Team Achieves First Living View of Brain’s Lymphatic System

A research team from Medical University of South Carolina (MUSC) and the University of Florida have reported the first non-invasive and near real-time visualization of the human brain’s waste-clearance system. The findings could enhance understanding of how the healthy brain functions as well as provide insights into what goes wrong in neurodegenerative diseases such as Alzheimer’s and how the brain recovers from traumatic brain injuries (TBIs).

The brain’s dense organization has made it difficult to visualize its lymphatic structures. “It had long been believed that the brain lacked lymphatic vessels,” says Sait Albayram, M.D., a professor in the Department of Neuroradiology at the University of Florida. It was originally thought that waste-laden fluid from the brain flowed out into the cerebrospinal fluid (CSF) along blood vessels, where it was transported out of the skull and into veins. “That thinking began to change about a decade ago, as the first reports from experiments in rodents hinted at lymphatic vessels surrounding the brain, side by side with blood vessels,” Sait Albayram says. “But evidence of lymphatic vessels in human brains remained scarce before this study.”

Another impediment to visualizing these vessels in action has been the toxicity of MRI contrasting agent gadolinium.  The team was able to overcome by using differences in the brain’s own protein content to create a gradient in contrast. Structures with low protein content appear dark and those with high protein content appear light, with high enough resolution to see intricate details. This enabled investigators to capture clear images of lymphatic vessels, with their high protein content—about 50-fold greater than that of CSF—as they connected areas within the brain to lymph nodes in the neck.

Onder Albayram, Ph.D., an assistant professor in the Department of Pathology and Laboratory Medicine and Department of Neuroscience at MUSC, said their work, published recently in Nature Communications, is the first to show the complete human brain lymphatic system architecture in living humans.  The research team then went on to compare how aged brains differ from younger ones, finding a reduction in waste clearance in older brains.  

Using this non-invasive MRI technique, researchers and physicians can now actually see what the lymphatic vessels of a healthy brain look like, said Onder Albayram, and study how they change as we age. They can also determine their role in the progression of neurodegenerative diseases, such as Alzheimer’s and related dementia.  The technique could also be used to study ways to increase the brain’s lymphatic output as we age and perhaps offer insight into recovery after TBI.

“Imagine again the brain in the jar, surrounded by delicate lymphatic vessels,” said Onder Albayram. “What happens during a TBI? Are the lymphatic vessels damaged, and how do they recover? This technique will enable us to begin to answer these questions.”