Gel embolic agents are increasingly recognized for their versatility in minimally invasive vascular interventions. However, their application in real-time imaging, post-operative monitoring, and thermal treatment remains underexplored. In this study, we present a novel transcatheter injectable nanoclay-alginate (NCA) gel embolic agent integrated with indocyanine green (ICG) for dual fluorescence imaging and thermal ablation. The NCA/ICG embolic gel exhibits excellent shear-thinning properties, transcatheter injectability, and mechanical stability. Furthermore, the mechanism to enhance fluorescence for real-time imaging enhancement and extended post-operative monitoring was discussed. A 28-day fluorescence persistence shows the NCA/ICG gel's long-lasting fluorescent signal, which was significantly stronger and longer compared to current clinically used ICG aqueous solution. Furthermore, the gel can effectively convert near-infrared (NIR) laser energy into heat for potential photothermal therapy. The biocompatibility and enhanced antibacterial properties further highlight the potential clinical benefits of this embolic agent as a multifunctional agent for vascular embolization.

BackgroundPost-operative anastomotic leaks (AL) are one of the most challenging complications of bariatric surgery and can be detrimental. Indocyanine green (ICG) is a fluorescence dye that can provide a real-time intraoperative assessment of organ tissue perfusion. Its use in bariatric operations is still being debated. The present review aims to evaluate the intraoperative utility of ICG during bariatric surgery to focus future research on a reliable tool to reduce the incidence of postoperative leaks.MethodsA systematic search of PubMed, EMBASE, MEDLINE, Scopus, and the Cochrane Library for published studies took place until December 2024, evaluating the use of ICG during bariatric surgical procedures. Studies were included if they assessed the ICG application in various bariatric operations to prevent and reduce AL rates.ResultsEleven studies were included, which involved a total of 887 patients. 643 patients underwent ICG-based intraoperative assessments, while 244 were in the control group. The mean age of participants was 43.8 years, and the mean BMI was 43.3 kg/m3. All included patients underwent various bariatric procedures. ICG was used alone in most studies, although it was mixed with methylene blue in one study. ICG administration protocols varied significantly. There were no reported complications from ICG administration. The utility of ICG has changed the intraoperative surgical decision-making of 4.2% of patients.ConclusionsICG is a promising technique for successfully preventing or timely managing AL in bariatric surgery. Large, randomised controlled studies are needed to confirm its utility for routine use in primary and revisional bariatric cases.

BackgroundAlthough there is evidence that indocyanine green angiography (ICGA) can predict mastectomy skin flap necrosis during breast reconstruction, consensus on optimal protocol is lacking. This study aimed to evaluate various technical factors which can influence ICG fluorescence intensity and thus interpretation of angiograms.MethodSingle institution retrospective study (2015-2021) of immediate implant-based breast reconstructions postmastectomy using a standardized technique of ICGA, controlling for modifiable factors of ambient lighting, camera distance and ICG dose. "Time to perfusion" assessment was defined as elapsed time from ICG administration to perfusion assessment. Intraoperative "absolute" and "relative" IGCA perfusion values of mastectomy flaps, taken at different time points (30, 60 and 90 seconds), were correlated with postoperative flap outcomes.ResultsThere were 260 breast reconstructions with a 3.1% necrosis rate. ICGA perfusion values, when measured at 60 and 90 seconds, were significantly lower for cases that developed necrosis compared to cases that did not, and were both good predictors of necrosis (area under ROC curves, 0.84 and 0.85, respectively). Fluorescence intensity increased as "time to perfusion" assessment increased for flaps that did not develop necrosis (correlation coefficient, 0.9, P < 0.001). Perfusion value cut-off thresholds for predicting necrosis were higher for a longer "time to perfusion" assessment.ConclusionsA standardized ICGA protocol is recommended as ICG fluorescence intensity increased with "time to perfusion" assessment, and ≤30 seconds did not allow for accurate perfusion analysis. Using a perfusion recording of 60 or 90 seconds, and the corresponding perfusion value cut-off, may optimize reliability of perfusion assessments.

Near-infrared fluorescence cholangiography improves the clinical effects of laparoscopic cholecystectomy. However, the administration of indocyanine green remains controversial. Both the intraoperative strategy (IS, 0.05 mg) and preoperative strategy (PS, 0.25 mg/kg body weight, 1 day before operation) have been shown to be superior to the standard strategy (2.5 mg, intraoperative). This trial was designed to determine whether IS offers noninferior visualization of biliary ducts compared with PS.

A total of 168 eligible patients undergoing laparoscopic cholecystectomy were enrolled in this noninferiority, open-label, randomized controlled trial at Zhujiang hospital between August 2023 and November 2023. Participants were randomized in a 1:1 ratio into PS and IS groups after stratification by BMI and inflammation level. The fluorescence visualization of biliary structures was assessed by comparing the signal-to-background ratio (SBR) and surgeon evaluations.

The common bile duct-liver SBR did not significantly differ between IS and PS groups (3.0 ± 0.8 vs 3.1 ± 1.2; p = 0.636). The liver fluorescence intensity of the IS group was significantly lower than that of the PS group (46.3 ± 12.9 vs 70.4 ± 26.2; p < 0.01). The visualization score of common hepatic ducts was significantly greater in the IS than in the PS group (4.1 ± 0.7 vs 3.7 ± 0.6; p< 0.01). The critical view of safety was achieved more rapidly in the IS group compared with the PS group (9.4 vs 11.0 minutes, p < 0.01).

Although IS did not improve the SBR, it significantly reduced the fluorescence intensity of the liver background, potentially enhancing the surgeon's subjective perception and thereby increasing the visualization score. Compared with PS, IS offers greater convenience and is more effective in facilitating critical view of safety exposure.

