Molecular imaging may shed light on lymphedema

By Ruth SoRelle, M.P.H.

The story of blood and its circulation throughout the body is a familiar one. Less familiar is the story of the lymph system, its role in the body and what happens when it goes wrong. One factor in that lack of awareness may be the fact that it has been – until now – invisible.

Eva Sevick-Muraca, Ph.D., professor of radiology at Baylor College of Medicine and head of that department's division of molecular imaging (http://www.bcm.edu/molecularimaging/), hopes to change that. Already, using near-infrared technology and trace amounts of fluorescent imaging agents, she and her colleagues can show moving images of lymph flowing through lymph vessels in both normal and abnormal tissues of human subjects.

Eventually, she hopes their work will shed new light on many aspects of the lymph system and more specifically, a disease called lymphedema, which affects 100 million people worldwide.

Lymph system

The lymphatic system circulates a protein-rich material called lymph throughout your body. It transports invading organisms such as viruses or bacteria to your lymph nodes where immune responses to these foreign substances are mounted. In addition, the lymphatics help to maintain fluid balance in tissues, by taking up excess fluid filtered from the blood vascular system.

"Lymph is important because it's part of the circulation," said Sevick. "Yet, medical students receive, on average, a few minutes of lecture on the lymphatic system because so little is known about it. However, it plays an important recognized role in obesity, diabetes, and asthma – all diseases of increasing incidence."

Together with translational and molecular medicine graduate student, Ruchi Sharma, Sevick and her colleagues have uncovered new information about the lymph system. Before the team generated images of lymph flow, most experts thought lymph flowed slowly at a velocity of microns (billionths of a meter) per second. "Now we know that lymph flows at centimeters (100th of a meter) per second," Sevick said.

Images of lymph flow

Right now, the research team is generating images of both normal subjects and those with lymphedema, a swelling of the legs and arms that occurs when there is some obstruction of lymph flow. People can be born with lymphedema or it is sometimes acquired through disease or becomes manifest as a result of some injury to the lymph vessels and nodes – often as a result of surgery. Women who have had breast surgery for breast cancer and men who have lymph nodes removed in prostate cancer surgery disease sometimes have lymphedema as a consequence. There is no cure for lymphedema and it is important to be able to prevent or predict those patients who might be susceptible to the disease.

In the division of molecular imaging, staff members under the direction of chemist. Wei Wang, Ph.D., actually synthesize new molecular imaging agents that might one day diagnose which cancer patients might be susceptible to lymphedema after surgery. After administered in small quantities under the skin, these agents are thought to target markers of lymph disease and fluoresce when exposed to a near-infrared light that literally shines through the skin. The fluorescence is captured by near-infrared imaging technology re-engineered for medical imaging.

Near-infrared imaging

The near-infrared imaging technology was first popularized during the first Gulf War, Sevick said, when the night-time war maneuvers were caught and recorded using night vision goggle technology. Today, BCM is the only place that this technology has been re-engineered specifically for diagnostic imaging enabling personalized medicine. With a team of engineers, including John C. Rasmussen who directs instrumentation development in the division, FDA-approved devices are built and used clinically to image lymph flow in projects funded by the American Cancer Society and the National Cancer Institute.

While the technology promises advances in a number of areas, for now Sevick is excited about the potential for imaging lymph flow because like the blood circulation, the lymph circulation is probably associated with a number of prevalent diseases, including asthma, obesity, cancer metastasis, and diabetes.

"This imaging technology might lend some new insight to these diseases," she said.

Quantifying lymph function

The near-infrared imaging technique allows her research team to quantify lymph function in humans. Their results so far show that normal subjects have active propulsion of lymph flow and that people with lymphedema have demonstrably reduced lymph flow that her imaging shows can be improved with therapy. Currently, her studies are designed to determine if people with lymphedema of either a leg or an arm have generally slow lymph flow in the opposite, unaffected limb.

Sevick is also testing the technology's use in identifying cancer cells that cluster in lymph nodes. Often, doctors remove lymph nodes in breast and prostate cancer surgeries to either determine how far the disease has spread or prevent its further spread. If the NIR imaging technology and the use of molecular imaging agents could reduce the need for surgical removal of lymph nodes and eliminate the lymphedema that can consequentially result, then the impact to cancer patients could be substantial.

People who have lymphedema as a result of cancer surgery or family history and who are interested in taking part in Sevick's imaging studies can call 713-798-6003.