Environmental variation associated with overwintering elicits marked metabolic plasticity in a temperate salmonid, Salvelinus fontinalis.

Poleward winters commonly expose animals, including fish, to frigid temperatures and low food availability. Fishes that remain active over winter must therefore balance trade-offs between conserving energy and maintaining physiological performance in the cold, yet the extent and underlying mechanisms of these trade-offs are not well understood. We investigated the metabolic plasticity of brook char (Salvelinus fontinalis), a temperate salmonid, from the biochemical to whole-animal level in response to cold and food deprivation. Acute cooling (1°C day-1) from 14°C to 2°C had no effect on food consumption but reduced activity by 77%. We then assessed metabolic performance and demand over 90 days with exposure to warm (8°C) or cold winter (2°C) temperatures while fish were fed or starved. Resting metabolic rate (RMR) decreased substantially during initial cooling from 8°C to 2°C (Q10=4.2-4.5) but brook char exhibited remarkable thermal compensation during acclimation (Q10=1.4-1.6). Conversely, RMR was substantially lower (40-48%) in starved fish, conserving energy. Thus, the absolute magnitude of thermal plasticity may be masked or modified under food restriction. This reduction in RMR was associated with atrophy and decreases in in vivo protein synthesis rates, primarily in non-essential tissues. Remarkably, food deprivation had no effect on maximum oxygen uptake rates and thus aerobic capacity, supporting the notion that metabolic capacity can be decoupled from RMR in certain contexts. Overall, our study highlights the multi-faceted energetic flexibility of Salvelinus spp. that likely contributes to their success in harsh and variable environments and may be emblematic of winter-active fishes more broadly.

Ultrasound imaging guided precision histotripsy: Effects of pulse settings on ablation properties in rat brain.

A high-frequency 6 MHz miniature handheld histotripsy device with an endoscopic form factor and co-registered high-resolution ultrasound imaging was developed. This device could allow precision histotripsy ablation during minimally invasive brain tumor surgeries with real-time image guidance. This study characterized the outcome of acute histotripsy in the normal in vivo rat brain using the device with a range of histotripsy pulse settings, including number of cycles, pulse repetition frequency, and pressure, as well as other experimental factors. The stability and shape of the bubble cloud were measured during ablations, as well as the post-histotripsy ablation shape in ultrasound B-mode and histology. The results were compared between histological images and the ultrasound imaging data to determine how well ultrasound data reflected observable damage in histology. The results indicated that while pulse settings can have some influence on ablation shape, sample-to-sample variation had a larger influence on ablation shape. This suggests that real-time ablation monitoring is essential for accurate knowledge of outcomes. Ultrasound imaging provided an accurate real-time indication of ablation shape both during ablation and post-ablation.

In vivo measurement of basilar membrane vibration in the unopened chinchilla cochlea using high frequency ultrasound.

The basilar membrane and organ of Corti in the cochlea are essential for sound detection and frequency discrimination in normal hearing. There are currently no methods used for real-time high resolution clinical imaging or vibrometry of these structures. The ability to perform such imaging could aid in the diagnosis of some pathologies and advance understanding of the causes. It is demonstrated that high frequency ultrasound can be used to measure basilar membrane vibrations through the round window of chinchilla cochleas in vivo. The basic vibration characteristics of the basilar membrane agree with previous studies that used other methods, although as expected, the sensitivity of ultrasound was not as high as optical methods. At the best frequency for the recording location, the average vibration velocity amplitude was about 4 mm/s/Pa with stimulus intensity of 50 dB sound pressure level. The displacement noise floor was about 0.4 nm with 256 trial averages (5.12 ms per trial). Although vibration signals were observed, which likely originated from the organ of Corti, the spatial resolution was not adequate to resolve any of the sub-structures. Improvements to the ultrasound probe design may improve resolution and allow the responses of these different structures to be better discriminated.

An 8 mm endoscopic histotripsy array with integrated high-resolution ultrasound imaging.

