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. Author manuscript; available in PMC: 2015 Mar 27.
Published in final edited form as: Audiol Neurootol. 2014 Mar 27;19(3):184–192. doi: 10.1159/000358003

Correlation Between Histologic and Radiographic Reconstruction of Intracochlear Electrode Position in Human Temporal Bones

Jennifer T O’Malley 1, Barbara J Burgess 1, MengYu Zhu 1, Hugh D Curtin 2,3, Joseph B Nadol Jr 1,4
PMCID: PMC4123416  NIHMSID: NIHMS579955  PMID: 24686209

Abstract

In our laboratory, human temporal bone specimens from patients who in life have undergone cochlear implantation are routinely processed with the implant in situ, embedded in araldite, sectioned at 20 μm and serially photographed during cutting, stained with toluidine blue and mounted on glass slides. From the images, 2D and 3D reconstructions can be made and a very accurate implant insertion depth can be calculated from the 3D reconstructions. However, this method precludes subsequent special stains and further molecular investigations of the tissue including proteomics and immunostaining which is now possible with celloidin embedded tissue. In this study, we correlated measurement of the implant array insertion depth calculated from histologic 3D reconstruction with that measured from 3D radiologic multiplanar reconstruction.

Four human temporal bones with cochlear implants underwent post-fixation pre-processing CT imaging with a Siemens Somatom Sensation Scanner. The CT scans from these four bones were downloaded into the Voxar software application, reformatted using the multiplanar reconstruction tool, viewed in three dimensions and measurements of intracochlear insertion lengths of the implants were obtained. The bones were processed routinely for in situ araldite embedding, serial images were made of the block during sectioning, post-processed using PV-Wave® software, aligned with Amira® software, and used to create histologic 3D reconstructions. From these 3D reconstructions, the insertion depth of the electrode array was mathematically calculated.

The range of insertion depths was 15.9 mm (case #1) to 26.6 mm (case #4). The two methods, radiographic multiplanar reconstruction and 3D reconstruction, differed by 0.4 – 0.9%. This provides confidence that important localization information about the electrode in situ can be gleaned from CT scans, thereby allowing us to extract the implants prior to processing for celloidin embedment and allow further techniques such as special stains and immunostaining to be accomplished in order to evaluate molecular mechanisms involved in cochlear implantation.

Keywords: temporal bone, cochlear implant, intracochlear length, CT, multiplanar reconstruction, histology, celloidin

Introduction

Histopathologic study of temporal bones from patients, who in life had undergone cochlear implantation, may be facilitated by a technique developed to section specimens with the electrode remaining in situ [Nadol et al. 1994, 2001, Lee et al 2011, Lee et al. 2011]. This technique allows the electrode to be visualized in approximation to native tissues of the inner ear, and to the biologic responses to the presence of electrodes during life. In addition, the insertion depth of the electrode array can be determined by 3-D reconstruction of serial sections [Somdas et al. 2007].

The disadvantages of maintaining the cochlear implant electrode in situ include the requirement to use an embedding material such as Araldite, in turn requiring smaller specimens, and considerable limitations on subsequent histologic processing of the sections. For example, special stains that can be used with celloidin embedding including Luxol Fast Blue to study the integrity of myelin, or Movat’s pentachrome stain used to evaluate ground substance, elastic fibers, and collagen cannot be used with araldite sections. More importantly, Araldite embedment precludes immunostaining which is possible with celloidin sections [Keithley et al., 1995, Ganbo et al., 1997, Markaryan et al., 2008, O’Malley et al., 2009, and Balaker et al., 2013].

Celloidin embedment also makes proteomic investigations of temporal bones with cochlear implants possible. This field of study, while still very young, has some proven success with archival celloidin tissue [Markaryan et al., 2010, Aarnisalo et al., 2010, and Richard et al., ARO abstract 546, 2013] and would open an entire new avenue of research for temporal bones with cochlear implants. One of our goals for future cochlear implant research is to preserve the ability to obtain a 3D reconstruction of the electrode in situ and be able to accomplish such techniques as immunostaining and special stains. This necessitates the removal of the electrode from the temporal bone prior to processing and embedment in celloidin.

