Transforming biliary surgery: Innovations in fluorescence-guided imaging and indocyanine green application

Abstract

In this editorial, we comment on the article by Li et al. We specifically focus on the novel use of multicolor near-infrared fluorescence imaging (MCFI) with indocyanine green in laparoscopic cholecystectomy, which is an innovative approach for enhancing biliary visualization during laparoscopic cholecystectomy. This study also highlighted the limitations of conventional single-color fluorescence imaging (SCFI), which relies solely on a green fluorescence signal, leading to challenges such as visual fatigue and difficulty in distinguishing biliary structures from background hepatic tissue. Given the complex anatomy of the biliary system and the challenges of visual fatigue encountered with SCFI, MCFI addresses these issues by enabling the differentiation of biliary structures by mapping the fluorescence intensity across a unique blue-to-purple color spectrum, thus improving the clarity of anatomical structures and reducing the visual strain for surgeons. We also focus specifically on the complications and cautious usage of indocyanine green in this context, as well as the advantages and disadvantages of MCFI and SCFI. Overall, MCFI represents a significant advancement in fluorescence-guided surgery, with the potential to become a standard imaging modality for safer and more effective laparoscopic procedures.

Key Words: Indocyanine green; Near-infrared fluorescence; Fluorescence imaging; Multicolor fluorescence imaging; Laparoscopic cholecystectomy

Core Tip: Multicolor near-infrared fluorescence imaging using indocyanine green has emerged as a transformative tool in laparoscopic cholecystectomy, enhancing the real-time visualization of biliary anatomy and reducing bile duct injuries. This innovative technique improves the identification of critical structures, such as the cystic and common bile ducts even in challenging cases involving inflammation or anatomical variations. By offering superior safety, cost-effectiveness, and the potential for surgical training, indocyanine green fluorescence cholangiography demonstrates advantages over conventional methods. However, challenges such as tissue penetration and workflow integration require further investigation through standard protocols and multicenter trials to establish its role as a standard of care.

INTRODUCTION

Laparoscopic cholecystectomy (LC) is reportedly the most commonly performed treatment for gallbladder disease worldwide, but it is not free of complications. A rare but severe complication is bile duct injury, which is most commonly caused by anatomic interpretation errors. In contrast, traditional approaches, such as conventional intraoperative cholangiography, have limitations that include radiation exposure and increased procedural time[1,2]. Fluorescence imaging methods are now widely used in surgical oncology because they optimize the identification of nerves and tumors during surgery and are minimally invasive procedures that provide real-time visualization of anatomical and pathological structures[1,3]. Fluorescence-guided surgery with multicolor near-infrared fluorescence imaging (MCFI) using indocyanine green (ICG) is an effective innovation in intraoperative imaging [4] that improves anatomical guidance and decisions during surgery[5].

MCFI TECHNOLOGY

MCFI with a single RGB-infrared complementary metal-oxide-semiconductor sensor is a low-cost, compact imaging system that helps to detect tumors (Table 1). Agents such as ICG enhance deep-tissue imaging with little scattering and minimal tissue absorption in the near-infrared spectrum[6]. The real-time simultaneous acquisition of visible light and fluorescence signals available in devices with RGB-infrared complementary metal-oxide-semiconductor sensors allows for precise mapping of important structures during surgical procedures. Development of multicolor fluorescence imaging was a major step in improving cancer detection by providing an alternative to dependence on a single targeted fluorescence signal[6].

Table 1 Comparison of imaging methods in laparoscopic cholecystectomy.

Feature	Multicolor fluorescence imaging	Single-color fluorescence imaging	Non-ICG methods (white-light or conventional IOC)
Fluorescence signal	Multicolor spectrum (blue-to-purple)	Single green fluorescence	No fluorescence
Visualization of biliary anatomy	Enhanced differentiation of structures	Moderate clarity, visual fatigue risk	Poor visualization without contrast agents
Impact on surgeon fatigue	Reduced visual strain due to color mapping	Higher visual strain from single-color imaging	No impact from fluorescence, but relies on other techniques
Effectiveness in complex cases	Effective in inflammatory edema, fatty liver	Limited in complex cases	High dependency on contrast agents or preoperative imaging
Risk of liver fluorescence contamination	Lower	Higher	N/A
Cost and accessibility	Higher cost, newer technology	Lower cost, widely available	Varies, IOC requires X-ray and contrast dye
Safety concerns	Minimal toxicity, but requires further validation	Minimal toxicity	Exposure to radiation (IOC) and risk of bile duct injury

ICG: Indocyanine green; IOC: Intraoperative colonoscopy; N/A: Not applicable.