An 8 mm diameter, image-guided, annular array histotripsy transducer was fabricated and characterized. The array was laser etched on a 5 MHz, 1-3 dice and fill, PZT-5H/epoxy composite with a 45 % volume fraction. Flexible PCBs were used to electrically connect to the array elements using wirebonds. The array was backed with a low acoustic impedance epoxy mixture. A 3.6 by 3.8 mm, 64-element, 30 MHz phased array imaging probe was positioned in the center hole, to co-align the imaging plane with the bubble cloud produced by the therapy array. A custom 16-channel high voltage pulse generator was used to test the annular array for focal lengths ranging from 3- to 8-mm. An aluminum lens-focussed transducer with a 7 mm focal length was fabricated using the same piezocomposite and backing material and tested along with the histotripsy array. Simulated results from COMSOL FEM models were compared to measured results for low voltage characterization of the array and lens-focussed transducer. The measured transmit sensitivity of the array ranged from 0.113 to 0.167 MPa/V, while the lens-focussed transducer was 0.192 MPa/V. Simulated values were 0.160 to 0.174 MPa/V and 0.169 MPa/V, respectively. The measured acoustic fields showed a significantly increased depth-of-field compared the lens-focussed transducer, while the beamwidths of the array focus were comparable to the lens. The measured cavitation voltage in water was between 254 V and 498 V depending on the focal length, and 336 V for the lens-focussed transducer. The array had a lower cavitation voltage than the lens-focussed transducer for a comparable operating depth. The histotripsy array was tested in a tissue phantom and an in vivo rat brain. It was used to produce an elongated lesion in the brain by electronically steering the focal length from 3- to 8-mm axially. Real time ultrasound imaging with a Doppler overlay was used to target the tissue and monitor ablation progress, and histology confirmed the targeted tissue was fully homogenized.

Sealworm Pseudoterranova decipiens s.s. infection of European smelt Osmerus eperlanus in German coastal waters: ecological implications.

European smelt Osmerus eperlanus (n = 501) from the German Wadden Sea (North Sea) near the city of Cuxhaven were examined for their infestation with parasitic anisakid nematodes, especially with sealworms of the genus Pseudoterranova. The distribution of third-stage larvae (L3) in the musculature and viscera of the fish was analyzed. In total, we isolated 543 L3 from the hosts' body cavity and musculature. A subsample of 105 larvae were identified as the (sibling) species P. decipiens s.s. using direct sequencing of the highly variable ribosomal ITS1-5.8S-ITS2 genetic marker. The mean abundance was 1.1, the mean intensity was 2.3 P. decipiens s.s. and the prevalence was 47.3%. Total length and total weight, but not Fulton's condition factor (K), were significantly different in infected compared to uninfected smelt. No correlation was found between the total length of infected fish and the intensity of anisakid nematodes. The vast majority of P. decipiens s.s. was found in the musculature of the smelt. More than half (55.7%) of all nematodes were located in the 3 parts of the epaxial musculature, whereas 18.4 and 26.0% were found in the hypaxial musculature and the compartments of the tail muscles, respectively.

Finite-Element Modelling Based on Optical Coherence Tomography and Corresponding X-ray MicroCT Data for Three Human Middle Ears.

PURPOSE: Optical coherence tomography (OCT) is an emerging imaging modality which is non-invasive, can be employed in vivo, and can record both anatomy and vibrations. The purpose here is to explore the application of finite-element (FE) modelling to OCT data. METHODS: We recorded vibrations for three human cadaver middle ears using OCT. We also have X-ray microCT images from the same ears. Three FE models were built based on geometries obtained from the microCT images. The material properties and boundary conditions of the models were obtained from previously reported studies. RESULTS: Tympanic-membrane (TM) vibration patterns were computed for the three models and compared with the patterns measured using OCT. Frequency responses were also computed for all three models for several locations in the middle ear and compared with the OCT displacements and with the literature. The three models were compared with each other in terms of geometry and function. Parameter sensitivity analyses were done and the results were compared among the models and with the literature. The simulated TM displacement patterns are qualitatively similar to the OCT results. The simulated displacements are closer to the OCT results for 500 Hz and 1 kHz but the differences are greater at 2 kHz. CONCLUSION: This study provides an initial look at the combined use of OCT measurements and FE modelling based on subject-specific anatomy. The geometries and parameters of the existing FE models could be modified for individual patients in the future to help identify abnormalities in the middle ear.