In an effort to gain more information on each temporal bone specimen containing a cochlear implant, but not lose the ability to obtain a 3D reconstruction, we have compared intracochlear insertion lengths of cochlear implants calculated radiographically and histologically. The radiographic study of cochlear implant arrays has been utilized to study various electrode and cochlear parameters including 3D cochlear lengths, electrode array insertion depths [Ketten et al. 1998, Skinner et al. 2002, Verbist et al. 2010, and Kong et al. 2012] as well as electrode migration [van der Marel et al. 2012] postoperatively in living patients. In addition, there have been numerous reports of computed tomography in cadaveric human temporal bones [Meshik et al. 2010, Schumann et al. 2010, and Teymouri et al. 2011]. Correlating histopathology with CT findings has been used to study scala communis defect, facial canal enlargement, and otosclerosis [Makary et al., 2010, Moonis et al., 2011 and Quesnel et al., 2013]. If radiologic estimates of the intracochlear implant length in situ are comparable to the histologic estimates, this will allow removal of the electrode in subsequent specimens and embedment in celloidin, in turn allowing such techniques as immunostaining and proteomic analysis.

Materials and Methods

Radiologic Multiplanar Reconstruction

Computed tomography (CT) (Siemens Somatom Sensation) was performed in the orientation that was estimated to be close to the axial plane (Figure 1a–4a) using external landmarks of the specimen. The scan was performed prior to specimen processing. Scanning was done with 0.6mm collimation, 120 kV, and 320 milliampere-seconds (mAs). The data set was reformatted with 0.6mm slices every 0.2mm using a 512 × 512 matrix and a 65–70mm field of view. The resulting 3D volume data set was loaded into the Voxar imaging system (Toshiba Medical Visualization Systems©) for multiplanar reformatting. This orientation appears as a mirror image of the histological block (compare A and B for all four figures) because the imaging convention is to display the axial scan as though viewed from inferiorly.

Figure 1.

Figure 1

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Figure 1A shows a CT scan of case #1 (Nucleus Perimodiolar Contour Advance 22 Electrode Array) in the axial plane (left ear). The cochleostomy site (circle), implant array (IA), and posterior canal (PC) are noted. Figure 1B shows the same specimen embedded in araldite mounted on a block during cutting. The sectioning is at the level of the cochleostomy site (circle). The implant array (IA) and posterior canal (PC) are noted. Figure 1C demonstrates a CT scan of case #1 in the coronal plane. The implant array (IA) and cochleostomy site (circle) are noted. Figure 1D is the same image as 1C with a line drawn along the midpoint of the implant array to simulate the line that is drawn in Voxar with the “curve” tool. The arrowhead is pointing toward the insertion point of the implant array. Figure 1E is the resultant image from the “measure curve” tool using Voxar as the software unwinds the array and measures it linearly. Figure 1F shows the araldite block during sectioning at a level that is superior to Figure 1B. The implant array (IA) can be seen hugging the modiolus in the scala vestibuli (SV).

Figure 4.

Figure 4

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Figure 4A shows a CT scan of case #4 (Ineraid 6 Electrode Array) in the axial plane (right ear). The cochleostomy site (circle), implant array (IA), and posterior canal (PC) are noted. Figure 4B shows the same specimen embedded in araldite mounted on a block during cutting. The sectioning is at the level of the cochleostomy site (circle). The implant array (IA) and posterior canal (PC) are noted. Figure 4C demonstrates a CT scan of case #4 in the coronal plane. The implant array (IA) and cochleostomy site (circle) are noted. Figure 4D is the same image as 4C with a line drawn along the midpoint of the implant array to simulate the line that is drawn in Voxar with the “curve” tool. The arrowhead is pointing toward the insertion point of the implant array. Figure 4E is the resultant image from the “measure curve” tool using Voxar as the software unwinds the array and measures it linearly. Figure 4F shows the araldite block during sectioning at a level that is superior to Figure 4B. An electrode (E4) can be seen in the scala vestibuli (SV). Its carrier is located just to the left of the electrode. There is clear separation between the electrode and its carrier which is part of the implant array (IA).

