Home Cellular health A near real-time view of the drains inside the human brain

A near real-time view of the drains inside the human brain


A new non-invasive technique provides a near real-time view of waste disposal vessels in the human brain.

A joint research team from the Medical University of South Carolina (MUSC) and the[{” attribute=””>University of Florida describes the first non-invasive and near real-time visualization of the human brain’s waste-clearance system in Nature Communications. The brain is densely organized, and visualizing the structures dedicated to waste removal, also known as lymphatic structures, had been a limitation in the field.

“This is the first report to show the complete human brain lymphatic system architecture in living humans,” said Onder Albayram, Ph.D., an assistant professor in the Department of Pathology and Laboratory Medicine and Department of Neuroscience at MUSC, who led the research team and is senior author of the article.

Albayram was intrigued by the possibility of lymphatic structures in the brain. “The lymphatic clearance system is all over the body for different organs,” he said. “I asked myself simply, ‘Why not the brain?’”

Brain's Drains

MRI showing the dorsal flow of the brain’s waste-clearance system. Credit: Dr. Onder Albayram, Medical University of South Carolina

Improved visualization of the brain’s waste-clearance system could enhance our understanding of how the healthy brain functions. It could also provide insight into what goes wrong in neurogenerative diseases such as Alzheimer’s and how the brain recovers from traumatic brain injuries (TBIs).

Pound for pound, the brain is the most metabolically demanding mass in the body – weighing around 3 pounds but requiring 20% of total oxygen consumption. That metabolic demand comes with the need to dispose of waste regularly.

As blood carrying oxygen permeates tissues to deliver vital nutrients, it collects pathogens, damaged cells, and waste. This fluid then drains into lymphatic vessels to be filtered through lymph nodes, which dispose of any unwanted waste products.

MRI showing the dorsal flow of the brain’s waste disposal system (in green). Credit: Dr Onder Albayram, Medical University of South Carolina

“It has long been believed that the brain lacks lymphatic vessels,” said Sait Albayram, MD, a professor in the Department of Neuroradiology at the University of Florida, who is the lead author of the paper.

“That thinking began to change about a decade ago, when early reports of rodent experiments hinted at lymphatic vessels surrounding the brain, side-by-side with blood vessels. But evidence of lymphatic vessels in the human brain remained rare before this study.

Onder Albayram compares the brain in the skull to an apple suspended inside a jar. The inside of the “jar”, or skull, is lined with a layer of delicate membranes called meninges. A fluid known as cerebrospinal fluid (CSF) surrounds the brain. The conventional thought was that waste-laden fluid from the brain drained into the CSF along the blood vessels, was carried out of the skull and then drained into the veins. Research over the past decade has instead hinted that the process is more complex and has suggested the existence of dedicated lymph vessels in the brain for waste disposal.

“The lymphatic clearance system is present throughout the body for different organs. I just thought, ‘Why not the brain?’ — Onder Albayram, Ph.D.

However, seeing these vessels in action in a living human brain posed technical limitations. Chief among them is the required use of the toxic rare earth metal gadolinium, a toxic rare earth metal used as a contrast agent during MRI, a technique used to visualize and differentiate brain structures.

In this study, the researchers were able to overcome this limitation and use MRI to visualize the lymphatic vessels in the meninges without the need for a contrast agent. Instead, the team used differences in brain protein content to create a contrast gradient. Low-protein structures appear dark and high-protein structures appear bright, with high enough resolution to see intricate detail.

“The discovery of meningeal lymphatic networks in mammals over the past decade has opened a new chapter in our understanding of cellular waste management in the brain,” said Adviye Ergul, MD, Ph.D., professor in the Department pathology and laboratory. Medicine at MUSC, who was not one of the study authors.

“This new study goes one step further by eliminating the need to inject contrast agents to visualize lymphatic vessels,” she said. “This is a major achievement that will reinvigorate the field to go deeper into the brain and expand our knowledge of the brain’s lymphatic system.”

This simple yet innovative approach allowed the researchers to capture clear images of the lymphatic vessels, with their high protein content – around 50 times that of CSF – as they connected areas of the brain to lymph nodes in the neck.

The research team then compared the differences between older and younger brains, and found a reduction in waste disposal in older brains.

Using this noninvasive MRI technique, researchers and doctors can now see what the lymphatic vessels of a healthy brain look like, Onder Albayram said, and study how they change with age. They may also determine their role in the progression of neurodegenerative diseases, such as Alzheimer’s disease and related dementias. The technique could also be used to investigate ways to increase lymphatic production in the brain as we age and perhaps offer insight into recovery after TBI.

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

Reference: “Noninvasive MRI Imaging of Human Brain Lymphatic Networks with Cervical Lymph Node Connections” by Mehmet Sait Albayram, Garrett Smith, Fatih Tufan, Ibrahim Sacit Tuna, Mehmet Bostancıklıoğlu, Michael Zile and Onder Albayram, January 11, 2022, Nature Communication .
DOI: 10.1038/s41467-021-27887-0

About MUSC

Founded in 1824 in Charleston, MUSC is home to the oldest medical school in the South as well as the state’s only integrated academic health sciences center, with a unique charge of serving the state through education, research and patient care. Each year, MUSC educates and trains more than 3,000 students and nearly 800 residents in six colleges: dentistry, graduate studies, health professions, medicine, nursing and pharmacy. MUSC contributed more than $327.6 million in biomedical research funding in fiscal year 2021, continuing to lead the state in securing federal and state institutes of health funding with more than $220 million of dollars.