Fabrication and Characterization of a 5 mm × 5 mm Aluminum Lens-Based Histotripsy Transducer.

Two 5 mm by 5 mm square aluminum lenses with a 6 mm depth of focus were machined and tested for histotripsy with a 40% volume fraction 1-3 PZT-5A composite and a Meggitt Pz-39 porous ceramics lapped to 315 [Formula: see text] as the piezoelectric elements. The devices were air-backed, and an 89 [Formula: see text] layer of Parylene-C was deposited on the lens, matching aluminum to water. Both devices were driven single-ended at 5.8 MHz, their optimal frequency after bonding to the lens, with ten cycles at a PRF of 1 kHz. The composite-based device showed no sign of free-field cavitation in water up to a drive level of 600 V, whereas the Pz39-based device was able to cavitate in water at a drive level of 220 V. In vivo ablation of a rat brain tissue was demonstrated through an opening in the skull and required the drive voltage be increased to 280 V. The ablation was monitored using B-mode imaging with an endoscopic 30 MHz ultrasound phased array and power Doppler overlay. Ablation was maintained for 12 s and, in the power Doppler image, the ablation zone grew steadily over this time to 1.9 mm by 3.4 mm. Immediately after treatment, the ablated area appeared anechoic, slowly filling with specular material.

Endoscopic Coregistered Ultrasound Imaging and Precision Histotripsy: Initial In Vivo Evaluation.

Objective. Initial performance evaluation of a system for simultaneous high-resolution ultrasound imaging and focused mechanical submillimeter histotripsy ablation in rat brains. Impact Statement. This study used a novel combination of high-resolution imaging and histotripsy in an endoscopic form. This would provide neurosurgeons with unprecedented accuracy in targeting and executing nonthermal ablations in minimally invasive surgeries. Introduction. Histotripsy is a safe and effective nonthermal focused ablation technique. However, neurosurgical applications, such as brain tumor ablation, are difficult due to the presence of the skull. Current devices are too large to use in the minimally invasive approaches surgeons prefer. We have developed a combined imaging and histotripsy endoscope to provide neurosurgeons with a new tool for this application. Methods. The histotripsy component had a 10 mm diameter, operating at 6.3 MHz. Affixed within a cutout hole in its center was a 30 MHz ultrasound imaging array. This coregistered pair was used to ablate brain tissue of anesthetized rats while imaging. Histological sections were examined, and qualitative descriptions of ablations and basic shape descriptive statistics were generated. Results. Complete ablations with submillimeter area were produced in seconds, including with a moving device. Ablation progress could be monitored in real time using power Doppler imaging, and B-mode was effective for monitoring post-ablation bleeding. Collateral damage was minimal, with a 100 µm maximum distance of cellular damage from the ablation margin. Conclusion. The results demonstrate a promising hardware suite to enable precision ablations in endoscopic procedures or fundamental preclinical research in histotripsy, neuroscience, and cancer.

Investigating the Electrical Properties of Different Cochlear Implants.

AIM: This study characterises and compares electrical properties and current spread across four different makes of cochlear implants with differing electrode designs using a 3D-printed artificial cochlear model. BACKGROUND: Cochlear implants are currently limited by current spread within the cochlea, which causes low spectral resolution of auditory nerve stimulation. Different cochlear implant makes vary in electrode size, shape, number, and configuration. How these differences affect cochlear implant current spread and function is not well known. METHOD: Each cochlear implant was inserted into a linear cochlear model containing recording electrodes along its length. Biphasic monopolar stimulation of each implant electrode was carried out, and the resultant waveform and transimpedance matrix (TIM) data obtained from the recording electrodes. This was repeated with each implant rotated 180 degrees in the cochlea model to examine the effects of electrode orientation. Impedance spectroscopy was also carried out at the apex, middle, and base of the model. RESULTS: The four cochlear implants displayed similar TIM profiles and waveforms. One hundred eighty degrees rotation of each cochlear implant made little difference to the TIM profiles. Impedance spectroscopy demonstrated broad similarities in amplitude and phase across the implants, but exhibited differences in certain electrical parameters. CONCLUSION: Implants with different designs demonstrate similar electrical performance, regardless of electrode size and spacing or electrode array dimension. In addition, rotatory maneuvers during cochlear implantation surgery are unlikely to change implant impedance properties.

