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Otology & Neurotology 33:481Y489 ! 2012, Otology & Neurotology, Inc. Sheep as a Large Animal Model for Middle and Inner Ear Implantable Hearing Devices: A Feasibility Study in Cadavers *Johannes Schnabl, *Rudolf Glueckert, †Gudrun Feuchtner, †Wolfgang Recheis, *Thomas Potrusil, ‡Volker Kuhn, *Astrid Wolf-Magele, *Herbert Riechelmann, and *Georg M. Sprinzl Departments of *Otolaryngology, ÞRadiology, and þTraumatology, University Hospital, Medical University Innsbruck, Innsbruck, Austria Objective: Currently, no large animal model exists for surgicalexperimental exploratory analysis of implantable hearing devices. In a histomorphometric study, we sought to investigate whether sheep or pig cochleae are suitable for this purpose and whether device implantation is feasible. Methods: Skulls of pig and sheep cadavers were examined using high-resolution 128-slice computed tomography (CT) to study anatomic relationships. A cochlear implant and an active middle ear implant could be successfully implanted into the sheep’s inner and middle ear, respectively. Correct device placement was verified by CT and histology. The cochlear anatomy of the sheep was further studied by micro-CT and histology. Results: Our investigations indicate that the sheep is a suitable animal model for implantation of implantable hearing devices. The implantation of the devices was successfully performed by access through a mastoidectomy. The histologic, morphologic, and micro-CT study of the sheep cochlea showed that it is highly similar to the human cochlea. The temporal bone of the pig was not suitable for these microsurgical procedures because the middle and inner ear were not accessible owing to distinct soft and fatty tissue coverage of the mastoid. Conclusion: The sheep is an appropriate large animal model for experimental studies with implantable hearing devices, whereas the pig is not. Key Words: Active middle ear implantVAnimal modelVCochleaVCochlear implantationVMicro-CTVSheepV Vibrant Soundbridge. In view of the rapid progress in the development of new technical features and new surgical techniques for implantable hearing devices, an animal model would be desirable for testing device capabilities/functionality before using them in humans. Various small animal models for the development of cochlear implants (CIs) are described in the literature, including a mouse model (1), a gerbil model (2Y5), a cat model (6Y10), a guinea pig model (11Y19), and a rat model (20). What these models have in common is that the anatomic proportions are much smaller than in humans, and this implies that a lot of forward-looking analysis with human CI and Vibrant Soundbridge (VSB) devices cannot be made. To date, no large animal model for a surgicalexperimental exploratory analysis of implantable hearing devices has been established. We hypothesized that, given their similarities with human anatomy, the temporal bones of the sheep and the pig might be suitable for implantation with CIs and active middle ear implants such as the Vibrant Soundbridge (VSB). Hence, our study results would provide some basic information for the further development of an in vivo large animal model. Several publications have described the sheep ear as an appropriate model for surgical trainingVfor example, for middle ear proceduresVowing to similarities in sheep and human external and middle ear anatomy (21Y24). Lavinsky and Goycoolea (22) were the first to describe the sheep as a possible animal model for otologic surgery because of these significant similarities in ear anatomy. Gurr et al. (25) proposed lamb and pig temporal bones as alternatives in ENT education. In a computed tomography (CT) study by Seibel et al. (26), computed tomographic scans from inner ear structures in sheep were compared with human cases. They described inner ear anatomic structures that were similar to but smaller than those of humans. Otol Neurotol 33:481Y489, 2012. Address correspondence and reprint requests to Georg M. Sprinzl, M.D., AnichstraQe 35, 6020 Innsbruck, Austria; E-mail: Georg.Sprinzl@ i-med.ac.at The authors disclose no conflicts of interest. 481 Copyright © 2012 Otology & Neurotology, Inc. Unauthorized reproduction of this article is prohibited. 