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Introduction
Background
Indocyanine green (ICG) is a contrast agent with near-infrared spectral properties [1]. Because of its non-radioactive nature, high safety, and minimal impact on liver function, ICG is widely used in the assessment of liver reserve function, diagnosis of liver diseases, and intraoperative navigation during liver surgeries [2]. In the field of anatomical liver resection, where ICG is most widely applied, it primarily achieves fluorescence visualization of liver segments or lobes via “positive staining” or “negative staining” techniques through the portal vein [3]. Compared with traditional techniques, ICG fluorescence staining not only delineates the boundaries of liver segments or lobes on the liver surface but also clearly shows the inter-segmental planes in the deeper parenchyma, especially in areas without hepatic veins. It has thus become an important technical means for precise anatomical liver resection [4, 5, 6–7].
Although laparoscopic anatomical liver resection (LALR) using near-infrared fluorescence (NIF) technology is widely used in the treatment of malignant liver tumors, there is still a lack of high-level clinical evidence to clarify the optimal timing and dosage of ICG injection. In 2021, the guidelines for fluorescence imaging technology in hepatobiliary surgery, led by Wang et al. [3], recommended “slow intravenous injection of 2.5 mg ICG via peripheral veins” when using ICG for negative staining. In 2023, Wakabayashi et al. [8] conducted a systematic review specifically addressing the timing and dosage of ICG for intraoperative navigation in liver surgery. After analyzing 26 studies on negative staining fluorescence imaging in liver resection, they found that the dosage of ICG varied significantly from 0.025 mg to 25 mg. It was discussed that the guideline-recommended dosage by Wang et al. [3] is not necessarily the “optimal” but rather the “most commonly used (without validation by research)” dose, as it is based on data from previous studies. In 2020, Xu et al. [9] reported that the success rate of negative staining in laparoscopic liver resection using 2.5 mg as the ICG injection dose was only 52% (14/27). Current research indicates [10, 11] that after intravenous injection, ICG rapidly binds to plasma proteins and is specifically taken up by hepatocytes, thus enabling real-time visualization of liver tumors and parenchyma. However, ICG also has some limitations, such as poor water solubility, susceptibility to concentration-dependent...