Different techniques have been proposed to reduce the incidence of the intraoperative bile duct injury during laparoscopic cholecystectomy (LC). Among these, Near-Infrared Fluorescence Cholangiography (NIFC) with Indocyanine Green (ICG) represents a relatively recent addition. At present, there is considerable variation in the protocols for the administration of ICG.

The aim of this randomized multicenter clinical trial (RCT) is to ascertain whether there are differences between the dosage and administration intervals of ICG, with a view to optimizing a good-quality NIFC during LC. Furthermore, an analysis was conducted to determine the potential impact of different factors on the outcomes of this technique. The trial was approved by the local institutional Ethics Committee.

From June 2022 to June 2023, 200 patients were randomized in four arms (G1: 2.5 mg ICG > 3 h prior to surgery, G2: 2.5 mg ICG 15-30 min prior to surgery, G3: 0.05 mg/kg ICG > 3 h prior to surgery and G4: 0.05 mg/kg ICG 15-30 min prior to surgery). We found differences in the DISTURBED score between the groups (p < 0.001), suggesting that ICG administration 15-30 min before surgery was worse than administration > 3 h after LC (p = 0.02). Additionally, it was observed that body mass index (BMI), gender, ASA Classification System, previous liver and biliary disease and the type of surgery had influence on NIFC. Finally, the NIFC had an impact in intraoperative and postoperative complications, operative time and hospital length of stay.

The administration of ICG > 3 h improve liver background fluorescence in the NIFC during LC. There are different factors may affect NIFC results (BMI, ASA grade, previous liver disease, presence of gallbladder inflammation and type of surgery). Finally, high-quality NIFC was associated with fewer surgical complications, shorter surgical time and shorter length of hospital stay.

The advantages of indocyanine green (ICG) fluorescence cholangiography have been emphasized, but its disadvantages remain unclear. This study investigated the advantages and disadvantages of this modality, particularly the optimal timing of administration of ICG fluorescence.

This was a retrospective analysis of prospectively collected patient data.

Data were gathered from a single institution.

69 patients scheduled for cholecystectomy were included.

We administered intravenous ICG injections at three different times: preoperatively (5 mg/body weight (BW), 15 min before incision), morning of the surgery (12.5 mg/BW 4 hours before surgery), and on the day before the surgery (25 mg/BW, 20 hours before surgery). The PINPOINT or SPY-PHI (Stryker) systems were used for fluorescence imaging.

The course of the common bile and cystic ducts was identified using fluorescence imaging. The visualization quality was graded on a three-point scale: good, poor, and unobservable.

There were 17 patients for preoperative administration, 14 on the morning of the surgery, and 38 on the day before the surgery. The cystic duct could not be visualized in five patients because of insufficient dose, impacted gallstones, cystic duct stones, after endoscopic retrograde biliary drainage (ERBD), and severe cholecystitis. The observations were poor in 14 patients. The reasons for the poor visualization were cholecystitis after ERBD and a low signal-to-noise ratio due to intense light emission from the liver, which is a characteristic of preoperative administration.

The cystic and common bile ducts were well visualized using ICG fluorescence cholangiography, except in patients with impacted gallstones, cystic duct stones, ERBD, and severe cholecystitis. The most effective timing for ICG administration was the day before the surgery. ICG fluorescence cholangiography is not a substitute for intraoperative cholangiography or preoperative biliary imaging; however, it would be desirable in all patients who undergo cholecystectomy.

jRCTs041180006.

Indocyanine green (ICG) is a fluorescent dye with an emission wavelength of about 840 nm, which is selectively absorbed by the liver after intravenous or bile duct injection, and then it is excreted into the intestines through the biliary system. With the rapid development of fluorescence laparoscopy, ICG fluorescence imaging is safe, feasible, and widely used in hepatobiliary surgery. ICG fluorescence imaging is of great significance in precise preoperative and intraoperative localization of liver lesions, real-time visualization of hepatic segmental anatomy, intrahepatic and extrahepatic biliary tract visualization, and liver transplantation. ICG fluorescence imaging facilitates efficient intraoperative hepatobiliary decision-making and improves the safety of minimally invasive hepatobiliary surgery. Advances in imaging systems will increase the use of fluorescence imaging as an intraoperative navigation tool, improving the safety and accuracy of open and laparoscopic/robotic hepatobiliary surgery. Herin, we have reviewed the status of ICG applications in hepatobiliary surgery, aiming to provide new insights for the development of hepatobiliary surgery.

This study aims to compare the visualization of the cystic duct-common bile duct junction with indocyanine green (ICG) among 3 groups of patients divided according to the difficulty of elective laparoscopic cholecystectomy.

Conducted at a single center, this non-randomized, prospective, observational study encompassed 168 patients who underwent elective laparoscopic cholecystectomy and were assessed with a preoperative risk score to predict difficult cholecystectomies, including clinical factors and radiological findings. Three groups were identified: low, moderate, and high risk. A dose of 0.25 mg of IV ICG was administered during anesthesia induction and the different objectives were evaluated.

The visualization of the cystic duct-common bile duct junction was achieved in 28 (100%), 113 (91.1%), and 10 (63%) patients in the low, moderate, and high-risk groups, respectively. The high-risk group had longer total operative time, higher conversion, more complications and longer hospital stay. In the surgeon's subjective assessment, ICG was considered useful in 36% of the low-risk group, 58% in the moderate-risk group, and 69% in the high-risk group. Additionally, there were no cases where ICG modified the surgeon's surgical approach in the low-risk group, compared to 11% in the moderate-risk group and 25% in the high-risk group (p < 0.01).

The results of this study confirm that in the case of difficult cholecystectomies, the visualization of the cystic duct-common bile duct junction is achieved in 63% of cases and prompts a modification of the surgical procedure in one out of four patients.