In Voxar, the data from 4 temporal bone specimens with cochlear implants were reformatted into 3 planes utilizing the multiplanar reconstruction (MPR) tool, viewed in three dimensions, and measurements of intracochlear insertion lengths were made. A specific plane was chosen to align the stacks to closely approximate the plane of section subsequently used in histologic preparation. Once aligned to the desired plane, the multiplanar curved (MPR-curved) tool was employed in the coronal plane (Figures 1c, d – 4c, d). Curved MPR allows non-planar structures such as blood vessels, or in our case, in situ cochlear implant arrays, which cannot be viewed in a single plane, to be isolated and examined in a more useful way. A curve direction was chosen for either left or right ears. The curve direction orients the data set and defines how the curved MPR view will be generated. The point of insertion of the cochlear implant was determined by paging through the stack of images to find the cochleostomy site. The midpoint of the implant (mid-width as it passed through the cochleostomy site just inside the cochlea) was determined (Figures 1c and d – 4c and d). Using this as the insertion point (the starting point for the measurement), the Curve Tool and Measure Curve Tool were utilized to determine the intracochlear length (length of the cochlear implant array within the cochlea) by clicking the mouse at approximately 1mm intervals along the midline of the array from the base of the cochlea to the most apical tip (Figures 1d – 4d). The curve tool “drops” user defined control points orthogonal to the desired curve. The curve is a “polyline” consisting of a set of points that are joined together by short segments of straight lines. Proprietary Voxar algorithms are employed to calculate coordinates of a curved sheet that is extruded from the user defined points and then flattened into a 2D curved MPR image on the user interface window (Figure 1e–4e). The length of the curve is the sum of the shorter line segments and is obtained by clicking the Measure Curve Tool icon. The measurement appears on the flattened 2D curved MPR image window (Figures 1e–4e). The points were drawn and measurements were made multiple times and an average was taken. The results appear in Table 1, column 3 (Radiographic Multiplanar Reconstruction).

Table 1.

Average Intracochlear Insertion Length (mm)*

CI case Type of Implant Radiographic Multiplanar Reconstruction 3D Histologic Reconstruction 2D Histologic Reconstruction
#1 CI24RE(CA) – Nucleus Perimodiolar
Contour Advance
22 Electrode Array		 15.9 16.0 16.8
#2 Ineraid 6
Electrode Array		 21.0 21.0 15.8
#3 Clarion Enhanced
Bipolar 16
Electrode Array		 23.3 23.1 20.4
#4 Ineraid 6
Electrode Array		 26.6 26.5 20.2
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*

Along midpoint of array from cochleostomy to electrode tip.

For purposes of comparison, measurements were also made along the inner margin and the outer margin of the array in all of the cases. These values were compared to the values obtained when the center or midline of the array was used (as described above). Multiple measures were made and averages were determined. The results appear in Table 2. Percent differences were calculated for inner spiral vs. midpoint, outer spiral versus midpoint, and for inner spiral versus outer spiral.

Table 2.

Average Intracochlear Insertion Length (mm) using Radiographic Multiplanar Reconstruction

As measured along
CI case		 Inner Spiral of Implant Array Midpoint of Implant Array Outer Spiral of Implant Array
#1 14.2 15.9 18.6
#2 19.4 21.0 23.3
#3 20.1 23.3 27.2
#4 23.9 26.6 29.4
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Histologic Three Dimensional Reconstruction Measurement

Temporal bones were fixed in 10% buffered formalin. Decalcification was accomplished in 0.27M ethylenediaminetetraacetic acid. The temporal bones were rinsed in distilled water and dehydrated in ethanols, passed through several changes of propylene oxide and infiltrated with low, then high concentrations of Araldite 502 (EMS, Hatfield, PA). The specimens were exchanged through several changes of Araldite. A low vacuum was used at this stage to facilitate infiltration. Finally, the bones were hardened in a 45° and then a 60° oven. Sectioning was accomplished in the axial plane on a sliding microtome with a tungsten carbide profile D knife (Leica, Germany).

Two Ineraid 6 electrode arrays, one Enhanced Bipolar Clarion 16 Electrode array and one Nucleus perimodiolar Contour Advance 22 electrode Array were examined. The embedded temporal bones with electrode arrays in situ were serially sectioned in the axial plane. The thickness of each section, delta z, was approximately 20μm. Using a Canon Power Shot Pro1 Camera, a 2272 × 1704 jpg image of the block before each section was taken. The serial pictures were then rotated and cropped to 900 × 600 pixels using the PV-WAVE® software program. The serial images were aligned using Amira®. The pixel size, delta x, and delta y were obtained using the “measure and analyze tool” in Image J.

