Towards standardising retinal OCT angiography image analysis with open-source toolbox OCTAVA.

Quantitative assessment of retinal microvasculature in optical coherence tomography angiography (OCTA) images is important for studying, diagnosing, monitoring, and guiding the treatment of ocular and systemic diseases. However, the OCTA user community lacks universal and transparent image analysis tools that can be applied to images from a range of OCTA instruments and provide reliable and consistent microvascular metrics from diverse datasets. We present a retinal extension to the OCTA Vascular Analyser (OCTAVA) that addresses the challenges of providing robust, easy-to-use, and transparent analysis of retinal OCTA images. OCTAVA is a user-friendly, open-source toolbox that can analyse retinal OCTA images from various instruments. The toolbox delivers seven microvascular metrics for the whole image or subregions and six metrics characterising the foveal avascular zone. We validate OCTAVA using images collected by four commercial OCTA instruments demonstrating robust performance across datasets from different instruments acquired at different sites from different study cohorts. We show that OCTAVA delivers values for retinal microvascular metrics comparable to the literature and reduces their variation between studies compared to their commercial equivalents. By making OCTAVA publicly available, we aim to expand standardised research and thereby improve the reproducibility of quantitative analysis of retinal microvascular imaging. Such improvements will help to better identify more reliable and sensitive biomarkers of ocular and systemic diseases.

Acute and definitive management of oropharyngeal hemorrhage in patients with squamous cell carcinoma of the oropharynx.

BACKGROUND: Massive oropharyngeal bleeding post-chemoradiotherapy is a life-threatening condition that requires emergent management. METHODS: This retrospective case series included 11 patients with oropharyngeal squamous cell carcinoma who suffered from massive bleeding during or following treatment with definitive chemoradiotherapy. Details of acute and definitive management of oropharyngeal bleeding are reported. RESULTS: Nine of 11 hemorrhagic events occurred a mean (SD) of 88.6 days (53.6) after radiotherapy. Airway intubation and embolization were performed in 10 of 11 patients, followed by surgery in 7 of 11 patients. The most commonly embolized vessels were the external carotid and lingual arteries. At the time of discharge, 3 of 11 patients had a tracheostomy, and 7 of 11 continued to use a gastrostomy tube. Four patients died. CONCLUSIONS: Hemorrhagic complications in oropharyngeal cancer treatment require emergent responses. Developing a workflow for coordination between multidisciplinary teams can maximize probability of survival and decrease morbidity.

Masseteric Nerve Transfer for Facial Paralysis Secondary to Parotid Malignancy: A Retrospective Case Series.

Background: The objective outcomes of masseteric nerve transfer in the setting of parotid malignancy are unclear. Objective: To measure objective facial reanimation outcomes of masseteric nerve transfer in patients with parotid malignancy who underwent parotidectomy with facial nerve resection. Materials and Methods: Retrospective review of patients who underwent masseteric nerve transfer for facial paralysis secondary to parotid malignancy was carried out at a tertiary referral hospital from August 2017 to November 2021. Objective facial reanimation outcomes were analyzed using Emotrics. Minimal follow-up of 6 months was required for inclusion. Results: Eight patients (five males) with a median age of 75.5 years (range 53-91) met inclusion criteria. Fifty percent had metastatic squamous cell carcinoma, and 50% had primary parotid malignancy. Five patients underwent concomitant cancer resection with facial nerve reconstruction. Seven patients received postoperative adjuvant radiotherapy. After reinnervation, patients had improved oral commissure excursion (from 1.51 mm ±1.27 to 3.77 mm ±1.81; p < 0.01) and facial symmetry during smile. Conclusion: In this study, masseteric nerve transfer enhanced oral commissure excursion and facial symmetry during smile in patients with parotid malignancy and facial nerve resection.

Comparison of da Vinci Single Port vs Si Systems for Transoral Robotic-Assisted Surgery: A Review With Technical Insights.

