Variability in Manual Segmentation of Temporal Bone Structures in Cone Beam CT Images.

PURPOSE: Manual segmentation of anatomical structures is the accepted "gold standard" for labeling structures in clinical images. However, the variability in manual segmentation of temporal bone structures in CBCT images of the temporal bone has not been systematically evaluated using multiple reviewers. Therefore, we evaluated the intravariability and intervariability of manual segmentation of inner ear structures in CBCT images of the temporal bone. METHODS: Preoperative CBCTs scans of the inner ear were obtained from 10 patients who had undergone cochlear implant surgery. The cochlea, facial nerve, chorda tympani, mid-modiolar (MM) axis, and round window (RW) were manually segmented by five reviewers in two separate sessions that were at least 1 month apart. Interreviewer and intrareviewer variabilities were assessed using the Dice coefficient (DICE), volume similarity, mean Hausdorff Distance metrics, and visual review. RESULTS: Manual segmentation of the cochlea was the most consistent within and across reviewers with a mean DICE of 0.91 (SD = 0.02) and 0.89 (SD = 0.01) respectively, followed by the facial nerve with a mean DICE of 0.83 (SD = 0.02) and 0.80 (SD = 0.03), respectively. The chorda tympani had the greatest amount of reviewer variability due to its thin size, and the location of the centroid of the RW and the MM axis were also quite variable between and within reviewers. CONCLUSIONS: We observed significant variability in manual segmentation of some of the temporal bone structures across reviewers. This variability needs to be considered when interpreting the results in studies using one manual reviewer.

Post-operative evaluation of computed tomography imaging following cochlear implantation.

PURPOSE: This study utilized an automated segmentation algorithm to assess the cochlear implant electrode array within the cochlea and investigate its impact on audiologic outcomes as measured by post-operative speech perception scores. Furthermore, manual evaluations of electrode placement were compared to automatic segmentation methods to determine their accuracy in predicting post-operative audiologic outcomes. MATERIALS AND METHODS: This retrospective chart review was conducted at a tertiary care referral center involving adult post-lingually deafened cochlear implant recipients implanted from 2015 to 2019. Patients with appropriate postoperative imaging and speech testing were included. Patients were excluded if non-English speaking, had a cognitive deficit, or a labyrinthine malformation. Automated and manual methods were used to analyze computed tomography (CT) scans and correlate the findings with post-operative speech perception scores and detection of electrode translocation. RESULTS: Among the 47 patients who met inclusion criteria, 15 had electrode translocations confirmed by automatic segmentation methods. Controlling for CI usage and pre-operative AzBio scores, patients with translocation exhibited significantly lower consonant-nucleus consonant (CNC) and AzBio scores at 6-months post-implantation compared to patients with ST insertions. Moreover, the number of translocated electrode contacts was significantly associated with post-operative CNC scores. Manual evaluations of electrode location were predictive but less sensitive to electrode translocations when compared with automated 3D segmentation. CONCLUSIONS: Placement of CI electrode contacts within ST without translocation into SV, leads to improved audiologic outcomes. Manual assessment of electrode placement via temporal bone CT, without 3D reconstruction, provides a less sensitive method to determine electrode placement than automated methods. LEVEL OF EVIDENCE: Level 4. LAY SUMMARY: This study investigated the impact of electrode placement on speech outcomes for cochlear implant recipients. Using advanced imaging techniques, the researchers compared automated and manual methods for evaluating electrode position and examined the relationship between electrode translocation and audiologic outcomes. The findings revealed that proper placement within the cochlea without translocation into inappropriate compartments inside the cochlea improves speech understanding. Manual evaluations were somewhat accurate but less sensitive in detecting translocations compared to automated methods, which offer more precise predictions of patient outcomes. These results contribute to our understanding of factors influencing cochlear implant success and highlight the importance of optimizing electrode placement for improved speech outcomes.

Automated human induced pluripotent stem cell colony segmentation for use in cell culture automation applications.