For the Ineraid electrode arrays and Enhanced Bipolar Clarion electrode arrays, the x and y coordinates of the middle points along the length of the carrier were read into a data file using a customized PV-WAVE® program. The section number was obtained at the same time as the z coordinate. The measurement of the insertion depth (ID) was calculated using the equation:

ID=∑i=0n−2(x(i+1)−x(i))2dx2+(y(i+1)−y(i))2dy2+(z(i+1)−z(i))2dz2

where x and y are coordinates, delta x (dx) and delta y (dy) represent pixel size, z is section number, delta z (dz) is section thickness, and n is the total number of the middle points. The “i” is a segment variable from 0 to n-2, a total of n-1 segments.

The Nucleus perimodiolar Contour array’s design makes it possible to accurately follow the middle points of the electrode’s surface. So rather than the carrier midpoints being measured as for the Ineraid and Enhanced Bipolar arrays, the center point of the half band shaped electrode surface itself was picked in measuring the insertion length for Case #1.

Histologic Two Dimensional Reconstruction

Both types of three dimensional reconstructions (radiologic and histologic) were compared to the conventional two dimensional reconstruction technique introduced by Guild in 1921. The method was described in detail by Schuknecht (1993). Briefly, the cochlea was reconstructed on gridded (0.5 cm) graph paper using the heads of the pillar cells to form the curve representing the cochlea. The histological slides were analyzed and the tangential cuts through the heads of the pillars were plotted corresponding to their slide number. Semicircles were drawn to connect the appropriate slides and draw the resultant curve. Using a compass and defined distance, millimeter increments were marked along the length of the curve. The established curve was used to determine cochlear length. Hair cells and other cochlear structures can be plotted on the curve as well as the approximate location of a cochlear implant.

Results

Radiologic Multiplanar Reconstruction

The results for the radiologic multiplanar reconstructions appear in Table 1, column 3 and in Figures 1E–4E. The values in the figures do not match the table because the table values are the result of averaging many measurements and the figures show only a snapshot of one measurement. The range in values for intracochlear insertion length was from 15.9 mm in case #1 to 26.6 mm in case #4.

Radiologic Multiplanar Reconstruction–A Comparison of Length versus Spiral Location

Table 2 contains the insertion lengths using radiologic multiplanar reconstruction at different locations along the width of the array. Measurements along the inner margin of the electrode arrays ranged from 14.2 mm in case #1 to 23.9 mm in case #4. Measurements along the midpoint are the same as those that appear in Table 1, column 3 and ranged from 15.9 mm in case #1 to 26.6 in case #4. Measurements along the outer margin of the electrode arrays ranged from 18.6 mm in case #1 to 29.4 mm in case #4.

Histologic Three Dimensional Reconstruction Measurement

The results for the three dimensional histologic reconstruction calculations appear in Table 1, column 4. The range for insertion length was from 16.0 mm (Case #1) to 26.5 mm (Case #4).

Histologic Two Dimensional Reconstruction

The results for the 2D histologic reconstruction appear in Table 1, column 5. The insertion length ranged from 15.8 mm (Case #2) to 20.4 mm (Case #3).

Discussion

There was essentially no difference between the radiographic multiplanar reconstruction and the 3D histologic reconstruction methods. Case #2 measured exactly the same with both methods and Cases 1, 3, and 4 differed by 0.4 – 0.9% with the two methods. Currently, a detailed three-dimensional histological reconstruction created from images of an araldite block during sectioning affords a precise way to measure the intracochlear insertion length. However, alignment of the images is necessary for an accurate 3D reconstruction. If the block requires re-infiltration, it must be removed from the microtome and camera setup. This makes alignment of the images more difficult post re-infiltration. During the sectioning, if the camera used to photograph the block is moved the subsequent images are not aligned with the previous images. Our results show that a post-fixation pre-processing CT scan, which gives us a stack of images completely aligned, combined with the ability of the multiplanar reconstruction to manipulate those images in all three planes (axial, coronal, and sagittal) is equally as good a method to determine the intracochlear insertion length of an implanted human temporal bone. Although the CT scan has lower resolution than histological images, (compare Figures 1A–4A with 1F–4F) for purposes of finding the cochleostomy site and the apical tip of the electrode array, the differences in contrast are such that measuring the insertion length is usually straight forward.