Importance: Transoral robot-assisted surgery (TORS) continues to have a major role in the treatment of oropharyngeal cancer. As new iterations of robotic technology are increasingly utilized, it is important to share learning experiences and clinical outcomes data, to optimize technical efficiency and clinical care. Observations: This was a retrospective review of a large academic institution's initial clinical use of the da Vinci Single Port (SP) compared with the da Vinci Si (Si) system. A total of 205 TORS cases were reviewed: 109 in the SP group (November 22, 2018, through September 30, 2020), and 96 in the Si group (January 1, 2016, through November 12, 2018). Both groups had comparable operative times, rates of postoperative pharyngeal hemorrhage, length of hospital stay, and duration of nasogastric feeding tube use. There was no difference in pathological characteristics, rates of positive margins, or indications for or time to initiation of adjuvant therapy between the groups. The collective experience of 6 faculty members-who have trained 139 TORS surgeons for the SP system rollout-was compiled to provide a summary of learning experiences and technical notes on safe and efficient operation of the SP system. Conclusions and Relevance: This Review found that the functional and oncologic outcomes were comparable between TORS cases performed with the Si and SP systems, and they had similar complication rates. Recognized advantages of the SP over the Si system include the availability of bipolar-energized instruments, a usable third surgical arm, and improved camera image quality.

Special Section on Selected Topics in Biophotonics: Translating Novel Photonics Technology into Clinical Applications.

The editorial introduces the JBO Special Section on Selected Topics in Biophotonics: Translating Novel Photonics Technology into Clinical Applications.

Spatially offset optical coherence tomography: Leveraging multiple scattering for high-contrast imaging at depth in turbid media.

The penetration depth of optical coherence tomography (OCT) reaches well beyond conventional microscopy; however, signal reduction with depth leads to rapid degradation of the signal below the noise level. The pursuit of imaging at depth has been largely approached by extinguishing multiple scattering. However, in OCT, multiple scattering substantially contributes to image formation at depth. Here, we investigate the role of multiple scattering in OCT image contrast and postulate that, in OCT, multiple scattering can enhance image contrast at depth. We introduce an original geometry that completely decouples the incident and collection fields by introducing a spatial offset between them, leading to preferential collection of multiply scattered light. A wave optics-based theoretical framework supports our experimentally demonstrated improvement in contrast. The effective signal attenuation can be reduced by more than 24 decibels. Notably, a ninefold enhancement in image contrast at depth is observed in scattering biological samples. This geometry enables a powerful capacity to dynamically tune for contrast at depth.

Effect of Virtual Reality on Pain Management and Opioid Use Among Hospitalized Patients After Head and Neck Surgery: A Randomized Clinical Trial.

Importance: Optimal postoperative pain management is challenging. Virtual reality (VR) provides immersive, 3-dimensional experiences that may improve pain control and reduce reliance on pharmacologic pain management. Objective: To evaluate use of VR on postoperative pain management after head and neck surgery. Design, Setting, and Participants: This prospective, pilot randomized clinical trial was conducted at Oregon Health & Science University from July 2020 to October 2021 and included patients hospitalized after major head and neck surgery. Interventions: Similar 15-minute interactive gaming experiences (Angry Birds) using an Oculus Quest VR headset (VR intervention) or a handheld smartphone device (control). Main Outcomes and Measures: The primary outcome was postintervention pain reduction. Pain scores were obtained preintervention, immediately after intervention, and then hourly for 4 hours. Secondary outcomes included changes in opioid use, measured as milligram morphine equivalents (MMEs), and patient experiences with their intervention using 5-point Likert scales. Results: Of the 30 patients randomized for inclusion, the final population included 14 patients in the VR cohort and 15 patients in the control cohort; the majority of patients were male (26 of 29 [90%]), and the mean (SD) age was 58.3 (13.8) years. After outlier removal, there were clinically meaningful reductions in postintervention pain among patients in the VR group immediately after intervention (mean difference, -1.42; 95% CI, -2.15 to -0.70; d = 1.50), at 1 hour (mean difference, -0.86; 95% CI, -1.90 to 0.14; d = 0.67), 2 hours (mean difference, -1.07; 95% CI, -2.30 to 0.14; d = 0.69), and 3 hours (mean difference, -1.36; 95% CI, -2.80 to 0.13; d = 0.71) compared with patients in the control group. Patients in the VR group also demonstrated reductions in 4-hour postintervention opioid use compared with 4-hour preintervention opioid use (mean difference, -9.10 MME; 95% CI, -15.00 to -1.27 MME; d = 0.90) and 8-hour postintervention opioid use compared with 8-hour preintervention opioid use (mean difference, -14.00 MME; 95% CI, -25.60 to -2.40 MME; d = 0.94). There were no meaningful differences in subjective patient experiences with their respective interventions. Conclusions and Relevance: In this randomized clinical trial, VR reduced pain scores and opioid use compared with a control intervention. Virtual reality may be a useful adjunct for postoperative pain management after head and neck surgery. Trial Registration: ClinicalTrials.gov Identifier: NCT04464304.

