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. Author manuscript; available in PMC: 2025 Mar 1.
Published in final edited form as: Otol Neurotol. 2024 Jan 17;45(3):311–318. doi: 10.1097/MAO.0000000000004105

Inner Ear Breaches from Vestibular Schwannoma Surgery: Revisiting the Incidence of Otologic Injury from Retrosigmoid and Middle Cranial Fossa Approaches

Nir Ben-Shlomo 1, Amina Rahimi 2, Abdullah M Abunimer 3, Jeffrey P Guenette 4, Amy Juliano 5, Jacqueline R Star 6, Jagadeesan Jayender 7, C Eduardo Corrales 8
PMCID: PMC10922915  NIHMSID: NIHMS1949513  PMID: 38238921

Abstract

Objective:

To assess the rate of iatrogenic injury to the inner ear in vestibular schwannoma resections

Study Design:

Retrospective case review

Setting:

Multiple academic tertiary care hospitals

Patients:

Patients who underwent retrosigmoid or middle cranial fossa approaches for vestibular schwannoma resection between 1993–2015

Intervention:

Diagnostic with therapeutic implications

Main Outcome Measure:

Drilling breach of the inner ear as comfirmed by operative note or postoperative CT

Results:

21.5% of patients undergoing either retrosigmoid or middle fossa approaches to the internal auditory canal were identified with a breach of the vestibulocochlear system. Due to the lack of postoperative CT imaging in this cohort, this is likely an underestimation of the true incidence of inner ear breaches. Of all postoperative CT scans reviewed, 51.8% had an inner ear breach. As there may be bias in patients undergoing postoperative CT, a middle figure based on sensitivity analyses estimates the incidence of inner ear breaches from lateral skull base surgery to be 34.7%.

Conclusions:

A high percentage of vestibular schwannoma surgeries via retrosigmoid and middle cranial fossa approaches result in drilling breaches of the inner ear. This study reinforces the value of preoperative image analysis for determining risk of inner ear breaches during vestibular schwannoma surgery and the importance of acquiring CT studies postoperatively to evaluate the integrity of the inner ear.

Introduction:

In recent years, the outcomes for vestibular schwannoma resections have evolved from preservation of life to preservation of function. In patients with serviceable preoperative hearing, the two most popular operative strategies employ the retrosigmoid (suboccipital) and middle cranial fossa approaches. The tumor is classically composed of two parts, the cisternal component which resides in the posterior fossa and the intracanalicular component, which resides in the internal auditory canal (IAC). In order to access the intracanalicular portion of the tumor from these approaches, the surgeon is required to drill through the temporal bone in close proximity to the posterior semicircular canal and vestibule (retrosigmoid approach) or in proximity to the cochlea and superior semicircular canal (middle cranial fossa approach). There exists a great degree of variability of the location of the inner ear structures,(1–3) and from the operative perspective, frequently, there are no clear landmarks that can reliably predict the location of inner ear structures within the petrous bone.(4) In this critical step of the operation, it can be challenging for the surgeon to adequately drill the opaque temporal bone to gain wide enough exposure of the IAC for sufficient tumor removal while attempting to preserve the integrity of the inner ear, and thus preserve hearing.

Review of the literature to assess the incidence of inner ear breaches from vestibular schwannoma surgery resulted in studies published by Tatagiba et. al. (1992) reporting a breach of the inner ear of 30% of surgical resections of vestibular schwannomas,(5) Matthies et. al. (1997) reporting breach of the inner ear 24% of cases,(6) and Yokoyama et. al. (1996) reporting a breach in 20% of cases.(7) All aforementioned studies confirmed inner ear dehiscence by postoperative CT. When injured iatrogenically, the inner ear has been reported to cause hearing loss as well as other third window phenomena including autophony and Tullio phenomena (vertigo and nystagmus induced by loud noises). Recent attention has been drawn to postoperative hearing loss and third window symptomatology after breaches of the inner ear from lateral skull base surgery.(8–10)

With the technological advances in imaging and intraoperative navigation, there exists a paucity of data re-examining the rates of inner ear breaches in the literature from the past 20 years. This study aims to quantify the rates of iatrogenic inner ear injury from vestibular schwannoma surgery across a multi-institutional, multi-provider healthcare network to evaluate the modern incidence of this surgical complication.

