MRI for the Detection of Small Bowel Ischemic Injury in Arterial Acute Mesenteric Ischemia: Preclinical Study in a Porcine Model.

BACKGROUND: MRI is the reference for the diagnosis of arterial cerebral ischemia, but its role in acute mesenteric ischemia (AMI) is poorly known. PURPOSE: To assess MRI detection of early ischemic bowel lesions in a porcine model of arterial AMI. STUDY TYPE: Prospective/cohort. ANIMAL MODEL: Porcine model of arterial AMI obtained by embolization of the superior mesenteric artery (seven pigs). FIELD STRENGTH/SEQUENCE: A 5-T. T1 gradient-echo-weighted-imaging (WI), half-Fourier-acquisition-single-shot-turbo-spin-echo, T2 turbo-spin-echo, true-fast-imaging-with-steady-precession (True-FISP), diffusion-weighted-echo-planar (DWI). ASSESSMENT: T1-WI, T2-WI, and DWI were performed before and continuously after embolization for 6 hours. The signal intensity (SI) of the ischemic bowel was assessed visually and quantitatively on all sequences. The apparent diffusion coefficient (ADC) was assessed. STATISTICAL TESTS: Paired Student's t-test or Mann-Whitney U-test, significance at P < 0.05. RESULTS: One pig died from non-AMI-related causes. The remaining pigs underwent a median 5 h53 (range 1 h24-6 h01) of ischemia. Visually, the ischemic bowel showed signal hyperintensity on DWI-b800 after a median 85 (57-276) minutes compared to the nonischemic bowel. DWI-b800 SI significantly increased after 2 hours (+19%) and the ADC significant decrease within the first hour (-31%). The ischemic bowel was hyperintense on precontrast T1-WI after a median 87 (70-171) minutes with no significant quantitative changes over time (P = 0.46-0.93). The ischemic bowel was hyperintense on T2-WI in three pigs with a significant SI increase on True-FISP after 1 and 2 hours. DATA CONCLUSION: Changes in SI and ADC can be seen early after the onset of arterial AMI with DWI. The value of T2-WI appears to be limited. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

Hyperspectral Imagery for Assessing Laser-Induced Thermal State Change in Liver.

This work presents the potential of hyperspectral imaging (HSI) to monitor the thermal outcome of laser ablation therapy used for minimally invasive tumor removal. Our main goal is the establishment of indicators of the thermal damage of living tissues, which can be used to assess the effect of the procedure. These indicators rely on the spectral variation of temperature-dependent tissue chromophores, i.e., oxyhemoglobin, deoxyhemoglobin, methemoglobin, and water. Laser treatment was performed at specific temperature thresholds (from 60 to 110 °C) on in-vivo animal liver and was assessed with a hyperspectral camera (500-995 nm) during and after the treatment. The indicators were extracted from the hyperspectral images after the following processing steps: the breathing motion compensation and the spectral and spatial filtering, the selection of spectral bands corresponding to specific tissue chromophores, and the analysis of the areas under the curves for each spectral band. Results show that properly combining spectral information related to deoxyhemoglobin, methemoglobin, lipids, and water allows for the segmenting of different zones of the laser-induced thermal damage. This preliminary investigation provides indicators for describing the thermal state of the liver, which can be employed in the future as clinical endpoints of the procedure outcome.

Preoperative endoscopic marking of the gastrointestinal tract using fluorescence imaging: submucosal indocyanine green tattooing versus a novel fluorescent over-the-scope clip in a survival experimental study.

BACKGROUND: Intraoperative localization of endoluminal lesions is can be difficult during laparoscopy. Preoperative endoscopic marking is therefore necessary. Current methods include submucosal tattooing using visible dyes, which in case of transmural injection can impair surgical dissection. Tattooing using indocyanine green (ICG) coupled to intraoperative near-infrared (NIR) laparoscopy has been described. ICG is only visible under NIR-light, therefore, it doesn't impair the surgical workflow under white light even if there is spillage. However, ICG tattoos have rapid diffusion and short longevity. We propose fluorescent over-the-scope clips (FOSC), using a novel biocompatible fluorescent paint, as durable lesion marking. METHODS: In six pigs, gastric and colonic endoscopic tattoos using 0.05 mg/mL of ICG and markings using the fluorescent OSC were performed (T0). Simultaneously, NIR laparoscopy was executed. Follow-up laparoscopies were conducted at postoperative day (POD) 4-6 (T1) and POD 11-12 (T2). During laparoscopy, fluorescence intensity was assessed. In one human cadaver, FOSC was used to mark a site on the stomach and on the sigmoid colon, respectively. Intraoperative detection during NIR laparoscopy was assessed. RESULTS: Gastric and colonic ICG tattooing and OSC markings were easily visible using NIR laparoscopy on T0. All FOSC were visible at T1 and T2 in both stomach and colon, whereas the ICG tattooing at T1 was only visible in the stomach of 2 animals and in the colon of 3 animals. At T2, tattoos were not visible in any animal. FOSC were still visible in both stomach and colon of the human cadaver at 10 days. CONCLUSION: Endoscopic marking using FOSC can be an efficient and durable alternative to standard methods.

