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Biomedical subjects

S A Xu

Publications and source records attributed to S A Xu.

15 recordsLinked to original sources

Improved and simplified methods for specifying positions of the electrode bands of a cochlear implant array.

OBJECTIVE: To develop techniques for measuring the positions of the individual electrodes of a multiple channel cochlear implant and for estimating associated characteristic frequencies. BACKGROUND: Information concerning the positions of the individual electrodes of a cochlear implant array is important for analyzing speech perception or psychophysical data and for optimizing speech-processing strategies. This study presents two techniques for obtaining such information from postoperative plain film radiographs. METHODS: A template spiral shape, derived from analysis of the radiographs of 30 cochlear implant patients, is used to obtain measurements of the angular positions of the electrode bands within scala tympani. A research technique measures angular positions and estimates characteristic frequencies for all electrode bands but requires that the positions of two cochlear landmarks and all electrode bands be digitized. A clinical technique provides similar angle and frequency estimates but requires a minimum of information to be extracted visually from the radiograph. The lateral positions of the bands are estimated, in the research technique, using mean outer and inner wall functions obtained from 11 Silastic molds of scala tympani. RESULTS: The mean position of the implanted array relative to the mean scala tympani outer wall function was consistent with published histologic observations of implanted temporal bones. Measured angles did not vary greatly with experimenter or with rotation of the cochlea relative to the radiographic beam by up to 20 degrees. CONCLUSIONS: The techniques described allow, principally, measurement of the longitudinal positions of the bands of a cochlear implant in scala tympani and estimation of corresponding characteristic frequencies.

Cochlea

Investigations on a curved intracochlear array.

A curved electrode array and inserting tool have been developed at the University of Melbourne. This electrode array can be successfully implanted with few modifications to the surgical procedure presently in use. When implanted, the curved electrode array adopts a position closer to the modiolus than does the standard straight electrode array.

Cochlear Implants

Cochlear pathology following reimplantation of a multichannel scala tympani electrode array in the macaque.

The histopathologic consequence of removing and reimplanting intracochlear electrode arrays on residual auditory nerve fibers is an important issue when evaluating the safety of cochlear prostheses. The authors have examined this issue by implanting multichannel intracochlear electrodes in macaque monkeys. Macaques were selected because of the similarity of the surgical technique used to insert electrodes into the cochlea compared to that in humans, in particular the ability to insert the arrays into the upper basal turn. Five macaques were bilaterally implanted with the Melbourne/Cochlear banded electrode array. Following a minimum implant period of 5 months, the electrode array on one side of each animal was removed and another immediately implanted. The animals were sacrificed a minimum of 5 months following the reinsertion procedure, and the cochleas prepared for histopathologic analysis. Long-term implantation of the electrode resulted in a relatively mild tissue response within the cochlea. Results also showed that inner and outer hair cell survival, although significantly reduced adjacent to the array, was normal in 8 of the 10 cochleas apicalward. Moreover, the electrode reinsertion procedure did not appear to adversely affect this apical hair cell population. Significant new bone formation was frequently observed in both control and reimplanted cochleas close to the electrode fenestration site and was associated with trauma to the endosteum and/or the introduction of bone chips into the cochlea at the time of surgery. Electrode insertion trauma, involving the osseous spiral lamina or basilar membrane, was more commonly observed in reimplanted cochleas. This damage was usually restricted to the lower basal turn and resulted in a more extensive ganglion cell loss. Finally, in a number of cochleas part of the electrode array was located within the scala media or scala vestibuli. These electrodes did not appear to evoke a more extensive tissue response or result in more extensive neural degeneration compared with electrodes located within the scala tympani. In conclusion, the present study has shown that the reimplantation of a multichannel scala, tympani electrode array can be achieved with minimal damage to the majority of cochlear structures. Increased insertion trauma, resulting in new bone formation and spiral ganglion cell loss, can occur in the lower basal turn in cases where the electrode entry point is difficult to identify due to proliferation of granulation and fibrous tissue.

