Clinical and computational development of a patient-calibrated ICGFA bowel transection recommender.

INTRODUCTION: Intraoperative indocyanine green fluorescence angiography (ICGFA) aims to reduce colorectal anastomotic complications. However, signal interpretation is inconsistent and confounded by patient physiology and system behaviours. Here, we demonstrate a proof of concept of a novel clinical and computational method for patient calibrated quantitative ICGFA (QICGFA) bowel transection recommendation. METHODS: Patients undergoing elective colorectal resection had colonic ICGFA both immediately after operative commencement prior to any dissection and again, as usual, just before anastomotic construction. Video recordings of both ICGFA acquisitions were blindly quantified post hoc across selected colonic regions of interest (ROIs) using tracking-quantification software and computationally compared with satisfactory perfusion assumed in second time-point ROIs, demonstrating 85% agreement with baseline ICGFA. ROI quantification outputs detailing projected perfusion sufficiency-insufficiency zones were compared to the actual surgeon-selected transection/anastomotic construction site for left/right-sided resections, respectively. Anastomotic outcomes were recorded, and tissue lactate was also measured in the devascularised colonic segment in a subgroup of patients. The novel perfusion zone projections were developed as full-screen recommendations via overlay heatmaps. RESULTS: No patient suffered intra- or early postoperative anastomotic complications. Following computational development (n = 14) the software recommended zone (ROI) contained the expert surgical site of transection in almost all cases (Jaccard similarity index 0.91) of the nine patient validation series. Previously published ICGFA time-series milestone descriptors correlated moderately well, but lactate measurements did not. High resolution augmented reality heatmaps presenting recommendations from all pixels of the bowel ICGFA were generated for all cases. CONCLUSIONS: By benchmarking to the patient's own baseline perfusion, this novel QICGFA method could allow the deployment of algorithmic personalised NIR bowel transection point recommendation in a way fitting existing clinical workflow.

Geotemporal Fluorophore Biodistribution Mapping of Colorectal Cancer: Micro and Macroscopic Insights.

Fluorescence-guided oncology promises to improve both the detection and treatment of malignancy. We sought to investigate the temporal distribution of indocyanine green (ICG), an exogenous fluorophore in human colorectal cancer. This analysis aims to enhance our understanding of ICG's effectiveness in current tumour detection and inform potential future diagnostic and therapeutic enhancements. METHODS: Fifty consenting patients undergoing treatment for suspected/confirmed colorectal neoplasia provided near infrared (NIR) video and imagery of transanally recorded and ex vivo resected rectal lesions following intravenous ICG administration (0.25 mg/kg), with a subgroup providing tissue samples for microscopic (including near infrared) analysis. Computer vision techniques detailed macroscopic 'early' (<15 min post ICG administration) and 'late' (>2 h) tissue fluorescence appearances from surgical imagery with digital NIR scanning (Licor, Lincoln, NE, USA) and from microscopic analysis (Nikon, Tokyo, Japan) undertaken by a consultant pathologist detailing tissue-level fluorescence distribution over the same time. RESULTS: Significant intra-tumoural fluorescence heterogeneity was seen 'early' in malignant versus benign lesions. In all 'early' samples, fluorescence was predominantly within the tissue stroma, with uptake within plasma cells, blood vessels and lymphatics, but not within malignant or healthy glands. At 'late' stage observation, fluorescence was visualised non-uniformly within the intracellular cytoplasm of malignant tissue but not retained in benign glands. Fluorescence also accumulated within any present peritumoural inflammatory tissue. CONCLUSION: This study demonstrates the time course diffusion patterns of ICG through both benign and malignant tumours in vivo in human patients at both macroscopic and microscopic levels, demonstrating important cellular drivers and features of geolocalisation and how they differ longitudinally after exposure to ICG.

Impact of standardising indocyanine green fluorescence angiography technique for visual and quantitative interpretation on interuser variability in colorectal surgery.