Precision image-guided colonic surgery: proof of concept for enhanced preoperative and intraoperative vascular imaging.

BACKGROUND: Colorectal surgery has benefited from advances in precision medicine such as total mesorectal resection, and recently, mesocolon resection, fluorescent perfusion imaging, and fluorescent node mapping. However, these advances fail to address the variable quality of mesocolon dissection and the directed extent of vascular dissection (including high ligation) or pre-resection anastomotic perfusion mapping, thereby impacting anastomotic leaks. We propose a new paradigm of precision image-directed colorectal surgery involving 3D preoperative resection modeling and intraoperative fluoroscopic and fluorescence vascular imaging which better defines optimal dissection planes and vascular vs. anatomy-based resection lines according to our hypothesis. METHODS: Six pigs had preoperative CT with vascular 3D reconstruction allowing for the preoperative planning of vascular-based dissection. Laparoscopic surgery was performed in a hybrid operating room (OR). Superselective arterial catheterization was performed in branches of the superior mesenteric artery (SMA) or the inferior mesenteric artery (IMA). Intraoperative boluses of 0.1 mg/kg or a continuous infusion of indocyanine green (ICG) (0.01 mg/mL) were administered to guide fluorescent-based sigmoid and ileocecal resections. Fluorescence was assessed using proprietary software at several regions of interest (ROI) in the right and left colon. RESULTS: The approach was feasible and safe. Selective catheterization took an average of 43 min. Both bolus and continuous perfusion clearly marked pre-identified vessels (arteries/veins) and the target colon segment, facilitating precise resections based on the visible vascular anatomy. Quantitative software analysis indicated the optimal resection margin for each ROI. CONCLUSION: Intra-arterial fluorescent mapping allows visualization of major vascular structures and segmental colonic perfusion. This may help to prevent any inadvertent injury to major vascular structures and to precisely determine perfusion-based resection planes and margins. This could enable tailoring of the amount of colon resected, ensure good anastomotic perfusion, and improve oncological outcomes.

Quantification of ICG fluorescence for the evaluation of intestinal perfusion: comparison between two software-based algorithms for quantification.

BACKGROUND: Indocyanine green fluorescence imaging (ICG-FI) can be used to evaluate intestinal perfusion prior to anastomosis. Several software for the quantification of fluorescence have emerged, but these have not previously been compared. The aim of this study was to compare the results from quantitative ICG-FI analysis of relative perfusion in an experimental setting using two different software-based quantification algorithms (FLER and Q-ICG). METHODS: Twenty pigs received a laparotomy, and ischemic areas were created in three segments of the small intestine of each pig. For each ischemic area, fluorescence imaging was performed and the fluorescence recordings were quantitatively analyzed using FLER and Q-ICG. The quantitative analysis resulted in a set of perfusion lines for each software for either 30%, 60% or 100% relative perfusion. The perfusion lines were compared by registering the normalized slope for each set of perfusion lines, calculating the relative perfusion percentage in the FLER perfusion line according to Q-ICG, and measuring the length of the ischemic area for each analysis. RESULTS: Fifty-four fluorescence recordings from 18 pigs were included. The ischemic segment for FLER was significantly longer in the 30% perfusion group and significantly shorter in the 100% perfusion group as compared to Q-ICG. The normalized slope for the FLER perfusion lines was significantly higher in the 30% perfusion group and significantly lower in the 100% perfusion group as compared to the Q-ICG perfusion lines. For the perfusion lines defined by FLER as 30%, 60%, and 100%, Q-ICG found 35.2% (p = 0.07), 63.7% (p = 0.31), and 84.1% perfusion (p = 0.003) respectively. CONCLUSION: The two software demonstrated significant differences in quantitative fluorescence analysis when perfusion was either very high or very low. The clinical relevance of these differences is unclear.

Simultaneous multipurpose fluorescence imaging with IRDye® 800BK during laparoscopic surgery.