The judgment of the division point of the bile duct has always been one of the difficulties of laparoscopic left lateral sectionectomy (LLLS). The purpose of this study was to assess the effects of indocyanine green (ICG) fluorescence cholangiography during LLLS on the occurrence of biliary complications in both donors and recipients. The optimal dose and injection time of ICG were also investigated.

This is a retrospective cohort study. From October 2016 to December 2022, the clinical data of 103 donors who underwent LLLS and relevant recipients were retrospectively analyzed. According to whether ICG fluorescence cholangiography was used, they were divided into a non-ICG group (n=46) and an ICG group (n=57). Biliary complications were observed and the optimal dose and injection time of ICG were explored.

Three donors in the non-ICG group suffered from bile leakage. Four grafts had multiple bile duct openings and biliary complications were observed in the relevant recipients who received these grafts in the non-ICG group. Two recipients had bile leakage, and the other two had biliary stenosis. There was no biliary complications both in donors and recipients in the ICG group. The fluorescence intensity of the liver was 108.1±17.6 at a dose of 0.004 mg/kg 90 minutes after injection, significantly weaker than that at 0.05 mg/kg 30 minutes (200.3±17.6, P=0.001) and 90 minutes after injection (140.2±15.4, P=0.001). The fluorescence intensity contrast value at a dose of 0.004 mg/kg was stronger than that at 0.05 mg/kg, both measured 90 minutes after injection (0.098±0.032 vs. 0.078±0.022, P=0.021).

ICG fluorescence cholangiography is safe and feasible in LLLS. It reduces biliary complications in both donors and recipients. The optimal ICG dose was 0.004 mg/kg, and 90 minutes after injection was the best observation time. ICG fluorescence cholangiography is recommended for routine use in LLLS.

Landmark arteries during endoscopic sinus surgery are currently identified on the basis of anatomy, CT imaging and navigation, and Doppler flowmetry. However, the advantage of intraoperative fluorescence imaging during endoscopic sinus surgery has not been demonstrated. This study aimed to investigate whether Indocyanine Green (ICG) is useful for visualizing landmark arteries during endoscopic sinus and skull base surgery.

Eight patients who underwent endoscopic sinus and pituitary surgeries and consented to study participation were included. After planned procedures were performed as usual, landmark arteries were examined by ICG endoscope. Recorded video and preoperative CT images were analyzed for identification of five landmark arteries: anterior ethmoidal artery (AEA), posterior ethmoidal artery (PEA), internal carotid artery (ICA), sphenopalatine artery (SPA), and postnasal artery (PNA). Identification of arteries was evaluated three grades: identifiable, locatable, unrecognizable.

Eight patients and eleven sides were evaluated. The ICG dose was 2.5 mg/body and a single shot was sufficient for evaluation. 100 % of AEA was identified (9/9 sides), 86 % of PNA (6/7 sides), 56 % of ICA (5/9 sides), and 25 % of PEA and SPA (2/8 sides).

ICG could visualize landmark arteries, even thin arteries like AEA, during endoscopic sinus and skull base surgeries. Visualization was affected by thickness of bone or soft tissue above arteries, blood clots, sensitivity setting, and angle and distance of near-infrared light irradiation. ICG visualization of landmark arteries may help avoid vascular injuries during endoscopic sinus and skull base surgeries, particularly of AEA, PNA and ICA.

Near-infrared fluorescence (NIRF) angiography with intraoperative administration of indocyanine green (ICG) has rapidly disseminated in clinical practice. Another clinically approved, and widely available dye, methylene blue (MB), has up to now not been used for this purpose. Recently, we demonstrated promising results for the real-time evaluation of intestinal perfusion using this dye. The primary aim of this study was to perform a quantitative analysis of bowel perfusion assessment for both ICG and MB.

Four mature female Landrace pigs underwent laparotomy under general anesthesia. An ischemic bowel loop with five regions of interest (ROIs) with varying levels of perfusion was created in each animal. An intravenous (IV) injection of 0.25 mg/kg-0.50 mg/kg MB was administered after 10 min, followed by NIRF imaging in MB mode and measurement of local lactate levels in all corresponding ROIs. This procedure was repeated in ICG mode (IV dose of 0.2 mg/kg) after 60 min. The quest spectrum fluorescence camera (Quest Medical Imaging, Middenmeer, The Netherlands) was used for NIRF imaging of both MB and ICG.

Intraoperative NIRF imaging of bowel perfusion assessment with MB and ICG was successful in all studied animals. Ingress (i/s) levels were calculated and correlated with local lactate levels. Both MB and ICG ingress values showed a significant negative correlation (r = - 0.7709; p =  < 0.001; r = - 0.5367, p = 0.015, respectively) with local lactate levels. This correlation was stronger for MB compared to ICG, although ICG analysis showed higher absolute ingress values.

Our fluorescence quantification analysis validates the potential to use MB for bowel perfusion assessment besides the well-known and widely used ICG. Further human studies are necessary to translate our findings to clinical applications.

Intraoperative bile duct injury is a significant complication in laparoscopic cholecystectomy (LC). Near-infrared fluorescence cholangiography (NIFC) can reduce this complication. Therefore, determining the optimal indocyanine green (ICG) dosage for effective NIFC is crucial. This study aimed to determine the optimal ICG dosage for NIFC.

This was a prospective, randomized, double-blind clinical trial at a single tertiary referral center, including 195 patients randomly assigned to three groups: lower dose (0.01 mg/BMI) ICG (n = 63), medium dose (0.02 mg/BMI) ICG (n = 68), and higher dose (0.04 mg/BMI) ICG (n = 64). Surgeon satisfaction and detection rates for seven biliary structures were compared among the three dose groups.

Demographic parameters did not significantly differ among the groups. The medium dose (72.1%) and higher dose ICG groups (70.3%) exhibited superior visualization of the common hepatic duct compared to the lower dose group (41.3%) (p < 0.001). No differences existed between the medium and higher dose groups. Similar trends were observed for the common bile duct and cystic common bile duct junction.

