Chapter 1 these optical techniques are near‐infrared fluorescence imaging and diffuse reflectance spectroscopy. Near‐infrared fluorescence imaging using exogenous contrasts Near‐infrared fluorescence imaging is based on the introduction of exogenous contrasts. Fluorescent visualization of tissues can be obtained after administration of a near‐infrared dye or fluorophore (i.e. an exogenous contrast agent with fluorescent characteristics) in combination with a dedicated imaging system, which is sensitive in the invisible near‐infrared (NIR) light spectrum (wavelength range 700‐900 nm). The great advantage of NIR light over visible light is an increased tissue penetration depth, at present up to 10 millimeters. No additional radiological support is needed and no ionizing radiation is involved. NIR fluorophores provide the possibility of tissue‐specific 10 visualization in relation to surrounding tissues: e.g. delineation of vital anatomical structures from their surroundings or under a layer of fatty tissue6, or tumor demarcation from healthy tissue7. Route and timing of administration are factors that influence contrast between the target tissue and the background tissue. Over the past years the NIR fluorescence technique has been introduced for several clinical applications for both anatomical imaging and tumor imaging8‐11. Fluorescence imaging systems for clinical and preclinical research purposes are already available for open9,12, laparoscopic8, and robotic surgery13. Currently only indocyanine green (ICG, 800 nm fluorophore14) and methylene blue (MB, 700 nm fluorophore15) are approved by the Food and Drug Administration (FDA) and clinically available for fluorescence imaging. ICG is rapidly and exclusively excreted into bile, making it useful for biliary imaging6. MB is renally cleared and therefore also useful for ureter imaging16. Other NIR dyes are being developed, but not yet FDA cleared for clinical use. For example, CW800‐CA (a carboxylate of NIR fluorophore IRDye® 800CW, LI‐COR, Lincoln, Nebraska14) is a relatively new fluorophore, which like ICG also has 800 nm fluorescent capabilities. It has equal low risk of toxicity as ICG and incorporates favourable characteristics for fluorescence imaging of vital anatomy. The most advantageous characteristic of CW800‐CA is its increased hydrophilicity, resulting in improved secretion into bile and earlier fluorescence illumination of the bile ducts. Furthermore it is both hepatically and renally cleared, increasing its clinical applicability: e.g. not only bile duct imaging, but also ureteral detection14,15.
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