BACKGROUND: IRDye® 800BK is a fluorophore, currently undergoing clinical translation, which has both biliary and renal clearance. To date, there is no description of a fluorophore, which can be simultaneously used for non-invasive, near-infrared fluorescence-based (NIRF) visualization of different structures and perfusion evaluation. The purpose of this study was to evaluate IRDye® 800BK for the simultaneous assessment of bowel perfusion, lymphography, ureter and bile duct delineation. METHODS: Six pigs received a 0.15 mg/kg dye as a single bolus intravenous injection (IV). With the FLER (fluorescence-based enhanced reality) software, fluorescence intensity (FI) of 5 regions of interest (ROI) in an ischemic bowel loop was measured along with the time to reach the FI peak, and capillary lactate was measured from the same ROI, followed by the assessment of the ureters and bile ducts for a maximal duration of 180 min after dye administration. In 3 animals, the procedure was initiated via gastroscopic injection of a 0.6 mg (1 mg/mL) dye in the gastric submucosa followed by lymphography in a NIRF setting. RESULTS: Excellent visualization of the ureters and bowel perfusion was obtained under NIRF imaging. Additionally, the bile duct and gastric lymph ducts and nodes were visualized. A positive correlation was found between the time to peak FI in the ischemic bowel loop and the corresponding capillary lactate levels (rho 0.59, p < 0.001). CONCLUSION: In this study, we successfully demonstrated the simultaneous multipurpose IRDye® 800BK applicability during laparoscopic surgery. This fluorophore has the potential to become a powerful and versatile image-guided surgery tool.

Computer-assisted quantification and visualization of bowel perfusion using fluorescence-based enhanced reality in left-sided colonic resections.

BACKGROUND: Fluorescence-based enhanced reality (FLER) is a computer-based quantification method of fluorescence angiographies to evaluate bowel perfusion. The aim of this prospective trial was to assess the clinical feasibility and to correlate FLER with metabolic markers of perfusion, during colorectal resections. METHODS: FLER analysis and visualization was performed in 22 patients (diverticulitis n = 17; colorectal cancer n = 5) intra- and extra-abdominally during distal and proximal resection, respectively. The fluorescence signal of indocyanine green (0.2 mg/kg) was captured using a near-infrared camera and computed to create a virtual color-coded cartography. This was overlaid onto the bowel (enhanced reality). It helped to identify regions of interest (ROIs) where samples were subsequently obtained. Resections were performed strictly guided according to clinical decision. On the surgical specimen, samplings were made at different ROIs to measure intestinal lactates (mmol/L) and mitochondria efficiency as acceptor control ratio (ACR). RESULTS: The native (unquantified) fluorescent signal diffused to obvious ischemic areas during the distal appreciation. Proximally, a lower diffusion of ICG was observed. Five anastomotic complications occurred. The expected values of local capillary lactates were correlated with the measured values both proximally (3.62 ± 2.48 expected vs. 3.17 ± 2.8 actual; rho 0.89; p = 0.0006) and distally (4.5 ± 3 expected vs. 4 ± 2.5 actual; rho 0.73; p = 0.0021). FLER values correlated with ACR at the proximal site (rho 0.76; p = 0.04) and at the ischemic zone (rho 0.71; p = 0.01). In complicated cases, lactates at the proximal resection site were higher (5.8 ± 4.5) as opposed to uncomplicated cases (2.45 ± 1.5; p = 0.008). ACR was reduced proximally in complicated (1.3 ± 0.18) vs. uncomplicated cases (1.68 ± 0.3; p = 0.023). CONCLUSIONS: FLER allows to image the quantified fluorescence signal in augmented reality and provides a reproducible estimation of bowel perfusion (NCT02626091).

Quantitative serosal and mucosal optical imaging perfusion assessment in gastric conduits for esophageal surgery: an experimental study in enhanced reality.