There was a large range in the results of the 3D histologic versus the 2D histologic reconstruction as well as between the radiographic multiplanar versus the 2D histologic methods. Comparing these methods gave differences ranging from close to 5% up to nearly 25%. The 2D method of reconstruction created by Guild relies on the position of the pillar cells to create the curve representing the cochlea. The path a cochlear implant takes in the cochlea is intended to be in the scala tympani and does not follow the same path as the pillar cells. Very often an implant, although intended to hug the modiolus, veers outward toward the lateral wall (Figure 1F), quite a distance from the heads of the pillar cells in the organ of Corti. In addition, implant arrays can penetrate the basilar membrane into the scala media or scala vestibuli. In some implant cases, the pillar cells are displaced or destroyed, making 2D histological reconstruction more difficult. Using the 2D histological reconstruction on graph paper is a poor fit for the actual placement of an array in the cochlea. The 2D reconstruction provides a rough estimate of where the implant is inside the cochlea, but does not result in accurate insertion depths. Implant arrays can also bend and kink during insertion which is difficult to accurately represent and metrically interpret on a 2D plot. In both radiologic and histologic 3D reconstruction, the track an implant takes in space as it traverses the cochlea is more accurately determined.

Using the radiologic multiplanar reconstruction method, the array lengths were measured along different portions of the spiral. As would be expected, the inner spiral lengths were shortest and the outer spiral lengths were longest. The percent difference between individual measures varied widely. When values presented in Table 2 are compared to each other for inner spiral versus midline, the percent difference ranged from 7.6% (case 2) – 13.7% (case 3) and averaged 10.6%. For outer spiral versus midline, the percent difference ranged from 9.5% (case 4) – 14.5% (case 1) and averaged 12.1%. For inner spiral versus outer spiral, the percent difference ranged from 16.7% (case 2) – 26.1% (case 3) and averaged 21.3%. These numbers are instructive when thinking about the 2D histologic method as well. They demonstrate how different a value can be if the array is actually along the lateral wall of the cochlea instead of beneath the heads of the pillar cells. It is important to measure along the midline of the array with both the radiologic and histologic method in order to determine the most accurate inserted length of an implant.

In summary, the intra-cochlear length of an implant array as measured by a CT scan of the temporal bone with multiplanar reconstruction reliably corresponds to the more laborious 3D histologic reconstruction. This provides confidence that removal of the electrode from the cochlea after CT-scanning will preserve important localization information and allow embedment in celloidin and a wide variety of techniques such as immunostaining.

Figure 2.

Figure 2

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Figure 2A shows a CT scan of case #2 (Ineraid 6 Electrode Array) in the axial plane (right ear). The cochleostomy site (circle), implant array (IA), and posterior canal (PC) are noted. Figure 2B shows the same specimen embedded in araldite mounted on a block during cutting. The sectioning is at the level of the cochleostomy site (circle). The implant array (IA) and posterior canal (PC) are noted. Figure 2C demonstrates a CT scan of case #2 in the coronal plane. The implant array (IA) and cochleostomy site (circle) are noted. Figure 2D is the same image as 2C with a line drawn along the midpoint of the implant array to simulate the line that is drawn in Voxar with the “curve” tool. The arrowhead is pointing toward the insertion point of the implant array. Figure 2E is the resultant image from the “measure curve” tool using Voxar as the software unwinds the array and measures it linearly. Figure 2F shows the araldite block during sectioning at a level that is superior to 2B. Note the Implant array (IA), electrode balls (EB), and new bone (NB).

Figure 3.