482 TABLE 1. J. SCHNABL ET AL. Anatomic study of the sheep and pig cochlea with high-resolution 128-slice CT EAC, mm Length Minimal diameter Angulation of EAC to sagittal plane, degrees Mastoid soft and fatty tissue coverage, mm Sheep Pig 11 4.9 62 13 33 3.8 28 52 To our knowledge, no report on the feasibility of implanting hearing devices in the sheep or pig has been published. Furthermore, no exact data on the lengths and volumes of sheep and pig cochleae, or on the areas of the round windows, exist. This information is important for planning new surgical techniques and for determining whether the sheep is an appropriate large animal model for implantable hearing devices. The primary aim of our study was to investigate whether the placement of a CI or a VSB in a sheep or pig skull is feasible. We used endoscopic and high-resolution 128slice CT to check correct device placement. The secondary aim of this study was to perform a morphometric-anatomic study of the sheep cochleaV including performing measurements related to the feasibility of placing implantable hearing devicesVby using micro-CT and histology as reference methods. MATERIALS AND METHODS Study Design Skulls from the cadavers of a sheep (weighing 22 kg) and a pig (weighing 12 kg) were obtained from the local slaughterhouse. All skulls from the slaughterhouse are so-called ‘‘byproducts,’’ hence no animal was killed for this study. First, the skulls of the lamb and the pig were scanned with a 128-slice dual-source CT scanner (Definition Flash; Siemens, Erlangen, Germany) for anatomic study purposes. Next, 3 additional skulls from sheep aged between 4 and 8 months were obtained from the same slaughterhouse under circumstances identical to those described above. Within a few minutes after the sheep’s deaths, the skulls were split into 6 skull halves. Three of those halves were used for histology and micro-CT studies. Two of the halves were implanted with a VSB and then with a CI, then a 128-slice CT examination and a micro-CT were performed, and finally, the 2 cochleae were analyzed histologically. One skull half was destroyed during the preparation. The preparation and implantation was done in our specialized temporal bone lab. Preliminary Anatomic-Morphometric Study of the Sheep and Pig Temporal Bones by CT To study the anatomy, we scanned the skulls of a sheep and a pig with 128-slice dual-source CT (Siemens Definition Flash). The computed tomographic scan parameters were as follows: detector collimation, 128 ! 0.6 mm; gantry rotation time, 0.28 seconds; tube voltage, 120 kV; image reconstruction, 0.7 mm effective slice width at 0.5 increment; ultra high-resolution mode (0.2-mm spatial resolution), 512 ! 512 pixel matrix; sharp convolution kernel, U 70. On a dedicated external workstation, 3-D volume-rendering reconstruction, multiplanar reformations of the temporal bone of the sheep and pig were made. The following distances were measured with a digital caliper by 2 independent observers and repeated after 6 weeks: 1) length of external auditory channel (EAC), 2) angulation of EAC to the sagittal plane, and 3) thickness of the mastoid soft and fatty tissue. The mean value was taken for final data presentation. Preparation of the Sheep Skull and Implantation of the Hearing Devices The skulls were fixed in a special tray in our temporal bone laboratory, and a surgical microscope was used. The first step was the removal of soft tissue surrounding the temporal bone. After exposure of the temporal bone and the external auditory canal, we prepared the temporal line, the mastoid tip, and the mastoid portion. We performed the mastoidectomy between the temporal line and the posterior canal wall with a conventional burr. After opening the middle ear, the anatomic structures were exposed and documented with a 0-degree endoscope attached to FIG. 1. Computed tomographic scans: coronal view of the temporal bones from pig (A) and sheep (B) showing longer EACs with a higher angulation and a thicker mastoid (M) and soft tissue coverage (asterisk) in the pig (A). Otology & Neurotology, Vol. 33, No. 3, 2012 Copyright © 2012 Otology & Neurotology, Inc. Unauthorized reproduction of this article is prohibited. SHEEP AS A MODEL FOR MIDDLE/INNER EAR IMPLANTS 483 cess of the incus, after bending the clip by 90 degrees. This incus Vibroplasty