Meta-analysis Comparing Fluorescence Imaging with Radioisotope and Blue Dye-Guided Sentinel Node Identification for Breast Cancer Surgery.

INTRODUCTION: Conventional methods for axillary sentinel lymph node biopsy (SLNB) are fraught with complications such as allergic reactions, skin tattooing, radiation, and limitations on infrastructure. A novel technique has been developed for lymphatic mapping utilizing fluorescence imaging. This meta-analysis aims to compare the gold standard blue dye and radioisotope (BD-RI) technique with fluorescence-guided SLNB using indocyanine green (ICG). METHODS: This study was registered with PROSPERO (CRD42019129224). The MEDLINE, EMBASE, Scopus, and Web of Science databases were searched using the Medical Subject Heading (MESH) terms 'Surgery' AND 'Lymph node' AND 'Near infrared fluorescence' AND 'Indocyanine green'. Studies containing raw data on the sentinel node identification rate in breast cancer surgery were included. A heterogeneity test (using Cochran's Q) determined the use of fixed- or random-effects models for pooled odds ratios (OR). RESULTS: Overall, 1748 studies were screened, of which 10 met the inclusion criteria for meta-analysis. ICG was equivalent to radioisotope (RI) at sentinel node identification (OR 2.58, 95% confidence interval [CI] 0.35-19.08, p < 0.05) but superior to blue dye (BD) (OR 9.07, 95% CI 6.73-12.23, p < 0.05). Furthermore, ICG was superior to the gold standard BD-RI technique (OR 4.22, 95% CI 2.17-8.20, p < 0.001). CONCLUSION: Fluorescence imaging for axillary sentinel node identification with ICG is equivalent to the single technique using RI, and superior to the dual technique (RI-BD) and single technique with BD. Hospitals using RI and/or BD could consider changing their practice to ICG given the comparable efficacy and improved safety profile, as well as the lesser burden on hospital infrastructure.

The Impact of Temporal Variation in Indocyanine Green Administration on Tumor Identification During Fluorescence Guided Breast Surgery.

BACKGROUND: On average, 21% of women in the USA treated with Breast Conserving Surgery (BCS) undergo a second operation because of close positive margins. Tumor identification with fluorescence imaging could improve positive margin rates through demarcating location, size, and invasiveness of tumors. We investigated the technique's diagnostic accuracy in detecting tumors during BCS using intravenous indocyanine green (ICG) and a custom-built fluorescence camera system. METHODS: In this single-center prospective clinical study, 40 recruited BCS patients were sub-categorized into two cohorts. In the first 'enhanced permeability and retention' (EPR) cohort, 0.25 mg/kg ICG was injected ~ 25 min prior to tumor excision, and in the second 'angiography' cohort, ~ 5 min prior to tumor excision. Subsequently, an in-house imaging system was used to image the tumor in situ prior to resection, ex vivo following resection, the resection bed, and during grossing in the histopathology laboratory to compare the technique's diagnostic accuracy between the cohorts. RESULTS: The two cohorts were matched in patient and tumor characteristics. The majority of patients had invasive ductal carcinoma with concomitant ductal carcinoma in situ. Tumor-to-background ratio (TBR) in the angiography cohort was superior to the EPR cohort (TBR = 3.18 ± 1.74 vs 2.10 ± 0.92 respectively, p = 0.023). Tumor detection reached sensitivity and specificity scores of 0.82 and 0.93 for the angiography cohort and 0.66 and 0.90 for the EPR cohort, respectively (p = 0.1051 and p = 0.9099). DISCUSSION: ICG administration timing during the angiography phase compared with the EPR phase improved TBR and diagnostic accuracy. Future work will focus on image pattern analysis and adaptation of the camera system to targeting fluorophores specific to breast cancer.

Establishing key research questions for the implementation of artificial intelligence in colonoscopy: a modified Delphi method.

