Surgical Anatomy of the Human Round Window Region: Implication for Cochlear Endoscopy Through the External Auditory Canal

CE: ; ON-16-1; Total nos of Pages: 6; ON-16-1

Otology & Neurotology xx:xx–xx ß 2016, Otology & Neurotology, Inc.

yTakeshi Fujita, y§Jung Eun Shin, zMaryBeth Cunnane, yKyoko Fujita, jjSimon Henein, jjDemetri Psaltis, and yKonstantina M. Stankovic

Eaton Peabody Laboratories, Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts; yDepartment of Otology and Laryngology; zDepartment of Radiology, Harvard Medical School, Boston, Massachusetts; §Department of Otorhinolaryngology–Head and Neck Surgery, Konkuk University Medical Center, Seoul, South Korea; and jjSchool of Engineering, E´cole Polytechnique Fe´de´rale de Laussane (EPFL), Lausanne, Switzerland

Objective: To enable development of an endoscope for were excluded because of pathology. The opening of the cellular-level optical imaging of the inner ear. RW niche was located posteriorly in six bones (13%), Study Design: A prospective study of 50 cadaveric human inferiorly in 18 bones (39%), and postero-inferiorly in 22 temporal bones to define detailed surgical anatomy of the bones (48%). The angles were not statistically different round window (RW) region and the range of angles among the three orientations of the RW niche. necessary to reach the RW membrane perpendicularly via Conclusions: By correlating measurement from cadaveric the external ear canal. human temporal bones and their CT scans, we defined key Main Outcome Measure: The transcanal angle to the RW parameters necessary for designing an endoscope for intraco- membrane was surgically measured in 3D intact specimens, chlear imaging using a minimally invasive approach through and correlated with the angle calculated from temporal bone the external auditory canal. The excellent correlation computed tomography (CT) scans of the same specimens between the measurement on the CT scan and the actual obtained before and after measurements in situ. shape of the probe that was able to reach the RW through Results: Surgically measured transcanal angles to the RW the ear canal enables selection of the probe using the CT membrane correlated well with the radiographically data. Key Words: Endoscopy—Human temporal bones— measured angles. The angles ranged from 110 to 127 Round window—Sensorineural hearing loss. degrees, with the median of 115 degrees and the middle 50% ranging from 109 to 119 degrees. Four temporal bones Otol Neurotol 37:xxx–xxx, 2016.

Sensorineural hearing loss is the most common sen- hearing loss, are very insensitive—they may be normal sory deficit worldwide and it most commonly originates even when 80% of cochlear neurons are missing (2). from the inner ear (1). However, state of the art clinical There is an unmet medical need to develop diagnostic imaging of the inner ear today relies on computed tools to establish cell-specific, early diagnosis of sensor- tomography (CT) scans and magnetic resonance imaging ineural hearing loss while using minimally invasive (MRI), neither of which allows identification of individ- approaches. ual cells in the inner ear. Autopsy specimens are pres- To address that need, we have explored optical imag- ently the only source of information about the cellular ing of the inner ear because optical approaches provide basis of human deafness. Clinical audiograms, which are higher spatial resolution at a lower cost than CT or MRI the current gold standard for establishing the degree of scans. We have demonstrated, in mice, that two photon imaging through the intact round window (RW) provides Address correspondence and reprint requests to Konstantina M. unprecedented resolution of unstained cochlear cells, Stankovic, 243 Charles St Boston, MA 02114, U.S.A.; including sensory hair cells and cochlear neurons, and E-mail: [email protected] their intracellular organelles (3,4). Based on these results Authors Takeshi Fujita and Jung Eun Shin contributed equally. This in mice, we aim to develop an endoscope for optical project was supported by the Bertarelli Foundation (DP, KMS), Wyss Center for Bio and Neuroengineering (DP, KMS), Lauer Tinnitus imaging of the human cochlea through the intact RW to Research Center (KMS), and Nancy Sayles Day Foundation (KMS). establish, for the first time, cellular-level diagnosis The authors disclose no conflicts of interest. of sensorineural hearing loss. A critical part of the

