients undergoing radiosurgery for vestibular schwannomas. American Association of Otolaryngology-Head and Neck Surgery (AAO-HNS) class A or B and Gardner-Robertson (GR) classification I or II were defined as having preserved hearing. A total of 5825 patients (74 articles) met our inclusion criteria. Practitioners who delivered an average dose of 12.5 Gy as the marginal dose reported having a higher hearing preservation rate (12.5 Gy=59% vs. >12.5 Gy=53%, p=0.0285). Age of the patient was not a significant prognostic factor for hearing preservation rates (<65 years=58% vs. >65 years=62%; p=0.4317). The average overall follow-up was 41.2 months. Our data suggest that an overall hearing preservation rate of about 57% can be expected after radiosurgical treatment, and patients treated with 12.5 Gy were more likely to have preserved hearing.

Aims: To assess the dosimetric effect of using a split-organ delineation approach during intensity-modulated radiotherapy (IMRT) treatment planning for advanced T-stage nasopharyngeal carcinoma (NPC)., Materials and Methods: Twenty NPC patients with T3-4 tumours were studied. A reference (REF) IMRT plan was generated based on a standard treatment planning protocol, with a set of user-defined dose constraints for optimisation. An investigative (INV) IMRT plan was then generated based on the same protocol, but treating several organs at risk (OARs; parotid glands, temporal lobes, cochlea, auditory nerves and planning organ at risk volume [PRV] of the brainstem) as split organs consisting of target-overlapping and non-target-overlapping sub-segments. These sub-segments were assigned independent dose constraints. The REF and INV plans were compared with respect to target coverage and OAR sparing. Target coverage was evaluated by the Dmin (minimum dose), V66/V60 (percentage volume of gross target volume [GTV]/planning target volume [PTV] receiving 66 Gy/60 Gy), target conformity index (CI), and tumour control probability (TCP). The sparing of OARs was evaluated by the commonly used dose end points for the respective OAR, and normal tissue complication probability (NTCP)., Results: For PTV coverage, the INV plan was superior to the REF plan in terms of Dmin (P=0.000), CI (P=0.005) and TCP (P=0.002). This is attributed to an increase in dose to the PTV-OAR overlapping sub-segments. Regarding the sparing of OARs, there was a significant reduction in the mean dose of the parotid glands (P=0.002), and a slight, but non-significant, increase in NTCP of the temporal lobes, cochlea and brainstem., Conclusions: Using a split-organ delineation approach in IMRT treatment planning for advanced T-stage NPC, a significant improvement in the target coverage and TCP could be achieved, whereas the mean dose of the parotid was reduced significantly. There was insignificant change in the NTCP of the temporal lobe, parotid gland, cochlea and brainstem, but a significant change in the NTCP of the auditory nerve. The approach provides the planner extra room to manipulate the dose constraints during optimisation, and to obtain the desired result in less attempts. This approach also has the potential to be used in a broader context for IMRT planning for other tumour sites.

Object: The purpose of this study was to measure the dose of radiation delivered to the cochlea during a Gamma knife surgery (GKS) procedure for treatment of patients with vestibular schwannomas (VSs), and to analyze the relationship between cochlear irradiation and the hearing outcome of these patients., Methods: Eighty-two patients with VSs were treated with GKS using a marginal dose of 12 Gy. No patient had neurofibromatosis Type 2 disease, and all had a Gardner-Robertson hearing class of I to IV before treatment, and a radiological and audiological follow-up of at least 1-year after GKS. The dosimetric data of the volume of the cochlea were retrospectively analyzed and were correlated with the auditory outcome of patients., Results: The mean radiation dose delivered to the cochlear volume ranged from 1.30 to 10.00 Gy (median 4.15 Gy). The cochlea received significantly higher radiation doses in patients with worsening of hearing after GKS. A highly significant association between the cochlear and the intracanalicular dose of radiation delivered during GKS was found., Conclusions: During GKS for VSs, relatively high doses of radiation can be delivered to the cochlea. Worsening of hearing after GKS can be the consequence of either radiation injury to the cochlea or the irradiation dose delivered into the auditory canal, or both.