AIM/BACKGROUND: Intra-operative colonic perfusion assessment via indocyanine green fluorescence angiography (ICGFA) aims to address malperfusion-related anastomotic complications; however, its interpretation suffers interuser variability (IUV), especially early in ICGFA experience. This work assesses the impact of a protocol developed for both operator-based judgement and computational development on interpretation consistency, focusing on senior surgeons yet to start using ICGFA. METHODS: Experienced and junior gastrointestinal surgeons were invited to complete an ICGFA-experience questionnaire. They subsequently interpreted nine operative ICGFA videos regarding perfusion sufficiency of a surgically prepared distal colon during laparoscopic anterior resection by indicating their preferred site of proximal transection using an online annotation platform (mindstamp.com). Six ICGFA videos had been prepared with a clinical standardisation protocol controlling camera and patient positioning of which three each had monochrome near infrared (NIR) and overlay display. Three others were non-standardised controls with synchronous NIR and overlay picture-in-picture display. Differences in transection level between different cohorts were assessed for intraclass correlation coefficient (ICC) via ImageJ and IBM SPSS. RESULTS: 58 clinicians (12 ICGFA experts, 46 ICGFA inexperienced of whom 23 were either finished or within one year of finishing training and 23 were junior trainees) participated as per power calculations. 63% felt that ICGFA should be routinely deployed with 57% believing interpretative competence requires 11-50 cases. Transection level concordance was generally good (ICC = 0.869) across all videos and levels of expertise (0.833-0.915). However, poor agreement was evident with the standardised protocol videos for overlay presentation (0.208-0.345). Similarly, poor agreement was seen for the monochrome display (0.392-0.517), except for those who were trained but ICG inexperienced (0.877) although even here agreement was less than with unstandardised videos (0.943). CONCLUSION: Colorectal ICGFA acquisition and display standardisation impacts IUV with this specific protocol tending to diminish surgeon interpretation consistency. ICGFA video recording for computational development may require dedicated protocols.

Evaluating clinical near-infrared surgical camera systems with a view to optimizing operator and computational signal analysis.

Significance: As clinical evidence on the colorectal application of indocyanine green (ICG) perfusion angiography accrues, there is also interest in computerizing decision support. However, user interpretation and software development may be impacted by system factors affecting the displayed near-infrared (NIR) signal. Aim: We aim to assess the impact of camera positioning on the displayed NIR signal across different open and laparoscopic camera systems. Approach: The effects of distance, movement, and target location (center versus periphery) on the displayed fluorescence signal of different systems were measured under electromagnetic stereotactic guidance from an ICG-albumin model and in vivo during surgery. Results: Systems displayed distinct fluorescence performances with variance apparent with scope optical lens configuration (0 deg versus 30 deg), movement, target positioning, and distance. Laparoscopic system readings fitted inverse square function distance-intensity curves with one device and demonstrated a direction dependent sigmoid curve. Laparoscopic cameras presented central targets as brighter than peripheral ones, and laparoscopes with angled optical lens configurations had a diminished field of view. One handheld open system also showed a distance-intensity relationship, whereas the other maintained a consistent signal despite distance, but both presented peripheral targets brighter than central ones. Conclusions: Optimal clinical use and signal computational development requires detailed appreciation of system behaviors.

Real-time administration of indocyanine green in combination with computer vision and artificial intelligence for the identification and delineation of colorectal liver metastases.

Introduction: Fluorescence guided surgery for the identification of colorectal liver metastases (CRLM) can be better with low specificity and antecedent dosing impracticalities limiting indocyanine green (ICG) usefulness currently. We investigated the application of artificial intelligence methods (AIM) to demonstrate and characterise CLRMs based on dynamic signalling immediately following intraoperative ICG administration. Methods: Twenty-five patients with liver surface lesions (24 CRLM and 1 benign cyst) undergoing open/laparoscopic/robotic procedures were studied. ICG (0.05 mg/kg) was administered with near-infrared recording of fluorescence perfusion. User-selected region-of-interest (ROI) perfusion profiles were generated, milestones relating to ICG inflow/outflow extracted and used to train a machine learning (ML) classifier. 2D heatmaps were constructed in a subset using AIM to depict whole screen imaging based on dynamic tissue-ICG interaction. Fluorescence appearances were also assessed microscopically (using H&E and fresh-frozen preparations) to provide tissue-level explainability of such methods. Results: The ML algorithm correctly classified 97.2 % of CRLM ROIs (n = 132) and all benign lesion ROIs (n = 6) within 90-s of ICG administration following initial mathematical curve analysis identifying ICG inflow/outflow differentials between healthy liver and CRLMs. Time-fluorescence plots extracted for each pixel in 10 lesions enabled creation of 2D characterising heatmaps using flow parameters and through unsupervised ML. Microscopy confirmed statistically less CLRM fluorescence vs adjacent liver (mean ± std deviation signal/area 2.46 ± 9.56 vs 507.43 ± 160.82 respectively p < 0.001) with H&E diminishing ICG signal (n = 4). Conclusion: ML accurately identifies CRLMs from surrounding liver tissue enabling representative 2D mapping of such lesions from their fluorescence perfusion patterns using AIM. This may assist in reducing positive margin rates at metastatectomy and in identifying unexpected/occult malignancies.