was also documented with the camera. In this case, too, the FMT was removed, and after opening the round window membrane, a cochlear implantation with a Standard electrode from MED-EL was performed. The Standard electrode has a length of 31.5 mm and a maximum diameter of 1.3 mm. After the 2 CIs were implanted, a 128-slice CT was performed to ascertain correct device placement. The same scan parameters as described above were used, and the cochlea with the inserted electrode was reconstructed with multiplanar reformations and in 3-D volume-rendering reconstruction. The cochleae with the inserted electrodes were then excised and used for further detailed anatomic-histologic studies by microCT and histology (see the sections on micro-CT and histology). Micro-CTVSheep FIG. 2. Endoscopic view of the ossicles and promontorium after a mastoidectomy. We can see the malleus (M), the head of the malleus (HM), the incus (I) with the long process (Ilp) and the short process (Isp), the stapes (S), the ligament of the stapes (SL), the chorda tympani (CT), the promontorium (P), and the round window (RW). a 3-megapixel digital camera (Coolpix 995; Nikon; Düsseldorf, Germany). The next step was the preparation of the promontorium and the exposure of the round window. A floating mass transducer (FMT) from the VSB device (Vibrant MED-EL, Innsbruck, Austria) normally used for surgical training was prepared by removing the clip and placing it on the round window. This special FMT is slightly smaller in size (diameter, 1.65 mm; length, 2.21 mm) than the normal FMT (diameter, 1.8 mm; length, 2.3 mm) used in humans. This round window Vibroplasty was documented with the camera. After removing the FMT, the round window membrane was opened, and a cochlear implantation was performed with a FlexEAS electrode (MED-EL) for surgical practice. The FlexEAS had a length of 24 mm and a diameter of 0.8 mm. A mastoidectomy was performed on another skull half, and an FMT for surgical training was clipped on to the long pro- FIG. 3. Micro-CTs have system-inherent limitations in signal-tonoise ratio performance owing to their small voxel size and relatively low x-ray exposure level but can be used effectively to scan bony structures such as the cochlea. In our case, micro-CT was performed with a SCANCO Viva (Scanco Medical AG; Bruettisellen, Switzerland) 40 KCT with 10.5 and 19 Km isotropic voxel size (depending on the size of the specimen) and with 70 kV, 43 KA tube current, 380-millisecond exposure time, and 1,000 projections. The acquired image stacks had an average size of 1,300 ! 1,300 ! 1,500 voxels with 16-bit gray value resolution. Data were transferred to a high-performance 64-bit PC with 8-GB RAM featuring Amira 5.3.3 (Visage Imaging, Richmond, Australia) and ImageJ containing macros developed in-house for segmentation and measuring purposes (27). Five cochlea samples were scanned following the protocol described; in 2 cochleae, CIs (FlexEAS electrode and Standard electrode; MED-EL) were inserted. Owing to the lack of reference data, 2 coworkers (T.P. and W.R.) independently segmented and measured the cochlea lengths, round window areas, and volumes of the scala tympani. Length Measurement. The lengths of the cochleae were measured manually on each slice along the visually recognizable borders of the basilar membrane using ImageJ (Fig. 6). Surface Measurements. The round windows were segmented manually using Amira. The membrane of the round window was determined by choosing a narrow windowing of the microYcomputed tomographic scans offering the possibility of manual segmentation. Furthermore, the normal projection of the A, The promontorium with a round window Vibroplasty. B, The incus with an incus Vibroplasty on the long process. Otology & Neurotology, Vol. 33, No. 3, 2012 Copyright © 2012 Otology & Neurotology, Inc. Unauthorized reproduction of this article is prohibited. 