What is fluorescence-guided surgery?

  1. What is fluorescence-guided surgery?
  2. Vascular perfusion imaging
  3. Vital structures
  4. Cancer imaging

Fluorescence-guided surgery is an intraoperative optical imaging method that provides surgeons with real-time guidance for the identification and delineation of tumours or vital structures.  

After the administration of a near-infrared dye or fluorophore, exogenous NIRF imaging can be obtained using imaging systems which are sensitive to invisible NIR light spectrum wavelengths of 700 to 900nm. The NIR light wavelength largely determines the degree of penetration of photons into the tissue. In the visible light range, photons have a depth penetration limited to a few millimeters and are suitable to detect superficial targets. However, photons in the NIR range can penetrate up to approximately a centimeter through tissue, which also allows for the detection of targets below the tissue surface.

NIR fluorophores enhance tissue-specific visualization and contrast it with surrounding tissues. Examples include the delineation of vital anatomical structures in relation to their adjacent structures and tumor delineation of healthy tissue. The fluorescence signal can either be visualized directly on the operating field or can be captured through dedicated cameras and displayed on the screen.

Intraoperative NIRF imaging relies on the availability of an intraoperative imaging system and a contrast agent to visualize the target structure/organ during surgery. The basic components of a fluorescence imaging system are (I) an NIR light source, (II) an NIR camera, (III) optics and filters, (IV) instrument control, acquisition and imaging software, and (V) computer, input and imaging hardware.

The most popular current clinical applications in surgery worldwide include fluorescence cholangiography, lymph node identification, real-time detection of cancerous tumors and assessment of tissue perfusion. In addition, fluorescence can also be used for, amongst others, the detection of (the course of) the ureters, the urethra, parathyroid glands and foci of endometriosis.

The selection of the correct dye depends on the target organ/structure. To visualize the anatomical course of the ureter or biliary tract, the selection of a dye that is cleared by the kidney or by the liver respectively, is of utmost importance. Conjugating an NIR dye to a molecule, protein or antibody that targets an extracellular disease marker enables diagnostic molecular imaging, which is a promising method for NIR fluorescence guided resection of cancers. Several dyes are available or currently under development and can be divided into targeted and non-targeted fluorophores. In current clinical practice, non-targeted fluorophores are the most commonly used.

Since ICG has been approved for clinical use for decades, it is the most widely used NIR dye. After administration, ICG is rapidly and exclusively excreted in the bile. The emission peak is at 822 nm and the excitation peak at 807 nm. ICG is known for its established clinical applications, which have facilitated the introduction to new applications.

MB is a weak NIR dye, with NIR properties inferior to those of ICG. The emission peak is at 680 nm and MB is partially excreted in the urine, allowing for visualization of the ureters.

SF has a peak emission wavelength of 520 nm and is FDA-approved for the visualization of the retina and iris vasculature. It is used off-label or for research purposes to visualize fluid structures such as blood, lymph, cerebrospinal fluid or urine, among other things.

With an emission peak at 635 nm, 5-ALA has been used in a wide spectrum of treatments in urology, dermatology, gastroenterology, neurosurgery and gynaecology.

Targeted fluorophores are designed to bind to a specific ligand, allowing the visualization of individual tissue overexpressing this ligand. In particular, targeted fluorophores are being investigated to visualize cancer cells, detect cancer at an early stage, achieve precise tumor delineation and enable radical resection.

The most common route of administering a NIR dye is the intravascular injection of the diluted dye through a peripheral vein. However, depending on the target organ, the dye may be administered by other routes, such as topically, intradermally, intraluminally or via tubes or catheter. Another relatively new method of dye delivery is by coating catheters/tubes/clips with a fluorescent dye so that only the structure into which they are inserted will fluoresce.