Development and validation of a surgical planning tool for bone-conduction implants.

Background: The BONEBRIDGE® (Med-El GmbH) is a bone-conduction device comprising an external audio processor and an internal Bone Conduction-Floating Mass Transducer (BC-FMT) surgically anchored to the temporal bone. Due to the implant's size, its placement may be challenging in certain anatomies, necessitating thorough surgical planning. Manual planning methods are laborious, time-intensive, and prone to errors. This study aimed to develop and validate an automated algorithm for determining skull thickness, aiding in the surgical planning of the BONEBRIDGE and other devices requiring similar bone thickness estimations. Materials and methods: Twelve cadaveric temporal bones underwent clinical computed tomography (CT). A custom Python algorithm was developed to automatically segment bone from soft tissue, generate 3D models, and perform ray-tracing to estimate bone thickness. Two thickness colormaps were generated for each sample: the cortical thickness to the first air cell and the total thickness down to the dura. The algorithm was validated against expert manual measurements to achieve consensus interpretation. Results: The algorithm estimated bone-to-air thicknesses (mean = 4.7 mm, 95% Confidence Interval [CI] of 4.3-5.0 mm) that closely matched the expert measurements (mean = 4.7 mm, CI of 4.4-5.0 mm), with a mean absolute difference (MAD) of 0.3 mm. Similarly, the algorithm's estimations to the dura (6.0 mm, CI of 5.4-6.5 mm) were comparable to the expert markings (5.9 mm, CI of 5.4-6.5 mm), with a MAD of 0.3 mm. Conclusions: The first automated algorithm to calculate skull thickness to both the air cells and dura in the temporal bone was developed. Colormaps were optimized to aid with the surgical planning of BONEBRIDGE implantation, however the tool can be generalized to aid in the surgical planning of any bone thickness application. The tool was published as a freely available extension to the open-source 3D Slicer software program (www.slicer.org).

Unlocking the human inner ear for therapeutic intervention.

The human inner ear contains minute three-dimensional neurosensory structures that are deeply embedded within the skull base, rendering them relatively inaccessible to regenerative therapies for hearing loss. Here we provide a detailed characterisation of the functional architecture of the space that hosts the cell bodies of the auditory nerve to make them safely accessible for the first time for therapeutic intervention. We used synchrotron phase-contrast imaging which offers the required microscopic soft-tissue contrast definition while simultaneously displaying precise bony anatomic detail. Using volume-rendering software we constructed highly accurate 3-dimensional representations of the inner ear. The cell bodies are arranged in a bony helical canal that spirals from the base of the cochlea to its apex; the canal volume is 1.6 µL but with a diffusion potential of 15 µL. Modelling data from 10 temporal bones enabled definition of a safe trajectory for therapeutic access while preserving the cochlea's internal architecture. We validated the approach through surgical simulation, anatomical dissection and micro-radiographic analysis. These findings will facilitate future clinical trials of novel therapeutic interventions to restore hearing.

A Synchrotron and Micro-CT Study of the Human Endolymphatic Duct System: Is Meniere's Disease Caused by an Acute Endolymph Backflow?

Background: The etiology of Meniere's disease (MD) and endolymphatic hydrops believed to underlie its symptoms remain unknown. One reason may be the exceptional complexity of the human inner ear, its vulnerability, and surrounding hard bone. The vestibular organ contains an endolymphatic duct system (EDS) bridging the different fluid reservoirs. It may be essential for monitoring hydraulic equilibrium, and a dysregulation may result in distension of the fluid spaces or endolymphatic hydrops. Material and Methods: We studied the EDS using high-resolution synchrotron phase contrast non-invasive imaging (SR-PCI), and micro-computed tomography (micro-CT). Ten fresh human temporal bones underwent SR-PCI. One bone underwent micro-CT after fixation and staining with Lugol's iodine solution (I2KI) to increase tissue resolution. Data were processed using volume-rendering software to create 3D reconstructions allowing orthogonal sectioning, cropping, and tissue segmentation. Results: Combined imaging techniques with segmentation and tissue modeling demonstrated the 3D anatomy of the human saccule, utricle, endolymphatic duct, and sac together with connecting pathways. The utricular duct (UD) and utriculo-endolymphatic valve (UEV or Bast's valve) were demonstrated three-dimensionally for the first time. The reunion duct was displayed with micro-CT. It may serve as a safety valve to maintain cochlear endolymph homeostasis under certain conditions. Discussion: The thin reunion duct seems to play a minor role in the exchange of endolymph between the cochlea and vestibule under normal conditions. The saccule wall appears highly flexible, which may explain occult hydrops occasionally preceding symptoms in MD on magnetic resonance imaging (MRI). The design of the UEV and connecting ducts suggests that there is a reciprocal exchange of fluid among the utricle, semicircular canals, and the EDS. Based on the anatomic framework and previous experimental data, we speculate that precipitous vestibular symptoms in MD arise from a sudden increase in endolymph pressure caused by an uncontrolled endolymphatic sac secretion. A rapid rise in UD pressure, mediated along the fairly wide UEV, may underlie the acute vertigo attack, refuting the rupture/K+-intoxication theory.

