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A new non-invasive technique provides a nearly real-time view of the human brain's waste removal system.

Medical University of South Carolina news on February 24

A joint research team from the Medical University of South Carolina (MUSC) and the University of Florida (UF) describes for the first time in the journal Nature Communications the effects of the human brain's waste removal system. Non-invasive and near real-time visualization. The brain is very densely organized, so visualizing the structures that process waste, also known as lymphoid structures, has been a limitation of the field.

The research was published in the journal Nature Communications (latest impact factor: 14.919) on January 11, 2022

"This is the first complete report showing the structure of the lymphatic system in a living human brain," said Dr. Onder Albayram, who led the research team and is an assistant professor in the Departments of Pathology and Laboratory Medicine and Neuroscience at MUSC and the author of the article. Senior author.

Albayram was intrigued by the possible presence of lymphatic structures in the brain. "The lymphatic clearance system is all over the body," he said. "I asked myself, 'Why don't we have it in our brains?'"

Improved visualization of the brain's waste removal system could enhance our understanding of how a healthy brain works. It can also help us understand the causes of neurodegenerative diseases such as Alzheimer's disease, and how the brain recovers from traumatic brain injury (TBI).

At the same weight, the brain is the most metabolically demanding part of the body, weighing about 3 pounds, but requiring 20% of total oxygen consumption. This metabolic demand is accompanied by the need to regularly dispose of waste.

As oxygen-carrying blood transports vital nutrients through tissues, it collects pathogens, damaged cells and waste. This fluid then flows into the lymphatic vessels, where it is filtered through the lymph nodes, which dispose of any unwanted waste.

"For a long time, people have thought that the brain lacks lymphatic vessels," said Sait Albayram, MD, professor in the Department of Neuroradiology at the University of Florida and lead author of the article.

"This thinking started to change about 10 years ago, when the first reports of experiments in rodents suggested that there are lymphatic vessels around the brain, juxtaposed with blood vessels. But before this study, lymphatics were present in the human brain. Evidence is still scant."

Onder Albayram likens the brain in the skull to an apple hanging in a jar. Covering the inside of the "jar," or skull, is a fragile membrane called the meninges. A fluid called cerebrospinal fluid (CSF) surrounds the brain. Conventional thinking is that waste-laden fluid in the brain flows along blood vessels into the cerebrospinal fluid, which then travels out of the skull and into veins. Research over the past decade has shown that the process is more complex, with the presence of lymphatic vessels (also called the glymphatic system) in the brain that specialize in removing waste.

However, there are technical limitations to observing the activity of these lymphatic vessels in the human brain. Chief among these is the need for the use of the toxic rare-earth metal Gadolinium, a toxic rare-earth metal used as a contrast agent in magnetic resonance imaging (MRI), a technique used to see and differentiate the brain structural technology.

In this study, the researchers were able to overcome this limitation and use MRI to visualize lymphatic vessels in the meninges without the use of contrast agents. Instead, the team used differences in the brain's own protein content to create a contrast gradient. Structures with low protein content are darker, and structures with high protein content are brighter, with high enough resolution to see intricate details.

The discovery of the meningeal lymphatic network in mammals over the past decade has turned a new page in our understanding of cellular waste management in the brain," said Adviye Ergul, MD, professor in the Department of Pathology and Laboratory Medicine at MUSC University. Not the author of this study.

She said: "This novel study takes it a step forward by eliminating the need to inject a contrast agent to visualize lymphatic vessels. This is a major achievement that will bring the field deeper into the brain and expand our knowledge of brain lymphatics. system awareness.”

This simple and innovative method allowed the researchers to capture clear images of lymphatic vessels, which are high in protein and about 50 times more abundant than CSF, as they connect the brain region to the lymph nodes in the neck.

The team then compared how the brains of older adults differed from those of younger adults and found that older adults had reduced brain waste removal.

Using this non-invasive MRI technique, researchers and doctors can now actually see what the lymphatic vessels of a healthy brain look like and study how they change as we age, says Onder Albayram. They can also determine their role in the progression of neurodegenerative diseases, such as Alzheimer's disease and related dementia. The technique could also be used to study ways of increasing the brain's lymphatic output with age, perhaps providing insights into recovery after traumatic brain injury (TBI).

Onder Albayram said: "Imagine again the brain in a bottle, surrounded by thin lymphatic vessels. What happens during TBI? Are lymphatic vessels damaged and how do they recover? This technology will allow us to start answering those questions."

Reference

Source：Medical University of South Carolina

A first glimpse of the human brain’s drains

Reference：

Albayram, M.S., Smith, G., Tufan, F. et al. Non-invasive MR imaging of human brain lymphatic networks with connections to cervical lymph nodes. Nat Commun 13, 203 (2022). https://doi.org/10.1038/s41467-021-27887-0