BACKGROUND : Artificial intelligence (AI) research in colonoscopy is progressing rapidly but widespread clinical implementation is not yet a reality. We aimed to identify the top implementation research priorities. METHODS : An established modified Delphi approach for research priority setting was used. Fifteen international experts, including endoscopists and translational computer scientists/engineers, from nine countries participated in an online survey over 9 months. Questions related to AI implementation in colonoscopy were generated as a long-list in the first round, and then scored in two subsequent rounds to identify the top 10 research questions. RESULTS : The top 10 ranked questions were categorized into five themes. Theme 1: clinical trial design/end points (4 questions), related to optimum trial designs for polyp detection and characterization, determining the optimal end points for evaluation of AI, and demonstrating impact on interval cancer rates. Theme 2: technological developments (3 questions), including improving detection of more challenging and advanced lesions, reduction of false-positive rates, and minimizing latency. Theme 3: clinical adoption/integration (1 question), concerning the effective combination of detection and characterization into one workflow. Theme 4: data access/annotation (1 question), concerning more efficient or automated data annotation methods to reduce the burden on human experts. Theme 5: regulatory approval (1 question), related to making regulatory approval processes more efficient. CONCLUSIONS : This is the first reported international research priority setting exercise for AI in colonoscopy. The study findings should be used as a framework to guide future research with key stakeholders to accelerate the clinical implementation of AI in endoscopy.

Eigenvalue calibration method for 3 × 3 Mueller polarimeters.

3×3 Mueller polarimetry has shown potential for tissue characterization applications, however, calibration has not been fully addressed. We demonstrate a 3×3 Mueller polarimeter eigenvalue calibration method, inspired by those for full Mueller polarimeters. We also investigate the optimal combination of calibration measurements. Our method does not rely on modeling the polarization state generator, polarization state analyzer, or precise knowledge of calibration sample properties or orientations. It is therefore easy to implement, and the experimental results of a linear polarizer test sample, as well as a biological specimen, are presented.

Polyfunctionalised Nanoparticles Bearing Robust Gadolinium Surface Units for High Relaxivity Performance in MRI.

The first example of an octadentate gadolinium unit based on DO3A (hydration number q=1) with a dithiocarbamate tether has been designed and attached to the surface of gold nanoparticles (around 4.4 nm in diameter). In addition to the superior robustness of this attachment, the restricted rotation of the Gd complex on the nanoparticle surface leads to a dramatic increase in relaxivity (r1 ) from 4.0 mm-1 s-1 in unbound form to 34.3 mm-1 s-1 (at 10 MHz, 37 °C) and 22±2 mm-1 s-1 (at 63.87 MHz, 25 °C) when immobilised on the surface. The one-pot synthetic route provides a straightforward and versatile way of preparing a range of multifunctional gold nanoparticles. The incorporation of additional surface units for biocompatibility (PEG and thioglucose units) and targeting (folic acid) leads to little detrimental effect on the high relaxivity observed for these non-toxic multifunctional materials. In addition to the passive targeting attributed to gold nanoparticles, the inclusion of a unit capable of targeting the folate receptors overexpressed by cancer cells, such as HeLa cells, illustrates the potential of these assemblies.

Characterization of an imaging multimode optical fiber using a digital micro-mirror device based single-beam system.

This work demonstrates experimental approaches to characterize a single multimode fiber imaging system without a reference beam. Spatial light modulation is performed with a digital micro-mirror device that enables high-speed binary amplitude modulation. Intensity-only images are recorded by the camera and processed by a Bayesian inference based algorithm to retrieve the phase of the output optical field as well as the transmission matrix of the fiber. The calculated transmission matrix is validated by three standards: prediction accuracy, transmission imaging, and focus generation. Also, it is found that information on mode count and eigenchannels can be extracted from the transmission matrix by singular value decomposition. This paves the way for a more compact and cheaper single multimode fiber imaging system for many demanding imaging tasks.

Bayes' theorem-based binary algorithm for fast reference-less calibration of a multimode fiber.