Vestibular Organ and Cochlear Implantation-A Synchrotron and Micro-CT Study.

Background: Reports vary on the incidence of vestibular dysfunction and dizziness in patients following cochlear implantation (CI). Disequilibrium may be caused by surgery at the cochlear base, leading to functional disturbances of the vestibular receptors and endolymphatic duct system (EDS) which are located nearby. Here, we analyzed the three-dimensional (3D) anatomy of this region, aiming to optimize surgical approaches to limit damage to the vestibular organ. Material and Methods: A total of 22 fresh-frozen human temporal bones underwent synchrotron radiation phase-contrast imaging (SR-PCI). One temporal bone underwent micro-computed tomography (micro-CT) after fixation and staining with Lugol's iodine solution (I2KI) to increase tissue contrast. We used volume-rendering software to create 3D reconstructions and tissue segmentation that allowed precise assessment of anatomical relationships and topography. Macerated human ears belonging to the Uppsala collection were also used. Drilling and insertion of CI electrodes was performed with metric analyses of different trajectories. Results and Conclusions: SR-PCI and micro-CT imaging demonstrated the complex 3D anatomy of the basal region of the human cochlea, vestibular apparatus, and EDS. Drilling of a cochleostomy may disturb vestibular organ function by injuring the endolymphatic space and disrupting fluid barriers. The saccule is at particular risk due to its proximity to the surgical area and may explain immediate and long-term post-operative vertigo. Round window insertion may be less traumatic to the inner ear, however it may affect the vestibular receptors.

Aeration of the Human Prussak's Space: A 3D Synchrotron Imaging Study.

OBJECTIVES: Prussak's space (PS) is an intricate middle ear region which may play an essential role in the development of middle ear disease. The three-dimensional (3D) anatomy of the human PS and its drainage routes remain relatively unknown. Earlier studies have histologically analyzed PS, by micro-dissection and endoscopy. Here, we used synchrotron-radiation phase-contrast imaging (SR-PCI), 3D reconstructions, and modeling to study the framework of the human PS, including aeration pathways. It may lead to increased understanding of development of middle ear pathology. DESIGN: Nine human temporal bone specimens underwent in-line SR-PCI at the Canadian Light Source in Saskatoon, Saskatchewan, Canada. Data were processed with volume-rendering software to create 3D reconstructions using scalar opacity mapping and segmentations to visualize its walls in fixed, undecalcified human temporal bones. RESULTS: The PS was found to be an irregular, variably shaped chamber with different aeration systems. Three different drainage pathways were found: 1) via the posterior malleolar pouch of von Tröltsch in seven of nine ears; 2) directly posterior-inferior into the mesotympanum medial to the posterior malleolar pouch in one ear; and 3) anteriorly in another. The posterior-inferior communications depended on the anatomy of the posterior malleolar fold. In one bilateral case, the aeration differed between the ears. Earlier descriptions of upper ventilation routes between the PS and the epitympanic spaces could not be substantiated. CONCLUSIONS: The 3D anatomy of the membrane folds organizing the PS in humans was demonstrated for the first time using in-line SR-PCI. The PS was always aerated into the mesotympanum, suggesting its relative independence of attic ventilation. The impact of its various drainage routes on middle ear ventilation and disease were discussed.

Three-dimensional tonotopic mapping of the human cochlea based on synchrotron radiation phase-contrast imaging.