2 T. FUJITA ET AL.

endoscope design is detailed understanding of the lateral aspect of the RW niche. The angle formed by Line 1, anatomy of the RW region. To gain that knowledge, drawn in parallel with the skull base, and Line 2, drawn in the we have studied cadaveric human temporal bones surgic- middle of the RW niche, was measured (Fig. 2A). We also ally and radiographically. measured the depth of the RW niche. The measurements were Endoscopic middle ear surgery is known to allow made from a single section of an axial scan reformatted for the angle measurement between the RW membrane and EAC as visualization around the corners of the three-dimension- described above. The distance between the center of the RW ally complex structures of the middle ear and mastoid. membrane to the RW niche entrance was measured (Fig. 1C). Endoscopic otologic surgery has been gaining popularity over the last few decades (5), and new angled instruments Measuring Transcanal Angles to RW Membrane in have been designed for endoscopic cholesteatoma Cadaveric Temporal Bone surgery (6). In earlier reports, endoscopes have been Otomicroscopic examination of the RW region in cadaveric used in the middle ear to evaluate the RW membrane temporal bones was performed using a transcanal tympanotomy in cases of suspected perilymphatic fistula (7,8). Recent approach after elevating a posterior tympanomeatal flap. Four advances in cochlear implant surgery and intratympanic temporal bones were excluded because of adhesive otitis media, drug applications made it necessary to observe closely EAC cholesteatoma or chronic otitis media with a tympanic the anatomical variation of the RW niche and its relations membrane perforation. The angulation of the RW niche open- to other middle ear landmarks (9). Specifically, identify- ing was categorized as inferior if oriented completely down- ing the position of the RW niche is essential in perform- ward, posterior if directly facing the posterior mesotympanum, and postero-inferior if oriented between the first two directions ing cochlear implant surgery through posterior (12). The RW niche was drilled out as described below to tympanotomy (10). It also has been suggested that the expose the RW membrane circumferentially. A straight, 0.69- evaluation of the RW membrane before intratympanic mm-diameter iron wire was inserted through the external drug application is important to ensure that the drug can auditory canal and bent at the tip to reach the RW membrane actually reach the RW membrane (11). perpendicularly (Fig. 3, A and B). The angle of the bent wire To enable intracochlear endoscopy through the RW, was measured, and correlated with the angle calculated from we have studied detailed surgical anatomy of the RW temporal bone CT scans obtained before and after surgical region and have defined the range of angles necessary to measurements. reach the RW membrane perpendicularly via the external ear canal. By correlating direct measurements from Statistical Analysis human cadaveric temporal bones with radiographic One-way ANOVA followed by Bonferroni’s correction for measurements from CT scans of the same specimens, multiple comparisons was used to compare the three groups (designated by angulation of the RW niche opening). Pearson we specify design parameters for a clinical endoscope for correlations were performed to evaluate the association future optical imaging of the human inner ear. To the best between the angles measured in cadaveric temporal bones of our knowledge, the present study is the largest exam- and their corresponding CT scans. All analyses were conducted ination of three-dimensionally intact human temporal using STATA (STATA 11.1, STATA Corp., College Station, bones and their corresponding CT scans. The results TX, U.S.A.). P-values less than 0.05 were considered indicate a possibility to select customized endoscopic statistically significant. probes based on preoperative CT scans. RESULTS