Perspectives in Biophotonics: a special issue in honor of the International Graduate Summer School on Biophotonics.

The guest editorial introduces the Journal of Biomedical Optics special collection, Perspectives in Biophotonics, https://www.spiedigitallibrary.org/biophotonics-tutorials.

Pedestal High-Contrast Gratings for Biosensing.

High-contrast gratings (HCG) are an excellent candidate for label-free detection of various kinds of biomarkers because they exhibit sharp and sensitive optical resonances. In this work, we experimentally show the performance of pedestal HCG (PHCG), which is significantly enhanced in comparison with that of conventional HCG. PCHGs were found to provide a 11.2% improvement in bulk refractive index sensitivity, from 482 nm/RIU for the conventional design to 536 nm/RIU. The observed resonance was narrower, resulting in a higher Q-factor and figure of merit. By depositing Al2O3, HfO2, and TiO2 of different thicknesses as model analyte layers, surface sensitivity values were estimated to be 10.5% better for PHCG. To evaluate the operation of the sensor in solution, avidin was employed as a model analyte. For avidin detection, the surface of the HCG was first silanized and subsequently functionalized with biotin, which is well known for its ability to bind selectively to avidin. A consistent red shift was observed with the addition of each of the functional layers, and the analysis of the spectral shift for various concentrations of avidin made it possible to calculate the limit of detection (LoD) and limit of quantification (LoQ) for the structures. PHCG showed a LoD of 2.1 ng/mL and LoQ of 85 ng/mL, significantly better than the values 3.2 ng/mL and 213 ng/mL respectively, obtained with the conventional HCG. These results demonstrate that the proposed PHCG have great potential for biosensing applications, particularly for detecting and quantifying low analyte concentrations.

Follow-Up Phone Interviews and Attendance Motivation From A Free Head and Neck Cancer Screening.

INTRODUCTION: Head and Neck Cancer Awareness and Screening Programs (HNCASP) are popular community outreach events hosted by academic and community otolaryngology departments. However, long-term follow-up of participants is lacking. PATIENTS AND METHODS: Participants of a HNCASP held at an academic cancer center prospectively filled out demographic and risk factor surveys followed by HNC screening examination. A phone interview was conducted for participants between 2012 and 2016 with suspicious findings to assess outcomes. RESULTS: Participants were largely Caucasian, female, and had health insurance, reflecting the setting at an academic medical center. Despite this, there were 156 (16.8%) positive screenings; 47 of these completed follow up interviews. Twelve (1.1% of all participants) cancer cases were confirmed. DISCUSSION: A significant proportion of HNCASP participants benefited from this screening opportunity. Education regarding HNC is the primary benefit and motivational factor for attendance of HNCASPs, although a significant subset of patients was identified that needed follow-up, and several cancers were detected.

Determinants of survival in sinonasal and skull base chondrosarcoma: An analysis of the National Cancer Database.

