Penn researchers to develop next-generation lymphatic system imaging with up to $7.8M award

Penn researchers will accelerate the development of advanced imaging methods for the liver and intestinal lymphatic system—critical, but poorly understood components of lymphatic circulation—after being awarded up to $7.8 million from the Advanced Research Projects Agency for Health (ARPA-H) Lymphatic Imaging, Genomics, and pHenotyping Technologies (LIGHT) program. The effort is led by Maxim Itkin, MD, director of the Penn Center for Lymphatic Disorders, together with a multidisciplinary team of imaging and chemistry experts at Penn, Monash University, and 3DT Holdings, and overseen by Kimberley Steele, MD, PhD, a program manager at ARPA-H.

“In many medical conditions, there is a gap between the symptoms someone is experiencing and our understanding of what underlying processes might be causing them,” said Itkin. “We believe that in a large number of conditions, this missing piece is the lymphatic system, if only we could see it.”

The body’s hidden plumbing system

The lymphatic system is a network of tiny vessels that collect fluid from tissues throughout the body and return it to the bloodstream, helping to maintain and “clean” tissue.  Much like a home’s plumbing system, it can become blocked or begin leaking—leading to swelling, fluid buildup, and inflammation.

“While we can use imaging techniques, like angiography, to see blood moving through blood vessels throughout the body, we don’t yet have the technology to be able to see how exactly lymph interacts with tissues and other systems,” said Itkin. “We hope to discover how the lymphatic system works, and contributes to conditions like heart failure, chronic kidney and liver diseases, autoimmune disorders, and possibly even neurodegenerative diseases.”

Millions of Americans live with lymphatic dysfunction, including an estimated 10 million with lymphedema, which is swelling around lymph nodes, primarily in the arms and legs. Because the lymphatic system is not well understood, patients with lymphatic disorders are often misdiagnosed, leading to inappropriate treatments, prolonged symptoms, and avoidable complications.

This project will concentrate on imaging the lymphatic systems of the intestines and liver, which together account for an estimated 80 percent of lymphatic flow in the body. While lymphatic disorders are often associated with swelling in the arms or legs, extremities represent only a secondary component of lymphatic circulation.

“Swollen arms and legs are the most visible manifestation of a malfunctioning lymphatic system, but they don’t tell us what exactly has gone wrong,” said Itkin. “Because current imaging technologies are so limited, not only are we unable to identify the underlying cause of lymphedema, but it is likely that there are other common symptoms or conditions that indicate an impaired lymphatic system, we just can’t see it yet.”

Making the invisible visible

Today, lymphatic imaging relies on an invasive procedure—which was developed at Penn—that requires clinicians to insert a needle directly into a lymph node, inject dye, and use X-Ray, MRI or CT imaging technologies to track the flow as it moves through the body. While effective in limited cases, these approaches are difficult to scale and offer an incomplete picture of lymphatic function—particularly in organs deep within the body.

The team will develop two new contrast agents—one taken orally to illuminate the intestinal lymphatics, and one given intravenously to visualize lymphatic flow through the liver. These agents will be designed to work with CT or MRI, illuminating lymphatic circulation throughout these organs.

“Ultimately, our goal is to give patients answers where none currently exist. With more precise imaging, we can begin to understand conditions that have long gone unexplained,” said Itkin.