MATERIALS AND METHODS The method for measuring the angulation of the RW membrane relative to the external auditory canal is Measuring Angles and Length in CT Scans of depicted on a key axial slice of a temporal bone CT Temporal Bones scan (Fig. 1A). The transcanal angle to the RW mem- Fifty cadaveric human temporal bones with no known oto- brane, measured radiographically, ranged from 103 logic disease were studied. Gender and age of the donors were unknown. The Ethics and Human Studies Committee at the degrees to 124 degrees. Median was 113.5 degrees; Massachusetts Eye and Ear Infirmary granted protocol exemp- 25th percentile was 110 degrees; 75th percentile was tion because our study focused on de-identified autopsy speci- 116 degrees (Fig. 1B). mens. The bones were imaged using high-resolution CT. CT A key sagittal section of a temporal bone CT scan was scans were performed with a multidetector CT scanner (GE used to measure the orientation of the RW niche relative Discovery) using 0.625 mm collimation. The raw data were to the long axis of the external auditory canal (Fig. 2, Aa reconstructed at 0.5 mm intervals. Using a 3-D work station (GE and Ab). A transcanal view of this plane is schematized in Advantage), all scans were reformatted to allow identical Fig. 2Ac. The orientation of the RW niche was catego- horizontal sectioning through a plane that contained key ana- rized as inferior, posterior or postero-inferior, as detailed tomical landmarks: basal turn of the cochlea, RW niche, RW in the methods. The 25th to 75th percentile of the angles membrane, manubrium of the malleus, and external auditory canal (EAC). This single index section was used to measure the ranged from 48 degrees to 58 degrees, 64 degrees to angle to the RW membrane via a straight line through the EAC 72 degrees, and 77 degrees to 95 degrees for inferiorly (Fig. 1A). We also measured the angulation of the opening of (n ¼ 18, 39%), postero-inferiorly (n ¼ 22, 48%), and the RW niche from sagittal sections. The measurements were posteriorly (n ¼ 6, 11%) opened RW niches, respectively made from the single sagittal section that captured the most (Fig. 2B). The depth of the RW niche from CT scans

Otology & Neurotology, Vol. xx, No. xx, 2016

SURGICAL ANATOMY OF TEMPORAL BONE FOR COCHLEAR ENDOSCOPY 3

FIG. 1. The angle measurements to the round window membrane through the external auditory canal in CT scans. A, Representative horizontal CT section used to measure the angle to the round window membrane via a straight line through the external auditory canal. B, Box plot of the range of transcanal angles to the round window membrane in CTsections. C, Representative axial section used to measure the depth of the round window niche. The length between the center of the RW membrane and the entrance of the RW niche (depth of the RW niche) was measured. D, Box plots illustrating the range of depths of the round window niche. CT indicates computed tomography; RW, round window.

FIG. 2. The orientation of the round window niche in CTscans. (Aa) Representative sagittal section used to measure the angle of the round window niche opening, defined as the angle between a line parallel with the skull base (Line 1), and a line drawn through the middle of the round window niche. (Ab) Schematic of the CT scan shown in panel (Aa) with labeled anatomical landmarks. (Ac) Schematized view of the sagittal plane shown in (Aa), as viewed through the external auditory canal. This panel is redrawn and modified from a published article (25). B, Box plots illustrating the range of the openings of the round window niche. CT indicates computed tomography.

Otology & Neurotology, Vol. xx, No. xx, 2016

4 T. FUJITA ET AL.

FIG. 3. Transcanal measurement of the angle to the round window membrane in cadaveric temporal bones. (Aa) Representative measurement of the angle between the straight portion of the wire in the external auditory canal and the bent portion perpendicular to the round window membrane in a human cadaveric temporal bone. (Ab) Schematic of a transcanal wire insertion. (Ac) Schematic of a coronal view of the wire insertion. B, Representative iron wire. C, Box plot of the range of transcanal angles to the round window membrane, as directly measured in human cadavers. D, Box plots of the range of orientations of the round window niche opening.

