The identification of structures that need to be resected (e.g. tumour tissue, lymph nodes) and structures that need to be spared (e.g. nerves, ureters, bile ducts) is of paramount importance in oncologic surgery. In daily surgical practice, surgeons mainly rely on palpation and visual inspection. However, tumour-positive resection margins and surgical morbidity as a result of damage to vital structures are not uncommon. Thus, there is a need for new intraoperative imaging modalities that can provide real-time assessment of tumour borders and affected lymph nodes, while eliminating the risk of damage to vital structures.
Optical imaging using near-infrared (NIR) fluorescence is a new technique that can be used to visualise structures in real-time during surgery. Advantages of NIR fluorescent light (700–900 nm) include high tissue penetration (millimetres to centimetres deep) and low autofluorescence, thereby providing sufficient contrast [1
]. Because the human eye is insensitive to NIR wavelengths, the use of NIR light does not alter the surgical field. Recently developed intraoperative imaging systems are able to provide simultaneous acquisition of surgical anatomy (white light, colour video) and NIR fluorescence signal [2
]. Therefore, the use of NIR fluorescence imaging could potentially be of great value in the intraoperative detection of critical anatomical structures and oncologic targets.
In addition to NIR fluorescence imaging systems, exogenous NIR fluorescent contrast agents are necessary to visualise specific tissues. Ideally, tumour cells are labelled by targeted contrast agents. However, the only fluorescent contrast agents currently registered by the FDA and EMA for clinical applications are indocyanine green (ICG; peak emission ≈ 820 nm), methylene blue (peak emission ≈ 700 nm), and fluorescein (peak emission ≈ 520 nm, below NIR spectrum). This review is focused on the clinical use of ICG, due to its preferable fluorescent characteristics and widespread use in clinical research. ICG provides a higher signal-to-background ratio because of lower autofluorescence and increased tissue penetration at 820 nm compared to lower wavelengths and has a greater “brightness” (i.e., quantum yield) compared to methylene blue [5
ICG is currently utilised in NIR fluorescence image-guided oncologic surgery for multiple indications. NIR fluorescence imaging has the potential to improve sentinel lymph node (SLN) mapping in multiple types of cancer, by real-time transcutaneous and intraoperative visualisation of lymphatic channels and subsequent detection of the SLN [3
]. Additionally, ICG NIR fluorescence is used for endoscopic marking of colorectal tumours and intraoperative identification of certain solid tumours after intravenous injection [30
]. Moreover, NIR fluorescence angiography using ICG can be used in intraoperative assessment of tissue perfusion in reconstructive surgery for ablative defects following oncologic surgery [33
The aim of this paper is to review the available clinical studies using ICG in NIR fluorescence-guided cancer surgery in order to understand current applications, limitations, and future prospects.