In patients undergoing fluorescent laparoscopic cholecystectomy, the 0.02 mg/BMI dose of indocyanine green demonstrated better biliary structure detection rates than the 0.01 mg/BMI dose and was non-inferior to the 0.04 mg/BMI dose.

Cholecystectomy is indicated for gallbladder mucoceles (GBM). Evaluating the patency of the biliary duct and precise biliary tree visualization is crucial for reducing the risk of compromised bile flow after surgery. Therefore, intraoperative cholangiography (IOC) is recommended during cholecystectomy to prevent biliary tract injury. Although indocyanine green (ICG) cholangiography has been extensively reported in human medicine, only one study has been conducted in veterinary medicine. Therefore, this study aimed to demonstrate the use of ICG for IOC to identify fluorescent biliary tract images and determine the patency of the common bile duct during cholecystectomy in dogs. This study comprised 27 dogs, consisting of 17 with gallbladder mucoceles (GBM) and 10 controls, specifically including dogs that had undergone elective cholecystectomy for GBM. ICG injection (0.25 mg/kg) was administered intravenously at least 45 minutes before surgery. During the operation, fluorescent images from cholangiography were displayed on the monitor and obtained in black-and-white mode for the comparison of fluorescence intensity (FI). The FI values of the gallbladders (GBs) and common bile duct (CBD) were measured using FI analyzing software (MGViewer V1.1.1, MetapleBio Inc.). The results demonstrated successful CBD patency identification in all cases. Mobile GBM showed partial gallbladder visibility, whereas immobile GBM showed limited visibility. Additionally, insights into the adequate visualization of the remaining extrahepatic biliary tree anatomy were provided, extending beyond the assessment of CBD patency and gallbladder intensity. Our study demonstrates the potential of fluorescent IOC using intravenous injection of ICG for assessing the patency of the cystic duct and common bile duct during cholecystectomy in patients with GBM, eliminating the need for surgical catheterization and flushing of the biliary ducts. Further research is warranted to investigate and validate the broader applicability of ICG cholangiography in veterinary medicine.

To determine the effect of indocyanine green (ICG) dose and timing of administration on near-infrared fluorescence (NIRF) imaging of the normal canine biliary tree.

Preclinical prospective study.

Eight purpose-bred beagles.

The dogs were randomized to receive two of four intravenous ICG dose (low [L]:0.05 mg/kg or high [H]:0.25 mg/kg)/time (0 and 3 h prior to NIRF) combinations. NIRF images were collected every 10 min for 120 min. Target (cystic duct)-to-background (liver) ratios were calculated for all timepoints and compared.

ICG cholangiography was successful in all dogs. The contrast ratio was above 1 in the L0 group by 20 min and reached its peak at 100 min. In the H0 group, the ratio was above 1 by 60 min and reached its peak at 90 min. Contrast ratios above 2 (fluorescence twice as bright in the cystic duct compared to the liver) were maintained from 180 to 300 min for L3 and H3 and was achieved after 80 min for L0.

Low dose ICG provided better ratios early after injection compared to the high dose which remained highly concentrated in the liver tissue after injection. Both doses provided excellent visualization of the biliary tree at 3 h post injection, low dose ICG provided better ratios from 3 to 5 h post injection. Based on these results, 0.05 mg/kg of ICG administered at anesthetic premedication, or as early as 3 h prior to laparoscopic surgery should yield optimal fluorescence images.

This study provides guidelines for NIRF cholangiography in clinically normal dogs.

Laparoscopic cholecystectomy (LC) remains one of the most commonly performed procedures in adult and paediatric populations. Despite the advances made in intraoperative biliary anatomy recognition, iatrogenic bile duct injuries during LC represent a fatal complication and consist an economic burden for healthcare systems. A series of methods have been proposed to prevent bile duct injury, among them the use of indocyanine green (ICG) fluorescence. The most commonly reported method of ICG injection is the intravenous administration, while literature is lacking studies investigating the direct intragallbladder ICG injection. This narrative mini-review aims to assess the potential applications, usefulness, and limitations of intragallbladder ICG fluorescence in LC. Authors screened the available international literature to identify the reports of intragallbladder ICG fluorescence imaging in minimally invasive cholecystectomy, as well as special issues regarding its use. Literature search retrieved four prospective cohort studies, three case-control studies, and one case report. In the three case-control studies selected, intragallbladder near-infrared cholangiography (NIRC) was compared with standard LC under white light, with intravenous administration of ICG for NIRC and with standard intraoperative cholangiography (IOC). In total, 133 patients reported in the literature have been administered intragallbladder ICG administration for biliary mapping during LC. Literature includes several reports of intragallbladder ICG administration, but a standardized technique has not been established yet. Published data suggest that NIRC with intragallbladder ICG injection is a promising method to achieve biliary mapping, overwhelming limitations of IOC including intervention and radiation exposure, as well as the high hepatic parenchyma signal and time interval needed in intravenous ICG fluorescence. Evidence-based guidelines on the role of intragallbladder ICG fluorescence in LC require the assessment of further studies and multicenter data collection into large registries.

Laparoscopic cholecystectomy is one of the most common gastrointestinal surgeries, and bile duct injury is one of its main complications. The use of real-time indocyanine green fluorescence cholangiography allows the identification of extrahepatic biliary structures, facilitating the procedure and reducing the risk of bile duct lesions. A better visualization of the bile duct may help to reduce the need for conversion to open surgery, and may also shorten operating time. The main objective of this study was to determine whether the use of indocyanine green is associated with a reduction in operating time in emergency cholecystectomies. Secondary outcomes are the postoperative hospital stay, the correct intraoperative visualization of the Calot's Triangle structures with the administration of indocyanine green, and the intraoperative complications, postoperative complications and morbidity according to the Clavien-Dindo classification.