ranged 1.39 mm to 2.12 mm. Median was 1.77 mm; 25th suture line in the posterior part of the EAC were percentile was 1.68 mm; 75th percentile was 1.92 mm rescanned and remeasured after drilling because of sig- (Fig. 1D). nificant changes in EAC anatomy. Narrowing of the EAC After completing the radiographic measurements, we was observed in 16 cases (35%) and posterior drilling proceeded with surgical measurements in the same was performed in six temporal bones (13%). Eight cadaveric temporal bones. The surgical approach to temporal bones (14%) from 30 bones with normal the RW membrane through the external auditory canal is depicted in Fig. 3A. A hand-held rigid probe is shown in a cadaveric specimen while looking down the ear canal (Fig. 3Aa). The approach is schematized in Figure 3, Ab and Ac. Transcanal angle to the RW membrane ranged from 100 degrees to 127 degrees. Median was 115 degrees; 25th percentile was 109 degrees; 75th percentile was 119 degrees (Fig. 3C). Eighteen RW niches were opened inferiorly (n ¼ 18, 39%); 22 were opened postero- inferiorly (n ¼ 22, 48%); six were opened posteriorly (n ¼ 6, 13%). The 25th to 75th percentile of angles ranged from 113 degrees to 119 degrees, 107 degrees to 117 degrees, and 117 degrees to 125 degrees for inferiorly-, postero-inferiorly-, and posteriorly opened RW niches, respectively. The differences were not statistically significant across the groups (Fig. 3D). Surgical measurements in cadaveric temporal bones correlated well with radiographic measurements from the respective CT scans (correlation coefficient ¼ 0.89) (Fig. 4). In eight temporal bones (17%) the RW was completely covered by pseudomembrane, and in 25 (46%), partial coverage or web-like pseudomembrane was observed. In 13 of the temporal bones (28%), there FIG. 4. Surgical measurements in cadaveric temporal bones correlate well with radiographic measurements from the respect- was no presence of pseudomembrane and the RW was ive CT scans (r ¼ 0.89). White dots indicate specimens with a directly visible. Five out of 15 temporal bones (33%) that prominent tympanomasoid suture line in the external auditory required drilling of the prominent tympanomastoid canal, requiring drilling. CT indicates computed tomography.