Animals

Partial hearing loss in the macaque following the co-administration of kanamycin and ethacrynic acid.

Co-administration of kanamycin (KA) with the loop diuretic ethacrynic acid (EA) rapidly produces a profound hearing loss in the cat while maintaining normal renal function [Xu et al., Hear. Res. 70, 205-215 (1993)]. In the present paper we have applied this deafening procedure to the old world monkey Macaca fascicularis (macaque). Following the co-administration of KA and EA, the hearing loss in the macaque developed far slower than we observed in the cat. Moreover, unlike the cat, there was evidence of a partial recovery in the animal's hearing, resulting in a bilaterally symmetrical high frequency hearing loss. The extent of this hearing loss was dependent on the dose of the EA administered. Finally, the most unexpected result of the present study was the degree of acute nephrotoxicity experienced by these animals following the drug administration. The sensitivity of this species to renal failure restricted the dose of EA that could be safely administered. In conclusion, the co-administration of KA and EA cannot reliably produce a profound hearing loss in the macaque. While it can produce a dose dependent high frequency hearing loss the animal will also experience acute renal failure that requires careful management.

Animals

Cochlear implantation in young children: histological studies on head growth, leadwire design, and electrode fixation in the monkey model.

For safe cochlear implantation in children under 2 years of age, the implant assembly must not adversely affect adjacent tissues or compromise head growth. Furthermore, growth changes and tissue responses should not impair the function of the device. Dummy receiver-stimulators, interconnect plugs, and leadwire-lengthening systems were implanted for periods of 36 months in the young monkey to effectively model the implantation of the young child. The results show that implanting a receiver-stimulator package has no adverse effects on skull growth or the underlying central nervous system. The system for fixing the electrode at the fossa incudis proved effective. There was marked osteoneogenesis in the mastoid cavity, resulting in the fixation of the leadwire outside the cochlea. This study provides evidence for the safety of cochlear implantation in young subjects.

Animals

Pediatric cochlear implantation. Radiologic observations of skull growth.

We investigated the effects of long-term implantation of auditory prostheses on skull growth in young animals. Four monkeys were implanted with dummy cochlear implants at 6 months of age. To simulate implantation in children, the bed for the receiver-stimulator or interconnecting plug was drilled across a calvarial suture down to the underlying dura. Plain skull roentgenograms were periodically taken to monitor head growth for up to 3 years after implantation. These longitudinal measurements revealed no significant asymmetric skull growth. Postmortem measurements using computed tomographic scans confirmed these results and showed no significant difference in the intracranial volumes between the implanted and control sides of each animal or between experimental and nonimplanted control monkeys. These results suggest that long-term cochlear implantation in very young children will not cause any significant deformity of the skull.

Animals

Profound hearing loss in the cat following the single co-administration of kanamycin and ethacrynic acid.

Co-administration of kanamycin (KA) with the loop diuretic ethacrynic acid (EA) has previously been shown to produce a rapid and profound hearing loss in guinea pigs. In the present study we describe a modified technique for developing a profound hearing loss in cats. By monitoring the animal's hearing status during the intravenous infusion of EA the technique minimizes the effects of individual variability to the drug regime. Seven cats received a subcutaneous injection of KA (300 mg/kg) followed by intravenous infusion of EA (1 mg/min). Click-evoked auditory brainstem responses (ABRs) were recorded to monitor the animal's hearing during the infusion. When the ABR thresholds rose rapidly to levels in excess of 90 dB SPL the infusion of EA was stopped. This occurred at EA doses of 10-25 mg/kg, indicating considerable individual variability to the deafening procedure. However, there was a strong negative correlation (r = -0.93) between the EA dose and body weight which accounted for much of this variability. Subsequent ABR monitoring showed that this profound hearing loss was both bilateral and permanent. Significantly, blood urea and creatinine levels, monitored for periods of up to three days after the procedure, remained within the normal range. Furthermore, there was no clinical evidence of renal dysfunction as indicated by weight loss or oliguria. Cochlear histopathology, examined after a two months to three year survival period, showed an absence of all inner and outer hair cells in the majority of cochleas. The extent of loss of spiral ganglion cells was dependent on their distance from the round window and the period of survival following the deafening procedure. Clearly, the degeneration of spiral ganglion cells continued for several years following the initial insult. Finally, we observed no evidence of renal histopathology. In conclusion, the co-administration of KA and EA produces a profound hearing loss in cats without evidence of renal impairment. Monitoring the animal's hearing status during the procedure ensures that the dose of EA can be optimised for individual animals. Moreover, it may be possible to adapt this procedure to produce animal models with controlled high frequency hearing losses.