Clinical application of machine learning and computer vision to indocyanine green quantification for dynamic intraoperative tissue characterisation: how to do it.

INTRODUCTION: Indocyanine green (ICG) quantification and assessment by machine learning (ML) could discriminate tissue types through perfusion characterisation, including delineation of malignancy. Here, we detail the important challenges overcome before effective clinical validation of such capability in a prospective patient series of quantitative fluorescence angiograms regarding primary and secondary colorectal neoplasia. METHODS: ICG perfusion videos from 50 patients (37 with benign (13) and malignant (24) rectal tumours and 13 with colorectal liver metastases) of between 2- and 15-min duration following intravenously administered ICG were formally studied (clinicaltrials.gov: NCT04220242). Video quality with respect to interpretative ML reliability was studied observing practical, technical and technological aspects of fluorescence signal acquisition. Investigated parameters included ICG dosing and administration, distance-intensity fluorescent signal variation, tissue and camera movement (including real-time camera tracking) as well as sampling issues with user-selected digital tissue biopsy. Attenuating strategies for the identified problems were developed, applied and evaluated. ML methods to classify extracted data, including datasets with interrupted time-series lengths with inference simulated data were also evaluated. RESULTS: Definable, remediable challenges arose across both rectal and liver cohorts. Varying ICG dose by tissue type was identified as an important feature of real-time fluorescence quantification. Multi-region sampling within a lesion mitigated representation issues whilst distance-intensity relationships, as well as movement-instability issues, were demonstrated and ameliorated with post-processing techniques including normalisation and smoothing of extracted time-fluorescence curves. ML methods (automated feature extraction and classification) enabled ML algorithms glean excellent pathological categorisation results (AUC-ROC > 0.9, 37 rectal lesions) with imputation proving a robust method of compensation for interrupted time-series data with duration discrepancies. CONCLUSION: Purposeful clinical and data-processing protocols enable powerful pathological characterisation with existing clinical systems. Video analysis as shown can inform iterative and definitive clinical validation studies on how to close the translation gap between research applications and real-world, real-time clinical utility.

Deconstructing mastery in colorectal fluorescence angiography interpretation.

INTRODUCTION: Indocyanine green fluorescence angiography (ICGFA) is commonly used in colorectal anastomotic practice with limited pre-training. Recent work has shown that there is considerable inconsistency in signal interpretation between surgeons with minimal or no experience versus those consciously invested in mastery of the technique. Here, we deconstruct the fluorescence signal patterns of expert-annotated surgical ICGFA videos to understand better their correlation and combine this with structured interviews to ascertain whether such interpretative capability is conscious or unconscious. METHODS: For fluorescence signal analysis, expert-annotated ICGFA videos (n = 24) were quantitatively interrogated using a boutique intensity tracker (IBM Research) to generate signal time plots. Such fluorescence intensity data were examined for inter-observer correlation (Intraclass Correlation Coefficients, ICC) at specific curve milestones: the maximum fluorescence signal (Fmax), the times to both achieve this maximum (Tmax), as well as half this maximum (T1/2max) and the ratio between these (T1/2/Tmax). Formal tele-interview with contributing experts (n = 6) was conducted with the narrative transcripts being thematically mapped, plotted, and qualitatively analyzed. RESULTS: Correlation by mathematical measures was excellent (ICC0.9-1.0) for Fmax, Tmax, and T1/2max (0.95, 0.938, and 0.925, respectively) and moderate (0.5-0.75) for T1/2/Tmax (0.729). While all experts narrated a deliberate viewing strategy, their specific dynamic signal appreciation differed in the manner of description. CONCLUSION: Expert ICGFA users demonstrate high correlation in mathematical measures of their signal interpretation although do so tacitly. Computational quantification of expert behavior can help develop the necessary lexicon and training sets as well as computer vision methodology to better exploit ICGFA technology.

Evaluation of inter-user variability in indocyanine green fluorescence angiography to assess gastric conduit perfusion in esophageal cancer surgery.