The human cochlea transforms sound waves into electrical signals in the acoustic nerve fibers with high acuity. This transformation occurs via vibrating anisotropic membranes (basilar and tectorial membranes) and frequency-specific hair cell receptors. Frequency-positions can be mapped within the cochlea to create a tonotopic chart which fits an almost-exponential function with lowest frequencies positioned apically and highest frequencies positioned at the cochlear base (Bekesy 1960, Greenwood 1961). To date, models of frequency positions have been based on a two-dimensional analysis with inaccurate representations of the cochlear hook region. In the present study, the first three-dimensional frequency analysis of the cochlea using dendritic mapping to obtain accurate tonotopic maps of the human basilar membrane/organ of Corti and the spiral ganglion was performed. A novel imaging technique, synchrotron radiation phase-contrast imaging, was used and a spiral ganglion frequency function was estimated by nonlinear least squares fitting a Greenwood-like function (F = A (10ax - K)) to the data. The three-dimensional tonotopic data presented herein has large implications for validating electrode position and creating customized frequency maps for cochlear implant recipients.

The BONEBRIDGE active transcutaneous bone conduction implant: effects of location, lifts and screws on sound transmission.

BACKGROUND: The BONEBRIDGE (MED-EL, Innsbruck, Austria) is a bone-conduction implant used in the treatment of conductive and mixed hearing loss. The BONEBRIDGE consists of an external audio processor and a bone-conduction floating mass transducer that is surgically implanted into the skull in either the transmastoid, retrosigmoid or middle fossa regions. The manufacturer includes self-tapping screws to secure the transducer; however, self-drilling screws have also been used with success. In cases where the skull is not thick enough to house the transducer, lifts are available in a variety of sizes to elevate the transducer away from the skull. The objective of the present study was to investigate the effects of screw type, lift thickness, and implant location on the sound transmission of the BONEBRIDGE. METHOD: Six cadaveric temporal bones were embalmed and dried for use in this study. In each sample, a hole was drilled in each of the three implant locations to house the implant transducer. At the middle fossa, six pairs of screw holes were pre-drilled; four pairs to be used with self-tapping screws and lifts (1, 2, 3, and 4 mm thick lifts, respectively), one pair with self-tapping screws and no lifts, and one pair with self-drilling screws and no lifts. At the transmastoid and retrosigmoid locations, one pair of screw holes were pre-drilled in each for the use of the self-tapping screws. The vibration of transmitted sound to the cochlea was measured using a laser Doppler vibrometry technique. The measurements were performed on the cochlear promontory at eight discrete frequencies (0.5, 0.75, 1, 1.5, 2, 3, 4 and 6 kHz). Vibration velocity of the cochlear wall was measured in all samples. Measurements were analyzed using a single-factor ANOVA to investigate the effect of each modification. RESULTS: No significant differences were found related to either screw type, lift thickness, or implant location. CONCLUSIONS: This is the first known study to evaluate the effect of screw type, lift thickness, and implant location on the sound transmission produced by the BONEBRIDGE bone-conduction implant. Further studies may benefit from analysis using fresh cadaveric samples or in-vivo measurements.

Synchrotron Radiation-Based Reconstruction of the Human Spiral Ganglion: Implications for Cochlear Implantation.

OBJECTIVE: To three-dimensionally reconstruct Rosenthal's canal (RC) housing the human spiral ganglion (SG) using synchrotron radiation phase-contrast imaging (SR-PCI). Straight cochlear implant electrode arrays were inserted to better comprehend the electro-cochlear interface in cochlear implantation (CI). DESIGN: SR-PCI was used to reconstruct the human cochlea with and without cadaveric CI. Twenty-eight cochleae were volume rendered, of which 12 underwent cadaveric CI with a straight electrode via the round window (RW). Data were input into the 3D Slicer software program and anatomical structures were modeled using a threshold paint tool. RESULTS: The human RC and SG were reproduced three-dimensionally with artefact-free imaging of electrode arrays. The anatomy of the SG and its relationship to the sensory organ (Corti) and soft and bony structures were assessed. CONCLUSIONS: SR-PCI and computer-based three-dimensional reconstructions demonstrated the relationships among implanted electrodes, angular insertion depths, and the SG for the first time in intact, unstained, and nondecalcified specimens. This information can be used to assess stimulation strategies and future electrode designs, as well as create place-frequency maps of the SG for optimal stimulation strategies of the human auditory nerve in CI.

Incus Necrosis and Blood Supply: A Micro-CT and Synchrotron Imaging Study.