484 J. SCHNABL ET AL. FIG. 4. A, Endoscopic view of the promontorium showing the inserted FlexEAS electrode. B, Three-dimensional reconstruction of the 128slice computed tomographic scan from the same cochlea with the inserted FlexEAS electrode. C, Endoscopic view of the promontorium with the inserted Standard electrode. D, Three-dimensional reconstruction of the computed tomographic scan from the cochlea with the inserted Standard electrode. round window was used to determine the diameters and normal surface areas. For visualization (Fig. 6), data were smoothed by producing a surface from a resampled label field. Volume MeasurementVSegmented Scala Tympani. The scala tympani were segmented with Amira by using the basilar membrane as the boundary between the scala tympani and scala vestibuli (Fig. 6). Scala volumes were calculated from the segmented data set. HistologyVSheep Temporal bones of 2 healthy sheep (approximately 3.5 mo old) were extracted in the course of slaughtering as described above. The head was removed and cut sagitally into 2 halves. After removal of the brain, the temporal bones were excised with bone forceps. The round and oval windows from the inner ears of 1 individual were immediately penetrated with a needle and 4% phosphate-buffered salineYbuffered formaldehyde freshly made FIG. 5. Micro-CT: 3-D visualization of the sheep cochlea. A, Three-dimensional top view of the sheep cochlea demonstrating 23 turns. B, Three-dimensional visualization of the round window of the sheep. Otology & Neurotology, Vol. 33, No. 3, 2012 Copyright © 2012 Otology & Neurotology, Inc. Unauthorized reproduction of this article is prohibited. SHEEP AS A MODEL FOR MIDDLE/INNER EAR IMPLANTS TABLE 2. Cochlea no. 1 2 3 4 5 Micro-CT: cochlea length Length, mm 32.72 35.64 37.8 32.94 31.46 TABLE 3. Variance, mm 0.86 0.67 0.97 0.56 0.44 from paraformaldehyde was gently flushed with a plastic pipette into the inner ear to ensure good fixation. The cochleae were fixed in this solution for 24 hours at 4-C. After scanning with micro-CT, the cochleae were decalcified with 20% EDTA at pH 7.4 for 6 weeks. After thoroughly washing the tissue in phosphate-buffered saline, the specimens were prepared for cryoembedding (28) and serially sectioned radial to the modiolus (10 Km thick). Standard hemalaun-eosin staining served to differentiate the structures. The temporal bones of another individual were stored at 4-C for approximately 60 minutes during CI implantation. After implantation, the inner ears were fixed through the oval window as described above and scanned by micro-CT. After decalcification in EDTA, the cochleae were embedded in gelatin (29) and postfixed with 8% paraformaldehyde for 1 week. This procedure fixed the gelatin proteins and ensured a solid matrix of the inner ear except for the parts of the cochlea filled by the electrode. Removal of the implant resulted in an electrode cast within the tissue. The gelatin block was then sectioned with a Leica VT1000S vibratome (Leica Microsystems; Wetzlar, Germany) (200 Km section). Staining with hemalaun-eosin also stained the gelatin matrix and delineated the space filled by the electrode. This made possible an evaluation of the electrode position at light microscopic level. Images were acquired with a Zeiss AxioImager M1 (Zeiss; Jena, Germany) equipped with an AxioCam HRc at 3900 ! 3090 pixels with AxioVision 4.8. The spiral ganglion diameter (the arithmetic mean of the longest and shortest diameters of neurons with a clearly visible nucleus, taken from 50 cells Cochlea no. 1 2 3 Micro-CT: round window area Projected area, mm2 Variance, mm2 Curved area, mm2 Variance, mm2 2.64 3.3 5.091 0.22 0.14 0.56 8.1 9.23 10.02 0.76 1.1 1.23 counted in the basal turn and apical turn) was estimated with the Zeiss software and evaluated with Microsoft Excel 2007 (Microsoft Corp., Redmond, WA, USA). RESULTS Preliminary Anatomic-Morphometric Study of Sheep and Pig Temporal Bones by CT The 128-slice CT measurements are presented in Table 1. The length of the osseous external auditory canal was higher in the pig, with a mean of 33 mm, than in the sheep, with a mean length of 11 mm. The minimal luminal diameter of the external ear canal in the pig and in the sheep were, on average, 3.8 and 4.9 mm, respectively. The external auditory canal angulation to the sagittal plane was 28 degrees for the pig and 62 degrees for the sheep. The mastoids of the pig and the sheep were covered with a layer of mixed soft tissue/fatty tissue of 52 and 13 mm thickness, respectively (Fig. 1, A and B). Preparation of the Sheep and Implantation of Hearing Devices A mastoidectomy was performed posterior to the external ear canal (on the mastoid plane) for