INTRODUCTION/OBJECTIVE: Gastric conduit (GC) is used for reconstruction after esophagectomy. Anastomotic leakage (AL) incidence remains high, given the extensive disruption of the gastric circulation. Currently, there is no reliable method to intraoperatively quantify gastric perfusion. Hyperspectral imaging (HSI) has shown its potential to quantify serosal StO2. Confocal laser endomicroscopy (CLE) allows for automatic mucosal microcirculation quantification as functional capillary density area (FCD-A). The aim of this study was to quantify serosal and mucosal GC's microperfusion using HSI and CLE. Local capillary lactate (LCL) served as biomarker. METHODS: GC was formed in 5 pigs and serosal StO2% was quantified at 3 regions of interest (ROI) using HSI: fundus (ROI-F), greater curvature (ROI-C), and pylorus (ROI-P). After intravenous injection of sodium-fluorescein (0.5 g), CLE-based mucosal microperfusion was assessed at the corresponding ROIs, and LCLs were quantified via a lactate analyzer. RESULTS: StO2 and FCD-A at ROI-F (41 ± 10.6%, 3.3 ± 3.8, respectively) were significantly lower than ROI-C (68.2 ± 6.7%, p value: 0.005; 18.4 ± 7, p value: 0.01, respectively) and ROI-P (72 ± 10.4%, p value: 0.005; 15.7 ± 3.2 p value: 0.001). LCL value at ROI-F (9.6 ± 4.7 mmol/L) was significantly higher than at ROI-C (2.6 ± 1.2 mmol/L, p value: 0.04) and ROI-P (2.6 ± 1.3 mmol/L, p value: 0.04). No statistically significant difference was found in all metrics between ROI-C and ROI-P. StO2 correlated with FCD-A (Pearson's r = 0.67). The LCL correlated negatively with both FCD-A (Spearman's r = - 0.74) and StO2 (Spearman's r = - 0.54). CONCLUSIONS: GC formation causes a drop in serosal and mucosal fundic perfusion. HSI and CLE correlate well and might become useful intraoperative tools.

Hyperspectral enhanced reality (HYPER) for anatomical liver resection.

BACKGROUND: Clinical evaluation of the demarcation line separating ischemic from non-ischemic liver parenchyma may be challenging. Hyperspectral imaging (HSI) is a noninvasive imaging modality, which combines a camera with a spectroscope and allows quantitative imaging of tissue oxygenation. Our group developed a software to overlay HSI images onto the operative field, obtaining HSI-based enhanced reality (HYPER). The aim of the present study was to evaluate the accuracy of HYPER to identify the demarcation line after a left vascular inflow occlusion during an anatomical left hepatectomy. MATERIALS AND METHODS: In the porcine model (n = 3), the left branches of the hepatic pedicle were ligated. Before and after vascular occlusion, HSI images based on tissue oxygenation (StO2), obtained through the Near-Infrared index (NIR index), were regularly acquired and superimposed onto RGB video. The demarcation line was marked on the liver surface with electrocautery according to HYPER. Local lactates were measured on blood samples from the liver surface in both ischemic and perfused segments using a strip-based device. At the same areas, confocal endomicroscopy was performed. RESULTS: After ligation, HSI demonstrated a significantly lower oxygenation (NIR index) in the left medial lobe (LML) (0.27% ± 0.21) when compared to the right medial lobe (RML) (58.60% ± 12.08; p = 0.0015). Capillary lactates were significantly higher (3.07 mmol/L ± 0.84 vs. 1.33 ± 0.71 mmol/L; p = 0.0356) in the LML versus RML, respectively. Concordantly, confocal videos demonstrated the absence of blood flow in the LML and normal perfusion in the RML. CONCLUSIONS: HYPER has made it possible to correctly identify the demarcation line and quantify surface liver oxygenation. HYPER could be an intraoperative tool to guide perfusion-based demarcation line assessment and segmentation.

Diagnostic Accuracy and Clinical Impact of Sentinel Lymph Node Sampling in Endometrial Cancer at High Risk of Recurrence: A Meta-Analysis.

PURPOSE: To assess the value of sentinel lymph node (SLN) sampling in high risk endometrial cancer according to the ESMO-ESGO-ESTRO classification. METHODS: We performed a comprehensive search on PubMed for clinical trials evaluating SLN sampling in patients with high risk endometrial cancer: stage I endometrioid, grade 3, with at least 50% myometrial invasion, regardless of lymphovascular space invasion status; or stage II; or node-negative stage III endometrioid, no residual disease; or non-endometrioid (serous or clear cell or undifferentiated carcinoma, or carcinosarcoma). All patients underwent SLN sampling followed by pelvic with or without para-aortic lymphadenectomy. RESULTS: We included 17 original studies concerning 1322 women. Mean detection rates were 89% for unilateral and 68% for bilateral. Pooled sensitivity was 88.5% (95%CI: 81.2-93.2%), negative predictive value was 96.0% (95%CI: 93.1-97.7%), and false negative rate was 11.5% (95%CI: 6.8; 18.8%). We noted heterogeneity in SLN techniques between studies, concerning the tracer and its detection, the injection site, the number of injections, and the surgical approach. Finally, we found a correlation between the number of patients included and the SLN sampling performances. DISCUSSION: This meta-analysis estimated the SLN sampling performances in high risk endometrial cancer patients. Data from the literature show the feasibility, the safety, the limits, and the impact on surgical de-escalation of this technique. In conclusion, our study supports the hypothesis that SLN sampling could be a valuable technique to diagnose lymph node involvement for patients with high risk endometrial cancer in replacement of conventional lymphadenectomy. Consequently, randomized clinical trials are necessary to confirm this hypothesis.

