The transoral approach to resecting oral and oropharyngeal tumors is associated with lower morbidity than open surgery, but is associated with a high positive margin rate. When margins are positive, it is critical that resection specimens be accurately oriented in anatomical context for gross and microscopic evaluation, and also that surgeons, pathologists, and other care team members share an accurate spatial awareness of margin locations. With clinical interest in digital pathology on the rise, this work outlines a proposed framework for generating 3D specimen models intraoperatively via robot-integrated stereovision, and using these models to visualize involved margins in both ex vivo (flattened) and in situ (conformed) configurations. Preliminary pilot study results suggest that stereo specimen imaging can be easily integrated into the transoral robotic surgery workflow, and that the expected accuracy of raw reconstructions is around 1.60mm. Ongoing data collection and technical development will support a full system evaluation.
Transoral robotic surgery (TORS) is an effective minimally invasive alternative to traditional open surgery with improved surgical outcomes and reduced morbidity. However, TORS utilizes the natural orifice approach and does not provide haptic feedback, resulting in difficulty in assessing the extent of tumor or identifying critical structures. Intra-operative surgical navigation with image guidance has the potential to compensate for the sensory deficit in TORS. The authors previously enabled intra-operative image guidance for TORS and demonstrated the feasibility of electromagnetic tracking of da Vinci robotic instruments. In this paper, the authors described the development of a TORS navigation framework with real-time tracking and integration with the da Vinci surgeon’s console, assessed the system efficacy in a multi-user phantom localization study, and discussed study limitations. Five participants with various experience levels performed target localization tasks without and with navigation and all achieved significantly reduced target localization error (TLE) (p≤0.05; α=0.05), with the lowest TLE being 2.1mm. The authors successfully demonstrated the potential of the navigation system in facilitating precise target localization and enabling accurate image-guided TORS (igTORS).
Positive surgical margins are a common complication of trans-oral tumor resection, and implementation of image guidance is typically hindered by significant tissue deformation introduced by oral retractors. Recent advances have produced multiple pathways for developing intraoperative trans-oral image guidance, which must ultimately be displayed to the surgeon in real time. This work presents a pipeline for automatically displaying CT-registered three-dimensional surface structures in the surgeon console of a da Vinci surgical system and assesses image-plane projection accuracy using Dice coefficient and intersection over union metrics. While coarse accuracy is acceptable (metric averages ⪆0.5), more accurate projections were obtained using registration methods based on optically tracking the endoscope shaft. Further improvement of registration, kinematic modeling, and endoscope calibration is necessary prior to use in preclinical evaluation of image guidance strategies for trans-oral robotic surgery.
Iatrogenic nerve injury is a common complication across all surgical specialties. Better nerve visualization and identification during surgery will improve outcomes and reduce nerve injuries. The Gibbs Laboratory at Oregon Health and Science University has developed a library of near-infrared, nerve-specific fluorophores to highlight nerves intraoperatively and aid surgeons in nerve identification and visualization; the current lead agent is LGW16-03. Prior to this study, testing of LGW16-03 was restricted to animal models; therefore, it was unknown how LGW16-03 performs in human tissue. To advance LGW16-03 to clinic, we sought to test this current lead agent in ex vivo human tissues from a cohort of patients and determine if the route of administration affects LGW16-03 fluorescence contrast between nerves and adjacent background tissues (muscle and adipose). LGW16-03 was applied to ex vivo human tissue from lower limb amputations via two strategies: (1) systemic administration of the fluorophore using our first-in-kind model for fluorophore testing, and (2) topical application of the fluorophore. Results showed no statistical difference between topical and systemic administration. However, in vivo human validation of these findings is required.