the surgical approach to the middle and inner ear structures. There was very poor mastoid pneumatization, and the mastoid was filled with adipose tissue. After the exploration of the posterior ear canal wall, during the mastoidectomy, the middle ear was opened (Fig. 2). In general, the ossicles were connected to the walls of the tympanic cavity by ligaments. The incus is composed of a large body and very similar in appearance to the human incus. The long and the short processes of the incus were standing at the same level and at right angles to each other. On visual inspection, the processes appeared to be of the same length. The stapes that articulated with the long process of the incus was located beneath the incus. The stapes was connected by its ligament to the wall of the tympanic cavity. Furthermore, the facial nerve, the chorda tympani, the promontorium, and the round window were identified, and their morphometric locations and courses were similar to those in humans. TABLE 4. Cochlea no. FIG. 6. Three-dimensional visualization of the round window, the scala tympani, and the length of a sheep cochlea from micro-CT data sets, which were used to measure the round window area, cochlea length, and scala tympani volume. 485 1 2 3 Micro-CT: volume of scala tympani Volume, Kl Variance, Kl 24.2 28.02 22.9 1.4 1.6 1.5 Otology & Neurotology, Vol. 33, No. 3, 2012 Copyright © 2012 Otology & Neurotology, Inc. Unauthorized reproduction of this article is prohibited. 486 J. SCHNABL ET AL. For a better visualization of the round window, the tympanic cavity was enlarged with a diamond burr and the window niche was drilled. Then the special FMTVwhich is normally used only for surgical training purposesVwas implanted on the round window after cutting and removing the clip. It was observed that the round window was large enough for placement of the FMT on the RW membrane with the best possible contact (Fig. 3A). After opening the round window membrane, a FlexEAS electrode (Fig. 4A) was successfully inserted. A postoperative computed tomographic scan showed the successful implantation of the electrode with complete insertion (Fig. 4B). In another temporal bone, a special FMT was clipped onto the long process of the incus. Because the young sheep was not fully grown and had tight anatomic structures, this incus Vibroplasty was only possible by bending the clip upward (Fig. 3B). After the removal of the FMT, the round window was exposed, and after opening the round window membrane, a MED-EL Standard electrode was implanted (Fig. 4C). FIG. 7. Histology of the sheep cochlea. A, Section through the temporal bone parallel to the modiolar plane. Neurons of the spiral ganglion (SG) are located within the Rosenthal canal. ST indicates scala tympani; SV, scala vestibuli. B and C, More highly magnified views of bipolar SGNs. D and E, Sensory organ with hair cells and supporting cells in the basal turn (D) and the apical turn (E). F, The stria vascularis of the basal turn showing typical tissue structure. Otology & Neurotology, Vol. 33, No. 3, 2012 Copyright © 2012 Otology & Neurotology, Inc. Unauthorized reproduction of this article is prohibited. SHEEP AS A MODEL FOR MIDDLE/INNER EAR IMPLANTS The accurate positioning of the electrode was shown by a computed tomographic scan including a 3-D reconstruction (Fig. 4D). TABLE 5. Comparison of sheep and human cochlea proportions Cochlea turns Cochlea length, mm Micro-CTVSheep The sheep cochlea had 23 turns, as shown in Figure 5A. Round Window Area The round window area could be measured in 3 of the 5 cochleae scanned with micro-CT (Figs. 5B and 6). Two implanted cochleae could not be measured because of missing or destroyed (during cochlear implantation) round window membranes. The mean area of the round window was 3.7 mm2 for the projected area and 9.11 mm2 for the curved area (Table 3). Sheep Human 23 34.1 22 33.0Y45.0 (30) 28.0Y42.0 (34) 2.29 (32) 2.14 (33) 29.22 (31) Round window (projected area), mm2 Volume of scala tympani, Kl Length of the Cochlea The average length of the 5 cochleae was 34.1 mm with a variance of 0.7 mm. The lengths of all cochleae are presented in Table 2. 