New MRI Study Reveals 3-D Grid-like Brain Structure

Using a high-powered diffusion magnetic resonance imaging scanner, scientists led by Van Wedeen, MD, of the Massachusetts General Hospital and Harvard Medical School, have determined the way the brain is wired is actually quite simple.

According to Wedeen, who with colleagues detailed the findings in the March 30 issue of Science, instead of fibers traveling through the brain in a chaotic, “spaghetti-like” pattern, they run in a grid-like pattern that is “quite elegant."

These patterns appeared in the brains of humans, as well as rhesus monkeys, owl monkeys, marmosets and galagos, the researchers reported.

“The crucial anatomy of the brain, unquestionably, is its connectivity,” said Wedeen. “That is the defining anatomy of the brain.”

The problem has been that the technology didn’t exist that could demonstrate what the three dimensional structure of this connectivity is.” Instead, said Wedeen, “We’ve been looking at a mess.”

“So what was needed was a way to see into this mess,” he said. To that end, Wedeen and his colleagues have been working on developing MRI technology that can map the fiber architecture of the brain.

Funded by the NIH Human Connectome Project (a collaborative effort to build a network map of the human brain), researchers at MGH, along with Siemens AG, co-developed the human connectome scanner, which is, according to Wedeen, 10 times as sensitive as existing clinical scanners.

“It’s most startling characteristic is a gradient that is 10 times stronger than the average clinical scanner,” Wedeen said. “But it’s balanced so well, it’s extremely quiet, although it is a bit of a beast from an engineering point of view. It has four parallel power supplies, so building these things and keeping them alive and well is not yet a trivial matter.”

With diffusion MRI, scientists are able to map the three-dimensional motion of water molecules in the brain. Those maps can then be run through a series of mathematical algorithms that infer from the water motion pattern the fiber architecture in question.

Wedeen said the question he and his colleagues asked themselves was, “When you look at a particular pathway of the brain, what is the structure of the stuff it touches or crosses as it moves though the brain?”

If the “spaghetti advocates” are correct, there shouldn’t be any pattern to it all, said Wedeen. But, instead, it appears that these brain pathways are organized like “woven sheets,” he said, with fibers running in two parallel directions, with a third direction running in a perpendicular direction.

So the connectivity of the brain follows runs horizontally, vertically and transversally, which limits the options for the growing nerve fibers to change direction during development - either left and right, or up and down.

“This makes perfect sense,” said Wedeen, pointing out that the simple grid structure allows for continuous re-wiring, both evolutionarily and developmentally.

What are the implications of his research for diagnostic imaging? Wedeen pointed to what he calls the “800-pound gorilla in the brain boat, which is mental disease.”

“So the idea of having quantitative imaging that would be beneficial for mental health would have a revolutionary impact on the relationship between diagnostic imaging and healthcare,” he said.

Wedeen called this natural coordinate system “alternative language for expressing brain architecture and its variability among humans” and said the future will involve clinical studies that will attempt to discover “the ways in which this variability correlates in meaningful ways with mental health issues, such as the likelihood of a particularly person to develop Asperger’s syndrome or autism, or their vulnerability to post-traumatic stress.”

“These are all things that people have been hypothesizing have connectional footprints,” Wedeen said. “And we need to build imaging that will capture these things.

Dieter Enzmann, MD, a neuroradiologist who serves as chair and professor of radiology at the UCLA School of Medicine, calls the work done by Wedeen’s group “an important, fundamental discovery.”

Enzmann compares it to studying freeway traffic patterns. “If you want to study Los Angeles traffic the first thing you need is a map and a structure of the freeways,” he said. “You need a basic anatomy of the pathways that traffic uses and then you can study the dynamics of that traffic.

“The analogy here is that in looking at the brain, the parts that people need to look at are the pathways, and those pathways aren’t well defined and the underlying structure is difficult,” he added. “What Van’s work helps clarify is how you can actually map those pathways.”

And once those pathways are mapped and researchers understand the underlying formula behind the formation of those pathways, then they can begin studying brain dynamics, Enzmann explained. Functional magnetic resonance imaging “is an attempt to study those dynamics and it’s greatly aided by understanding the structure of the brain.”

Functional MRI is being used in multiple disciplines, Enzmann said, and is already a biomarker for diseases like Alzheimer’s and autism. “It’s going to be a biomarker for drug effects, whether that’s choosing or monitoring the drug,” he said. “So having a much better grasp of brain pathways on the anatomical side, and then the dynamic side, is critical for using that kind of functional imaging in clinical use.”

Curvature in this DSI image of a whole human brain turns out to be folding of 2-D sheets of parallel neuronal fibers that cross paths at right angles. This picture came from the new Connectom scanner. Credit: Van Wedeen, MD, Massachusetts General Hospital and Harvard University Medical School.