Otology & Neurotology, Vol. xx, No. xx, 2016

SURGICAL ANATOMY OF TEMPORAL BONE FOR COCHLEAR ENDOSCOPY 5

EAC (65%) also required posterior drilling of the canal to cadaveric temporal bones and their corresponding CT expose the RWM and measure its angulation. scans for establishing surgical approaches, such as to the tympanic sinus (n ¼ 11) (15), petrous apex (n ¼ 30) (16), DISCUSSION and cochlear nerve (n ¼ 10) (17). Others have studied cochlear anatomy for cochlear implantation; n ¼ 22 (9), We have studied 50 human temporal bones to define n ¼ 9 (18), n ¼ 16 (19), n ¼ 10 (20), and n ¼ 40 (21). RW the range of angles required to reach the RW membrane niche visibility through the facial recess and the ability to perpendicularly through the external auditory canal—this predict its visibility through preoperative CT has been will facilitate intracochlear endoscopy through the RW. reported based on the study of 70 surgical cases (22). The The angles calculated from the CT scans correlated well RW’s accessibility for cochlear implant insertion has also with the angles measured in cadaveric specimens. The been studied in 50 surgical cases (23). Only one study excellent correlation between surgical and radiographic reports investigating the RW’s anatomy via a transcanal measurement suggests that a preoperative CT scan could approach in cadaveric temporal bones (11 dry bones and guide the choice of a customized endoscope to provide 9 wet bones) (12). To the best of our knowledge, we have optimal imaging of intracochlear structures. examined the largest number of cadaveric human Obstruction of the RW niche is fairly common. The temporal bones and their corresponding CT scans to RW niche has been reported to be fully or partially analyze details of the RW’s anatomy. In addition, our obstructed by false membrane, webs, or soft tissue plugs study focused on RW anatomy as relevant for transcanal in approximately one-third of all cases from 202 sec- intracochlear endoscopy. Other studies focused on fea- tioned temporal bones (13). Thus, it is essential to have tures relevant for cochlear implantation via a transmas- an extensive understanding of the anatomy around the toid, facial recess approach. RW niche for eventual intracochlear endoscopy. In our Our study contributes to the development of an endo- study, 33 out of 46 cases (72%) also showed partial or full scope for optical imaging of the human cochlea through a obstruction by a pseudomembrane. However, these false transcanal approach, without drilling the RW niche over- membranes were shallow and easily removed with a hang, to establish cellular-level diagnosis of sensorineural Rosen pick without damaging the true RW membrane. hearing loss. Our findings are also relevant for developing The RW niche is classically characterized by two bony devices that can directly administer therapeutic agents to overhangs—one anterioinferiorly and another posteriorly the cochlea through the RW (such as genes therapies, small (14). In a recent study of 20 temporal bones, the RW molecules, stem cells, and drugs) (24). opening was posterior in 15%, posterio-inferior in 40%, and inferior in 45% (12). Our study, which included more CONCLUSION than twice the number of samples investigated in the previous study (12), showed similar proportions of By correlating measurements from human cadaveric RW niche opening orientations. However, we noticed temporal bones with measurements from their respective fewer inferior openings (39%) and more posterio-inferior CT scans, we defined key parameters necessary for openings (48%). The difference between our results and designing an endoscope for intracochlear imaging using the published findings may be because of differences in a minimally invasive approach through the external sample size and/or patient population. auditory canal. As the depth of the RW niche (the distance between the hinge of the niche to the center of the RWM) from CT Acknowledgments: The authors thank Janani Iyer for helpful scans ranged from 1.39 mm to 2.12 mm, the length of the comments on the manuscript. angled tip of the endoscope needs to be designed in that range, possibly customized for a given patient. REFERENCES Aslan et al. (12) reported that the RW niche was visible 1. Ge´le´oc GS, Holt JR. Sound strategies for hearing restoration. in 75% of bones after removal of the tympanic mem- Science 2014;344:1241062. brane. Similarly, we found that the RW niche could be 2. Kujawa SG, Liberman MC. Adding insult to injury: cochlear seen in most specimens by elevating the tympanomeatal nerve degeneration after ‘‘temporary’’ noise-induced hearing loss. J Neurosci 2009;29:14077–85. flap. However, 15 of 46 temporal bones (33%) required 3. Yang X, Pu Y, Hsieh C-L, Ong CA, Psaltis D, Stankobic KM. Two- drilling of the tympanomastoid suture line to expose the photon microscopy of the mouse cochlea in situ for cellular entire RW membrane from the EAC. This result suggests diagnosis. J Biomed Opt 2013;18:31104. that the prominence of the tympanomastoid suture line 4. Tiede L, Steyger PS, Nichols MG, Hallworth R. Metabolic imaging can be an indication for posterior drilling of the EAC, of the organ of corti—a window on cochlea bioenergetics. Brain Res 2009;1277:37–41. especially in a patient population where exostoses are 5. Tarabichi M. Transcanal endoscopic management of cholestea- common. toma. Otol Neurotol 2010;31:580–8. Although the anatomy around the RW has been ana- 6. Yau AY, Mahboubi H, Maducdoc M, Ghavami Y, Djalilian HR. lyzed based on a large number of sectioned temporal Curved adjustable fiberoptic laser for endoscopic cholesteatoma surgery. Otol Neurotol 2015;36:61–4. bone slides (13,14), 3-D information from whole 7. Ogawa K, Kanzaki J, Ogawa S, Tsuchihashi N, Inoue Y, Yamamoto temporal bones is necessary for developing a new device M. Endoscopic diagnosis of idiopathic perilymphatic fistula. Acta or surgical approach. Some of the studies have used Otolaryngol 1994;514:63–5.