487 3.7 25.04 Volume of the Scala Tympani The mean volume of the scala tympani of the same 3 cochleae mentioned in a previous paragraph was 25.04 Kl (Table 4). HistologyVSheep Similar to human anatomy, the otic capsule was found to be completely fused with the surrounding temporal bone and showed the typical convoluted substructure of a woven-type bone with rich vasculature and more or less basophilic osteons and acidophilic areas in between (Fig. 7). The cochlea contained 23 turns, with a central bony modiolus housing mainly spiral ganglion neurons (SGNs), nerve fibers, and blood supply. A distinct bony channel filled with SGNs, referred to as Rosenthal canal, runs spirally in the distal wall of the modiolus and ends up in a bulge in the upper second turn (Fig. 7A). Spiral ganglion neuron density is higher in the upper turns than in the basal turn (Fig. 7, B and C). However, the size of the somata is equal (mean [SD] diameter: basal turn, 15.7 [1.67] Km; apical turn, 15.7 [1.63] Km). The organ of Corti presents the typical arrangement of hair cells and supporting cells (Fig. 7, D and E). In addition, the same trend of tonotopical differences in the size of cells within the sensory organ is obvious. Hensen and tectal cells form the prominent distal ridge in the more apical organ of Corti, whereas it is more flat in the basal area. Outer hair cells are around 30 Km in length in the apical turn (as measured in Fig. 7) and only 22 Km in the basal part of the cochlea. Compared with other mammals, the stria vascularis does not display any deviations in tissue composition (3 types of cells, rich vasculature) and has a profuse appearance of melanocytes that give the tissue a brownish color. Figure 8 shows the cochlea with the electrode, positioned in the scala tympani. DISCUSSION FIG. 8. A and B, Histology of the cochlea after implantation, confirming the placement of the electrode (E) into the scala tympani (ST). The scala media (SM) and scala vestibuli (SV) are shown adjacent. Our study demonstrates for the first timeVto the best of our knowledgeVthat the sheep is an appropriate animal model for the implantation of hearing devices, as proven by surgery, histology, high-resolution CT, and micro-CT. The sheep’s temporal bone is an adequate animal model for implantation of implantable hearing devices because of its anatomic similarity to the human temporal bone. In contrast, pigs are not suitable models. Otology & Neurotology, Vol. 33, No. 3, 2012 Copyright © 2012 Otology & Neurotology, Inc. Unauthorized reproduction of this article is prohibited. 488 J. SCHNABL ET AL. Our measurements of the external ear canal of the sheep and the pig are similar to those of previous studies (24,25). Our study also shows that the soft and fatty tissue layers of the mastoid are significantly thicker in the pig than in the sheep, inhibiting a successful surgical approach. However, we could successfully implant both the VSB and the CI in the sheep, which provides fundamental knowledge regarding the most promising direction for the future development of an in vivo study for establishing a large animal model. We have demonstrated that the pig is less suitable as an animal model for implantable hearing devices. The approach through the large soft and fatty tissue coverage of the mastoid is more demanding in the pig and could be associated with more complications. The findings and anatomic descriptions established during preparation of the sheep temporal bones, especially the middle ear, confirm the results of previous studies (22,25). We find that the middle ear of the sheep is morphologically equivalent to the human middle ear, although some structures in the sheep’s middle ear were smaller than the corresponding structures in human ears. We have proven for the first time, by high-resolution CT and micro-CT imaging, that it is possible to perform a cochlear implantation and an incus and round window Vibroplasty in the sheep. Moreover, histology confirmed correct electrode placement within the scala tympani. In addition, we are the first research group to perform a separate study of the morphometric dimensions of the sheep cochlea with specific regard to the planning of CI and VSB, by using the most accurate imaging modality available for our research group: micro-CT. Our results, therefore, expand the knowledge obtained from previous CT morphologic studies (26). In particular, we measured the following dimensions that