Materials and Methods:

Formal approval of the study was provided by our institution’s Institutional Review Board (#2017P002162) and the study was performed in accordance with the Health Insurance Portability and Accountability Act (HIPAA). Informed consent was waived. A search was conducted using our healthcare system’s database across providers at multiple centers between 1993–2015. Keywords of “vestibular schwannoma,” “acoustic neuroma,” and “acoustic schwannoma,” were combined with CPT procedure codes for surgery. From this cohort of patients, a review of the electronic medical records for operative notes, demographic data, and both preoperative and postoperative radiological images was performed. (Fig. 1) Our investigation was focused on assessing the integrity of the labyrinth in retrosigmoid and middle cranial fossa approaches, and for this reason translabyrinthine cases were excluded from our analysis. Each patient chart was analyzed in three parts: preoperative imaging, operative notes, and postoperative imaging.

Figure 1.

Figure 1

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Schematic display of database search results. *Excluded cases included 114 translabyrinthine approaches as well as 23 cases with diagnoses not relevant to this study.

Preoperative Assessment

For the patients with preoperative MRI imaging, measurements were gathered as displayed in Fig. 2. The tumor anterior-posterior (AP) tumor diameter was measured on axial images at the slice showing the tumor’s maximal diameter. The IAC measurements were made by drawing a line antero-posteriorly to delineate the interface between the posterior fossa and the internal auditory canal. From this line, measurements were made to assess the depth of tumor invasion as well as the total depth of the IAC. A tumor invasion percentage was calculated by dividing the depth of tumor invasion by the total anatomical depth of the IAC. A measurement was made between the posterior semicircular canal and the posterior fossa at the point where this distance was shortest. The sigmoid-fundus (S-F) line was drawn as described previously by Tatagiba et. al.(5) and shown in Fig. 2B. Due to the popularity of high resolution MRI exams for preoperative evaluation, the vast majority of patients did not receive a preoperative CT for anatomical evaluation, and the S-F line was drawn on high resolution MRI images that were able to clearly depict the sigmoid sinus and labyrinthine structures.

Figure 2.

Figure 2

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(A) Measurements from Preoperative MRI 3D FIESTA Sequence. Line A: A-P diameter of the tumor. In this case the maximal A-P diameter coincided with the line delineating the IAC opening. Line B: Depth of tumor invasion into the IAC. Line C: Total depth of IAC. Line D: Distance from posterior semicircular canal to the posterior fossa. This patient has a tumor:IAC depth ratio of 0.67 and posterior fossa distance of 2mm. (B) Line E: S-F line drawn from the posteromedial border of the sigmoid sinus to the fundus of the IAC. This patient’s anatomy situates the common crus on the line (O-category), placing this patient in the medium risk category for inner ear injury from drilling to reach the IAC according to Yokoyama’s classification.

Patients were categorized into three groups based on the location of the labyrinth in relation to the S-F line according to the classification proposed by Yokoyama et. al.: the L group, where the vestibule/common crus was lateral to the S-F line, the O group where the vestibule/common crus was on the line, and the M group where the vestibule/common crus was medial to the line.(7)

Intraoperative Assessment

The operative note was reviewed for each case. Special attention was placed on the date of the operation, the instruments used, whether the surgeon recognized that there was a breach of the inner ear, whether the surgeon intended to breach the inner ear, and whether the vestibular nerve(s) were resected as part of the procedure. Intention of drilling through the labyrinth was determined based on the interpretation by a neurotologic surgeon who reviewed the language in the operative note describing drilling portion of the operation. Phrases such as “During drilling, the posterior canal was used as a landmark and followed down to the vestibule and the fundus of the IAC” were considered intentional, whereas phrases such as “the posterior canal was opened during drilling” were considered non-intentional inner ear breaches.

Postoperative Assessment

All charts were reviewed for CT imaging acquired any time after tumor resection. Due to the variability of CT protocols pooled from multiple institutions, CT images of slice thickness 0.5–3mm was considered for review. In retrosigmoid approaches, screenshots of axial slices were captured when a possible dehiscence was identified. Two neuroradiologists with subspecialty expertise in head and neck imaging reviewed the screenshots together to determine in consensus whether dehiscence of the bony labyrinth was present. In cases in which the screenshots were considered to not provide definitive proof, the radiologists reviewed the entire imaging examination to make a determination on bony labyrinth dehiscence. In cases utilizing the middle fossa approach, a breach of the superior semicircular canal was determined based on the operative note findings and postoperative coronal or sagittal CT images of slice thickness <1mm.

