Indocyanine green lymphangiography

Indocyanine green (ICG) lymphangiography is an emerging imaging technique used to visualize lymphatic vessels and map their course as they drain to sentinel lymph nodes. 

History

Indocyanine green is a fluorescent dye discovered by researchers at Kodak working on near-infrared photography in 1955, and was first approved for clinical use in 1956 ⁶. It took until the mid-1960s to be used for angiography, although it was not until the early 1970s that it became routinely used in ophthalmology for retinal angiography ⁶.

Indocyanine green

Indocyanine green has a broad absorption spectrum from 600 nm and 900 nm, however in plasma it demonstrates peak absorptivity at 760 nm - 780 nm. ICG demonstrates fluorescence behavior with an emission spectrum that extends from 750 nm to 950 nm however in plasma the peak fluorescence wavelength is 830 nm. ICG demonstrates non-linear fluorescence intensity with plasma concentration. 

Biologically ICG is beneficial as it ⁶:

• is restricted to the circulation due to its complexing with plasma proteins
• has a low toxicity
• experiences rapid excretion from the body, virtually solely via the hepatobiliary route

Limitations of ICG include:

• it is not photostable
• it degrades in solutions 
• sodium iodide required in its solutions potentiating its allergenicity
• no chemically-derived indocyanine green compounds exist so it currently cannot be used to target specific antigens 

Indications

Lymphedema

Indocyanine green lymphangiography has been shown to be more diagnostically effective than lymphoscintigraphy for the evaluation of lymphedema ⁷ and its role in the management of lymphedema includes:

• early identification of stage 0 disease
• targeting of manual lymphatic drainage
• delineation of lymphatic channels for surgery including lymphaticovenous anastomosis, lymphaticolymphatic bypass and vascularized lymph node transfer
• postoperative assessment of lymphatic flow after surgery

Procedure

Technique

The indocyanine green lymphangiography technique involves administration of indocyanine green into the region of interest:

• 2.5 mg/mL indocyanine green solution is usually used
• 0.1 mL to 0.4 mL of the ICG solution is injected via intradermal or subcutaneous routes into a webspace or adjacent to a flexural crease e.g. of the wrist or ankle
• the region of interest is then illuminated with a light source emitting from 760 nm to 780 nm while simultaneously imaging in the near-infrared spectrum at 830 nm. Dermal and subdermal lymphatics can be identified to an approximate depth of 15 mm.
• both static and dynamic protocols may be used
• dynamic protocol: the patient receives manual lymphatic massage during imaging to qualitatively evaluate the capacity for drainage in individual lymphatic channels

Complications

• Some indocyanine green preparations may contain iodine compounds and reported side effects with subcutaneous administration include urticaria, pruritus and rarely anaphylaxis