Figure 3

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Figure 3A shows a CT scan of case #3 (Clarion Enhanced Bipolar 16 Electrode Array) in the axial plane (right ear). The cochleostomy site (circle), implant array (IA), and posterior canal (PC) are noted. Figure 3B shows the same specimen embedded in araldite mounted on a block during cutting. The sectioning is at the level of the cochleostomy site (circle). The implant array (IA) and posterior canal (PC) are noted. Figure 3C demonstrates a CT scan of case #3 in the coronal plane. The implant array (IA) and cochleostomy site (circle) are noted. Figure 3D is the same image as 3C with a line drawn along the midpoint of the implant array to simulate the line that is drawn in Voxar with the “curve” tool. The arrowhead is pointing toward the insertion point of the implant array. Figure 3E is the resultant image from the “measure curve” tool using Voxar as the software unwinds the array and measures it linearly. Figure 3F shows the araldite block during sectioning at a level that is superior to 3B. Electrodes 7 (E7) and 8 (E8) are paired together and embedded on the carrier. Electrode 7 is oriented toward the lateral wall and electrode 8 is oriented toward the modiolus. Electrode 12 (E12) is also clearly seen.

Acknowledgments

We would like to thank the following individuals for their expertise and assistance: Renee Mitchell from our Department of Radiology, for CT scanning our human temporal bone specimens and Leena Hamburg who assisted in developing a method for measuring with Voxar; and from our Otopathology laboratory, Diane Jones who assisted in the processing of the specimens.

This work was supported by NIDCD/NIH grant #RO1DC000152.