In cases where the patient had only postoperative MRI, a determination could not be made regarding the integrity of the bone overlying the inner ear. In addition, integrity of the inner ear could not be determined in cases where no postoperative imaging was found. Any cases without explicit breaches of the inner ear on postoperative CT or in the operative note were classified by default as “non-dehiscent.”

Statistical Analysis

After observing that the majority of patients did not undergo postoperative CT imaging, we developed a sensitivity analysis to explore the effect of missing data on the estimated incidence of injury and its 95% exact confidence interval (95% CI)(Stata, version 16.1, College Station, TX). The low value assumed that no other breach injury occurred other than those identified through postoperative CT imaging or in operative notes; the middle value assumed that the proportion of injuries missed in the operative notes was the same for patients who did and did not have postoperative CT scans; and the high value assumed that the proportion with breach injuries was the same in patients who did and did not undergo CT scanning. Comparisons between groups were completed using ordinary one-way ANOVA with post-hoc tukey tests (GraphPad Prism version 9.5.1, San Diego, CA).

Results:

The database search results provided 1290 patients for individual review of electronic medical records. Translabyrinthine approaches were identified in 114 patients, or 8.8% of total vestibular schwannoma resections across these institutions. These cases were excluded from further analysis due to the focus on approaches commonly utilized in hearing preservation surgery (retrosigmoid and middle cranial fossa approaches). Additionally, 23 patients were excluded for diagnoses unrelated to vestibular schwannoma surgery, resulting in 1153 patient charts reviewed. Retrosigmoid approaches represented the vast majority of cases in this cohort with 1075 patients (93%), as compared to 78 patients (7%) which underwent middle cranial fossa approaches. (Fig. 1)

Detailed information regarding chart review are presented in Fig 3. Operative notes were reviewed for all 1153 cases. Operative notes described drilling into the inner ear in 102 patients, of which 50 were confirmed with postoperative CT. In 66 patients (5.7%), language in the operative notes described entering the inner intentionally. This represents 26.6% of all the inner ear breaches identified in this cohort. 52 patients with breaches charted in the operative note did not have postoperative CT for review.

Figure 3.

Figure 3

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(A, Top Row) Findings from preoperative MRI imaging displaying mean values with standard deviation, as well as median values. (Second Row) Parameters assessed from operative notes divided by approach; retrosigmoid (RS) and middle cranial fossa (MCF). (Third Row) Parameters measured from postoperative imaging. Postoperative CT numbers reflect only retrosigmoid cases and exclude middle fossa approaches due to the lack of fidelity assessing superior canal integrity from axial slices on postoperative CT. *Unless a breach was mentioned in the operative note, patients without postoperative CT were considered to have “intact” inner ears. (B) Venn Diagram illustrating breaches identified on postoperative CT, operative notes, or both. #146 patients had inner ear injuries discovered on postoperative CT with no mention in the operative note.

CT imaging after the date of surgery was found for 378 patients. The CT protocols were highly variable with only a small portion having temporal bone CT protocol images with slice thickness ≤1.0mm. Many patients had lower resolution head CT protocol imaging ordered for a variety of indications, with 32% of CT scans ordered more than 200 days after the operation. Fig 4C. Independent review of CT scans by two neuroradiologists identified dehiscence of the bony labyrinth along the surgical margin in 196 patients (51.8% of CT scans reviewed; 95% CI 46.7%, 57.0%). Of these 196 patients with iatrogenic inner ear dehiscence, 146 had no mention of breaching the inner ear the operative note. The segments of the bony labyrinth that appeared dehiscent are displayed in Fig. 4A.

Figure 4.

Figure 4

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Dehiscent Structures on Postoperative CT (A) Total number of dehiscent inner ear structures by location of breach (B) Distribution of number of structures breached in each patient on postoperative CT. There were 29 cases where a single structure was breached, most commonly the vestibule. In 100 cases, or 51% of cases with iatrogenic inner ear dehiscence, four or more structures were breached corresponding with a wide drill-out of the inner ear. (C) Indication for ordering postoperative CT. Only 252 (22%) of patients received postoperative CT within 200 days of surgery. Patients undergoing CT greater than 200 days after surgery were considered indications unrelated to the surgery (D) This CT was ordered 2 years postoperatively for the evaluation of a possible stroke. Despite the low resolution image, the drilling path is clearly seen breaching the vestibule en route to the posterior wall of the IAC.