Human induced pluripotent stem cells (hiPSCs) have demonstrated great promise for a variety of applications that include cell therapy and regenerative medicine. Production of clinical grade hiPSCs requires reproducible manufacturing methods with stringent quality-controls such as those provided by image-controlled robotic processing systems. In this paper we present an automated image analysis method for identifying and picking hiPSC colonies for clonal expansion using the CellXTM robotic cell processing system. This method couples a light weight deep learning segmentation approach based on the U-Net architecture to automatically segment the hiPSC colonies in full field of view (FOV) high resolution phase contrast images with a standardized approach for suggesting pick locations. The utility of this method is demonstrated using images and data obtained from the CellXTM system where clinical grade hiPSCs were reprogrammed, clonally expanded, and differentiated into retinal organoids for use in treatment of patients with inherited retinal degenerative blindness.

Automating iPSC generation to enable autologous photoreceptor cell replacement therapy.

BACKGROUND: Inherited retinal degeneration is a leading cause of incurable vision loss in the developed world. While autologous iPSC mediated photoreceptor cell replacement is theoretically possible, the lack of commercially available technologies designed to enable high throughput parallel production of patient specific therapeutics has hindered clinical translation. METHODS: In this study, we describe the use of the Cell X precision robotic cell culture platform to enable parallel production of clinical grade patient specific iPSCs. The Cell X is housed within an ISO Class 5 cGMP compliant closed aseptic isolator (Biospherix XVivo X2), where all procedures from fibroblast culture to iPSC generation, clonal expansion and retinal differentiation were performed. RESULTS: Patient iPSCs generated using the Cell X platform were determined to be pluripotent via score card analysis and genetically stable via karyotyping. As determined via immunostaining and confocal microscopy, iPSCs generated using the Cell X platform gave rise to retinal organoids that were indistinguishable from organoids derived from manually generated iPSCs. In addition, at 120 days post-differentiation, single-cell RNA sequencing analysis revealed that cells generated using the Cell X platform were comparable to those generated under manual conditions in a separate laboratory. CONCLUSION: We have successfully developed a robotic iPSC generation platform and standard operating procedures for production of high-quality photoreceptor precursor cells that are compatible with current good manufacturing practices. This system will enable clinical grade production of iPSCs for autologous retinal cell replacement.

Patient-specific Virtual Temporal Bone Simulation Based on Clinical Cone-beam Computed Tomography.

OBJECTIVES: Patient-specific surgical simulation allows presurgical planning through three-dimensional (3D) visualization and virtual rehearsal. Virtual reality simulation for otologic surgery can be based on high-resolution cone-beam computed tomography (CBCT). This study aimed to evaluate clinicians' experience with patient-specific simulation of mastoid surgery. METHODS: Prospective, multi-institutional study. Preoperative temporal bone CBCT scans of patients undergoing cochlear implantation (CI) were retrospectively obtained. Automated processing and segmentation routines were used. Otologic surgeons performed a complete mastoidectomy with facial recess approach on the patient-specific virtual cases in the institution's temporal bone simulator. Participants completed surveys regarding the perceived accuracy and utility of the simulation. RESULTS: Twenty-two clinical CBCTs were obtained. Four attending otologic surgeons and 5 otolaryngology trainees enrolled in the study. The mean number of simulations completed by each participant was 16.5 (range 3-22). "Overall experience" and "usefulness for presurgical planning" were rated as "good," "very good," or "excellent" in 84.6% and 71.6% of the simulations, respectively. In 10.7% of simulations, the surgeon reported to have gained a significantly greater understanding of the patient's anatomy compared to standard imaging. Participants were able to better appreciate subtle anatomic findings after using the simulator for 60.4% of cases. Variable CBCT acquisition quality was the most reported limitation. CONCLUSION: Patient-specific simulation using preoperative CBCT is feasible and may provide valuable insights prior to otologic surgery. Establishing a CBCT acquisition protocol that allows for consistent segmentation will be essential for reliable surgical simulation. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:1855-1862, 2021.

Automated in-process characterization and selection of cell-clones for quality and efficient cell manufacturing.