A Dual-Frequency Lens-Focused Endoscopic Histotripsy Transducer.

A forward-looking miniature histotripsy transducer has been developed that incorporates an acoustic lens and dual-frequency stacked transducers. An acoustic lens is used to increase the peak negative pressure through focal gain and the dual-frequency transducers are designed to increase peak negative pressure by summing the pressure generated by each transducer individually. Four lens designs, each with an f -number of approximately 1, were evaluated in a PZT5A composite transducer. The finite-element model (FEM) predicted axial beamwidths of 1.61, 2.40, 2.84, and 2.36 mm for the resin conventional, resin Fresnel, silicone conventional, and silicone Fresnel lenses, respectively; the measured axial beamwidths were 1.30, 2.28, 2.71, and 2.11 mm, respectively. Radial beamwidths from the model were between 0.32 and 0.35 mm, while measurements agreed to within 0.2 mm. The measured peak negative was 0.150, 0.124, 0.160, and 0.160 MPa/V for the resin conventional, resin Fresnel, silicone conventional, and silicone Fresnel lenses, respectively. For the dual-frequency device, the 5-MHz (therapy) transducer had a measured peak negative pressure of 0.136 MPa/V for the PZT5A composite and 0.163 MPa/V for the PMN-PT composite. The 1.2-MHz (pump) transducer had a measured peak negative pressure of 0.028 MPa/V. The pump transducer significantly lowered the cavitation threshold of the therapy transducer. The dual-frequency device was tested on an ex vivo rat brain, ablating tissue at up to 4-mm depth, with lesion sizes as small as [Formula: see text].

Ultrasound-microbubble cavitation facilitates adeno-associated virus mediated cochlear gene transfection across the round-window membrane.

The round window of the cochlea provides an ideal route for delivering medicines and gene therapy reagents that can cross the round window membrane (RWM) into the inner ear. Recombinant adeno-associated viruses (rAAVs) have several advantages and are recommended as viral vectors for gene transfection. However, rAAVs cannot cross an intact RWM. Consequently, ultrasound-mediated microbubble (USMB) cavitation is potentially useful, because it can sonoporate the cell membranes, and increase their permeability to large molecules. The use of USMB cavitation for drug delivery across the RWM has been tested in a few animal studies but has not been used in the context of AAV-mediated gene transfection. The currently available large size of the ultrasound probe appears to be a limiting factor in the application of this method to the RWM. In this study, we used home-made ultrasound probe with a decreased diameter to 1.5 mm, which enabled the easy positioning of the probe close to the RWM. In guinea pigs, we used this probe to determine that (1) USMB cavitation caused limited damage to the outer surface layer or the RWM, (2) an eGFP-gene carrying rAAV could effectively pass the USMB-treated RWM and reliably transfect cochlear cells, and (3) the hearing function of the cochlea remained unchanged. Our results suggest that USMB cavitation of the RWM is a good method for rAAV-mediated cochlear gene transfection with clear potential for clinical translation. We additionally discuss several advantages of the small probe size.

An Instrumented Cochlea Model for the Evaluation of Cochlear Implant Electrical Stimulus Spread.

Cochlear implants use electrical stimulation of the auditory nerve to restore the sensation of hearing to deaf people. Unfortunately, the stimulation current spreads extensively within the cochlea, resulting in "blurring" of the signal, and hearing that is far from normal. Current spread can be indirectly measured using the implant electrodes for both stimulating and sensing, but this provides incomplete information near the stimulating electrode due to electrode-electrolyte interface effects. Here, we present a 3D-printed "unwrapped" physical cochlea model with integrated sensing wires. We integrate resistors into the walls of the model to simulate current spread through the cochlear bony wall, and "tune" these resistances by calibration with an in-vivo electrical measurement from a cochlear implant patient. We then use this model to compare electrical current spread under different stimulation modes including monopolar, bipolar and tripolar configurations. Importantly, a trade-off is observed between stimulation amplitude and current focusing among different stimulation modes. By combining different stimulation modes and changing intracochlear current sinking configurations in the model, we explore this trade-off between stimulation amplitude and focusing further. These results will inform clinical strategies for use in delivering speech signals to cochlear implant patients.