BACKGROUND: Chondrosarcomas are rare, malignant chondroid tumors that can occur in the sinonasal and skull base regions. Surgery is a mainstay of treatment, but complete resection can be challenging because of the close proximity of critical neurovascular structures. Because of their rarity and relatively indolent nature, optimal treatment regimens are not established. Our objective was to assess determinants of survival for sinonasal and skull base chondrosarcomas utilizing the National Cancer Database (NCDB). METHODS: The NCDB (2004-2017) was queried for cases of sinonasal and skull base chondrosarcoma. Multivariate hazard regression modeling was used to identify significant predictors of 60-month and 120-month overall survival (OS). RESULTS: Seven hundred thirty-six cases met inclusion criteria. OS for all treatment types was 84.7% [SE±0.02] at 60 months and 75.6% [SE±0.02] at 120 months. Surgery with or without adjuvant treatment was found to associate with highest OS at 60 and 120 months. For patients receiving adjuvant radiation during treatment, proton therapy had significantly better OS at 60 months (95.4% [SE±0.03] vs 82.3% [SE±0.03], -2  = 5.27; p = 0.02) and 120 months (85.1% [SE±0.08] vs 72.8% [SE±0.05], -2  = 4.11; p = 0.04) compared with conventional external beam. After adjustment for primary site, multivariate Cox regression modeling (n = 561) identified cofactors significantly associated with variation in mortality risk at 60 and 120 months, including age, Charlson-Deyo total score ≥ 3, insurance provision status, and tumor grade. CONCLUSIONS: Sinonasal and skull base chondrosarcoma are primarily treated with surgery with favorable OS. Adjuvant treatment may be required and proton radiation was associated with improved 60-month and 120-month survival compared with conventional radiation.

No Additive Clinical or Physiological Effects of Short-term Anti-inflammatory Treatment to Physical Rehabilitation in the Early Phase of Human Achilles Tendinopathy: A Randomized Controlled Trial.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used in the treatment of Achilles tendinopathy, but whether they have any additive clinical effect on physical rehabilitation in the early phase of tendinopathy remains unknown. PURPOSE/HYPOTHESIS: To investigate whether an initial short-term NSAID treatment added to a physical rehabilitation program in the early phase of Achilles tendinopathy would have an additive effect. We hypothesized that the combination of NSAID and rehabilitation would be superior to rehabilitation alone. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: A total of 69 patients with early phase Achilles tendinopathy (lasting <3 months) were randomly assigned to either a naproxen group (7 days of treatment; 500 mg twice daily; n = 34) or a placebo group (7 days of placebo treatment; n = 35). Both groups received an identical 12-week physical rehabilitation program. The clinical outcome of the study was evaluated using the Victorian Institute of Sports Assessment-Achilles (VISA-A) questionnaire and a numerical rating scale (NRS), and the physiological outcome was evaluated using ultrasonography, magnetic resonance imaging (MRI), and ultra-short time to echo T2* mapping MRI (UTE T2* MRI). Follow-up was performed at 1 week, 3 months, and 1 year. Time effects are presented as mean difference ± SEM. RESULTS: No significant differences were found between the 2 treatment groups for any of the outcome measures at any time point (P > .05). For the VISA-A score, a significant time effect was observed between baseline and 3-month follow-up (14.9 ± 2.3; P < .0001), and at 1-year follow-up, additional improvements were observed (6.1 ± 2.3; P < .01). Furthermore, the change in VISA-A score between baseline and 3-month follow-up was greater in patients with very short symptom duration (<1 month) at baseline compared with patients who had longer symptom duration (>2 months) (interaction between groups, 11.7 ± 4.2; P < .01). Despite clinical improvements, total weekly physical activity remained lower compared with preinjury levels at 3 months (-2.7 ± 0.5 h/wk; P < .0001) and 1 year (-3.0 ± 0.5 h/wk; P < .0001). At baseline, ultrasonography showed increased thickness (0.12 ± 0.03 cm; P < .0001) and vascularity (0.3 ± 0.1 cm2; P < .005) on the tendinopathic side compared with the contralateral side, but no changes over time were observed for ultrasonography, MRI, or UTE T2* MRI results. CONCLUSION: Clinical symptoms in early tendinopathy improved with physical rehabilitation, but this improvement was not augmented with the addition of NSAID treatment. Furthermore, this clinical recovery occurred in the absence of any measurable structural alterations. Finally, clinical improvements after a physical rehabilitation program were greater in patients with very short symptom duration compared with patients who had longer symptom duration. REGISTRATION: NCT03401177 (ClinicalTrials.gov identifier) and BFH-2016-019 (Danish Data Protection Agency).