This is a randomized, prospective, controlled, multicenter trial with patients diagnosed with acute cholecystitis requiring emergency cholecystectomy. The control group will comprise 220 patients undergoing emergency laparoscopic cholecystectomy applying the standard technique. The intervention group will comprise 220 patients also undergoing emergency laparoscopic cholecystectomy for acute cholecystitis with prior administration of indocyanine green.

Due to the lack of published studies on ICG in emergency laparoscopic cholecystectomy, this study may help to establish procedures for its use in the emergency setting.

Indocyanine green (ICG) is an injectable fluorochrome that has recently gained popularity as a means of assisting intraoperative visualization during laparoscopic and robotic surgery. Many systematic reviews and meta-analyses have been published. We conducted a meta-review to synthesize the findings of these studies.

PubMed and Embase were searched to identify systematic reviews and meta-analyses coping with the uses of ICG in abdominal operations, including Metabolic Bariatric Surgery, Cholecystectomy, Colorectal, Esophageal, Gastric, Hepato-Pancreato-Biliary, Obstetrics and Gynecology (OG), Pediatric Surgery, Surgical Oncology, Urology, (abdominal) Vascular Surgery, Adrenal and Splenic Surgery, and Interdisciplinary tasks, until September 2023. We submitted the retrieved meta-analyses to qualitative analysis based on the AMSTAR 2 instrument.

We identified 116 studies, 41 systematic reviews (SRs) and 75 meta-analyses (MAs), spanning 2013-2023. The most thoroughly investigated (sub)specialties were Colorectal (6 SRs, 25 MAs), OG (9 SRs, 15 MAs), and HPB (4 SRs, 12 MAs). Interestingly, there was high heterogeneity regarding the administered ICG doses, routes, and timing. The use of ICG offered a clear benefit regarding anastomotic leak prevention, particularly after colorectal and esophageal surgery. There was no clear benefit regarding sentinel node detection after OG. According to the AMSTAR 2 tool, most meta-analyses ranked as "critically low" (34.7%) or "low" (58.7%) quality. There were only five meta-analyses (6.7%) that qualified as "moderate" quality, whereas there were no "high" quality reviews.

Regardless of the abundance of pertinent literature and reviews, surgeons should be cautious when interpreting their results on ICG use in abdominal surgery. Future reviews should focus on ensuring methodological vigor; establishing clear protocols of ICG dose, route of administration, and timing; and improving reporting quality. Other sources of data (e.g., registries) and novel methods of data analysis (e.g., machine learning) might also contribute to an enhanced role of ICG as a decision-making tool in surgery.

Indocyanine green (ICG) is effective for a variety of applications including liver tumour imaging and operates in the near-infrared window. Agents for near-infrared imaging are, however, still in clinical development. The present study aimed to prepare and investigate fluorescence emission properties of ICG in combination with Ag-Au in order to enhance their specific interactions with human hepatocellular carcinoma cell lines (HepG-2). The Ag-Au-ICG complex was prepared via physical adsorption, and hence evaluated for fluorescence spectra using a spectrophotometer. Ag-Au-ICG at an optimised dosage (Ag-Au:ICG = 0.0147:1 molar ratio) in Intralipid medium was added to HepG-2 to observe the maximum fluorescence signal intensity, which further enhanced HepG-2 contrast fluorescence. Ag-Au-ICG served as a fluorescence enhancer bound onto the liposome membrane, whilst free Ag, Au, and pure ICG induced low levels of cytotoxicity in HepG-2 and a normal human cell line. Thus, our findings provided new insights for the liver cancer imaging.HighlightsConcentration-dependent fluorescence peaking in the near-infrared window revealed ICG aggregation in Ag-Au molecules.Ag-Au-ICG fluorescence intensity depended strongly on the environmental media.Human hepatocellular carcinoma cell lines treated with Ag-Au-ICG in Intralipid enhanced the contrast of fluorescence microscopy images by decreasing the level of scattering in the cell lines with the contrast values being approximately five times those observed in pure ICG in Intralipid.

Indocyanine green (ICG) is a fluorescent dye that can be used intraoperatively to assess tissue perfusion, as well as perform leak testing. This study aims to summarize published manuscripts on outcomes of ICG use and reduction of complications compared to traditional leak test and tissue perfusion evaluation. A PubMed search using "ICG and bariatric surgery," "ICG and gastric sleeve," "ICG and gastric bypass," and "ICG and revisional bariatric surgery" was performed. The proportion of patients who underwent an intraoperative decision change due to ICG was 3.8% (95% CI: 2.0 to 7.2%). ICG fluorescent imaging in bariatric surgery is a valuable tool, and further studies are needed to confirm its utility for routine use in both standard or complex cases (PROSPERO #418126).

Ideal visualization of fluorescent cholangiography during laparoscopic cholecystectomy is when maximum fluorescence into biliary ducts and absent signal into liver parenchyma, defined as "signal to background ratio" (SBR), is obtained. Such condition is mainly dependent by indocyanine green (ICG) dose and timing. The aim of this study was to identify the ideal ICG dose to obtain the best possible intraoperative visualization of the extra-hepatic biliary tree.

The first part of the study was used to define a range of small weight-based ICG dosages using the mathematical function bisection method. During the second part of the study, the midpoint dose of the identified range, was tested in 50 consecutive cholecystectomies using a laser-based fluorescence laparoscopic camera (SynergyID system by Arthrex, Naples, FL, USA). Timing administration was set at 1 h before surgery, since this is the most common situation in clinical practice. Fluorescence intensity of bile ducts and liver parenchyma were assessed both subjectively, by blinded operative surgeon, as well as objectively, using an image analysis software (Fiji plugin), before and after Calot's triangle dissection.

