MRI images show for the first time how cerebrospinal fluid flushes the brain

By: Lennart 't Hart

Whereas it was thought for a long time that CSF mainly has a cushioning effect to protect the brain against mechanical impacts, it has recently been proposed that it also flushes the brain from waste materials. Until now, it has been difficult to measure how CSF moves through the brain. How it flows exactly, what drives that flow, and how it changes in disease were also hard to quantify. In earlier studies, researchers often used a contrast agent introduced via a spinal infusion, an unpleasant and invasive procedure. The new MRI technique, called CSF-STREAM, makes this unnecessary.

The new technique was specially developed to visualize cerebrospinal fluid, without needles or contrast agents. This makes it safer and more comfortable for patients. The method is so precise that researchers can see how CSF moves through the tiniest spaces around blood vessels.

Lead researcher Lydiane Hirschler: “The fact that we can now actually see how cerebrospinal fluid moves throughout the human brain non-invasively is a huge step forward. Especially since we observe such clear differences between CAA patients and healthy people. That opens up new possibilities.”

In sync with the body’s rhythms

The MRI scans take about 40 minutes. During that time, researchers measure how different rhythms in the body drive the flow of cerebrospinal fluid. Each heartbeat pushes the fluid a little. Breathing also plays a role, as does vasomotion, the slow, rhythmic contractions of blood vessels.

To visualize that last factor, the researchers gave participants a visual stimulus. Principal investigator Thijs van Osch : “People lying in the MRI scanner were shown a flickering checkerboard pattern with the same frequency as the slow waves that are observed when someone sleeps.”

For the study, the researchers also performed brain scans on eight CAA patients and eight healthy volunteers, in collaboration with researchers in Bonn. They then compared the motion of CSF in the perivascular spaces, small channels around blood vessels where waste is carried away.

A surprising difference in flow

In healthy people, cerebrospinal fluid moves smoothly through these channels, whereas in CAA patients, the motion was disrupted. The researchers also noticed something striking: in some brain regions, the CSF actually flowed faster than normal. The increase was most pronounced near the base of the brain.

“We had expected the flow in CAA to be slower,” Hirschler explains. “But we saw a 20% increase at the base of the brain. That was really surprising.”

According to Hirschler, there may be a logical explanation: “Because the ‘side channels’ — the small pathways leading deeper into the brain, are blocked, the cerebrospinal fluid might behave like a river that can’t branch off. It flows faster around the brain but doesn’t really perform its cleaning function.”

Hirschler emphasizes that this is still just a theory. Further research is needed to scientifically explain these differences.

Why cerebrospinal fluid is so important

To function properly, our brains constantly produce various substances, such as proteins. Over time, these proteins become damaged or unnecessary and must be cleared away. Elsewhere in the body, lymph nodes handle this cleanup, but the brain has none. “That’s why it has been proposed that cerebrospinal fluid is taking over that role, whereas those fundamental studies were performed in mice we are able to study CSF-mobility in the human brain,” says van Osch.

If that system fails, waste products remain behind, such as the protein amyloid-beta, which is linked to CAA, Alzheimer’s, and similar brain diseases. The buildup of amyloid-beta can cause brain hemorrhages and memory problems.

What can we do with this?

With CSF-STREAM, researchers can now see precisely where the brain’s cleaning system works well and where it doesn’t, for example, in CAA. This information helps us better understand such diseases and may, in the future, enable earlier detection and prevention.

Hirschler: “We now have a technique that finally shows us how cerebrospinal fluid moves. That opens up an entirely new world of research, to maybe improve diagnostics, and thus to support the search for treatments for brain diseases such as CAA.” The article was published in Nature Neuroscience.

This project reflects a broad collaborative effort across multiple institutions. Amsterdam UMC contributed innovative techniques for faster imaging; the University of Bonn conducted the CAA patient scans; and the Boston team provided critical expertise in vasomotion.