In this paper, we present a Bayes' theorem-based high-speed algorithm, to measure the binary transmission matrix of a multimode fiber using a digital micromirror device, in a reference-less multimode fiber imaging system. Based on conditional probability, we define a preset threshold to locate those digital-micromirror-device pixels that can be switched 'ON' to form a focused spot at the output. This leads to a binary transmission matrix consisting of '0' and '1' elements. High-enhancement-factor light focusing and raster-scanning at the distal end of the fiber are demonstrated experimentally. The key advantage of our algorithm is its capability for fast calibration of a MMF to form a tightly focused spot. In our experiment, for 5000 input-output pairs, we only need 0.26 s to calibrate one row of the transmission matrix to achieve a focused spot with an enhancement factor of 28. This is more than 10 times faster than the prVBEM algorithm. The proposed Bayes' theorem-based binary algorithm can be applied not only in multimode optical fiber focusing but also to other disordered media. Particularly, it will be valuable in fast multimode fiber calibration for endoscopic imaging.

Extended polar decomposition method of Mueller matrices for turbid media in reflection geometry.

The polar decomposition method for Mueller matrices proposed by Lu-Chipman has been demonstrated and validated for many applications. However, in some situations, e.g., when analyzing the Mueller matrix of birefringent turbid media with Mie-sized scatterers acquired in reflection geometry, the method may suffer from limitations due to the assumptions required by this method. Here we extend the Lu-Chipman method and show that it can provide more reasonable results for these situations. The method has been validated experimentally with turbid phantoms. Thus, this Letter may prove useful in tissue polarimetry.

Clinical Correlation between Real-Time Endocytoscopy, Confocal Endomicroscopy, and Histopathology in the Central Airways.

BACKGROUND: Lung cancer is one of the commonest malignancies with a worldwide incidence of 1.6 million cases each year. Although the main aetiological factor has been identified (cigarette smoking), the progression of lung cancer from early changes such as dysplasia through to cancer is still not fully understood. Furthermore, current research techniques are reliant on obtaining tissue biopsies, a process that alters the natural history of the very process under investigation. Hence, there is a need for developing optical biopsy techniques. OBJECTIVES: To prospectively evaluate the feasibility of endocytoscopy and confocal endomicroscopy in the detection of malignant and pre-malignant changes in the airways. METHODS: Findings with endocytoscopy and endomicroscopy were compared with conventional biopsies obtained from the same areas in 25 patients undergoing bronchoscopy for evaluation of endobronchial abnormalities and in 5 healthy control subjects. RESULTS: Endocytoscopy was technically more difficult, and interpretable images were only obtained in 21 of the patients evaluated, and hence, complete information including histopathological information was available in 21 patients. Endocytoscopy appeared to correlate with the histopathological findings on tissue biopsy, and was able to distinguish normal epithelium from dysplasia and carcinoma. Confocal endomicroscopy was a more reliable technique with adequate visual information obtained in all patients examined but was unable to distinguish between dysplasia and carcinoma. CONCLUSION: This feasibility study suggests that endocytoscopy may have the potential to fulfil the role of optical biopsy in the evaluation of the pathogenesis of lung cancer.

The role of technology in minimally invasive surgery: state of the art, recent developments and future directions.

The diffusion of minimally invasive surgery has thrived in recent years, providing substantial benefits over traditional techniques for a number of surgical interventions. This rapid growth has been possible due to significant advancements in medical technology, which partly solved some of the technical and clinical challenges associated with minimally invasive techniques. The issues that still limit its widespread adoption for some applications include the limited field of view; reduced manoeuvrability of the tools; lack of haptic feedback; loss of depth perception; extended learning curve; prolonged operative times and higher financial costs. The present review discusses some of the main recent technological advancements that fuelled the uptake of minimally invasive surgery, focussing especially on the areas of imaging, instrumentation, cameras and robotics. The current limitations of state-of-the-art technology are identified and addressed, proposing future research directions necessary to overcome them.

Application of gold nanoparticles for gastrointestinal cancer theranostics: A systematic review.