Fourteen patients were included in the first part of the study and ICG dose between 0.01191406 and 0.0119873 mg/kg was identified. The second part confirmed previous results after testing the dosage equal to 0.0119 mg/kg (midpoint of the defined range) in 50 consecutive cholecystectomies. Cystic duct was identified in 66 and 100% of cases before and after dissection of Calot's triangle respectively. On the other hand, common bile duct was identified in 82 and 92% before and after dissection respectively. Subjective and objective SBRs confirmed the benefit of the identified ICG dose.

ICG dose calculated by 0.0119 mg/kg administered one hour before surgery allows an ideal intraoperative visualization of the extra-hepatic biliary tree.

ISRCTN10190039.

Indocyanine green (ICG) is a water-soluble fluorescent dye that is minimally toxic and widely used in gastrointestinal surgery. ICG facilitates anatomical identification of structures (e.g., ureters), assessment of lymph nodes, biliary mapping, organ perfusion and anastomosis assessment, and aids in determining the adequacy of oncological margins. In addition, ICG can be conjugated to artificially created antibodies for tumour markers, such as carcinoembryonic antigen for colorectal, breast, lung, and gastric cancer, prostate-specific antigen for prostate cancer, and cancer antigen 125 for ovarian cancer. Although ICG has shown promising results, the optimization of patient factors, dye factors, equipment, and the method of assessing fluorescence intensity could further enhance its utility. This review summarizes the clinical application of ICG in gastrointestinal surgery and discusses the emergence of novel dyes such as ZW-800 and VM678 that have demonstrated appropriate pharmacokinetic properties and improved target-to-background ratios in animal studies. With the emergence of robotic technology and the increasing reporting of ICG utility, a comprehensive review of clinical application of ICG in gastrointestinal surgery is timely and this review serves that aim.

When viewed under near-infrared light, indocyanine green (ICG) signal for kidney perfusion can be utilized in partial nephrectomy. Laser speckle contrast imaging (LSCI) uses coherent light to detect perfusion during real-time laparoscopic surgery.

Laser speckle contrast imaging or ActivSight, an imaging sensor adapter, was used during laparoscopy of an anesthetized porcine kidney model. ActivSight's "perfusion mode" and "quantification mode" displayed the blood flow as a heatmap and numerical signal intensity, respectively.

After the upper segmental renal artery was clamped, ICG was seen in the lower pole, and LSCI showed low unit (dark color) quantification and perfusion in the upper pole. Indocyanine green was retained in the lower pole after the upper segmental artery was unclamped, and LSCI perfusion was demonstrated in the entire kidney.

Laser speckle contrast imaging is a dye-free, repeatable, real-time adjunct for renal parenchymal perfusion assessment applicable to minimally invasive renal surgery to complement the technology of ICG near-infrared fluorescence and advance digital surgery.

(1) Introduction: Near-infrared fluorescence (NIRF) combined with tumour-targeted tracers, such as bevacizumab-800CW, could aid surgical decision-making. This study explored the use of IRDye800CW, conjugated to bevacizumab, with four commercially available NIRF laparoscopes optimised for indocyanine green (ICG). (2) Methods: A (lymph node) phantom was made from a calibration device for NIRF and tissue-mimicking material. Serial dilutions of bevacizumab-800CW were made and ICG functioned as a reference. System settings, working distance, and thickness of tissue-mimicking material were varied to assess visibility of the fluorescence signal and tissue penetration. Tests were performed with four laparoscopes: VISERA ELITE II, Olympus; IMAGE1 S™ 4U Rubina, KARL STORZ; ENDOCAM Logic 4K platform, Richard Wolf; da Vinci Xi, Intuitive Surgical. (3) Results: The lowest visible bevacizumab-800CW concentration ranged between 13-850 nM (8-512 times diluted stock solution) for all laparoscopes, but the tracer was not visible through 0.8 cm of tissue in all systems. In contrast, ICG was still visible at a concentration of 0.4 nM (16,384 times diluted) and through 1.6-2.4 cm of tissue. Visibility and tissue penetration generally improved with a reduced working distance and manually adjusted system settings. (4) Conclusion: Depending on the application, bevacizumab-800CW might be sufficiently visible with current laparoscopes, but optimisation would widen applicability of tumour-targeted IRDye800CW tracers.

Proteinoids-simple polymers composed of amino acids-were suggested decades ago by Fox and coworkers to form spontaneously by heat. These special polymers may self-assemble in micrometer structures called proteinoid microspheres, presented as the protocells of life on earth. Interest in proteinoids increased in recent years, in particular for nano-biomedicine. They were produced by stepwise polymerization of 3-4 amino acids. Proteinoids based on the RGD motif were prepared for targeting tumors. Nanocapsules form by heating proteinoids in an aqueous solution and slowly cooling to room temperature. Proteinoid polymers and nanocapsules suit many biomedical applications owing to their non-toxicity, biocompatibility and immune safety. Drugs and/or imaging reagents for cancer diagnostic, therapeutic and theranostic applications were encapsulated by dissolving them in aqueous proteinoid solutions. Here, recent in vitro and in vivo studies are reviewed.

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.

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.

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.

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.

One of the most severe complications in laparoscopic cholecystectomy (LC) is intraoperative bile duct injury (BDI). Despite its low incidence, the medical implications for the patient can be serious. Besides, BDI can also generate significant legal issues in healthcare. Different techniques have been described to reduce the incidence of this complication, and near-infrared fluorescence cholangiography with indocyanine green (NIRFC-ICG) is one of the latest additions. In spite of the great interest aroused by this procedure, there are currently great disparities in the usage or administration protocols of ICG.

This is a randomised, multicentre, per-protocol analysis, open clinical trial with four arms. The estimated duration of the trial is 12 months. The aim of the study is to analyse whether there are differences between the dose and administration ICG intervals to obtain good-quality NIRFC during LC. The primary outcome is the degree of identification of critical biliary structures during LC. In addition, different factors will be analysed that may have an influence on the results of this technique.