Animals

Comparison of half-band and full-band electrodes for intracochlear electrical stimulation.

It was hypothesized that intracochlear stimulating electrodes oriented toward the modiolus would require a lower stimulus current to elicit a threshold neural response than longitudinal band electrodes. Electrically evoked auditory brain stem responses (EABRs) and electrode impedances were recorded with full-band and oriented half-band scala tympani electrodes in anesthetized, deafened cats. To elicit a threshold EABR, the stimulus current required for stimulation through half-band electrodes oriented toward the modiolus was not significantly different from the current required for stimulation through full-band electrodes. The impedances of full-band electrodes were significantly lower than those of half-band electrodes. Considering the significantly higher impedance and current density of half-band electrodes in comparison to full-band electrodes, as well as the critical orientation of half-band electrodes during implantation, we believe that full-band electrodes have advantages over half-band electrodes for scala tympani implantation.

Acoustic Impedance Tests

Radiologic evaluation of multichannel intracochlear implant insertion depth.

Postoperative plain film x-rays are necessary in all multichannel cochlear implant patients to confirm intracochlear position, detect possible electrode kinking, and provide a reference if postoperative slippage occurs. In addition, precise documentation of multichannel intracochlear electrode insertion depths is necessary for comparison of speech recognition results among patients and may be of use for future speech processing strategies. In the present study, a method has been devised, using a modified Stenver's view, to more accurately document insertion depths of the electrode array and location of individual electrodes on 50 multichannel cochlear implant patients. Surgical estimates of insertion depth are shown to have great variability in regard to distance along the basilar membrane when compared with x-ray documentation. Additionally, there is preliminary evidence that insertion depth, as determined by x-ray studies, has a strong correlation with open-set speech discrimination.

Basilar Membrane

Evaluation of expandable leadwires for pediatric cochlear implants.

The development of cochlear implants for use in very young children (1-2 years old) will require techniques designed to accommodate temporal bone growth. Previous anatomic studies have shown that the leadwire of a cochlear implant must be capable of expanding up to 20 mm between the round window and the implanted receiver-stimulator in response to skull growth. In the present study morphologic and biomechanical evaluation of five expandable leadwire designs was conducted following their implantation in young cats. Two helical shaped leadwire designs frequently exhibited extensive fibrous tissue adhesions and broke during long-term implantation. In contrast, thin, flexible Silastic envelopes were effective in minimizing tissue adhesions. Residual V- and Z-shaped leadwires, placed in these envelopes, showed little evidence of fibrous tissue adhesions following implantation periods of up to 2 years. Moreover, these leadwires readily expanded both during the growth of the animal and when biomechanical expansion studies performed at the completion of the implant period. These expandable leadwire designs appear to be appropriate candidates for use in pediatric cochlear implants.

Animals

Cochlear pathology following chronic electrical stimulation of the auditory nerve. I: Normal hearing kittens.