References

  1. Aarnisalo AA, Green KM, O’Malley J, Makary C, Adams J, Merchant SN, Evans JE. A method for MS(E) differential proteomic analysis of archival formalin-fixed celloidin-embedded human inner ear tissue. Hear Res. 2010 Dec 1;270(1–2):15–20. doi: 10.1016/j.heares.2010.08.003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Balaker AE, Ishiyama P, Lopez IA, Ishiyama G, Ishiyama A. Immunocytochemical localization of the translocase of the outer mitochondrial membrane (Tom20) in the human cochlea. The Anatomical Record. 2013;296:326–332. doi: 10.1002/ar.22622. [DOI] [PubMed] [Google Scholar]
  3. Ganbo T, Sando I, Balaban CD, Suzuki C, Sudo M. Immunohistochemistry of lymphocytes and macrophages in human celloidin-embedded temporal bone sections with acute otitis media. Ann Otol Rhinol Laryngol. 1997 Aug;106(8):662–8. doi: 10.1177/000348949710600809. [DOI] [PubMed] [Google Scholar]
  4. Keithley EM, Horowitz S, Ruckenstein MJ. Na, K-ATPase in the cochlea lateral wall of human temporal bones with endolymphatic hydrops. Ann Otol Rhinol Laryngol. 1995 Nov;104(11):858–63. doi: 10.1177/000348949510401106. [DOI] [PubMed] [Google Scholar]
  5. Ketten DR, Skinner MW, Wang G, Vannier MW, Gates GA, Neely JG. In vivo measures of cochlear length and insertion depth of nucleus cochlear implant electrode arrays. Ann Otol Rhinol Laryngol. 1998;107:1–16. [PubMed] [Google Scholar]
  6. Kong WJ, Cheng HM, Ma H, Wang YJ, Han P. Evaluation of the implanted cochlear implant electrode by CT scanning with three-dimensional reconstruction. Acta Otoaryngol. 2012;132:116–122. doi: 10.3109/00016489.2011.626794. [DOI] [PubMed] [Google Scholar]
  7. Lee J, Nadol JB, Eddington DK. Factors associated with incomplete insertion of electrodes in cochlear implant surgery: a histopathologic study. Audiol Neurotol. 2011;16:69–81. doi: 10.1159/000316445. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Lee J, Eddington DK, Nadol JB. The histopathology of revision cochlear implantation. Audiol Neurotol. 2011;16:336–346. doi: 10.1159/000322307. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Makary C, Shin J, Caruso P, Curtin H, Merchant S. A histological study of scala communis with radiological implications. Audiol Neurotol. 2010;15(6):383–93. doi: 10.1159/000307345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Markaryan A, Nelson EG, Tretiakova M, Hinojosa R. Technical report: immunofluorescence and TUNEL staining of celloidin embedded human temporal bone tissues. Hear Res. 2008 Jul;241(1–2):1–6. doi: 10.1016/j.heares.2008.04.009. [DOI] [PubMed] [Google Scholar]
  11. Markaryan A, Nelson EG, Helseth LD, Hinojosa R. Proteomic analysis of formalin-fixed celloidin-embedded whole cochlear and laser microdissected spiral ganglion tissues. Acta Otolaryngol. 2010 Sep;130(9):984–989. doi: 10.3109/00016481003591749. [DOI] [PubMed] [Google Scholar]
  12. Meshik X, Holden TA, Chole RA, Hullar TE. Optimal cochlear implant insertion vectors. Otol Neurotol. 2010;31(1):58–63. doi: 10.1097/MAO.0b013e3181b76bb8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Moonis G, Mani K, O’Malley J, Merchant S, Curtin HD. A venous cause for facial canal enlargement: multidetector row CT findings and histopathologic correlation. Am J Neuroradiol. 2011;32:E83–E84. doi: 10.3174/ajnr.A2094. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Nadol JB, Jr, Ketten DR, Burgess BJ. Otopathology in a case of multichannel cochlear implantation. Laryngoscope. 1994 Mar;104(3 Pt 1):299–303. doi: 10.1288/00005537-199403000-00010. [DOI] [PubMed] [Google Scholar]
  15. Nadol JB, Jr, Shiao JY, Burgess BJ, Ketten DR, Eddington DK, Gantz BJ, Kos I, Montandon P, Coker NJ, Roland JT, Jr, Shallop JK. Histopathology of cochlear implants in humans. Ann Otol Rhinol Laryngol. 2001 Sep;110(9):883–91. doi: 10.1177/000348940111000914. [DOI] [PubMed] [Google Scholar]
  16. O’Malley JT, Merchant SN, Burgess BJ, Jones DD, Adams JC. Effects of fixative and embedding medium on morphology and immunostaining of the cochlea. Audiol Neurotol. 2009;14(2):78–87. doi: 10.1159/000158536. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Quesnel AM, Moonis G, Appel J, O’Malley J, McKenna MJ, Curtin HD, Merchant SN. Correlation of computed tomography with histopathology in otosclerosis. Otol Neurotol. 2013 Jan;34(1):22–8. doi: 10.1097/MAO.0b013e318277a1f7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Richard C, Fayad J, Linthicum F, Doherty J. Identification of target proteins involved in cochlear otosclerosis. ARO abstract 546. 2013;36 doi: 10.1097/MAO.0000000000000680. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Schuman TA, Noble JH, Wright CG, Wanna GB, Dawant B, Labadie RF. Anatomic verification of a novel method for precise intrascalar localization of cochlear implant electrodes in adult temporal bones using clinically available computed tomography. Laryngoscope. 2010;120:2277–2283. doi: 10.1002/lary.21104. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Schuknecht HF. Pathology of the Ear. 2. Philadelphia: Lea and Febiger; 1993. [Google Scholar]
  21. Skinner MW, Ketten DR, Holden LK, Harding GW, Smith PG, Gates GA, Neely JG, Kletzker GR, Brunsden B, Blocker B. CT-derived estimation of cochlear morphology and electrode array position in relation to word recognition in Nucleus-22 recipients. JARO. 2002;3:332–50. doi: 10.1007/s101620020013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Somdas MA, Li PMMC, Whiten DM, Eddington DK, Nadol JB., Jr Quantitative evaluation of new bone and fibrous tissue in the cochlea following cochlear implantation in the human. Audiol Neurotol. 2007;12:277–284. doi: 10.1159/000103208. [DOI] [PubMed] [Google Scholar]
  23. Teymouri J, Hullar TE, Holden TA, Chole RA. Verification of computed tomographic estimates of cochlear implant array position: a micro-CT and histological analysis. Otol Neurotol. 2011;32(6):980–986. doi: 10.1097/MAO.0b013e3182255915. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Van der Marel KS, Verbist BM, Briaire JJ, Joemai RMS. Electrode migration in cochlear implant patients: not an exception. Audiol Neurotol. 2012;17:275–281. doi: 10.1159/000338475. [DOI] [PubMed] [Google Scholar]
  25. Verbist BM, Joemai RMS, Briaire JJ, Teeuwisse WM, Veldkamp WJH, Frijns JHM. Cochlear coordinates in regard to cochlear implantation: a clinically individually applicable 3 dimensional CT-based method. Otol Neurotol. 2010;31:738–744. doi: 10.1097/MAO.0b013e3181d8d3c4. [DOI] [PubMed] [Google Scholar]

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