MCmatlab: an open-source, user-friendly, MATLAB-integrated three-dimensional Monte Carlo light transport solver with heat diffusion and tissue damage (Erratum).

The erratum corrects an error in the originally provided equation for ΔT.

Predictors of survival outcomes in sinonasal squamous cell carcinoma: an analysis of the National Cancer Database.

BACKGROUND: Sinonasal squamous cell carcinoma (SNSCC) is a rare malignancy that poses management challenges. Although surgery and chemoradiation therapy (CRT) remain therapeutic mainstays, induction chemotherapy (IC) has emerged as a useful adjunct with locally advanced disease. This study used the National Cancer Data Base (NCDB) to examine treatment outcomes for patients diagnosed with SNSCC. METHODS: The NCDB (2004-2015) was queried for cases with SNSCC. Multivariate hazard regression modeling was used to identify significant predictors of 24-month and 60-month overall survival (OS) including treatment modality. RESULTS: A total of 3516 patients with SNSCC met inclusion criteria, including 1750 patients (49.8%) treated with surgery ± adjuvant therapy, 1352 (38.5%) treated with definitive radiotherapy (RT) or CRT, 300 (8.5%) who underwent IC followed by definitive CRT, and 114 (3.2%) who received IC followed by surgery and adjuvant therapy. Hazard modeling for confirmed treatment modality significantly associated (p < 0.001) with OS after adjustment. Patients who received surgical intervention ± adjuvant therapy had lower 24-month and 60-month mortality risk compared to definitive RT or CRT (hazard ratio [HR] ≥ 1.97; p < 0.001) or IC followed by definitive CRT (HR ≥ 1.73; p < 0.001). Compared to primary surgery ± adjuvant therapy, patients undergoing IC then surgery had similar 24-month and 60-month OS (p ≥ 0.672) after adjustment. CONCLUSION: Multimodality therapy, including surgical intervention, associates with improved OS after multifactorial adjustments. IC followed by surgery associated with improved OS compared to IC, followed by CRT and CRT alone. Study results highlight the utility of surgery toward optimizing OS in patients with SNSCC and demonstrates the potential utility of IC when primary surgical management is not preferred.

Selecting optimal spectral bands for improved detection of autofluorescent biomarkers in multiphoton microscopy.

SIGNIFICANCE: In multiphoton microscopy, two-photon excited fluorescence (TPEF) spectra carry valuable information on morphological and functional biological features. For measuring these biomarkers, separation of different parts of the fluorescence spectrum into channels is typically achieved by the use of optical band pass filters. However, spectra from different biomarkers can be unknown or overlapping, creating a crosstalk in between the channels. Previously, establishing these channels relied on prior knowledge or heuristic testing. AIM: The presented method aims to provide spectral bands with optimal separation between groups of specimens expressing different biomarkers. APPROACH: We have developed a system capable of resolving TPEF with high spectral resolution for the characterization of biomarkers. In addition, an algorithm is created to simulate and optimize optical band pass filters for fluorescence detection channels. To demonstrate the potential improvements in cell and tissue classification using these optimized channels, we recorded spectrally resolved images of cancerous (HT29) and normal epithelial colon cells (FHC), cultivated in 2D layers and in 3D to form spheroids. To provide an example of an application, we relate the results with the widely used redox ratio. RESULTS: We show that in the case of two detection channels, our system and algorithm enable the selection of optimized band pass filters without the need of knowing involved fluorophores. An improvement of 31,5% in separating different 2D cell cultures is achieved, compared to using established spectral bands that assume NAD(P)H and FAD as main contributors of autofluorescence. The compromise is a reduced SNR in the images. CONCLUSIONS: We show that the presented method has the ability to improve imaging contrast and can be used to tailor a given label-free optical imaging system using optical band pass filters targeting a specific biomarker or application.

Special Section Guest Editorial: Fluorescence Lifetime Imaging, Optical Micromechanics, and Beyond.