Gold nanoparticles (GNPs) are readily synthesised structures that absorb light strongly to generate thermal energy which induces photothermal destruction of malignant tissue. This review examines the efficacy, potential challenges and toxicity from in vitro and in vivo applications of GNPs in oesophageal, gastric and colon cancers. A systematic literature search of Medline, Embase, Web of Science and Cochrane databases was performed using PRISMA guidelines. Two hundred and eighty-four papers were reviewed with sixteen studies meeting the inclusion criteria. The application of GNPs in eleven in vivo rodent studies with GI adenocarcinoma demonstrated excellent therapeutic outcomes but poor corroboration in terms of the cancer cells used, photothermal irradiation regimes, fluorophores and types of nanoparticles. There is compelling evidence of the translational potential of GNPs to be complimentary to surgery and feasible in the photothermal therapy of GI cancer but reproducibility and standardisation require development prior to GI cancer clinical trials. FROM THE CLINICAL EDITOR: Gold nanoparticles are one of the most potentially useful nanoparticles. This is especially true in cancer therapeutics because of their photothermal properties. In this comprehensive article, the authors reviewed the application and efficacy of gold nanoparticles in both the diagnosis and treatment of GI cancers. This review should provide a stimulus for researchers to further develop and translate these nanoparticles into future clinical trials.

Tracking shear waves in turbid medium by light: theory, simulation, and experiment.

Shear wave propagation provides rich information for material mechanical characterization, including elasticity and viscosity. This Letter reports tracking of shear wave propagation in turbid media by laser-speckle-contrast analysis. The theory is described, and a Monte Carlo simulation of light shear wave interaction was developed. Simulation and experiments on tissue-mimicking phantoms agree well and show tracking of shear wave at the phantom surface and at depth as well as multiple shear waves interacting within the object. The relationship between speckle contrast value and shear wave amplitude is also investigated.

Computational Polarization Imaging In Vivo through Surgical Smoke Using Refined Polarization Difference.

In surgery, the surgical smoke generated during tissue dissection and hemostasis can degrade the image quality, affecting tissue visibility and interfering with the further image processing. Developing reliable and interpretable computational imaging methods for restoring smoke-affected surgical images is crucial, as typical image restoration methods relying on color-texture information are insufficient. Here a computational polarization imaging method through surgical smoke is demonstrated, including a refined polarization difference estimation based on the discrete electric field direction, and a corresponding prior-based estimation method, for better parameter estimation and image restoration performance. Results and analyses for ex vivo, the first in vivo animal experiments, and human oral cavity tests show that the proposed method achieves visibility restoration and color recovery of higher quality, and exhibits good generalization across diverse imaging scenarios with interpretability. The method is expected to enhance the precision, safety, and efficiency of advanced image-guided and robotic surgery.

A YOLOv5-based network for the detection of a diffuse reflectance spectroscopy probe to aid surgical guidance in gastrointestinal cancer surgery.

PURPOSE: A positive circumferential resection margin (CRM) for oesophageal and gastric carcinoma is associated with local recurrence and poorer long-term survival. Diffuse reflectance spectroscopy (DRS) is a non-invasive technology able to distinguish tissue type based on spectral data. The aim of this study was to develop a deep learning-based method for DRS probe detection and tracking to aid classification of tumour and non-tumour gastrointestinal (GI) tissue in real time. METHODS: Data collected from both ex vivo human tissue specimen and sold tissue phantoms were used for the training and retrospective validation of the developed neural network framework. Specifically, a neural network based on the You Only Look Once (YOLO) v5 network was developed to accurately detect and track the tip of the DRS probe on video data acquired during an ex vivo clinical study. RESULTS: Different metrics were used to analyse the performance of the proposed probe detection and tracking framework, such as precision, recall, mAP 0.5, and Euclidean distance. Overall, the developed framework achieved a 93% precision at 23 FPS for probe detection, while the average Euclidean distance error was 4.90 pixels. CONCLUSION: The use of a deep learning approach for markerless DRS probe detection and tracking system could pave the way for real-time classification of GI tissue to aid margin assessment in cancer resection surgery and has potential to be applied in routine surgical practice.

Real-time classification of tumour and non-tumour tissue in colorectal cancer using diffuse reflectance spectroscopy and neural networks to aid margin assessment.

