Chapter 11 Near‐infrared fluorescence imaging: limitations and future perspectives As underlined by this thesis, near‐infrared fluorescence imaging enables identification of several vital anatomical structures (e.g. bile ducts, arteries, ureters), even when covered under a layer of fatty tissue. These are all hollow structures that can be delineated using endoluminal transported dyes. For nerve imaging, indirect nerve detection by illumination of a neurovascular bundle has been reported12. Nerve‐specific agents are not yet available for clinical testing. In vivo optical imaging of peripheral nerves using systemically administered myelin‐selective fluorescent dyes in a rat and pig model13 or nerve‐highlighting fluorescent peptides in mice14, have been described though. A new NIR fluorescent dye for use in the design of nerve‐targeted optical imaging probes is also being developed using a rat model15. Besides anatomical imaging, NIRF imaging is extensively explored for image‐guided cancer surgery (e.g. for sentinel lymph node detection in breast cancer, gastric cancer, melanoma and colorectal cancer surgery)16. Compared to conventional radiological imaging techniques, NIRF imaging has already been deemed cost‐effective19. Also, this new optical imaging technique is regarded as a safe, simple method with the great advantage of enabling real‐time imaging of tissues17,18,20‐22. The safety of the clinically approved fluorescent dyes ICG and methylene blue (MB) is supported by the absence of reported adverse reactions in the literature6,17,18,20‐34. To further minimize the risk of a possible adverse reaction to the iodine in ICG8, an iodine‐free preparation of ICG31 can be used for NIRF imaging. NIRF imaging has the potential and promise to become standard clinical practice during minimally invasive surgery when identification of a critical anatomical structure is required. However, this technique still has limitations that require optimization. The first of these limitations is the current state of the NIRF imaging systems. It is obvious that the presently available imaging systems will be subjected to further development to improve performance and user‐friendliness. Presently, the surgeon is merely “left in the dark” when viewing in fluorescence mode, so one of the improvements that can greatly influence the performance of NIRF imaging during surgery would be the ability to merge white light and fluorescence images in real‐time, thereby showing fluorescent structures in their anatomical context. Another limitation of NIRF imaging is the limited penetration depth at which structures can be visualized using the currently available dyes and imaging systems. Various values have been reported in the literature5,35, with a maximum penetration depth found of 10 mm in fatty tissue. Novel fluorescent dyes and dedicated NIRF imaging systems are needed to improve penetration depth, as in surgery essential structures are not seldom covered by a layer of ≥10 mm fatty tissue. 172
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