Normal linear lymphatic channels
Indocyanine green (ICG) is a green coloured fluorescent dye that has been used in medicine for over 40 years, mainly in ophthalmology for testing blood flow in the eye. ICG fluoresces in the near infrared range and therefore needs a special camera to be seen after injection. When used to test blood flow, large doses of ICG are injected intravenously and a scan is undertaken using an infrared camera. Over the last decade, low dose ICG injected into the subcutaneous tissue has been used to map lymphatics; this is known as ICG lymphography. The ICG binds to a protein called albumin, which is taken up into the lymphatics, and transported within the lymph fluid. In this way the function of the lymphatics can be assessed.
Firstly, after cleaning the skin with antiseptic, both the affected and unaffected arms or legs are injected with a small amount of local anaesthetic to provide a numb patch of skin. Next, both sites are painlessly injected with a tiny dose of ICG, typically 0.1ml (0.5mg) per injection. After a short period of time the infrared camera scans the affected area and a black and white image is displayed on a video screen.
In normally functioning lymphatics, ICG is quickly taken up by the lymphatic system. The dye is rapidly transported in normal linear channels to the groin or armpit. Often, the normal rhythmic contraction of the lymphatics (peristalsis) can be seen pushing the dye up the limb. One-way valves within the lymphatic channels prevent backflow of the fluid, meaning the dye can only flow in one direction.
In secondary lymphoedema, there is a blockage to the normal flow of lymphatic fluid out of the limb. This leads to an increase in pressure within the lymphatic channels, which in turn means that the channels dilate. This causes the one-way valves to become incompetent, and backflow of lymph fluid along the lymphatic channels is now possible. The increased pressure also means that backflow occurs into the microscopic lymphatic vessels that collect lymph fluid from the skin and subcutaneous tissue. The lymph fluid then leaks out into these tissues – so called dermal backflow. This dermal backflow of lymphatic fluid is diagnostic of lymphoedema. As lymphoedema progresses, characteristic dermal backflow patterns are seen on ICG lymphography. Initially, splash-back patterns occur, representing the presence of ICG within the microscopic dermal collecting lymphatics.
With further progression, a stardust pattern occurs. This is indicative of fluid pooling at the open ends of these dermal collecting lymphatics within the skin. In very severe lymphoedema, the dye pools throughout the skin and subcutaneous tissue, leading to a diffuse pattern.
In addition, important information regarding the function of the lymphatics can be gained from assessing the speed of lymphatic transport up the affected limb. Rapid transport of ICG despite the presence of dermal backflow indicates that the underlying lymphatic channels have retained useful function. Conversely, slow transport of dye indicates that the lymphatics have suffered secondary changes.
In primary lymphoedema, the findings on ICG lymphography are variable depending on the precise pathology causing lymphoedema. Some forms of primary lymphoedema are caused by a localized failure of development of part of the lymphatic system and therefore the patterns seen on ICG lymphography are similar to secondary lymphoedema. In other forms of primary lymphoedema there is a developmental problem with the actual lymphatic channels. Uptake and transport of the ICG is severely delayed and the ICG may just diffuse around the injection site, indicating no functioning lymphatics.
ICG lymphography is a very safe technique. Allergic reactions to ICG are very rare in general and no episodes of allergic reactions have ever been reported following the low dose subcutaneous injections used for ICG lymphography. There is a theoretical risk of introducing infection by giving injections into the limb affected by lymphoedema but this is unlikely as sterile needles and antiseptic skin preparation are used routinely. Furthermore, ICG lymphography does not involve exposure to radiation like lymphoscintigraphy. Local anaesthetic is routinely used in order to minimize the pain of injection of ICG. The dye has a green colour and may leave a small green patch of skin, like a bruise, for a few days following the test. After ICG lymphography, you can resume normal activities straight away, for example, it is fine for you to drive yourself home.
Normal linear lymphatic channels
Splash-back pattern of dermal backflow
Stardust pattern of dermal backflow
Diffuse pattern of dermal backflow