Repair of subtotal tympanic membrane perforations: A temporal bone study of several tympanoplasty materials.

The aim of this project was to investigate the effects of different types of graft material, and different remaining segments of the native TM on its motion. In twelve human temporal bones, controlled TM perforations were made to simulate three different conditions. (1) Central perforation leaving both annular and umbo rims of native TM. (2) Central perforation leaving only a malleal rim of native TM. (3) Central perforation leaving only an annular rim of native TM. Five different graft materials (1) perichondrium (2) silastic (3) thin cartilage (4) thick cartilage (5) Lotriderm® cream were used to reconstruct each perforation condition. Umbo and stapes vibrations to acoustic stimuli from 250 to 6349 Hz were measured using a scanning laser Doppler vibrometer. Results showed that at low frequencies: in the Two Rims condition, all grafting materials except thick cartilage and Lotriderm cream showed no significant difference in umbo velocity from the Normal TM, while only Lotriderm cream showed a significant decrease in stapes velocity; in the Malleal Rim condition, all materials showed a significant decrease in both umbo and stapes velocities; in the Annular Rim condition, all grafting materials except Lotriderm and perichondrium showed no significant difference from the Normal TM in stapes velocity. Umbo data might not be reliable in some conditions because of coverage by the graft. At middle and high frequencies: all materials showed a significant difference from the Normal TM in both umbo and stapes velocities for all perforation conditions except in the Annular Rim condition, in which silastic and perichondrium showed no significant difference from the Normal TM at umbo velocity in the middle frequencies. In the low frequencies, the choice of repair material does not seem to have a large effect on sound transfer. Our data also suggests that the annular rim could be important for low frequency sound transfer.

Auditory effects of autologous fat graft for TORP stabilization in the middle ear: a cadaveric study.

BACKGROUND: Total ossicular replacement prostheses (TORP) are often used to re-establish ossicular coupling of sound in an ear lacking a stapes supra-structure. The use of TORPs, however, is associated with a 2/3 five year failure rate due to their anatomic instability over time in the middle ear. The use of autologous fat to try and stabilize TORPs may improve long-term results with this challenging ossicular reconstruction technique. METHODS: A cadaveric temporal bone model was developed and laser Doppler vibrometry was used to measure and record round window membrane vibration in response to sound stimulation under the following conditions: normal middle ear, middle ear filled with fat, normal middle ear with TORP prosthesis, TORP prosthesis with fat around its distal end and TORP prosthesis with fat filling the middle ear. Fourteen temporal bones were used. RESULTS: There was a significant decrease in round window membrane velocity after filling the middle ear with fat in both the normal middle ear (- 8.6 dB; p < 0.0001) and prosthesis conditions (- 13.7 dB; p < 0.0001). However, there was no significant drop in round window membrane velocity associated with using fat around the distal end of the TORP prosthesis as compared to the prosthesis without fat condition (p > 0.05). CONCLUSIONS: Autologous fat around the distal end of a TORP prosthesis may not be associated with any additional hearing loss, as demonstrated in this cadaveric model. The additional hearing loss potentially caused by using fat to completely surround the prosthesis and fill the middle ear is probably not clinically acceptable at this time, especially given the unknown way in which the fat will atrophy over time in this context.

A Low-Cost Miniature Histotripsy Transducer for Precision Tissue Ablation.

