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Lighting up the lymphatic system

Jul 2009
Amanda D. Francoeur,

A new imaging technique using near-infrared night vision enables researchers to observe the inner workings of the lymphatic system by illuminating the clear fluid moving through tissue. The method could help diagnose lymphedema much sooner while advancing toward a development that could prevent this swelling in cancer patients.

On the basis of insufficient imaging techniques and poor understanding, “lymphatics are the ‘forgotten’ component of the circulatory system,” said Dr. Eva Sevick-Muraca, director of the Center for Molecular Imaging at the University of Texas Health Science Center. However, she added, “now that we are able to routinely visualize lymphatic architecture and function, we are learning new things about the lymphatic system.”

Fluorescent fluid

The lymphatic system is a network of channels that picks up interstitial fluid from tissue, creating lymph, a clear liquid that picks up cell waste and even tumor cells. Because lymphatic fluid is clear, scientists had been unable to see the system in operation. Nuclear practices showed some capability, but imaging was slow to capture fluid movement. Contrast agents for magnetic resonance imaging or x-rays are challenging to administer because the channels are extremely small, further hindering visualization.

To solve these difficulties, Sevick-Muraca and her colleagues – Drs. Milton Marshall, John Rasmussen, I-Chih Tan, Xuejuan Wang, Kristen Adams, Melissa Adams and Sunkuk Kwon from the center, and Drs. Caroline E. Fife, Latisha Smith, Renie Guilliod and Erik A. Maus from Memorial Hermann Hospital Lymphedema Clinic – developed a method of viewing lymph by using a night-vision camera, a small laser and a minuscule dose of fluorescent dye.

A lymphedema patient is shown with normal circulation of the lymphatic system in the left arm (top), and fluid retention and swelling in the right (bottom). By understanding how the lymphatic system works, researchers can experiment with massage devices to identify the effects of the therapy and determine its use with treatment.

The researchers administered a contrast medium, indocyanine green, just below the skin so that the lymphatic system could seize it, then used a laser at the tissue’s surface that emitted less than 1.9 mw/cm2 of excitation light. After exciting the fluorophores within the tissue at 785 nm, a military-grade, near-infrared-sensitive image intensifier and a custom charge-coupled camera photographed the fluorescence at 830 nm.

Video created

They also created a video to help visualize a functioning lymphatic system. “The camera integrated measurements for 200 ms, and the resulting images were compiled to generate a movie of lymphatic movement,” Sevick-Muraca said.

Another important factor of the study, she said, was being able to significantly limit the amount of contrast agent needed to perform the imaging. Called microdosing, the process helps reduce the risk of any adverse effects that may occur.

The lymphatic system can fail to drain the standard 6 liters of fluid per day and become backed up. This can cause fluid retention, or swelling, which could lead to lymphedema.

Many patients who undergo surgery and have their lymphatic system disturbed are at risk of developing lymphdema. Sevick-Muraca said that patients with melanoma, prostate or breast cancer who have had lymph node resections are more prone to experience lymphedema after surgery.

Currently, there is no cure for lymph-edema, but the researchers are conducting clinical experiments to determine the effects of massage devices that may treat the problem. They also are developing a comparative technique to visualize the system and its operation in animals. By using animal models, the process might lead to the discovery of pharmacological advancements and the recognition of genetic associations with lymphatic maladies.

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