ROLE OF ICG IN CHOLECYSTECTOMY

ICG fluorescence clearly delineates biliary anatomy by highlighting extrahepatic bile ducts during LC, even in difficult cases, such as acute cholecystitis or anatomical variations[7]. For example, ICG fluorescence cholangiography can clearly visualize biliary structures, such as the cystic duct and variant hepatic ducts, but it may not be clear for ducts affected by inflammation and edema. Some of the striking findings in cases studied by Wu et al[7] were abnormal ductal confluence and compression caused by gallstones. The value of ICG in identifying anatomical anomalies is crucial for preventing bile-duct injury during LC, as the anomalies have incidence rates of only 0.3%-3%[7]. Koong et al[8] demonstrated the ability of enhanced visualization of extrahepatic ducts by ICG fluorescence to improve the safety of the dissection of Calot’s triangle, even in the presence of fibrosis or scarring[8]. ICG fluorescence may also lead to decreased healthcare costs and improved surgical training, but more studies with large sample sizes are needed to fully support those benefits[8].

CHALLENGES OF FLUORESCENCE-GUIDED LAPAROSCOPIC SURGERY

Fluorescence-guided laparoscopic surgery faces several notable challenges (Table 2). Despite its benefits, fluorescence imaging is hindered by signal weakening from overlying tissue, which reduces visibility and enhances signal disruption by the surrounding surgical lights during open procedures. Distinguishing malignant tissues from benign tissues can be challenging because of overlapping sensitivity profiles[9]. Fluorescence-guided imaging techniques have shown false-positive rates owing to nonspecific-dye accumulation in benign tissue[5]. White-light illumination provides surgeons with the best visualization of the surgical field, particularly for assessing bleeding. However, transitioning between imaging modes may interrupt the surgical workflow and lead to delay[10]. Large molecules used in fluorescence imaging, such as monoclonal antibodies, tend to delay optimal imaging. For example, nonspecific agents may take up to 7 days after injection to provide adequate tumor contrast. Additionally, interactions between monoclonal antibodies and immune effector cells can produce misleading fluorescence signals that further complicate tumor detection[9]. Fluorescence imaging with infrared light is better suited for shallow lesions because of its limited depth of tissue penetration[5]. Variations in timing, dose, and mode of dye application significantly influence study outcomes[5].

Table 2 Advantages, disadvantages, and clinical applications of multicolor fluorescence imaging and single-color fluorescence imaging.

Factor	Multicolor fluorescence imaging	Single-color fluorescence imaging
Advantages	Enhanced anatomical differentiation; reduced visual fatigue for surgeons; improved visualization in complex cases	Simple and effective for routine case; more accessible and lower cost; established in current surgical practice
Disadvantages	Higher cost and limited availability; requires additional training for surgeons; need for standardization in protocols	Increased visual fatigue; poor performance in complex cases (e.g., severe inflammation, fatty liver); higher risk of liver fluorescence contamination
Clinical applications	Laparoscopic cholecystectomy, especially in complex biliary anatomy; potential applications in oncologic and colorectal surgeries; could be integrated into robotic-assisted procedures	Routine laparoscopic cholecystectomy; may be sufficient for standard biliary imaging; already widely used in clinical practice

FUTURE PERSPECTIVES

The evidence provided by Koong et al[8] encourages performing additional studies to determine whether ICG fluorescence has a role in teaching LC to aspiring surgeons by facilitating the training of less skilled practitioners. It has the potential to decrease the time and cost of procedures, especially for complicated gallbladder surgery[5]. Moreover, standardization of the dose, timing, and concentration of ICG administration is needed to achieve comparable study results (Table 2)[8]. It has been proposed that concrete guidelines be established within this surgical community[1]. Large, multicenter randomized controlled trials are justified to confirm the long-term improvement of surgical outcomes by near-infrared fluorescence imaging and whether it could become the standard of care in LC[2,8]. A study by Oh et al[6] found that reducing the outer diameter of the RGB-infrared imaging system was required for integration into endoscopic imaging before it could be used in minimally invasive procedures, such as screening of the gastrointestinal tract. This modification aimed to improve the clinical adaptability and practicality of the system[6].

CONCLUSION

The use of MCFI imaging with ICG in LC procedures was shown to benefit the intraoperative visualization of the biliary anatomy. It improved the safety of surgical dissection by identifying key structures, such as the cystic duct, common bile duct, and common hepatic duct in real time. Li et al[4] showed that near-infrared fluorescent-cholangiography significantly assisted surgeons by visualizing the biliary anatomy throughout the entire surgical procedure. It was useful for patients with normal body mass indexes (< 25 kg/m²) but was most valuable for those with high indexes (> 25 kg/m²). Other strengths include affordability, minimal toxicity, few reported allergic reactions, a simplified learning curve for surgeons, and seamless integration into robotic systems.