The trial will be conducted according to the recommendations for Clinical Trials in the Declaration of Helsinki Ethical Principles for Medical Research Involving Human Subjects and the recommendations of the Spanish Agency of Medicines and Medical Devices (AEMPs) for clinical trials. This trial was approved by the local institutional Ethics Committee and the AEMPs. The results of the study will be presented to the scientific community through publications, conferences or other means.

2022-000904-36.

V.1.4, 2 June 2022 TRIAL REGISTRATION NUMBER: NCT05419947.

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.

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.

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).

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.

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.

We aim to assess the impact of camera positioning on the displayed NIR signal across different open and laparoscopic camera systems.

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.

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.

Optimal clinical use and signal computational development requires detailed appreciation of system behaviors.

This article aims to analyze and to simplify the optimal dose and time of intravenous indocyanine green (ICG) administration to achieve the identification of the cystic duct and the common bile duct (CBD).

A consecutive series of 146 patients was prospectively analyzed and divided into three groups according to the time of ICG administration: at induction of anesthesia group (20-30 min); hours before group (between 2 and 6 h); and the day before group (≥6 h); and two groups according to the dose of ICG: 1 cc (2.5 mg) or weight-based dose (0.05 mg/kg).

The CBD was better visualized in the at induction of anesthesia group (85.4%), in the hours before group (97.1%) (p = 0.002) and in the 1cc group (p = 0.011). When we analyzed the 1 cc group (n = 126) a greater visualization of the CBD was observed in the at induction of anesthesia group (86.7%) and in the hours before group (97.1%) (p = 0.027).

Due to its simplicity and reproducibility, we suggest a dose of 2.5 mg administered 2-6 h before the procedure is the optimal. However, ICG administered 30 min prior to the surgery is enough for adequate visualization of biliary structures.

To determine if laser speckle contrast imaging (LSCI) mitigates variations and subjectivity in the use and interpretation of indocyanine green (ICG) fluorescence in the current visualization paradigm of real-time intraoperative tissue blood flow/perfusion in clinically relevant scenarios.

De novo laparoscopic imaging form-factor detecting real-time blood flow using LSCI and blood volume by near-infrared fluorescence (NIRF) of ICG was compared to ICG NIRF alone, for dye-less real-time visualization of tissue blood flow/perfusion. Experienced surgeons examined LSCI and ICG in segmentally devascularized intestine, partial gastrectomy, and the renal hilum across six porcine models. Precision and accuracy of identifying demarcating lines of ischemia/perfusion in tissues were determined in blinded subjects with varying levels of surgical experience.

Unlike ICG, LSCI perfusion detection was real time (latency < 150 ms: p < 0.01), repeatable and on-demand without fluorophore injection. Operating surgeons (n = 6) precisely and accurately identified concordant demarcating lines in white light, LSCI, and ICG modes immediately. Blinded subjects (n = 21) demonstrated similar spatial-temporal precision and accuracy with all three modes ≤ 2 min after ICG injection, and discordance in ICG mode at ≥ 5 min in devascularized small intestine (p < 0.0001) and in partial gastrectomy (p < 0.0001).

Combining LSCI for near real-time blood flow detection with ICG fluorescence for blood volume detection significantly improves precision and accuracy of perfusion detection in tissue locations over time, in real time, and repeatably on-demand than ICG alone.

Incorrect assessment of tissue perfusion carries a significant risk of complications in surgery. The use of near-infrared (NIR) fluorescence imaging with Indocyanine Green (ICG) presents a possible solution. However, only through quantification of the fluorescence signal can an objective and reproducible evaluation of tissue perfusion be obtained. This narrative review aims to provide an overview of the available quantification methods for perfusion assessment using ICG NIR fluorescence imaging and to present an overview of current clinically utilized software implementations.

PubMed was searched for clinical studies on the quantification of ICG NIR fluorescence imaging to assess tissue perfusion. Data on the utilized camera systems and performed methods of quantification were collected.

Eleven software programs for quantifying tissue perfusion using ICG NIR fluorescence imaging were identified. Five of the 11 programs have been described in three or more clinical studies, including Flow® 800, ROIs Software, IC Calc, SPY-Q™, and the Quest Research Framework®. In addition, applying normalization to fluorescence intensity analysis was described for two software programs.

Several systems or software solutions provide a quantification of ICG fluorescence; however, intraoperative applications are scarce and quantification methods vary abundantly. In the widespread search for reliable quantification of perfusion with ICG NIR fluorescence imaging, standardization of quantification methods and data acquisition is essential.

In hepatobiliary surgery, intra-operative indocyanine green (ICG) fluorescence imaging use started in the late 2000s with Japanese surgical teams and is now gaining popularity among surgeons all over the world to improve accuracy and safety of surgical procedures. However, even if ICG fluorescence has been shown to be a safe imaging modality, only a few clinical efficacity studies have been performed and no guidance has been established. This narrative review aims at assessing the potential applications of ICG fluorescence imaging in hepatobiliary surgery.

We screened the available international literature to identify the most used applications of ICG fluorescence imaging in hepatobiliary surgery.

Three main fields were identified: biliary duct visualization, hepatic segments' delimitation, and liver tumor detection. Comments, application protocols, prospects, and limitations of each technique were described.

These results could guide hepatobiliary surgeons in their use of ICG fluorescence imaging; nevertheless, further prospective studies are needed to assess the sensitivity and specificity of this modality.

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.

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.

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.

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.

Indocyanine green (ICG) is commonly used to assess perfusion, but quality defining features are lacking. We sought to establish qualitative features of esophageal ICG perfusion assessments, and develop an esophageal anastomotic scorecard to risk-stratify anastomotic outcomes.