A miniature, 10 mm aperture histotripsy transducer with an f-number of 0.7 was fabricated using an elliptically shaped aluminum lens, which was epoxy-bonded to an air-backed 5.0 MHz, PTZ-5A, 1-3 dice-and-fill piezoelectric composite, and the lens coupled to water using a quarter-wavelength matching layer of Parylene-C. A Krimholtz-Leedom-Matthaei model of the device and curved lens was developed. The epoxy layer resulted in an increased power output at 6.8 MHz compared to the 5 MHz composite design. Cavitation was observed in water by driving the composite with a 173 V single-cycle, unipolar 6.8 MHz pulse at a pulse repetition frequency of 50 Hz, and a bubble cloud 264 long by 124 wide was measured. A coregistered imaging and ablation device was also fabricated and characterized. The coregistered device was modified to include a mm square hole through the center, allowing access for a high-frequency imaging array, and both imaging and ablation are demonstrated in cerebral tissue with this device. Radial -3 dB beam widths were measured as 0.145 and 0.116 mm, and axial -3 dB depths of field were 0.698 and 0.752 mm for the noncoregistered and coregistered transducers, respectively. Total material cost for the transducer and pulser board is below $200 USD.

Effects of Cartilage Overlay on the Tympanic Membrane: Lessons From a Temporal Bone Study for Cartilage Tympanoplasty.

HYPOTHESIS: Placing cartilage grafts on different tympanic membrane (TM) locations will affect sound transfer function, and the effects will differ according to the part of the TM modified. BACKGROUND: Cartilage tympanoplasty is increasingly popular because of lower reperforation rates, and better long-term stability. In this temporal bone study, we investigated the effect of placing cartilage grafts over different parts of the normal TM on sound transmission. METHODS: In 10 human fresh frozen temporal bones, umbo and stapes vibrations to acoustic stimuli from 250 to 8000 Hz were measured at multiple points using a scanning laser vibrometer. Four different cartilage arrangements were measured in each temporal bone. 1) Overlay condition leaving an umbo rim of normal TM (Umbo Rim). 2) Overlay condition leaving annular rim of normal TM (Annular Rim). 3) Overlay condition leaving both rims of normal TM (Two Rims). 4) Overlay condition leaving no normal TM exposed (No Rims). RESULTS: At low frequencies, there was a statistically significant decrease in velocity from baseline for the No Rims (umbo mean -4 dB; stapes -6 dB) and Umbo Rim (umbo -4 dB; stapes -3.7 dB) conditions. All conditions showed significant decreases for middle frequencies (umbo -4.0, -5.9, -7.4 and -6.3 dB; stapes -10.8, -6.6, -6.3 and -7.7 dB) and high frequencies (umbo -13.2, -3.0, -3.1 and -5.5 dB; stapes -4.6, -2.4, -2.6 and -3.5 dB). Results are in order for No Rims, Umbo Rim, Two Rims, and Annular Rim conditions. CONCLUSION: In the low frequencies, it seems to matter where the cartilage is placed, and in particular the annular rim of the TM seems to be important for the low-frequency acoustic transfer function. In the higher frequencies, all graft placements caused some drop at all frequencies. In all frequencies, effects were modest by clinical standards.

No effect of prolonged pulsed high frequency ultrasound imaging of the basilar membrane on cochlear function or hair cell survival found in an initial study.

Miniature high frequency ultrasound devices show promise as tools for clinical middle ear and basal cochlea imaging and vibrometry. However, before clinical use it is important to verify that the ultrasound exposure does not damage the cochlea. In this initial study, electrophysiological responses of the cochlea were measured for a range of stimulus frequencies in both ears of anesthetized chinchillas, before and after exposing the organ of Corti region of one ear to pulsed focused ultrasound for 30 min. Measurements were again taken after an 11 day survival period. Cochlear tissue was examined with a confocal microscope for signs of damage to the cochlear hair cells. No significant change in response thresholds due to exposure was found, and no signs of ultrasound-induced tissue damage were observed, although one animal (out of ten) did have a region of extensive tissue damage in the exposed cochlea. However, after further analysis this was concluded to be not likely a result of the ultrasound exposure.

Real-time intracochlear imaging of automated cochlear implant insertions in whole decalcified cadaver cochleas using ultrasound.