Combining information from both operative note (102) and postoperative CT (146) data, a total of 248 patients were identified with inner ear breach after undergoing vestibular schwannoma surgery from review of either the operative note or postoperative CT (21.5%, 95% CI 19.2%, 24.0%).

Sensitivity Analyses

In estimating inner ear breach injury incidence under different assumptions regarding missing postoperative CT scans, the low value was 248/1153, or 21.5% (95% CI 19.2%, 24.0%) and the estimated high value was 51.8% (95% CI 48.9%, 54.7%). To arrive at the estimated middle value, we calculated the proportion of injuries “missed” in the operative notes among patients with postoperative scans: 146/196, or 74.5%. We divided the number of injured patients noted in the charts without postoperative CT imaging (n=52) by one minus this number (0.255) to give an estimated total of 204. Adding this to the 196 observed in patients with postoperative CT scans (196) gave 400, or an estimated “middle” incidence of 34.7% (95% CI 31.9%, 37.5%).

Validity of the LOM Classification

Preoperative MRI imaging was available for 401 patients, of which 399 included the borders of the sigmoid sinus for drawing the sigmoid-fundus line. 198 patients had both preoperative MRI and postoperative CT imaging, and these patients’ scans were used to assess the validity of the LOM classification scheme described by Yokoyama et al. Of these patients with preoperative MRI, postoperative CT imaging identified 130 patients with inner ear dehiscence after surgery, and operative notes were able to identify an additional 19 dehiscent cases. Lacking postoperative CT imaging in the remaining 182 cases in patients with preoperative imaging, we were unable to confirm the status of the inner ear postoperatively and thus classified them as non-dehiscent. The classification scheme by Yokoyama et. al. demonstrated significant delineation of risk for dehiscence, as is demonstrated in Fig. 5.

Figure 5.

Figure 5

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Location of inner ear in relation to Sigmoid-Fundus line according to classification by Yokoyama et al. in 399 patients where preoperative MRI delineated the borders of the sigmoid sinus. Patients without postoperative CT or mention of a breach in the operative note were considered to have “intact” inner ears postoperatively. Comparisons by one-way ANOVA with post hoc Tukey.

Discussion:

After reviewing 1153 cases of vestibular schwannoma resection carried out between 1993–2015 via hearing preservation approaches (retrosigmoid or middle cranial fossa), inner ear breaches were identified in 248 cases for an estimated dehiscence rate of 21.5%. Though congruent with estimates of 20–30% reported from previous studies,(5–7) this is likely an underestimation of the true incidence of inner ear drilling injuries in our cohort due to the low rates of postoperative CT imaging available for review combined with the low rates of breaches reported in operative notes.

Our analysis was strengthened by performing sensitivity analyses, i.e., recalculating incidence estimates under different assumptions regarding missing data. The assumption that there were no injuries other than those identified via postoperative CT imaging or the operative notes led to the estimated incidence of 21.5%.This is a form of extreme value imputation, and it reflects a “floor” for the estimated incidence because the data does not account for any patients that were missed by failure to mention an inner ear injury in the operative notes. In the 378 patients with postoperative CT imaging, 196 (51.8%) scans demonstrated inner ear dehiscence. This incidence rate may be represent a “high” estimate, because there is likely a bias in patients undergoing postoperative CT. A more plausible middle value assumes that the operative notes missed the same proportion of injuries regardless whether the patients underwent postoperative CT scans, giving an estimated incidence of 34.7%.

Identifying the Injury

The anatomic location of the IAC presents an ongoing challenge for achieving clear margins in vestibular schwannoma resection. Drilling of the temporal bone to reach the fundal portions of the tumor places multiple inner ear structures at risk. It is imperative that surgeons are aware of their location in relation to the inner ear structures while drilling and make every effort to mitigate the breaching the inner ear when there is an attempt to preserve hearing and balance.

In 66 patients (5.7%), review of the operative note described an intentional sacrifice of the integrity of the inner ear. However, an additional 182 patients (15.8%) did not include language in the operative note denoting an intentional breach, yet still were confirmed to have sustained a violation of the inner ear. Though 26.6% of the inner ear breaches were carried out “intentionally,” at least 59% of the inner ear breaches that were identified on postoperative CT were not charted in the operative note, suggesting that the surgeon was possibly unaware that the inner ear was breached intraoperatively.