Indocyanine Green Fluorescence Angiography (ICGFA) has been deployed to tackle malperfusion-related anastomotic complications. This study assesses variations in operator interpretation of pre-anastomotic ICGFA inflow in the gastric conduit. Utilizing an innovative online interactive multimedia platform (Mindstamp), esophageal surgeons completed a baseline opinion-practice questionnaire and proceeded to interpret, and then digitally assign, a distal transection point on 8 ICGFA videos of esophageal resections (6 Ivor Lewis, 2 McKeown). Annotations regarding gastric conduit transection by ICGFA were compared between expert users versus non-expert participants using ImageJ to delineate longitudinal distances with Shapiro Wilk and t-tests to ascertain significance. Expert versus non-expert correlation was assessed via Intraclass Correlation Coefficients (ICC). Thirty participants (13 consultants, 6 ICGFA experts) completed the study in all aspects. Of these, a high majority (29 participants) stated ICGFA should be used routinely with most (21, including 5/6 experts) stating that 11-50 cases were needed for competency in interpretation. Among users, there were wide variations in dosing (0.05-3 mg/kg) and practice impact. Agreement regarding ICGFA video interpretation concerning transection level among experts was 'moderate' (ICC = 0.717) overall but 'good' (ICC = 0.871) among seven videos with Leave One Out (LOO) exclusion of the video with highest disagreement. Agreement among non-experts was moderate (ICC = 0.641) overall and in every subgroup including among consultants (ICC = 0.626). Experts choose levels that preserved more gastric conduit length versus non-experts in all but one video (P = 0.02). Considerable variability exists with ICGFA interpretation and indeed impact. Even adept users may be challenged in specific cases. Standardized training and/or computerized quantitative fluorescence may help better usage.

Sigmoid volvulus: definitive surgery is safe and should be considered in all instances.

BACKGROUND: Acute sigmoid volvulus (ASV) represents a small but significant portion of cases of large bowel obstruction, especially in the elderly and co-morbid. Given the characteristics of the patient cohort most commonly affected, a non-operative/conservative approach is often undertaken but is associated with a high rate of recurrence. OBJECTIVE: We sought to evaluate outcomes for those patients who underwent non-operative management, emergency surgery or staged, semi-elective surgery following decompression for ASV at our institution. METHODS: Hospital in-patient enquiry (HIPE) data were used to identify all patients who presented with sigmoid volvulus between January 2005 and June 2020 inclusive. Patient notes were interrogated, including surgical and endoscopic procedures performed. Patient demographics and co-morbidities were recorded. RESULTS: Thirty-nine patients were treated over a 15-year period with a mean age of 73 years at first presentation (range 36-93). Twenty-two patients (56%) had just a single admission for ASV with three deaths in this group. Seventeen patients (44%) had more than one admission with volvulus due to recurrence after a decompression-only strategy on the index admission. Of these, three succumbed to complications of their subsequent episodes of volvulus. Twenty-five patients underwent surgical intervention (fifteen on, or shortly following, their first admission and ten following at least two admissions for ASV). The overall mortality in the operative group was 2/25 (8%) with both deaths in those undergoing emergency surgeries. Five patients were treated successfully with endoscopic measures alone and had required no further interventions at the time of compiling data. CONCLUSION: There is a high recurrence rate following non-operative management of acute sigmoid volvulus and consequently, a cumulative increase in the attendant significant morbidity and mortality with subsequent episodes. Given the relatively low complication rate of definitive surgery, even in those patients perceived to be high risk, we contend that all patients should be considered for early surgery to prevent the likely recurrence of sigmoid volvulus.

Intraprocedural Artificial Intelligence for Colorectal Cancer Detection and Characterisation in Endoscopy and Laparoscopy.

In this article, we provide an evidence-based primer of current tools and evolving concepts in the area of intraprocedural artificial intelligence (AI) methods in colonoscopy and laparoscopy as a 'procedure companion', with specific focus on colorectal cancer recognition and characterisation. These interventions are both likely beneficiaries from an impending rapid phase in technical and technological evolution. The domains where AI is most likely to impact are explored as well as the methodological pitfalls pertaining to AI methods. Such issues include the need for large volumes of data to train AI systems, questions surrounding false positive rates, explainability and interpretability as well as recent concerns surrounding instabilities in current deep learning (DL) models. The area of biophysics-inspired models, a potential remedy to some of these pitfalls, is explored as it could allow our understanding of the fundamental physiological differences between tissue types to be exploited in real time with the help of computer-assisted interpretation. Right now, such models can include data collected from dynamic fluorescence imaging in surgery to characterise lesions by their biology reducing the number of cases needed to build a reliable and interpretable classification system. Furthermore, instead of focussing on image-by-image analysis, such systems could analyse in a continuous fashion, more akin to how we view procedures in real life and make decisions in a manner more comparable to human decision-making. Synergistical approaches can ensure AI methods usefully embed within practice thus safeguarding against collapse of this exciting field of investigation as another 'boom and bust' cycle of AI endeavour.