Objectives: The cochlea may be damaged by modern conventional radiotherapy (RT) for head and neck cancers when the ear is included in the radiation field. It is unclear however, if the retro-cochlear auditory pathways are affected as well, which has clinical significance in cochlear implantation. This study aims to investigate the integrity of the retro-cochlear auditory pathways in patients who had received RT for nasopharyngeal carcinoma., Study Design: Prospective study., Methods: Patients who were newly diagnosed with nasopharyngeal carcinoma and treated by RT alone were studied. Evoked response audiometry and PTAs were carried out prior to and after RT (at 3, 18, and 48 months postRT). In addition, evoked response audiometry was also performed during the 3rd, 5th, and 7th week of RT. Waves 1 to 5, 1 to 3, and 3 to 5 latencies were measured. The values recorded during and postRT were compared with those recorded before RT. In addition, a subset of ears that demonstrated postRT sensorineural hearing loss were identified so that their respective wave 1 to 5 interwave latencies could be similarly compared. Wilcoxon signed ranks test was used in the statistical analysis. To confirm that the cochlea and internal auditory meatus receive significant doses of radiation, the RT treatment plans of nine other nasopharyngeal carcinoma patients treated by the same RT technique were analyzed to derive dose-volume histograms of these structures., Results: Twenty-seven patients (20 males and 7 females) with a mean age of 51.2 (range 36-75) years participated in the study. There was no statistically significant difference in waves 1 to 5, 1 to 3, and 3 to 5 interwave latencies recorded during RT and postRT as compared with those recorded before RT (P > .05). Pre- and postRT wave 1 to 5 latencies of the 16 ears that had postRT hearing deterioration were also not statistically significant (P = .366). The mean radiation doses delivered to the cochlea and internal auditory meatus ranged from 24.1 to 62.2 Gy and 14.4 to 43.4 Gy, respectively., Conclusion: This study suggests in patients who have had RT for nasopharyngeal carcinoma, the retro-cochlear auditory pathways are functionally intact even in the longer term.

Nucleus angularis (NA), one of the two cochlear nuclei in birds, is important for processing sound intensity for localization and most likely has role in sound recognition and other auditory tasks. Because the synaptic properties of auditory nerve inputs to the cochlear nuclei are fundamental to the transformation of auditory information, we studied the properties of these synapses onto NA neurons using whole cell patch-clamp recordings from auditory brain stem slices from embryonic chickens (E16-E20). We measured spontaneous excitatory postsynaptic currents (EPSCs), and evoked EPSCs and excitatory postsynaptic potentials (EPSPs) by using extracellular stimulation of the auditory nerve. These excitatory EPSCs were mediated by AMPA and N-methyl-D-aspartate (NMDA) receptors. The spontaneous EPSCs mediated by AMPA receptors had submillisecond decay kinetics (556 micros at E19), comparable with those of other auditory brain stem areas. The spontaneous EPSCs increased in amplitude and became faster with developmental age. Evoked EPSC and EPSP amplitudes were graded with stimulus intensity. The average amplitude of the EPSC evoked by minimal stimulation was twice as large as the average spontaneous EPSC amplitude (approximately 110 vs. approximately 55 pA), suggesting that single fibers make multiple contacts onto each postsynaptic NA neuron. Because of their small size, minimal EPSPs were subthreshold, and we estimate at least three to five inputs were required to reach threshold. In contrast to the fast EPSCs, EPSPs in NA had a decay time constant of approximately 12.5 ms, which was heavily influenced by the membrane time constant. Thus NA neurons spatially and temporally integrate auditory information arriving from multiple auditory nerve afferents.

This paper presents an analysis of the effects of the electrode-to-fiber distance on the temporal response properties of an auditory nerve fiber stimulated by electric current pulses. This analysis was based upon results from a computational model of a mammalian auditory nerve fiber axon having 50 nodes of Ranvier, each consisting of 130 stochastic sodium channels and 50 stochastic potassium channels, making it possible to represent the temporal fluctuations of action potential initiation and conduction. A monopolar stimulus electrode was located above a central (26th) node at electrode-to-fiber distances of 1, 4, and 7 mm, while the recording electrode was located at the 36th node. Action potentials (spikes) were generated by the biophysical model using the Crank-Nicholson method to solve a diffusive partial differential equation. By observing the occurrence times of spikes in response to 2000 cathodic monophasic stimulus pulses, temporal jitter (i.e., the standard deviation of spike times) was calculated and the poststimulus time (PST) histogram was generated as well. Furthermore, by computing the PST histogram for each initiation node as functions of space (node number) and time (PST), it was shown that spike initiation was distributed not only spatially but also temporally for stimulus levels producing firing efficiencies (FEs) near 0.5. However, at levels producing FEs near 0.99, while temporal variations approached zero, the spatial distribution of initiating nodes was comparable to that observed for the FE near 0.5. As temporal fluctuations are important for speech coding in cochlear implants, we conclude that spatial characteristics of the electrode-auditory nerve fiber interface may play a significant role in influencing these stochastic temporal processes.