A high degree of care must be employed during drilling of the temporal bone in order to avoid missing inner ear dehiscences. In the case where a breach of the inner ear is found, immediate application of bone wax can be useful to avoid any excessive leak of labyrinthine fluid, and may negate the need for a secondary operation to alleviate third window symptomatology.(8–10)

In only 378 cases (32.8%) were we able to evaluate the integrity of the temporal bone with postoperative CT, and the vast majority of these imaging studies were ordered with indications unrelated to the inner ear. This suggests that there is a lack of assessment of the inner ear following vestibular schwannoma surgery using CT imaging. Patients are expected to experience hearing and vestibular changes after vestibular schwannoma surgery from the tumor, the anesthesia, or instrumentation of the nerves during surgery. However, the high rate of inner ear breaches from these approaches established in this cohort as well as past studies calls for more frequent postoperative CT evaluation of the temporal bone following vestibular schwannoma surgery. Acute awareness of the high incidence of this complication can guide preoperative patient counseling, or alter the surgical approach for vestibular schwannomas with tumor volumes deep within the fundus of the IAC, based on anatomical considerations such as the LOM scheme.

A recent assessment of complication rates from vestibular schwannoma surgery completed by Nuño et. al. reported CSF leaks (4.4%), hydrocephalus (3.0%), pulmonary embolism (0.5%), venous thrombosis (0.8%), and acute myocardial infarction (0.3%).(11) Their study reviewed symptomatology relating to inner ear function including hearing loss, disequilibrium, tinnitus, vertigo, facial weakness, headache, among others, but did not address the integrity of the inner ear structures postoperatively. Older studies by Samii et. al.,(12) Slattery et. al.,(13) and Sanna et. al.(14) reported overlapping categories of surgical complications, but similarly do not address the status of the inner ear after surgery. Though postoperative hearing outcomes are regularly reported, the literature fails to address damage to the inner ear from these surgeries.

In our review, the structures breached most often from temporal bone drilling included the vestibule, posterior semicircular canal, and common crus. In 22% of cases with identified dehiscence, five or more inner ear structures were breached from drilling, corresponding to a very wide drill-out of the inner ear. (Fig. 4B) In these cases, the surgeon was more likely to report in the operative note that they had intentionally used the inner ear as a landmark for reaching the IAC. However, in 49% of cases with identified dehiscence, three or fewer inner ear structures were breached from drilling, and these cases were less likely to have been reported in the operative note.

In only 163 cases (14%) in our cohort was an endoscope used, and the addition of an angled visualization of the drilling area may help diagnose a breach of the otic capsule intraoperatively. Incorporating an angled endoscope with angled instruments can ensure that the deepest portions of the IAC can be reached for tumor resection without requiring extensive temporal bone drilling which may place the inner ear structures at risk.(15)

In their 1992 study, Tatagiba et. al. reported that deafness was significantly more frequent in patients with injured labyrinths than in patients with intact labyrinths.(5) Breaching the inner ear from drilling thus dramatically limits the aims of pursuing a hearing preservation approach. In addition to poor hearing outcomes, any breach to the vestibular labyrinth can lead to vertigo, tinnitus, and other debilitating third window symptoms. (8–10)

When viewed chronologically, results from this cohort suggest the rates of inner ear dehiscence are increasing. Between the years 1998–2000, the greatest number of vestibular schwannoma resections were completed but the incidence of confirmed dehiscence was 12%, whereas in recent years, incidence rates of confirmed inner ear breaches are rising to above 30%. (Fig. 6) As this is a multi-institutional cohort with multiple providers this change is unlikely due to surgical proficiency or altered surgical techniques but rather this is more likely attributed to improved documentation or increased postoperative surveillance with CT imaging in recent years. However, one might expect that the incidence of inner ear breaches would decline with recent technological advancements such as improvements in preoperative imaging, intraoperative navigation, and the widespread availability of endoscopes. Review of this cohort suggests that the incidence of inner ear breaches has not decreased since the reports from Tatagiba et al., Matthies et. al., and Yokoyama et al.

Figure 6.

Figure 6

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Incidence of drilling injury from vestibular schwannoma surgery over time. Data is plotted as a percentage of total hearing preservation approaches performed. Numbers above each bar indicate the total number of vestibular schwannoma resections performed during the time interval.