Multimodality Imaging and Artificial Intelligence for Tumor Characterization: Current Status and Future Perspective.

Research in medical imaging has yet to do to achieve precision oncology. Over the past 30 years, only the simplest imaging biomarkers (RECIST, SUV,…) have become widespread clinical tools. This may be due to our inability to accurately characterize tumors and monitor intratumoral changes in imaging. Artificial intelligence, through machine learning and deep learning, opens a new path in medical research because it can bring together a large amount of heterogeneous data into the same analysis to reach a single outcome. Supervised or unsupervised learning may lead to new paradigms by identifying unrevealed structural patterns across data. Deep learning will provide human-free, undefined upstream, reproducible, and automated quantitative imaging biomarkers. Since tumor phenotype is driven by its genotype and thus indirectly defines tumoral progression, tumor characterization using machine learning and deep learning algorithms will allow us to monitor molecular expression noninvasively, anticipate therapeutic failure, and lead therapeutic management. To follow this path, quality standards have to be set: standardization of imaging acquisition as it has been done in the field of biology, transparency of the model development as it should be reproducible by different institutions, validation, and testing through a high-quality process using large and complex open databases and better interpretability of these algorithms.

A Novel Technique to Improve Anastomotic Perfusion Prior to Esophageal Surgery: Hybrid Ischemic Preconditioning of the Stomach. Preclinical Efficacy Proof in a Porcine Survival Model.

Esophagectomy often presents anastomotic leaks (AL), due to tenuous perfusion of gastric conduit fundus (GCF). Hybrid (endovascular/surgical) ischemic gastric preconditioning (IGP), might improve GCF perfusion. Sixteen pigs undergoing IGP were randomized: (1) Max-IGP (n = 6): embolization of left gastric artery (LGA), right gastric artery (RGA), left gastroepiploic artery (LGEA), and laparoscopic division (LapD) of short gastric arteries (SGA); (2) Min-IGP (n = 5): LGA-embolization, SGA-LapD; (3) Sham (n = 5): angiography, laparoscopy. At day 21 gastric tubulation occurred and GCF perfusion was assessed as: (A) Serosal-tissue-oxygenation (StO2) by hyperspectral-imaging; (B) Serosal time-to-peak (TTP) by fluorescence-imaging; (C) Mucosal functional-capillary-density-area (FCD-A) index by confocal-laser-endomicroscopy. Local capillary lactates (LCL) were sampled. Neovascularization was assessed (histology/immunohistochemistry). Sham presented lower StO2 and FCD-A index (41 ± 10.6%; 0.03 ± 0.03 respectively) than min-IGP (66.2 ± 10.2%, p-value = 0.004; 0.22 ± 0.02, p-value < 0.0001 respectively) and max-IGP (63.8 ± 9.4%, p-value = 0.006; 0.2 ± 0.02, p-value < 0.0001 respectively). Sham had higher LCL (9.6 ± 4.8 mL/mol) than min-IGP (4 ± 3.1, p-value = 0.04) and max-IGP (3.4 ± 1.5, p-value = 0.02). For StO2, FCD-A, LCL, max- and min-IGP did not differ. Sham had higher TTP (24.4 ± 4.9 s) than max-IGP (10 ± 1.5 s, p-value = 0.0008) and min-IGP (14 ± 1.7 s, non-significant). Max- and min-IGP did not differ. Neovascularization was confirmed in both IGP groups. Hybrid IGP improves GCF perfusion, potentially reducing post-esophagectomy AL.

Noninvasive Near-Infrared Fluorescence Imaging of the Ureter During Robotic Surgery: A Demonstration in a Porcine Model.

Background: Iatrogenic ureteral injury is one of the feared complications during intrapelvic surgery. There are limited data on the use of novel near-infrared fluorescence (NIRF) imaging dyes for the purpose of noninvasive ureteral visualization in robot-assisted laparoscopic surgery (RALS). In this study, we evaluated the feasibility of NIRF imaging of the ureter using the IRDye® 800BK dye as the fluorescence dye and a robotic platform with Firefly™ technology as an imaging system. Materials and Methods: An intravenous dose of 0.15 mg/kg was administered in 3 pigs and NIRF imaging was performed for a total duration of 60 minutes. The intraoperative video recordings were analyzed to determine fluorescence intensities and the target-to-background ratio (TBR). Results: In all included animals, a clear delineation of the ureter was achieved from 5 minutes after dye administration until the end of the study. During this time period, the ureter was clearly distinguishable from its surroundings and no statistical differences in TBR were observed. Conclusion: The IRDye 800BK dye, a novel NIRF dye currently undergoing clinical translation, is a promising contrast agent used for noninvasive ureteral imaging, which has the potential to be valuable during RALS.