The editorial introduces the Journal of Biomedical Optics Special Section on Selected Topics in Biophotonics: Fluorescence Lifetime Imaging and Optical Micromechanics.

Morpho-molecular ex vivo detection and grading of non-muscle-invasive bladder cancer using forward imaging probe based multimodal optical coherence tomography and Raman spectroscopy.

Non-muscle-invasive bladder cancer affects millions of people worldwide, resulting in significant discomfort to the patient and potential death. Today, cystoscopy is the gold standard for bladder cancer assessment, using white light endoscopy to detect tumor suspected lesion areas, followed by resection of these areas and subsequent histopathological evaluation. Not only does the pathological examination take days, but due to the invasive nature, the performed biopsy can result in significant harm to the patient. Nowadays, optical modalities, such as optical coherence tomography (OCT) and Raman spectroscopy (RS), have proven to detect cancer in real time and can provide more detailed clinical information of a lesion, e.g. its penetration depth (stage) and the differentiation of the cells (grade). In this paper, we present an ex vivo study performed with a combined piezoelectric tube-based OCT-probe and fiber optic RS-probe imaging system that allows large field-of-view imaging of bladder biopsies, using both modalities and co-registered visualization, detection and grading of cancerous bladder lesions. In the present study, 119 examined biopsies were characterized, showing that fiber-optic based OCT provides a sensitivity of 78% and a specificity of 69% for the detection of non-muscle-invasive bladder cancer, while RS, on the other hand, provides a sensitivity of 81% and a specificity of 61% for the grading of low- and high-grade tissues. Moreover, the study shows that a piezoelectric tube-based OCT probe can have significant endurance, suitable for future long-lasting in vivo applications. These results also indicate that combined OCT and RS fiber probe-based characterization offers an exciting possibility for label-free and morpho-chemical optical biopsies for bladder cancer diagnostics.

Optical Radiomic Signatures Derived from Optical Coherence Tomography Images Improve Identification of Melanoma.

The current gold standard for clinical diagnosis of melanoma is excisional biopsy and histopathologic analysis. Approximately 15-30 benign lesions are biopsied to diagnose each melanoma. In addition, biopsies are invasive and result in pain, anxiety, scarring, and disfigurement of patients, which can add additional burden to the health care system. Among several imaging techniques developed to enhance melanoma diagnosis, optical coherence tomography (OCT), with its high-resolution and intermediate penetration depth, can potentially provide required diagnostic information noninvasively. Here, we present an image analysis algorithm, "optical properties extraction (OPE)," which improves the specificity and sensitivity of OCT by identifying unique optical radiomic signatures pertinent to melanoma detection. We evaluated the performance of the algorithm using several tissue-mimicking phantoms and then tested the OPE algorithm on 69 human subjects. Our data show that benign nevi and melanoma can be differentiated with 97% sensitivity and 98% specificity. These findings suggest that the adoption of OPE algorithm in the clinic can lead to improvements in melanoma diagnosis and patient experience. SIGNIFICANCE: This study describes a noninvasive, safe, simple-to-implement, and accurate method for the detection and differentiation of malignant melanoma versus benign nevi.

MCmatlab: an open-source, user-friendly, MATLAB-integrated three-dimensional Monte Carlo light transport solver with heat diffusion and tissue damage.

While there exist many Monte Carlo (MC) programs for solving the radiative transfer equation (RTE) in biological tissues, we have identified a need for an open-source MC program that is sufficiently user-friendly for use in an education environment, in which detailed knowledge of compiling or UNIX command-line cannot be assumed. Therefore, we introduce MCmatlab, an open-source codebase thus far consisting of (a) a fast three-dimensional MC RTE solver and (b) a finite-element heat diffusion and Arrhenius-based thermal tissue damage simulator, both run in MATLAB. The kernel for both of these solvers is written in parallelized C and implemented as MATLAB MEX functions, combining the speed of C with the familiarity and versatility of MATLAB. We compare the RTE solver to Steven Jacques' mcxyz, which it is inspired by, and present example results generated by the thermal model. MCmatlab is easy to install and use and can be used by students and experienced researchers alike for simulating tissue light propagation and, optionally, thermal damage.