Current strategies for preventing the occurrence of inner ear dehiscence in vestibular schwannoma surgery include increased awareness of the risk to the inner ear while drilling, improved preoperative planning with the use of the LOM classificaction scheme, as well as the use of endoscopes and angled instruments to safely access tumor lying deep in the IAC. Emerging technologies may prove useful for providing increased awareness and visualization of the inner ear structures intraoperatively. The application of 3D anatomic segmentation to provide intraoperative guidance such as drill tip position tracking with proximity alerts,(16) projecting inner ear structures with augmented reality,(17) and 3D surface reconstruction technologies(18) show promise for decreasing the incidence of iner ear breaches in the future.

Limitations:

Though we define the retrosigmoid and middle crania fossa approaches as hearing preservation approaches, this may not reflect the hearing status of the individual patient, and this study does not address preoperative hearing or postoperative hearing or balance status of these patients. Retrosigmoid and middle cranial fossa approaches are classically performed without violation of the otic capsule, and for this reason we investigate these approaches in the context of hearing preservation. This study aims only to present an estimate of the incidence of inner ear breaches from vestibular schwannoma resections from these approaches. Characterizing postoperative hearing and balance in the context of inner ear breach is an avenue for further investigation.

We understand that at times the surgeon may elect for one of these approaches with the predetermined intent to drill through the inner ear, and likewise, there arise intraoperative scenarios that require the deliberate decision to drill through the inner ear. The retrospective nature of this study is unable to elucidate the complex decision making process encountered for any given patient. This study did not examine clinic notes where this preoperative decision making process could potentially be described, and instead relied on intraoperative documentation and postoperative imaging for characterizing the incidence of inner ear injury. While we believe the express intent to enter the inner ear should be addressed in the surgeon’s operative note, we appreciate there may be reasons to avoid describing this in the operative note, ie medicolegal or other reasons. More concerning however, is the possibility that the surgeon was unaware of an unintentional breach of the inner ear, and our cohort demonstrated a high proportion (59%) of inner ear breaches identified on CT had no mention in the operative note.

CT is the only definitive postoperative imaging modality to clearly visualize the drilling path and for diagnosing a breach of the inner ear structures. Current protocols at these institutions is to monitor for tumor recurrence using serial MRI imaging, and in our cohort only 32.8% of patients received any head CT imaging after surgery. The vast majority of postoperative CT studies were ordered for reasons unrelated to the surgery, sometimes as far as years postoperatively for an unrelated condition. For this reason, the majority of postoperative CT images reviewed were not high-resolution scans with slice thickness >1.0mm. However, the integrity of the otic capsule was able to be characterized for a majority of postoperative CT scans, as is demonstrated in Fig. 4D. Postoperative scans were not ordered for 67.2% of patients in this cohort. Due to the inability to assess the inner ear integrity in these patients and the high proportion of inner ear breaches absent from reporting in the operative notes, our findings of 21.5% of patients sustaining confirmable inner ear breaches from vestibular schwannoma resection is likely an underestimate of the true incidence of this operative occurrence.

Conclusion:

Drilling to reach the internal auditory canal in hearing preservation approaches endangers the inner ear, and therefore can lead to hearing loss and extended postoperative dizziness or other third window symptomatology. In a retrospective analysis of 1153 patients in a multi-institutional, multi-provider healthcare network, iatrogenic drilling breaches of the inner ear could be confirmed in either postoperative CT studies or operative notes for 21.5% percent of patients undergoing retrosigmoid and middle cranial fossa approaches. This number is likely an underestimation of the true prevalence of inner ear drilling injuries due to limited postoperative CT imaging in this cohort. This study reinforces the value of preoperative image analysis for determining risk of inner ear breaches during vestibular schwannoma surgery and the importance of acquiring CT studies after surgery in order to evaluate the integrity of the inner ear.

Conflicts of Interest and Source of Funding

This work was supported in part by the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health through Grant Numbers R01EB025964 and P41EB028741 (JJ). This work was also supported in part by the National Institutes of Health Institutional National Research Award, T32 #5T32DC000040 (NB). Unrelated to this publication, Jagadeesan Jayender owns equity in Navigation Sciences, Inc. He is a co-inventor of a navigation device to assist surgeons in tumor excision that is licensed to Navigation Sciences. Dr. Jagadeesan’s interests were reviewed and are managed by BWH and Partners HealthCare in accordance with their conflict of interest policies. This work was conducted with support from Harvard Catalyst. The Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, National Institutes of Health Award UL1 TR002541) (JRS) and financial contributions from Harvard University and its affiliated academic healthcare centers. The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic healthcare centers, or the National Institutes of Health.

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