Quantitative fluorescence angiography versus hyperspectral imaging to assess bowel ischemia: A comparative study in enhanced reality.

BACKGROUND: Fluorescence-based enhanced reality is a software that provides quantitative fluorescence angiography by computing the fluorescence intensity time-to-peak after intravenous indocyanine green. Hyperspectral imaging is a contrast-free, optical imaging modality which measures tissue oxygenation. METHODS: In 8 pigs, an ischemic bowel segment created by dividing the arcade branches was imaged using hyperspectral imaging and fluorescence-based enhanced reality. Tissue oxygenation values were acquired through a hyperspectral imaging system. Subsequently, fluorescence angiography was performed using a near-infrared laparoscopic camera after intravenous injection of 0.2 mg/kg of indocyanine green. The time-to-peak fluorescence signal was analyzed through a proprietary software to realize a perfusion map. This was overlaid onto real-time images to obtain fluorescence-based enhanced reality. Simultaneously, 9 adjacent regions of interest were selected and superimposed onto the real-time video, thereby obtaining hyperspectral-based enhanced reality. Fluorescence-based enhanced reality and hyperspectral-based enhanced reality were superimposed allowing a comparison of both imaging modalities. Local capillary lactate levels were sampled at the regions of interest. Two prediction models using the local capillary lactate levels were extrapolated based on both imaging systems. RESULTS: For all regions of interest, the mean local capillary lactate levels were 4.67 ± 4.34 mmol/L, the mean tissue oxygenation was 45.9 ± 18.9%, and the mean time-to-peak was 10 ± 9.4 seconds. Pearson's test between fluorescence-based enhanced reality-time-to-peak and hyperspectral imaging-tissue oxygenation at the corresponding regions of interest gave an R = -0.66 (P < .0001). The hyperspectral imaging lactate prediction model proved more accurate than the fluorescence-based enhanced reality-based model (P < .0001). CONCLUSION: Bowel perfusion was quantified using hyperspectral imaging and fluorescence angiography. Hyperspectral imaging yielded more accurate results than fluorescence angiography. Hyperspectral-based enhanced reality may prove to be a useful, contrast-free intraoperative tool to quantify bowel ischemia.

Fluorescence-based cholangiography: preliminary results from the IHU-IRCAD-EAES EURO-FIGS registry.

INTRODUCTION: Near-infrared fluorescence cholangiography (NIRF-C) is a popular application of fluorescence image-guided surgery (FIGS). NIRF-C requires near-infrared optimized laparoscopes and the injection of a fluorophore, most frequently Indocyanine Green (ICG), to highlight the biliary anatomy. It is investigated as a tool to increase safety during cholecystectomy. The European registry on FIGS (EURO-FIGS: www.euro-figs.eu ) aims to obtain a snapshot of the current practices of FIGS across Europe. Data on NIRF-C are presented. METHODS: EURO-FIGS is a secured online database which collects anonymized data on surgical procedures performed using FIGS. Data collected for NIRF-C include gender, age, Body Mass Index (BMI), pathology, NIR device, ICG dose, ICG timing of administration before intraoperative visualization, visualization (Y/N) of biliary structures such as the cystic duct (CD), the common bile duct (CBD), the CD-CBD junction, the common hepatic duct (CHD), Visualization scores, adverse reactions to ICG, operative time, and surgical complications. RESULTS: Fifteen surgeons (12 European surgical centers) uploaded 314 cases of NIRF-C during cholecystectomy (cholelithiasis n = 249, cholecystitis n = 58, polyps n = 7), using 4 different NIR devices. ICG doses (mg/kg) varied largely (mean 0.28 ± 0.17, median 0.3, range: 0.02-0.62). Similarly, injection-to-visualization timing (minutes) varied largely (mean 217 ± 357; median 57), ranging from 1 min (direct intragallbladder injection in 2 cases) to 3120 min (n = 2 cases). Visualization scores before dissection were significantly correlated, at univariate analysis, with ICG timing (all structures), ICG dose (CD-CBD), device (CD and CD-CBD), surgeon (CD and CD-CBD), and pathology (CD and CD-CBD). BMI was not correlated. At multivariate analysis, pathology and timing remained significant factors affecting the visualization scores of all three structures, whereas ICG dose remained correlated with HD visualization only. CONCLUSIONS: The EURO-FIGS registry has confirmed a wide disparity in ICG dose and timing in NIRF-C. EURO-FIGS can represent a valuable tool to promote and monitor FIGS-related educational and consensus activities in Europe.