Fluorescence molecular imaging using ABY-029, an epidermal growth factor receptor (EGFR)-targeted synthetic Affibody peptide labeled with a near-infrared fluorophore, is under investigation for surgical guidance during head and neck squamous cell carcinoma (HNSCC) resection. However, tumor-to-normal tissue contrast is confounded by intrinsic physiological limitations of heterogeneous EGFR expression. In this study, a machine learning-based optomics analysis, which interprets the textural pattern differences in EGFR expression conveyed by fluorescence, was applied to optical ABY-029 fluorescence image data of HNSCC surgical specimens. The study objective was to determine the correlations between optomics method classification performance and tissue inherent EGFR expression level. Fluorescence image data were collected through a Phase 0 clinical trial of ABY-029, which involved a total of 20,073 sub-image patches (size of 1.8×1.8 mm2) extracted from 24 bread-loafed slices of HNSCC surgical resections from 12 patients who were stratified into three dose groups (30, 90, and 171 nanomoles). The optomics approach utilized a supervised machine learning pipeline. Each dose group was randomly partitioned on the specimen-level 75%/25% into training/testing sets, then all training and testing sets were aggregated. A total of 1,472 standardized optomic features were extracted from each patch and evaluated by minimum redundancy maximum relevance feature selection, and 25 top-ranked features were used to train a support vector machine classifier. A conceptual framework of correlation analysis to evaluate the relationship between optomics tumor classification performance and underlying EGFR expression level was provided, but the present results are underpowered. Some generalized conclusions about the ABY-029 fluorescence optomics method correlating to varied levels of EGFR expression were summarized, suggesting that optomics method using fluorescence molecular imaging data offers a potentially stable image analysis technique for cancer detection for fluorescence-guided surgery applications; however, further study with additional samples is needed to validate this conclusion.
Transoral robotic surgery (TORS) has demonstrated improved surgical outcomes with reduced morbidity when compared to traditional open surgical treatments. However, it is more difficult to assess the extent of tumor and localize critical structures due to lack of haptic feedback and the natural orifice approach. Enabling image-guided TORS (igTORS) to compensate for the sensory deficit requires a surgical navigation system that is compatible with both the TORS procedures and the da Vinci surgical system. Previously, the authors developed an imaging compatible oral retractor system for TORS to allow artifact-free intraoperative CT images for use in image guidance. In this work, we developed a surgical navigation system for TORS that utilizes intraoperative images and electromagnetic (EM) tracking. A cadaver experiment simulating a standard TORS procedure was performed to examine system feasibility and accuracy. A da Vinci Bovie instrument was tracked, and its real-time location was visualized in tri-planar CT images and displayed on the surgeon’s console and on the bedside vision cart using the TilePro feature. Target localization error (TLE) was computed to be 3.46±0.77 mm. This was the first time that surgical navigation in TORS was demonstrated with intraoperative image guidance and EM tracking of da Vinci instruments in a cadaver experiment.
Currently-available metallic retractors typically used in transoral robotic surgery (TORS) cause significant artifacts in CT imaging and cannot be safely used in MRI. The lack of imaging-compatible oral retractors poses a significant challenge to enabling intraoperative imaging in TORS. This work introduces a customizable compact 3D-printed polymer retractor system that enables multiple modes of adjustability, artifact-free CT and MR images, and adequate surgical exposure. The polymer retractor design was modeled after the traditional metal FK and Crowe-Davis retractors and can be used with an acrylic suspension system that rests over the patient’s chest. Finite element analysis was conducted to evaluate the mechanical performance in relevant clinical loading conditions. Cadaver experiments followed by endoscopic, CT, and MR imaging were performed to demonstrate functionality. Artifact-free CT and MR images were obtained. An interincisive distance of 42.50 mm and 200.09 cm3 working volume were achieved, which allow the introduction of robotic arms and necessary instruments in TORS. This polymer retractor system makes it possible to acquire intraoperative images and establishes a critical step to make image-guided TORS both feasible and effective.
Tumor phantoms (TP) have been described for the purposes of training surgical residents and further understanding tissue characteristics in malignancy. To date, there has not been a tumor phantom described for the purposes of research and training in oncologic surgery of the head and neck focusing on the larynx and pharynx. With the goal of providing radiographic, visual, and physical mimicry of head and neck squamous cell carcinoma (HNSCC), a phantom was developed as a proposed training and research tool for trans-oral surgical procedures such as transoral laser microsurgery (TLM) and transoral robotic surgery (TORS). TP’s were constructed with an agar-gelatin chicken stock base to approximate reported physical properties, then glutaraldehyde and Omnipaque-350 were used as a fixative and to enhance CT-visualization respectively. Further, to ensure heterogeneity in radiographic imaging, other materials like olive oil and condensed milk were explored. These ingredients were combined with the use of a novel, 3D printed, syringe adaptor designed to allow for the direct injection of the liquid tumor into model tissue. TP’s fixed quickly in vivo upon implantation and were imaged using CT and segmented. This injection-based model was piloted in bovine tissue and verified in porcine tissue with excess Omnipaque-350 for volumetric reliability then optimized utilizing 6 well plates. Following radiographic optimization, the viscoelastic properties of TP’s were measured through uniaxial compression. We observed a Young’s modulus similar to published literature values and consistent reproducibility. Most notably, our proposed TP can be used by multiple specialties by altering the color and concentration of agar in the base solution to approximate physical properties.