Background: When compared to radiosurgery, fractionated stereotactic radiotherapy (FSR) for acoustic neuroma (AN) offers escalation of tumor dose (Gy) and potential sparing of auditory and facial nerve functions., Method: Over the past 6.5 years 287 consecutive patients have received FSR for AN. One hundred fifty patients have follow up greater than 1 year and comprise this report. Non-invasive, repeat-fixation mask allowed simulation via spiral CT. Differential collimation and beam weighting achieved conformality. Three distinct schedules for total dose and fractionation were used. For AN<3.0 cm diameter (mean volume 1.5+/-0.2 cc), > or =3.0 and < or =3.9 cm (mean volume 8.7+/-1.0 cc) and > or =4.0 cm (mean volume 28.3 cc (one case) doses of 5 Gy given in 5 consecutive daily fractions (25 Gy total) (131 patient), 10 fractions of 3 Gy (30 Gy total) (18 pts), or 20 fractions of 2 Gy (1 patient) were given. All treatments were prescribed to the 80% isodose and given via the dedicated 10 MeV accelerator., Findings: The percentage decreases in tumor size were 14+/-1 (range: 0-100), 15+/-3 (range 0-38) and 8 for the 25, 30 and 40 Gy regimens, respectively. No patient had growth of AN or developed facial weakness. Two patients developed transient decrease in facial sensation. Rates of hearing preservation were similar for both the larger and smaller tumors., Interpretation: Fractionated stereotactic radiotherapy may preserve normal function and control both small and large acoustic neuromas.

Background: Stereotactic radiosurgery (SRS) and, more recently, fractionated stereotactic radiotherapy (SRT) have been recognized as noninvasive alternatives to surgery for the treatment of acoustic schwannomas. We review our experience of acoustic tumor treatments at one institution using a gamma knife for SRS and the first commercial world installation of a dedicated linac for SRT., Methods: Patients were treated with SRS on the gamma knife or SRT on the linac from October 1994 through August 2000. Gamma knife technique involved a fixed-frame multiple shot/high conformality single treatment, whereas linac technique involved daily conventional fraction treatments involving a relocatable frame, fewer isocenters, and high conformality established by noncoplanar arc beam shaping and differential beam weighting., Results: Sixty-nine patients were treated on the gamma knife, and 56 patients were treated on the linac, with 1 NF-2 patient common to both units. Three patients were lost to follow-up, and in the remaining 122 patients, mean follow-up was 119 +/- 67 weeks for SRS patients and 115 +/- 96 weeks for SRT patients. Tumor control rates were high (> or =97%) for sporadic tumors in both groups but lower for NF-2 tumors in the SRT group. Cranial nerve morbidities were comparably low in both groups, with the exception of functional hearing preservation, which was 2.5-fold higher in patients who received conventional fraction SRT., Conclusion: SRS and SRT represent comparable noninvasive treatments for acoustic schwannomas in both sporadic and NF-2 patient groups. At 1-year follow-up, a significantly higher rate of serviceable hearing preservation was achieved in SRT sporadic tumor patients and may therefore be preferable to alternatives including surgery, SRS, or possibly observation in patients with serviceable hearing.

The purpose of this paper is to present the experimental device and the work in progress performed in search for objective organic correlation of damage to hearing, examining possible acoustic otofunctional effects on the cochlear epithelium of the rat due to exposure to microwaves (900 MHz). Two experiments using male Sprague-Dawley rats were carried out with a far-field exposure in a cubic chamber. No statistically significant evidence was obtained at both specific absorption rate (SAR) values. The exposure system and the diagnostic apparatus are extremely useful to investigate a potential effect on the auditory system: however, with the parameters applied in these experiments, no evidence was observed.

We investigated effects of lipo-pro-prostaglandin E1 (lipo-[11alpha, 13E, 15S]-11,15-dihydroxy-9-[1-oxobutoxy]-prosta-8, 13-dien-1-oic acid butyl ester), AS-013 in two models of hearing disturbance and equilibrium dysfunction induced by rat inner ear microcirculatory thrombosis. Inner ear microcirculatory thrombosis was induced by photochemical reaction between systemic injection of Rose Bengal and irradiation of green light to the cochlea and vestibule. Photochemical reaction causes endothelial injury followed by platelet adhesion, aggregation and formation of a platelet- and fibrin-rich thrombus. In the hearing disturbance model, a compound cochlear nerve action potential was recorded by electrocochleography every minute. Photochemical reaction induced inner ear microcirculatory thrombosis, followed by disappearance of the action potential. AS-013 significantly (P<0.05) prolonged time to disappearance of the action potential compared with control group. In the equilibrium dysfunction model, the irradiation to the vestibule was applied for 10 min after Rose Bengal injection. The behavior of rats in the swimming test and nystagmus were observed 24 h after the completion of irradiation. In the swimming test, two of 12 animals treated with AS-013 showed no rotating about their longitudinal axes, which indicates equilibrium dysfunction and the duration of well-balanced swimming prolonged. AS-013 suppressed the appearance of nystagmus. These results suggest that lipo-pro-prostaglandin E1, AS-013 may prevent hearing disturbance and equilibrium dysfunction due to inner ear microcirculatory disorders.