BACKGROUND: Colorectal cancer is the third most commonly diagnosed malignancy and the second leading cause of mortality worldwide. A positive resection margin following surgery for colorectal cancer is linked with higher rates of local recurrence and poorer survival. The authors investigated diffuse reflectance spectroscopy (DRS) to distinguish tumour and non-tumour tissue in ex-vivo colorectal specimens, to aid margin assessment and provide augmented visual maps to the surgeon in real-time. METHODS: Patients undergoing elective colorectal cancer resection surgery at a London-based hospital were prospectively recruited. A hand-held DRS probe was used on the surface of freshly resected ex-vivo colorectal tissue. Spectral data were acquired for tumour and non-tumour tissue. Binary classification was achieved using conventional machine learning classifiers and a convolutional neural network (CNN), which were evaluated in terms of sensitivity, specificity, accuracy and the area under the curve. RESULTS: A total of 7692 mean spectra were obtained for tumour and non-tumour colorectal tissue. The CNN-based classifier was the best performing machine learning algorithm, when compared to contrastive approaches, for differentiating tumour and non-tumour colorectal tissue, with an overall diagnostic accuracy of 90.8% and area under the curve of 96.8%. Live on-screen classification of tissue type was achieved using a graduated colourmap. CONCLUSION: A high diagnostic accuracy for a DRS probe and tracking system to differentiate ex-vivo tumour and non-tumour colorectal tissue in real-time with on-screen visual feedback was highlighted by this study. Further in-vivo studies are needed to ensure integration into a surgical workflow.

Fluorescence guided surgery imaging systems for breast cancer identification: a systematic review.

Significance: Breast-conserving surgery (BCS) is limited by high rates of positive margins and re-operative interventions. Fluorescence-guided surgery seeks to detect the entire lesion in real time, thus guiding the surgeons to remove all the tumor at the index procedure. Aim: Our aim was to identify the optimal combination of a camera system and fluorophore for fluorescence-guided BCS. Approach: A systematic review of medical databases using the terms "fluorescence," "breast cancer," "surgery," and "fluorescence imaging" was performed. Cameras were compared using the ratio between the fluorescent signal from the tumor compared to background fluorescence, as well as diagnostic accuracy measures, such as sensitivity, specificity, and positive predictive value. Results: Twenty-one studies identified 14 camera systems using nine different fluorophores. Twelve cameras worked in the infrared spectrum. Ten studies reported on the difference in strength of the fluorescence signal between cancer and normal tissue, with results ranging from 1.72 to 4.7. In addition, nine studies reported on whether any tumor remained in the resection cavity (5.4% to 32.5%). To date, only three studies used the fluorescent signal for guidance during real BCS. Diagnostic accuracy ranged from 63% to 98% sensitivity, 32% to 97% specificity, and 75% to 100% positive predictive value. Conclusion: In this systematic review, all the studies reported a clinically significant difference in signal between the tumor and normal tissue using various camera/fluorophore combinations. However, given the heterogeneity in protocols, including camera setup, fluorophore studied, data acquisition, and reporting structure, it was impossible to determine the optimal camera and fluorophore combination for use in BCS. It would be beneficial to develop a standardized reporting structure using similar metrics to provide necessary data for a comparison between camera systems.

Monoclonal Antibodies for Targeted Fluorescence-Guided Surgery: A Review of Applicability across Multiple Solid Tumors.

This study aims to review the status of the clinical use of monoclonal antibodies (mAbs) that have completed or are in ongoing clinical trials for targeted fluorescence-guided surgery (T-FGS) for the intraoperative identification of the tumor margins of extra-hematological solid tumors. For each of them, the targeted antigen, the mAb generic/commercial name and format, and clinical indications are presented, together with utility, doses, and the timing of administration. Based on the current scientific evidence in humans, the top three mAbs that could be prepared in a GMP-compliant bank ready to be delivered for surgical purposes are proposed to speed up the translation to the operating room and produce a few readily available "off-the-shelf" injectable fluorescent probes for safer and more effective solid tumor resection.