are important for cochlear implantation and round window Vibroplasty: the average curved length of the sheep cochlea, at 34.1 mm, is slightly smaller than the human cochlea length of 42.0 mm (30). This length can be regarded as sufficient for cochlear implantation because the MED-EL Standard electrode has a maximal insertion depth of 31.5 mm, and the MED-EL FlexEAS electrode has a maximal insertion depth of 24.0 mm. For more exact sizing, we calculated the volume of the scala tympani using 3-D micro-CT data sets, revealing an average volume of 25.04 Kl. This volume is similar to that of the human mean of 29.22 Kl (31). With respect to the planning of round window Vibroplasty, we measured 2 areas from the round window of the sheep: first, the projected area for comparison with previous literature; and second, the curved area, which gives a more accurate estimate of its real dimensions. Our study found the average projected area to be 3.7 mm2. This is larger than that in humans, which has been reported as 2.29 mm2 (32) and 2.14 mm2 (33). The average curved area, at 9.11 mm2, was also larger than in humans. In short, the area of the round window of the sheep is large enough for FMT placement because the FMT has an area of 2.54 mm2. In summary, we found surprising and impressive morphometric and morphologic similarities between human and sheep cochlear anatomy. The length of the cochlea and the number of turns are nearly equal. Individual variation in cochlea length is known to be high in humans, having been reported as 33 to 45 mm (30) and 28 to 42 mm (34,35). This may also hold true for sheep, but we cannot draw any conclusions on this issue because the number of specimens investigated in our study was too small. The dimensions of the scala tympani allow the use of standard electrodes (for human use) for insertion via the round window. To underline the similarities of the sheep and the human cochlea, a comparison is shown in Table 5. However, there are also evident differences between human and sheep anatomy. In sheep, cochlear neurons reach a mean diameter of around 15 to 16 Hm, which is about half of the size measured in humans (36). This implies differences in electrical stimulation. A bipolar cochlear neuron can be described in an equivalent circuit model containing resistance and capacitors. Charging the somatic capacitance is the main barrier for the action potential traveling from the hair cell to the nervus cochlearis. Rattay et al. (37) have shown in a computer simulation using a modified Hodgkin-Huxley model that the somatic delay of a myelinated cat neuron with a diameter of 20 Km is 118 Ks. Because of the fact that the current needed to charge the somatic capacitance is proportional to the somatic surface (38), it can be assumed that an action potential will traverse a sheep neuron faster than that of a cat. Regarding the electrode positioning, we can demonstrate that the electrodes are positioned in the scala tympani. Particularly for purposes of EAS treatment, an atraumatic insertion and electrode positioning in the scala tympani are important (39,40). A possible placement for the implantation of the CI or VSB receiver in an in vivo animal model could be the parietal or intraparietal bone of the sheep’s skull, but this must first be investigated in future experiments. In conclusion, the sheep’s temporal bone is an ideal animal model for implantable hearing devices because of its similarity to human middle and inner ear structures. The implantation of both a VSB and a CI in the sheep is feasible. Our results provide the basics for the development of an in vivo large animal model. Furthermore, the temporal bones of sheep are a good alternative for surgical training in implantation of both CIs and VSBs. Acknowledgments: The authors thank Michael Verius for supporting cochlea length measurement and Mario Bitsche and Anneliese Schrott-Fischer for supporting the neurotology work. 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Cochlear implantation via the round window membrane minimizes trauma to cochlear structures: a histologically controlled insertion study. Acta Otolaryngol 2004;124:807Y12. Otology & Neurotology, Vol. 33, No. 3, 2012 Copyright © 2012 Otology & Neurotology, Inc. Unauthorized reproduction of this article is prohibited.