Since the first treatment of acoustic neurinoma using the gamma-knife by Leksell, a series of cases have been reported with good control rates. However, the most frequent complication is delayed hearing loss which occurs in more than 50% of patients. The purpose of this study was to define a safe dose by analyzing the radiosurgical dose-response relationship and histological effects on the normal cochlear nerve in rabbit. The rabbits had computed tomography (CT)-guided stereotactic radiosurgery on their cochlear nerves in the internal auditory canal with a 4 mm collimator focusing of a gamma-unit. Maximum doses of 10, 20, 30, 40, 60, 80, 100, 200 and 500 Gy were administered. After the radiosurgery, auditory brain stem responses (ABR) and the behavior of the rabbits were evaluated periodically. At the conclusion, histological investigations were performed. No physiological or histological findings were observed from doses of 30 Gy or below during the 12 month period after the radiosurgery. A dose of 100 Gy caused a severe ABR threshold elevation, vestibular dysfunction and facial palsy. Necrosis and demyelination of nerves were observed pathologically. In this study, we determined that the safe dose to the normal cochlear nerve during radiosurgery was under 40 Gy in rabbits, and complications seemed to vary due to individual differences in radiation tolerance.

Action potentials of neurons in cat dorsal and posteroventral cochlear nuclei were recorded extracellularly with glass microelectrodes while the head of the cat was exposed to microwave pulses at 915 MHz using a diathermy applicator. Response thresholds to acoustic tones, acoustic clicks, and microwave pulses were determined for auditory units with characteristic frequencies (CFs) from 278 Hz to 39.2 kHz. Tests with pulsatile stimuli were performed for durations of 20-700 mus, principally 20, 70, and 200 mus. Brainstem midline specific absorption rate (SAR) threshold was as small as 11.1 mW/g per pulse, and specific absorption (SA) threshold was a small as 0.6 muJ/g per pulse. Microwave thresholds were generally lower for CF less than 9 kHz, as were most acoustic thresholds. However, microwave threshold was only weakly related to click threshold and CF-tone threshold of each unit.

The function and morphology of the vestibular and cochlear parts of the inner ear have been examined after prenatal irradiation on the 12th, 13th and 16th gestational days in the CBA/CBA mouse. Irradiation was performed with a 0.5, 1 or 2 Gy single dose, whole body irradiation of the pregnant female. The irradiated fetuses were born after full term pregnancies and reached maturity (were 1--2 months old) before inner ears were analyzed with regard to vestibular tests, auditory thresholds and morphology. Morphology was studied by light microscopy (LM), transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Auditory function was analyzed by frequency specific auditory brainstem response (ABR). Irradiation doses exceeding 2 Gy caused death to the pregnant female, abortion or malformed litters which were eaten by their mothers. Doses of 0.5, 1 and 2 Gy caused malformed cristae ampullares and maculae utriculi, in particular after exposure on the 12th or 13th gestational days. After those doses no abnormality of clinical behaviour of the animals was found. Ultrastructurally, type I hair cells (HC) of the vestibular part seemed more vulnerable to irradiation than the type II HC while the outer (OHC) and inner (IHC) hair cells appeared equally vulnerable. The ultrastructural changes of hair cells were predominantly localized to the hair cell surface showing a defect cuticle which was sometimes malformed and bulging. Sensory hair fusion occurred with a resulting poor maturation of sensory hair rootlets. The efferent nerve endings were estimated to be reduced in number but, if present, they had a normal ultrastructure. Otoconia showed severe morphological damage following irradiation particularly if exposed on the 16th gestational day. Malformed and fused otoconia were frequent having a disarrayed matrix. The irradiation induced morphological alterations in vivo could be reproduced in the in vitro systems. In addition, a retarded growth of the in vitro developing inner ear anlage was estimated to be the same for the vestibular and cochlear parts. The cochlear part of the inner ear showed a dose and age dependent hearing loss following irradiation. A shift of the ABR threshold was recorded in all exposed groups that were irradiated with 2 Gy. A correlation was found between the individual ABR-audiograms and the degree of morphological HC damage in the cochlea along the basilar membrane. The 12th gestational day inner ear anlage was most vulnerable to irradiation. The 13th gestational day inner ear was almost equally vulnerable and showed a dose-response relationship.(ABSTRACT TRUNCATED AT 400 WORDS)