OBJECTIVES: This study aimed to determine the feasibility of combining high-frequency ultrasound imaging, automated insertion, and force sensing to yield more information about cochlear implant insertion dynamics. METHODS: An apparatus was developed combining these aspects along with software to control implant and imaging probe positions. Decalcified unfixed human cochleas were implanted at various speeds, insertion sites, and implant models while imaging near the implant tip throughout insertion and recording force data from the cochlea mounting stage. Ultrasound video data were also captured. RESULTS: The basilar membrane (BM) was frequently penetrated by the implant in either the mid-basal or lower middle turn. Measurements were also performed of apical BM motion in response to upstream implant movement at varying insertion speeds. Increasing insertion speed resulted in greater BM displacement. DISCUSSION: Multiple insertions per cochlea increase the volume of data per specimen while also reducing variability due to differences between cochleas. However, to image inside the cochlea with ultrasound, the bone had to be decalcified, which likely had a significant effect upon the response of tissue to contact by the implant. As calcified bone strongly reflects ultrasound, we also found ultrasound imaging to be an excellent method for easily assessing bone decalcification progress. CONCLUSION: This technique may be very useful for some studies, although the confounding effects of bone decalcification may make results of other studies too difficult to generalize. The approach could be adapted to other real-time imaging modalities, such as optical coherence tomography.

Structural and Ultrastructural Changes to Type I Spiral Ganglion Neurons and Schwann Cells in the Deafened Guinea Pig Cochlea.

Sensorineural hearing loss is commonly caused by damage to cochlear sensory hair cells. Coinciding with hair cell degeneration, the peripheral fibres of type I spiral ganglion neurons (SGNs) that normally form synaptic connections with the inner hair cell gradually degenerate. We examined the time course of these degenerative changes in type I SGNs and their satellite Schwann cells at the ultrastructural level in guinea pigs at 2, 6, and 12 weeks following aminoglycoside-induced hearing loss. Degeneration of the peripheral fibres occurred prior to the degeneration of the type I SGN soma and was characterised by shrinkage of the fibre followed by retraction of the axoplasm, often leaving a normal myelin lumen devoid of axoplasmic content. A statistically significant reduction in the cross-sectional area of peripheral fibres was evident as early as 2 weeks following deafening (p < 0.001, ANOVA). This was followed by a decrease in type I SGN density within Rosenthal's canal that was statistically significant 6 weeks following deafening (p < 0.001, ANOVA). At any time point examined, few type I SGN soma were observed undergoing degeneration, implying that once initiated, soma degeneration was rapid. While there was a significant reduction in soma area as well as changes to the morphology of the soma, the ultrastructure of surviving type I SGN soma appeared relatively normal over the 12-week period following deafening. Satellite Schwann cells exhibited greater survival traits than their type I SGN; however, on loss of neural contact, they reverted to a non-myelinating phenotype, exhibiting an astrocyte-like morphology with the formation of processes that appeared to be searching for new neural targets. In 6- and 12-week deafened cochlea, we observed cellular interaction between Schwann cell processes and residual SGNs that distorted the morphology of the SGN soma. Understanding the response of SGNs, Schwann cells, and the complex relationship between them following aminoglycoside deafening is important if we are to develop effective therapeutic techniques designed to rescue SGNs.

High Frequency Ex Vivo Ultrasound Imaging of the Middle Ear to Show Simulated Ossicular Pathology.

HYPOTHESIS: To illustrate the ability of high frequency ultrasound (HFUS) using a transducer array to demonstrate a variety of simulated clinical scenarios involving the ossicular chain. BACKGROUND: HFUS (>20 MHz) is a relatively new area of ultrasonic imaging that provides an order of magnitude better image resolution than the conventional low-frequency systems. HFUS may be a real-time imaging system that could be used in the clinic and would complement computed tomography (CT) and magnetic resonance imaging (MRI) to enhance the decision-making process for patients with middle ear pathology. METHODS: Using a commercially available HFUS scanner, we imaged a variety of simulated clinical scenarios to demonstrate the ability of HFUS to image middle ear pathology. RESULTS: We were able to clearly demonstrate real-time visualization of ossicular pathology in human temporal bones, whereas there are some limitations in the current technique to be addressed before it is used in vivo. CONCLUSION: HFUS allows excellent visualization of middle ear anatomy and pathology through an intact tympanic membrane (TM), and these experiments go some way towards giving the otologist access to high resolution, real-time imaging of the middle ear in the clinic.