Otology & Neurotology, Vol. xx, No. xx, 2016

6 T. FUJITA ET AL.

8. Poe DS, Bottrill ID. Comparison of endoscopic and surgical explo- 17. Theunisse HJ, Gotthardt M, Mylanus EA. Surgical planning and rations for perilymphatic fistulas. Am J Otol 1994;15:735–8. evaluation of implanting a penetrating cochlear nerve implant in 9. Plontke SKR, Plinkert PK, Plinkert B, Koitschev A, Zenner H-P, human temporal bones using microcomputed tomography. Otol Lo¨wenheim H. Transtympanic endoscopy for drug delivery to the Neurotol 2012;33:1027–33. inner ear using a new microendoscope. Adv Otorhinolaryngol 18. Teymouri J, Hullar TE, Holden TA, Chole RA. Verification of 2002;59:149–55. computed tomographic estimates of cochlear implant array pos- 10. Hamamoto M, Murakami G, Kataura A. Topographical relation- ition: a micro-CT and histologic analysis. Otol Neurotol ships among the facial nerve, chorda tympani nerve and round 2011;32:980–6. window with special reference to the approach route for cochlear 19. Avci E, Nauwelaers T, Lenarz T, Hamacher V, Kral A. Variations in implant surgery. Clin Anat 2000;13:251–6. microanatomy of the human cochlea. J Comp Neurol 2014;522: 11. Plontke SK. Evaluation of the round window niche before local 3245–61. drug delivery to the inner ear using a new mini-otoscope. Otol 20. Kisser U, Ertl-Wagner B, Hempel JM, et al. High-resolution Neurotol 2011;32:183–5. computed tomography-based length assessments of the cochlea–an 12. Aslan A, Gu¨nhan K, Eskiizmir G, Elhan A. Anatomic observations accuracy evaluation. Acta Otolaryngol 2014;134:1011–5. on variations of the round window Niche and its relationship to the 21. Singla A, Sahni D, Gupta AK, Aggarwal A, Gupta T. Surgical tympanic membrane. J Int Adv Otol 2006;2:52–7. anatomy of the basal turn of the human cochlea as pertaining to 13. Alzamil KS, Linthicum FH. Extraneous round window membranes cochlear implantation. Otol Neurotol 2015;36:323–8. and plugs: possible effect on intratympanic therapy. Ann Otol 22. Kashio A, Sakamoto T, Karino S, Kakigi A, Iwasaki S, Yamasoba Rhinol Laryngol 2000;109:30–2. T. Predicting round window niche visibility via the facial recess 14. Su WY, Marion MS, Hinojosa R, Matz GJ. Anatomical measure- using high-resolution computed tomography. Otol Neurotol ments of the cochlear aqueduct, round window membrane, round 2015;36:18–23. window niche, and facial recess. Laryngoscope 1982;92:483–6. 23. Leong AC, Jiang D, Agger A, Fitzgerald-O’Connor A. Evaluation 15. Pickett BP, Cail WS, Lambert PR. Sinus tympani: anatomic of round window accessibility to cochlear implant insertion. Eur considerations, computed tomography, and a discussion of the Arch Oto-Rhino-Laryngology 2013;270:1237–42. retrofacial approach for removal of disease. Am J Otol 1995;16: 24. Swan EEL, Mescher MJ, Sewell WF, Tao SL, Borenstein JT. Inner 741–50. ear drug delivery for auditory applications. Adv Drug Deliv Rev 16. Co¨mert E, Co¨mert A, Cay N, Tunc¸el U, Tekdemir I. Surgical 2008;60:1583–99. anatomy of the infralabyrinthine approach. Otolaryngol Head Neck 25. Chittka L, Brockmann A. Perception space—the final frontier. PLos Surg 2014;151:301–7. Biol 2005;3:e137.

Otology & Neurotology, Vol. xx, No. xx, 2016