Minimally invasive approaches to treating tumors of the pharynx and larynx like trans-oral surgery have improved patient outcome, but challenges remain in localizing tumors for margin control. Introducing necessary retractors and scopes deforms the anatomy and the tumor, rendering preoperative imaging inaccurate and making tumor localization difficult. This paper describes a pipeline that uses preoperative imaging to generate a hybrid FEM-multibody model and then dynamically simulates tongue deformation due to insertion of an electromagnetically-tracked laryngoscope. We hypothesize that the simulation output will be a sufficient estimate of the final intraoperative state and thus provide the surgeon with more accurate guidance during surgical resection. This pipeline was trialed on a cadaver head. The skull, mandible, and laryngoscope were tracked, and fiducial clips were embedded in the tongue for calculating target localization error (TLE) between the simulated and real tongue deformation. Registration accuracies were 1.1, 1.3, and 0.8 mm, respectively, for the tracked skull, mandible, and laryngoscope, and tracking and segmentation validation between the last tracked frame and the ground-truth intraoperative CT was 0.8, 0.9, and 1.2 mm, respectively. TLE of 6.4±2.5 mm was achieved for the full pipeline, in contrast to the total tongue deformation of 37.2±11.4 mm (via tongue clips) between the preoperative and intraoperative CT. Use of tracking and deformation modeling is viable to estimate deformation of the tongue during laryngoscopy. Future work involves additional intraoperative data streams to help further refine model parameters and improve localization.
Short-wave infrared (SWIR/NIR-II) fluorescence imaging has received increased attention for use in fluorescence-guided surgery (FGS) due to the potential for higher resolution imaging of subsurface structures and reduced autofluorescence compared to conventional NIR-I imaging. As with any fluorescence imaging modality introduced in the operating room, an appropriate accounting of contaminating background signal from other light sources in the operating room is an important step. Herein, we report the background signals in the SWIR and NIR-I emitted from commonly-used equipment in the OR, such as ambient and operating lights, LCD screens and surgical guidance systems. These results can guide implementation of protocols to reduce background signal.
ABY-029, an anti-epidermal growth factor receptor (EGFR) Affibody molecule labeled with IRDye 800CW, has been used in three Phase 0 microdosing clinical trials for fluorescence guided surgery. In May of 2019, the clinical trials were put on hold because the ABY-029 produced under Good Manufacturing Practices (GMP) for human administration had come to the end of term in which the drug product was known to be stable. Stability testing was halted due to limitations in supply of a suitable reference standard and a required test product being discontinued from commercial sale. In order to complete the remaining patients in the three clinical trials, new stability tests were developed and the GMP batch of ABY- 029 drug product tested under the new protocols. The GMP batch of ABY-029 passed all stability tests under the new protocols and the Federal Drug Administration (FDA) has given permission to complete the remaining patients with stability testing of ABY-029 performed for each patient. The tests developed and used to test ABY-029 drug product stability are described here.
In trans-oral surgeries, large intraoperative deformations limit the surgeons’ use of preoperative images to accurately resect tumors while traditional metal instruments render intraoperative images ineffective. A CT/MR compatible laryngoscopy system was developed previously to allow for the study of these deformations with intraoperative imaging. For this study, we compare the deformation analysis of two patient groups: those who had received prior radiation to the upper aerodigestive tract (irradiated) and those who have not (non-irradiated). We speculate that differences in tissue deformation exist between these two groups due to radiation-induced fibrosis (RIF) and that quantifying these distinct deformation patterns will lead to more patient-specific tissue modeling. Thirteen patients undergoing diagnostic laryngoscopy were recruited; five had been irradiated and eight had not. Artifact-free images were obtained and registered. Mandible, hyoid, and tongue region displacements were quantified. For the bony structures, significant differences were observed in certain displacement directions as well as magnitude, with the irradiated patient group experiencing less anatomical shift (non-irradiated vs irradiated: (Mandible) 12.6±3.6mm vs 7.9±2.8mm, p=0.029; (Hyoid) 13.3±3.1mm vs 9.0±1.8mm, p=0.019). For the tongue, average displacements of tongue fiducials were 26.2±11.1mm vs 22.9±8.4mm respectively (p=0.033). The data from this study can serve as ground truth to generate and evaluate upper aerodigestive tract deformation models to predict the intraoperative state and provide guidance to the surgeons.
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