Inter-user variation in the interpretation of near infrared perfusion imaging using indocyanine green in colorectal surgery.

INTRODUCTION: Despite increasing endorsement of near-infrared perfusion assessment using indocyanine green (ICG) during colorectal surgery, little work has yet been done regarding learning curve and interobserver variation most especially on surgical video reflective of real-world usage. METHODS: Surgeons with established expertise in ICG usage were invited to participate in the study along with others without such experience including trainees. All participants completed an opinion questionnaire and interpreted video presentations of fluorescence angiograms in a variety of colorectal case scenarios. An interactive video platform (Mindstamp) enabled dynamic annotation. Statistical analysis of data was performed using Kruskal-Wallis and Mann-Whitney testing as well as Intraclass Correlation Coefficients and Fleiss Multi-rater Kappa Scoring. RESULTS: Forty participants (six experts) completed questionnaire data and provided judgement of 14 videos (nine showing proximal colonic transection site perfusion, four showing completed anastomoses and one an acutely strangulated bowel). 70% felt > 10 cases were needed for competency in use with the majority of experts advocating > 50 (p < 0.05). Overall agreement among experts was "good" for videos showing colonic transection perfusion (versus "moderate" among in-experts) with experts clustering more distally. In contrast, there was no interpretation concordance among experts or in-experts when judging ICG perfusion sufficiency on a yes/no basis. CONCLUSION: Significant experience is recommended before reliance on ICG perfusion angiograms. ICG fluorescence assessment is prone to variable interpretation and influenced by experience and, perhaps, knowledge of preassessment operative steps suggesting a role for objective flow analysis with artificial intelligence methods as the next phase of this technology.

Practical Perfusion Quantification in Multispectral Endoscopic Video: Using the Minutes after ICG Administration to Assess Tissue Pathology.

The wide availability of near infrared light sources in interventional medical imaging stacks enables non-invasive quantification of perfusion by using fluorescent dyes, typically Indocyanine Green (ICG). Due to their often leaky and chaotic vasculatures, intravenously administered ICG perfuses through cancerous tissues differently. We investigate here how a few characteristic values derived from the time series of fluorescence can be used in simple machine learning algorithms to distinguish benign lesions from cancers. These features capture the initial uptake of ICG in the colon, its peak fluorescence, and its early wash-out. By using simple, explainable algorithms we demonstrate, in clinical cases, that sensitivity (specificity) rates of over 95% (95%) for cancer classification can be achieved.

In vivo assessment of cervical movement in surgeons-results from open and laparoscopic procedures.

BACKGROUND: Musculoskeletal pain is commonly described in surgeons. Research suggests that 21-60% of at-risk physicians may experience significant work-related pain in their back, shoulders, neck or upper extremity and the consequences of this may impact negatively on patient care. Laparoscopic surgery in particular has become increasingly associated with musculoskeletal pain, especially in the cervical spine. Due to a number of constraints, however, it is difficult to evaluate musculoskeletal movement (particularly cervical spine motion) in the operating room environment. STUDY DESIGN: Three consultant general surgeons were fitted with an ambulatory strain gauge in an attempt to accurately measure and compare cervical motility during open and laparoscopic surgeries. Intraoperative figures pertaining to neck flexion, extension and rotation during forty surgical procedures were collected. The completed data consisted of twenty open and twenty laparoscopic procedures, and the results were compared. RESULTS: There was a statistically significant reduction (21.38%) in measured neck movement in laparoscopic surgery when compared with open surgery p = 0.004 (Table 2). A standard deviation of 18.97 was computed for open surgery indicating a larger variability in results deviation from the mean when compared with a value of 8.92 for laparoscopic surgery. Mean rotational neck movement was also reduced during laparoscopic procedures (23.5%) when compared with open procedures (87.9%). CONCLUSION: Based on our results, we believe that laparoscopic surgery requires more prolonged periods of static neck posture when compared with open surgery. This difference may assist in understanding the contributing factors for musculoskeletal (in particular cervical) pain encountered in minimally invasive surgeons. Further investigation of static posture in the operating surgeon is warranted.