Augmented reality in gynecologic laparoscopic surgery: development, evaluation of accuracy and clinical relevance of a device useful to identify ureters during surgery.

OBJECTIVE: To develop and evaluate a non-invasive surgical assistance based on augmented reality (AR) in the detection of ureters on animal model. METHOD: After an experimental prototyping step on two pigs to determine the optimal conditions for visualization of the ureter in AR, three pigs were operated three times at 1 week intervals. The intervention consisted of an identification of the ureter, with and without the assistance of AR. At the end of the intervention, a clip was placed on the AR-proposed ureter to evaluate its accuracy. By doing a cone beam computed tomography, we measured the distance between the contrasted ureter and the clips in the acquired volume. Thirteen videos were recorded, allowing subsequent evaluation of the clinical relevance of the device. RESULTS: The feasibility of the technique has been confirmed. The margin of error was 1.77 mm (± 1.56 mm) for ureter localization accuracy. In order to evaluate the perceived relevance and accuracy in the detection of AR-assisted ureter, 58 gynecological surgeons were shown the videos then questioned. Of the 754 responses obtained (13 videos × 58 surgeons), the ureter was identified in direct vision in 31.2% of cases versus 81.7% in AR (p value 3.62 × 10-7). When looking at pigs that had already had one or two operations, the ureter was identified in only 16% of cases with direct vision compared to 76.1% with AR (p-value 5.48 × 10-19). In addition, 67% of surgeons felt that AR allowed them to better identify the ureters and 61% that AR reconstruction was accurate. CONCLUSION: This first AR device showed a satisfactory precision in the detection of ureters with a favorable opinion of surgeons. This surgical assistance system could be helpful in the performance of difficult procedures, for example in the case of patients, which have undergone multiple surgeries in the past.

HYPerspectral Enhanced Reality (HYPER): a physiology-based surgical guidance tool.

BACKGROUND: HSI is an optical technology allowing for a real-time, contrast-free snapshot of physiological tissue properties, including oxygenation. Hyperspectral imaging (HSI) has the potential to quantify the gastrointestinal perfusion intraoperatively. This experimental study evaluates the accuracy of HSI, in order to quantify bowel perfusion, and to obtain a superposition of the hyperspectral information onto real-time images. METHODS: In 6 pigs, 4 ischemic bowel loops were created (A, B, C, D) and imaged at set time points (from 5 to 360 min). A commercially available HSI system provided pseudo-color maps of the perfusion status (StO2, Near-InfraRed perfusion) and the tissue water index. An ad hoc software was developed to superimpose HSI information onto the live video, creating the HYPerspectral-based Enhanced Reality (HYPER). Seven regions of interest (ROIs) were identified in each bowel loop according to StO2 ranges, i.e., vascular (VASC proximal and distal), marginal vascular (MV proximal and distal), marginal ischemic (MI proximal and distal), and ischemic (ISCH). Local capillary lactates (LCL), reactive oxygen species (ROS), and histopathology were measured at the ROIs. A machine-learning-based prediction algorithm of LCL, based on the HSI-StO2%, was trained in the 6 pigs and tested on 5 additional animals. RESULTS: HSI parameters (StO2 and NIR) were congruent with LCL levels, ROS production, and histopathology damage scores at the ROIs discriminated by HYPER. The global mean error of LCL prediction was 1.18 ± 1.35 mmol/L. For StO2 values > 30%, the mean error was 0.3 ± 0.33. CONCLUSIONS: HYPER imaging could precisely quantify the overtime perfusion changes in this bowel ischemia model.

Remote computer-assisted analysis of ICG fluorescence signal for evaluation of small intestinal anastomotic perfusion: a blinded, randomized, experimental trial.

