The lymphatic vasculature is an integral component of the circulatory and immune systems.1 It is composed of a network of vessels that interconnect the body’s interstitial spaces with the lymphoid organs (lymph nodes, spleen, thymus, and so on) and the systemic circulation. The lymphatic system is essential in maintaining the fluid homeostasis and optimal functioning of the immune system. Unlike the circulation of blood in the vascular system, lymphatic flow occurs through a low-pressure system. The interstitial fluid enters the distal lymphatics which coalesce into conduits of increasing caliber, ultimately draining lymph into the systemic circulation through the thoracic duct.
Lymphatics are found throughout the body, with the exception of the central nervous system, where the cerebrospinal fluid fulfills the role of the lymph. Lymphatic vasculature and lymphoid tissues are prevalent in organs that come in direct contact with the external environment, such as the skin, gastrointestinal (GI) tract, and lungs. This is reflective of the protective role of the lymphatics against infections. In the extremities, the lymphatic system consists of a superficial system that collects lymph from the skin and subcutaneous tissues and a deeper system that drains subfascial structures such as muscle, bone, and deep vasculature. The superficial and deep systems of the upper and lower extremities merge in the axillae and pelvis respectively. The two drainage systems function in an interdependent fashion such that the deep lymphatic system participates in lymph transport from the skin during superficial lymphatic obstruction. The superficial and deep systems drain at markedly different rates. In the normal leg, subfascial transport (the deep system) is slower than the superficial system and transports less lymph.
A wide spectrum of disease states result in an impaired ability of the lymphatic system to collect and transport lymph. Lymphedema is a condition associated with nonpitting swelling or edema usually associated with an extremity caused by an abnormality of the lymphatic system and is often difficult to treat. It is a chronic debilitating disease that is frequently misdiagnosed, treated too late, or not treated at all. It results from impaired lymphatic transport caused by injury to the lymphatics, infection, or a congenital abnormality (hypoplasia or aplasia). Common etiologies include sequelae of breast and pelvic cancer therapy, recurrent infections, injuries, and vascular surgery. Approximately 10 million people have lymphedema secondary to breast and pelvic cancer therapy, recurrent infections, injuries, or vascular surgery. Worldwide, about 90 million people have lymphedema, primarily because of parasitic infection; the most common cause is filariasis caused by Wuchereria bancrofti infection.2
The diagnosis of lymphedema relies heavily on the physical examination. Characteristic clinical findings include edema, peau d’orange, cutaneous fibrosis, and a positive Stemmer sign (inability of the examiner to tent the skin at the base of the digits in the involved extremity). If the diagnosis remains in question, the presence of lymphatic vascular insuffiency can be ascertained through imaging.
Lymphoscintigraphy is a minimally invasive procedure that requires intradermal or subcutaneous injection of the radiotracer.3 It has largely replaced the more invasive and technically difficult technique of contrast lymphangiography.
Technetium-99m (Tc-99m) sulfur colloid, Tc-99m albumin colloid, Tc-99m antimony sulfide colloid, and Tc-99m labeled human serum albumin (HSA) are the primary radiopharmaceuticals available for clinical use. These agents consist of the Tc-99m radiolabel, which is commonly used in clinical nuclear medicine imaging, combined with a microscopic particle that can be transported through the lymphatics. The radiotracer can be given by subcutaneous, intradermal, or subfascial injection. Intradermal injection is associated with rapid lymphatic transport and is the optimal technique for sentinel node lymphoscintigraphy. Subcutaneous injections produce more reliable results in lymphedema patients compared with intradermal injections. Subfascial injections are usually reserved for the evaluation of the deep lymphatic system.
Procedure. A small volume of radiotracer is injected subcutaneously into the first to third web spaces on each hand or foot. Both limbs are evaluated even if one appears normal because the comparison often provides useful information during interpretation. Images are acquired using a high-resolution, parallel-hole collimator. The arrival of the radiotracer at the knees and groin (or elbows and axillae) is timed. A transmission scan using a flood source is useful for anatomical localization. After 30 minutes, if no groin (or axillary) activity is demonstrated, the patient is encouraged to ambulate or exercise the extremities. The exercise maneuvers include walking, leg massage, cycling, repetitive squeezing of a rubber ball, and so on. The patient is then reimaged to see if the proximal lymphatic system is demonstrated. If there is still no activity, the patient is encouraged to ambulate or exercise again, and delayed images are obtained after 3 to 4 hours.
Interpretation. In patients with normal lymphatic anatomy, there should be symmetric transport of the radiotracer through well-defined lymph vessels (three to five lymph vessels in the calf; one or two vessels per thigh) and uptake within proximal lymph nodes bilaterally within 30 minutes of tracer injection. Sometimes the liver may be visualized because of systemic absorption of the radiotracer.
In primary lymphedema, there is characteristically delayed or absent radiotracer transport, absent or paucity of lymph vessels, poorly visualized or absent regional lymph nodes, and occasionally dermal backflow on early images.
In secondary lymphedema, scintigraphic findings include prominent or dilated lymph vessels, disruption of lymphatics, delayed transport of tracer, and dermal backflow on delayed images. If no regional nodes are identified by 30 minutes, reimaging after additional exercise may demonstrate lymph nodal activity.
In some instances, there may be a mixed cause of the lymphedema in which the scintigraphic features of both primary and secondary lymphedema are noted.
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