Single institution, retrospective analysis of children with an intraoperative ICG perfusion assessment of an esophageal anastomosis. Qualitative perfusion features were defined and a perfusion score developed. Associations between perfusion and clinical features with poor anastomotic outcomes (PAO, leak or refractory stricture) were evaluated with logistic and time-to-event analyses. Combining significant features, we developed and tested an esophageal anastomotic scorecard to stratify PAO risk.

From 2019 to 2021, 53 children (median age 7.4 months) underwent 55 esophageal anastomoses. Median (IQR) follow-up was 14 (10-19.9) months; mean (SD) perfusion score was 13.2 (3.4). Fifteen (27.3%) anastomoses experienced a PAO and had significantly lower mean perfusion scores (11.3 (3.3) vs 14.0 (3.2), p = 0.007). Unique ICG perfusion features, severe tension, and primary or rescue traction-induced esophageal lengthening [Foker] procedures were significantly associated with PAO on both logistic and Cox regression. The scorecard (range 0-7) included any Foker (+2), severe tension (+1), no arborization on either segment (+1), suture line hypoperfusion >twice expected width (+2), and segmental or global areas of hypoperfusion (+1). A scorecard cut-off >3 yielded a sensitivity of 73% and specificity of 93% (AUC 0.878 [95%CI 0.777 to 0.978]) in identifying a PAO.

A scoring system comprised of qualitative ICG perfusion features, tissue quality, and anastomotic tension can help risk-stratify esophageal anastomotic outcomes accurately.

Diagnostic - II.

Near-infrared indocyanine green fluorescence cholangiography (NIRF) has shown promising results on delineating extra-hepatic biliary anatomy during laparoscopic cholecystectomy to avoid bile duct injury. However its routine usage remains in question. In this study, the technique was evaluated further with learning curve estimation and learning factors were observed.

One hundred ninety-nine cases which underwent laparoscopic cholecystectomy for acute or chronic cholecystitis within a 2-year period including 51 cases with initial use of NIRF by 2 surgeons were studied retrospectively. The learning curve was evaluated for a surgeon as primary objective. A case-matched comparison of the operative time between NIRF and conventional group, in terms of acute and chronic cholecystitis was also conducted as a secondary calculation.

Learning curve was evaluated with 61% learning rate for NIRF experience. Cysto-biliary junction non-illuminated cases under fluorescent view, had mean operative time of 80.83 ± 22.82 min, which was shorter than the cysto-biliary junction illuminated cases. The NIRF group exhibited longer operative time compared with the conventional group with mean difference of 34.39 min (significant at P < .05).

While the initial learning phase might be affected by surgeons' behavior and attitude, our results may provide a reference to learn at one's own pace and to employ NIRF teaching strategies during surgical training programs to overcome the initial phase during training period itself and facilitate universal achievement.

Laparoscopic cholecystectomy (LC) is one of the most frequently performed gastrointestinal surgeries worldwide. Bile duct injury (BDI) represents the most serious complication of LC, with an incidence of 0.3%-0.7%, resulting in significant perioperative morbidity and mortality, impaired quality of life, and high rates of subsequent medico-legal litigation. In most cases, the primary cause of BDI is the misinterpretation of biliary anatomy, leading to unexpected biliary lesions. Near-infrared fluorescent cholangiography is widely spreading in clinical practice to delineate biliary anatomy during LC in elective and emergency settings. The primary aim of this article was to perform an up-to-date overview of the evolution of this method 12 years after the first clinical application in 2009 and to highlight all advantages and current limitations according to the available scientific evidence.

Surgery is the mainstay of treatment for resectable gallbladder cancer. Near-infrared fluorescence (NIRF) imaging using ICG is an innovation in laparoscopic surgery, which can provide real-time navigation during the whole operation. In this article, we present a 56-year older woman with gallbladder cancer, in which we evaluated the applicability of NIRF imaging using ICG for tumor and biliary tree visualization during the operative procedure of gallbladder cancer. The tumor and biliary tree were clearly visualized by utilizing a green fluorescence dye. The patient was successfully operated radical resection of gallbladder cancer under fluorescence laparoscope, without any complications. According to this case, the utilization of ICG based NIRF imaging is feasible and beneficial in identifying tumors and the biliary tree during radical resection. It can assist in the achievement of a negative margin and lymphatic clearance around the biliary tree. However, further studies are needed to corroborate the results of this case.

This study aims to evaluate the extrinsic effects of conditional factors affecting quantitative parameters and to establish the optimization of indocyanine green (ICG) angiography using in vitro experiments and a prospective observational study.

In vitro experiments were performed to evaluate the correlation between conditional factors such as camera distance, surrounding lighting, fluorescence emission sources and ICG doses. The fluorescence intensity was measured from the ICG-containing test tube in each condition. In the clinical study, ICG angiography was applied to patients with colorectal cancer (n = 164). The quantitative perfusion parameters were the maximal fluorescence intensity (F_MAX ), slope, T_1/2MAX and perfusion time ratio (TR). Camera position, distance to colon, fluorescence emission source, surrounding lighting, site of angiography and ICG specific mode were considered as conditional factors and compared with the quantitative parameters to identify the optimal condition of ICG angiography.

The fluorescence intensity had an inverse correlation with distance, and the transitional zone was shown at a distance of 4-5 cm by slope differential. F_MAX , T_1/2MAX and slope were affected significantly by camera distance, site of angiography, fluorescence emission source and ICG mode as conditional factors. On multivariate analysis, F_MAX was independently associated with spectral ICG mode with red inversion, laser mode and camera distance. Conversely, TR was not related to any conditional factors.

Since quantitative parameters of ICG angiography are influenced by various conditions, a standardized protocol is required. The application of ICG specific modes with a constant distance of 4-5 cm can provide optimized fluorescence images.