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Navigational view of the brain thanks to powerful X-rays

Georgia Institute of Technology Health and Medicine News Oct 20, 2017

If brain imaging could be compared to Google Earth, neuroscientists would already have a pretty good “satellite view” of the brain, and a great “street view” of neuron details. But navigating how the brain computes is arguably where the action is, and neuroscience’s “navigational map view” has been a bit meager.

Now, a research team led by Eva Dyer, a computational neuroscientist and electrical engineer, has imaged brains at that map-like or “meso” scale using the most powerful X-ray beams in the country. The imaging scale gives an overview of the intercellular landscape of the brain at a level relevant to small neural networks, which are at the core of the brain’s ability to compute.

Dyer, who recently joined the Georgia Institute of Technology and Emory University, also studies how the brain computes via its signaling networks, and this imaging technique could someday open new windows onto how they work. A powerful X-ray tomography scanner allowed the researchers to image particularly thick sections of the brains of mice, which afforded them views into intact neural areas much larger than are customary in microscope imaging. The scanner operated on the same basic principle as a hospital CT scanner, but this scan used high-energy X-ray photons generated in a synchrotron, a facility the size of dozens of football fields.

“Argonne National Laboratory (ANL) generates the highest-energy X-ray beams in the country at its synchrotron,” said Dyer, who co-led the study with ANL’s Bobby Kasthuri at the Advanced Photon Source synchrotron. “They’ve studied all kinds of materials with really powerful X-rays. Then they got interested in studying the brain.”

The technique also revealed capillary grids interlacing brain tissues. They dominated the images, with cell bodies of brain cells evenly speckling capillaries like pebbles in a steel wool sponge.

“Our brain cells are embedded in this sea of vasculature,” said Dyer, an assistant professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory.

The study on the new images appeared in the journal eNeuro October 17, 2017.

The team included researchers from Johns Hopkins University, the University of Chicago, Northwestern University, the Argonne National Laboratory, and the University of Pennsylvania. The work was funded by the U.S. Department of Energy, the National Institutes of Health, the Intelligence Advanced Research Projects Activity, and the Defense Advanced Research Projects Agency. Electron microscopy already captures neuronal details in impressive clarity. Functional magnetic resonance imaging (fMRI) makes great visuals of brain structures and broad neural signaling.

So, why do researchers even need mesoscale imaging?

“FMRIs image at a high level, and with many microscopes, you’re zoomed in too far to recognize the forest for the trees,” Dyer said. “Though you can see a lot with them, you also can miss a lot.”

“If you look at brain signaling on the level of individual neurons, it looks very mysterious, but if you take a step back and observe the activity of a population of hundreds of neurons instead, you might see simpler, clearer patterns that intuitively make more sense.”

In an earlier study, Dyer discovered that hand motion directions corresponded with reliable neural signaling patterns in the brain’s motor neocortex. The signals did not occur across single neurons or a few dozen but instead across groups of hundreds of neurons. Mesoscale imaging reveals a spatial view on that same order of hundreds of neurons.

The researchers have also been able to couple their new meso-level imaging technique with extremely detailed electron microscopy. And that has the potential to take them closer to a kind of Google Earth for the brain by combining mesoscale or map-like views with zoomed-in or street-like views.

“We have begun doing X-ra
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