The present study examines the histopathological effects of long-term intracochlear electrical stimulation in young normal hearing animals. Eight-week old kittens were implanted with scala tympani electrode arrays and stimulated for periods of up to 1500 h using charge balanced biphasic current pulses at charge densities in the range 21-52 microC cm-2 geom. per phase. Both click and electrically evoked auditory brainstem responses were periodically recorded to monitor the status of the hair cell and spiral ganglion cell populations. In addition, the impedance of the stimulating electrodes was measured daily to monitor their electrical characteristics during chronic implantation. Histopathological examination of the cochleas showed no evidence of stimulus induced damage to cochlear structures when compared with implanted, unstimulated control cochleas. Indeed, there was no statistically significant difference in the ganglion cell density adjacent to the stimulating electrodes when compared with a similar population in implanted control cochleas. In addition, hair cell loss, which was restricted to regions adjacent to the electrode array, was not influenced by the degree of electrical stimulation. These histopathological findings were consistent with the evoked potential recordings. Finally, electrode impedance data correlated well with the degree of tissue growth observed within the scala tympani. The present findings indicate that the young mammalian cochlea is no more susceptible to cochlear pathology following chronic implantation and electrical stimulation than is the adult.

Animals

Localization of the calmodulin- and the actin-binding sites of caldesmon.

Expression of the C-terminal third of chicken gizzard caldesmon in Escherichia coli, using the Nagai vector (Nagai, K., and Thøgersen, H.V. (1987) Methods Enzmol. 153, 461-481), produces a cII-caldesmon fusion protein (27 kDa) with caldesmon sequence beginning at Lys579. Degradation during purification yields five peptides with molecular masses of 24, 22, 19 (two peptides), and 15 kDa. The 24-kDa peptide begins at Phe581; the 22-kDa peptide begins at Leu597, the two 19-kDa peptides begin at Phe581 and Val629, respectively; the 15-kDa peptide also begins at Val629. We estimate that the 15-kDa and one of the 19-kDa peptides end near Leu710. Site-directed mutagenesis was used to produce truncated peptides with known C termini; one peptide (17 kDa) terminates at Asn675. Digestion of the fragments with chymotrypsin generates a second 15-kDa fragment that begins at Ser666 (15K'). All of the peptides, with the exception of 15K', bind Ca(2+)-calmodulin-Sepharose and share a common 37-amino acid peptide between Val629 and Ser666, suggesting this contains the calmodulin binding site. Comparison with published sequences (Takagi, T., Yazawa, M., Ueno, T., Suzuki, S., and Yagi, K. (1989) J. Biochem. (Tokyo) 106, 778-783 and Bartegi, A., Fattoum, A., Derancourt, J., and Kassab, R. (1990) J. Biol. Chem. 265, 15231-15238) for other calmodulin-binding fragments further restricts the binding site to 7 residues, Trp-Glu-Lys-Gly-Asn-Val-Phe, between Trp659 and Ser666. All of the fragments, except the two 15-kDa peptides, co-sediment with F-actin, indicating that there are two segments in the C-terminal third of caldesmon that can interact with F-actin: one between Leu597 and Val629, the other between Arg711 and Pro756. Although separated in the primary sequence, these domains may interact with the calmodulin-binding region in the folded structure.

Actins

Electrical stimulation of the auditory nerve in deaf kittens: effects on cochlear nucleus morphology.

The present study examines the effects of long-term electrical stimulation of the auditory nerve on the morphology of neurons in the cochlear nucleus in young, sensorineural deaf animals. Kittens, systemically deafened using kanamycin and ethacrynic acid, received bilateral cochlear implants and were stimulated unilaterally for periods of up to four months. After sacrifice, cross-sectional areas of neuron somata were measured with an image-analysis system and compared using nonparametric statistics. The areas of cell somata within the anteroventral cochlear nucleus (AVCN) on the stimulated side were significantly larger than those of corresponding somata on the control, unstimulated side (P less than 0.001). However, there was no statistically significant difference among dorsal cochlear nucleus (DCN) neurons. These results indicate that long-term electrical stimulation of the auditory nerve can at least partially negate some effects of early postnatal auditory deprivation at the level of the cochlear nucleus.

Animals