New 3D Brain Map May Help in Disease Management: Study

A team of researchers has created a three-dimensional (3D) map of the lymphatic vessels that drain the brain, and demonstrated that these vessels are organized similarly in mice and in humans.

The researchers propose measuring these vessels using MRI scans could “allow longitudinal imaging of disease progression that may be relevant for diagnostic and prognostic imaging” for people with multiple sclerosis (MS) and other neurological disorders.

Simply put, using this 3D map with MRI scans “may provide a diagnostic tool for patients with … drainage defects and neurological diseases,” the team wrote.

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The study, “Conserved meningeal lymphatic drainage circuits in mice and humans,” was published in the Journal of Experimental Medicine.

The lymphatic system acts like the body’s sewers, collecting fluid that drains through tissues so it can be filtered back into the bloodstream. The central nervous system — comprised of the brain and spinal cord — does not have any lymphatic vessels, but there are vessels in the membranes around the brain called meninges.

These meningeal lymphatic vessels, or MLVs, are important for collecting and filtering the fluid in the brain, known as the cerebrospinal fluid (CSF). Emerging research has indicated that MLV dysfunction may contribute to a range of neurological diseases. However, the precise physical architecture of MLVs in the head has not been thoroughly mapped out.

“Because of its involvement in many diseases, the meningeal lymphatic system has attracted a lot of therapeutic interest,” Laurent Jacob, PhD, the study’s first author, from the Paris Brain Institute in France, said in a press release.

“However, it remained unclear where the lymphatic recapture of CSF molecules occurs in the context of the whole head, in mice or in humans,” Jacob said.

Mapping the human brain

To learn more, scientists from the Paris Brain Institute at the Pitié-Salpêtrière Hospital, and from Yale University, in the U.S., conducted a series of experiments in mice. The team injected tracer molecules in the CSF of the mice, and then conducted whole-head imaging to track precisely how the tracer flowed through the brain and MLVs.

From these data, the scientists generated a 3D map of MLV architecture throughout the mouse head. The team highlighted several noteworthy features revealed by this map, including some MLVs that flowed through the bone of the skull. Also of note, the MLVs draining the brain were largely distinct and separate from lymphatic vessels draining the nose.

Using an imaging technique called vessel-wall MRI (VW-MRI), the scientists then examined MLV architecture in 11 people with brain-related diseases. The patients, including four individuals with MS, were undergoing MRI scans of the brain as part of routine care.

The VW-MRI technique simplistically involves injecting a tracer called gadobutrol, then taking multiple MRI scans over time to track how the tracer flows through the body’s tissues and vessels.

Results showed that the MLV architecture in the human head is largely comparable to what was found in the mice. This suggests that mouse models may be well-suited to study the role of MLVs in disease, as well as testing therapies that target MLV function.

One patient who had a bone disorder called Gorham-Stout disease had MLV enlargement, called hypertrophy, compared with the other 10 individuals. No other disease-related differences were noted.

The scientists stressed that the small number of patients, and the lack of healthy comparators, make it difficult to draw firm conclusions from these data.

“Additional MRI imaging of subjects without vascular stenosis or neurological diseases is needed to establish if MLV structural features are altered in these CNS [central nervous system] disorders,” the scientists wrote.

In this small sample, the researchers noted, MLV volume was markedly lower in men than in women.

“While the mechanisms by which sex may regulate MLVs and neuroimmunity remain unknown, it is interesting to speculate that the reduced MLV volume in females may relate to their increased vulnerability to” MS, the researchers wrote.

The study was funded by the Paris Brain Institute along with the European Research Council and the French National Research Agency.