BACKGROUND: Indocyanine green fluorescence imaging (ICG-FI) may be used to visualize intestinal perfusion prior to anastomosis. Methods for quantification of the fluorescence signal are required to ensure an objective evaluation. The aim of this study was to evaluate a method for quantification of relative perfusion and to investigate the correlation between the perfusion level and the anastomotic strength. METHOD: This blinded, randomized, experimental trial included twenty pigs. Each pig received three small intestinal anastomoses with 30%, 60%, or 100% perfusion, respectively. The perfusion levels were determined relative to healthy intestine using ICG-FI. Ischemia was induced by mesenteric ligation and the perfusion level of each anastomosis was determined using a software-based analysis of the fluorescence signal. On postoperative day 5, the anastomoses were subjected to tensile strength test and histopathological assessment. RESULTS: No anastomotic leakage occurred. The tensile strength of the 30% perfusion group was 9.09 N, which was significantly lower than the 60% perfusion group (11.5 N) and the 100% perfusion group (12.9 N). The difference between the 60% perfusion group and the 100% perfusion group was not significant. The histopathological assessment showed no significant differences between perfusion groups. CONCLUSIONS: A reduction in blood supply to 30%, as determined by ICG-FI, in small intestinal anastomoses was necessary to demonstrate a decrease in tensile strength.

Fluorescence-enabled assessment of adrenal gland localization and perfusion in posterior retroperitoneoscopic adrenal surgery in a preclinical model.

BACKGROUND: The posterior retroperitoneoscopic adrenal access represents a challenge in orientation and working space creation. The aim of this experimental acute study was to evaluate the impact of computer-assisted quantitative fluorescence imaging on adrenal gland identification and assessment of intraoperative remnant perfusion for adrenal resection in the posterior retroperitoneoscopic approach. METHODS: Six pigs underwent simultaneous (n = 5) or sequential (n = 1) bilateral posterior retroperitoneoscopic adrenalectomy (n = 12). Fluorescence imaging was obtained via intravenous administration of 3 mL of Indocyanine Green (ICG) and by switching the camera systems to near-infrared mode (D-LIGHT P, KARL STORZ; Germany). Fluorescence-based visualization of adrenal glands before vascular division (n = 4), after the main vascular pedicle ligation (negative control, n = 1) or after adrenal resection (n = 7), was followed by completion adrenalectomy. The fluorescence signal intensity dynamics were recorded and analyzed using proprietary software. For each pixel, the slope of fluorescence signal intensity evolution over time was translated into a color-coded perfusion cartography, which was superimposed onto real-time images obtained with the corresponding left and right camera systems. Quantitative fluorescence signal analysis in the regions of interest (ROIs) served to assess adrenal remnant perfusion in divided adrenal glands. RESULTS: In the retroperitoneum, the vascular anatomy was illuminated in fluorescence imaging first. The adrenal glands were promptly highlighted after primary intravenous ICG administration (n = 9) or showed a fluorescence signal intensity increase upon reinjection (n = 3). Quantitative fluorescence analysis showed a statistically significant difference between perfused and ischemic segments in divided glands (p = 0.0156). CONCLUSIONS: Fluorescence imaging provides real-time guidance during minimally invasive adrenal surgery. Prior to dissection, it allows to easily discriminate the adrenal gland from surrounding retroperitoneal structures. After adrenal gland division, ICG injection associated with a computer-assisted quantitative analysis helps to distinguish between well-perfused and ischemic segments. Further studies are underway to establish the correlation between remnant perfusion and viability.

Simultaneous computer-assisted assessment of mucosal and serosal perfusion in a model of segmental colonic ischemia.

BACKGROUND: Fluorescence-based enhanced reality (FLER) enables the quantification of fluorescence signal dynamics, which can be superimposed onto real-time laparoscopic images by using a virtual perfusion cartogram. The current practice of perfusion assessment relies on visualizing the bowel serosa. The aim of this experimental study was to quantify potential differences in mucosal and serosal perfusion levels in an ischemic colon segment. METHODS: An ischemic colon segment was created in 12 pigs. Simultaneous quantitative mucosal and serosal fluorescence imaging was obtained via intravenous indocyanine green injection (0.2 mg/kg), using two near-infrared camera systems, and computer-assisted FLER analysis. Lactate levels were measured in capillary blood of the colonic wall at seven regions of interest (ROIs) as determined with FLER perfusion cartography: the ischemic zone (I), the proximal and distal vascularized areas (PV, DV), and the 50% perfusion threshold proximally and distally at the mucosal and serosal side (P50M, P50S, D50M, D50S). RESULTS: The mean ischemic zone as measured (mm) for the mucosal side was significantly larger than the serosal one (56.3 ± 21.3 vs. 40.8 ± 14.9, p = 0.001) with significantly lower lactate values at the mucosal ROIs. There was a significant weak inverse correlation between lactate and slope values for the defined ROIs (r = - 0.2452, p = 0.0246). CONCLUSIONS: Mucosal ischemic zones were larger than serosal zones. These results suggest that an assessment of bowel perfusion from the serosal side only can underestimate the extent of ischemia. Further studies are required to predict the optimal resection margin and anastomotic site.