BACKGROUND: Incus necrosis is a common complication following stapes surgery and is associated with impaired microcirculation. The objective of this study was to investigate the vascular anatomy of the human incus by using light microscopy, micro-computed tomography (micro-CT), and synchrotron phase-contrast imaging (SR-PCI) for a novel three-dimensional (3D) analysis of the middle ear, mucosal folds, major vascular pathways, and intraosseous vascular bone channels. METHODS: One-hundred-and-fifty temporal bones from the Uppsala collection were analyzed under light microscopy. Twenty temporal bones underwent high-resolution micro-CT scanning, and an additional seven specimens underwent SR-PCI at the Canadian Lightsource in Saskatoon, Canada. One of these specimens was from an individual who had undergone stapes surgery. Data were processed with volume-rendering software to create 3D reconstructions using scalar opacity mapping for bone transparency, cropping, and soft tissue analyses. RESULTS: Micro-CT and SR-PCI with 3D rendering revealed the extensive vascular plexus within the un-decalcified incus bone communicating with the exterior surface. The relationship between the vessels, lenticular process, and incudostapedial joint were clearly observed. SR-PCI allowed for histologic-level detail while preserving the specimen and its 3D relationships. CONCLUSION: SR-PCI with 3D reconstructions confirmed the main vascular supply to the lenticular process along the intraosseous lenticular vessels. This is the first synchrotron analysis of a patient having undergone stapes surgery, and it suggests that incus necrosis associated with stapes surgery may be caused by a disruption of the lenticular blood flow induced by the prosthesis loop, and not by strangulation of mucosal vessels as has been previously described.

Improved middle-ear soft-tissue visualization using synchrotron radiation phase-contrast imaging.

High resolution images are used as a basis for finite-element modeling of the middle-ear structures to study their biomechanical function. Commonly used imaging techniques such as micro-computed tomography (CT) and optical microscopy require extensive sample preparation, processing or staining using contrast agents to achieve sufficient soft-tissue contrast. We compare imaging of middle-ear structures in unstained, non-decalcified human temporal bones using conventional absorption-contrast micro-CT and using synchrotron radiation phase-contrast imaging (SR-PCI). Four cadaveric temporal bones were imaged using SR-PCI and conventional micro-CT. Images were qualitatively compared in terms of visualization of structural details and soft-tissue contrast using intensity profiles and histograms. In order to quantitatively compare SR-PCI to micro-CT, three-dimensional (3D) models of the ossicles were constructed from both modalities using a semi-automatic segmentation method as these structures are clearly visible in both types of images. Volumes of the segmented ossicles were computed and compared between the two imaging modalities and to estimates from the literature. SR-PCI images provided superior visualization of soft-tissue microstructures over conventional micro-CT images. Intensity profiles emphasized the improved contrast and detectability of soft-tissue in SR-PCI in comparison to absorption-contrast micro-CT. In addition, the semi-automatic segmentations of SR-PCI images yielded accurate 3D reconstructions of the ossicles with mean volumes in accord with volume estimates from micro-CT images and literature. Sample segmentations of the ossicles and soft tissue structures were provided on an online data repository for benefit of the research community. The improved visualization, modeling accuracy and simple sample preparation make SR-PCI a promising tool for generating reliable FE models of the middle-ear structures, including both soft tissues and bone.

Laser Doppler vibrometry measurements of human cadaveric tympanic membrane vibration.

OBJECTIVE: To determine the feasibility of measuring tympanic membrane (TM) vibrations at multiple locations on the TM to differentiate normal eardrums from those with associated ossicular pathologies. DESIGN: Cadaveric human temporal bone study. SETTING: Basic science laboratory. METHODS: A mastoidectomy and facial recess approach was performed on four cadaveric temporal bones to obtain access to the ossicles without disrupting the TM. Ossicles were palpated to ensure normal mobility and an intact ossicular chain. Laser Doppler Vibrometry (LDV) measurements were then taken on all four TMs. LDV measurements were repeated on each TM following stapes footplate fixation, incudo-stapedial joint dislocation, and malleus head fixation. MAIN OUTCOME MEASURES: LDV measurements of TM vibration at the umbo, the lateral process of the malleus, and in each of the four quadrants of the TM. RESULTS: The best signal-to-noise ratios were found between 2 and 4 kHz, at the umbo, the anterior superior quadrant, the anterior inferior quadrant, and the posterior inferior quadrant. Since our goal was to assess the ossicular chain, we selected the TM locations closest to the ossicular chain (the umbo and lateral process of the malleus) for further analysis. Differences could be seen between normals and the simulated ossicular pathologies, but values were not statistically significant. CONCLUSIONS: LDV measurements are technically challenging and require optimization to obtain consistent measurements. This study demonstrates the potential of LDV to differentiate ossicular pathologies behind an intact tympanic membrane. Future studies will further characterize the clinical role of this diagnostic modality.