Delivery of safe, effective and reliable cellular therapies, whether based on mesenchymal stromal cells (MSCs) or induced pluripotent stem cells (iPSCs), demand standardization of cell culture protocols. There is a need to develop automation platform that enables the users to generate culture expanded human cell populations that improves the quality and reduces batch-to-batch variation with respect to biological potential. Cell X™ robot was designed to address these current challenges in the cell fabrication industry. It utilizes non-invasive large field of view quantitative image analysis to guide an automated process of targeted "biopsy" (cells or media), "picking" (selection) of desired cells or colonies, or "weeding" (removal) of undesired cells, thus providing an unprecedented ability to acquire quantitative measurement in a complex heterogeneous cell environment "in process" and then to act on those measurements to define highly reproducible methods for cell and colony "management" based on application specific critical quality attributes to improve the quality of the manufactured cell lines and cell products.

Translating the simulation of procedural drilling techniques for interactive neurosurgical training.

BACKGROUND: Through previous efforts we have developed a fully virtual environment to provide procedural training of otologic surgical technique. The virtual environment is based on high-resolution volumetric data of the regional anatomy. These volumetric data help drive an interactive multisensory, ie, visual (stereo), aural (stereo), and tactile, simulation environment. Subsequently, we have extended our efforts to support the training of neurosurgical procedural technique as part of the Congress of Neurological Surgeons simulation initiative. OBJECTIVE: To deliberately study the integration of simulation technologies into the neurosurgical curriculum and to determine their efficacy in teaching minimally invasive cranial and skull base approaches. METHODS: We discuss issues of biofidelity and our methods to provide objective, quantitative and automated assessment for the residents. RESULTS: We conclude with a discussion of our experiences by reporting preliminary formative pilot studies and proposed approaches to take the simulation to the next level through additional validation studies. CONCLUSION: We have presented our efforts to translate an otologic simulation environment for use in the neurosurgical curriculum. We have demonstrated the initial proof of principles and define the steps to integrate and validate the system as an adjuvant to the neurosurgical curriculum.

Virtual temporal bone dissection system: OSU virtual temporal bone system: development and testing.

OBJECTIVES/HYPOTHESIS: The objective of this project was to develop a virtual temporal bone dissection system that would provide an enhanced educational experience for the training of otologic surgeons. STUDY DESIGN: A randomized, controlled, multi-institutional, single-blinded validation study. METHODS: The project encompassed four areas of emphasis: structural data acquisition, integration of the system, dissemination of the system, and validation. RESULTS: Structural acquisition was performed on multiple imaging platforms. Integration achieved a cost-effective system. Dissemination was achieved on different levels including casual interest, downloading of software, and full involvement in development and validation studies. A validation study was performed at eight different training institutions across the country using a two-arm randomized trial where study subjects were randomized to a 2-week practice session using either the virtual temporal bone or standard cadaveric temporal bones. Eighty subjects were enrolled and randomized to one of the two treatment arms; 65 completed the study. There was no difference between the two groups using a blinded rating tool to assess performance after training. CONCLUSIONS: A virtual temporal bone dissection system has been developed and compared to cadaveric temporal bones for practice using a multicenter trial. There was no statistical difference between practice on the current simulator compared to practice on human cadaveric temporal bones. Further refinements in structural acquisition and interface design have been identified, which can be implemented prior to full incorporation into training programs and used for objective skills assessment.

Virtual simulation of mouse anatomy and procedural techniques.

Translational science requires the use of mouse models for the characterization of disease and evaluation of treatment therapies. However, often there is a lack of comprehensive training for scientists in the systemic and regional anatomy of the mouse that limits their ability to perform studies involving complex interventional procedures. We present our methodologies for the development, evaluation, and dissemination of an interactive 3D mouse atlas that includes designs for presenting emulation of procedural technique. We present the novel integration of super-resolution imaging techniques, depth-of-field interactive volume rendering of large data, and the seamless delivery of remote visualization and interaction to thin clients.

Translating surgical metrics into automated assessments.

In the effort to promote more continuous and quantitative assessment of surgical proficiency, there is an increased need to define and establish common surgical metrics. Furthermore, as various pressures such as limited duty hours and access to educational resources, including materials and expertise, place increased demands on training, the value of quantitative automated assessment becomes increasingly apparent. We present our methods to establish common surgical metrics within the otology and neurotology community and our initial efforts in the subsequent transfer of these metrics into objective automated assessments provided via a simulation environment.