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June 20,2013

The nooks and crannies of the human brain are now on display in 3-D, offering scientists an invaluable tool in the quest to better understand brain form and function.

The project is called BigBrain. In three dimensions and intricate detail, it reveals the anatomy of the brain as never seen before.

“These are images of a 3-D reconstructed human brain with a spatial resolution of 0.02 millimeters. So this is even thinner than a thin human hair, and it allows [us] to see the microstructure of the human brain in 3-D space,” said Katrin Amunts, director of the Vogt Institute for Brain Research at Germany's Heinrich Heine University, a partner in the project.

Researchers use a special tool called a microtome to cut slices from a brain preserved in paraffin wax into tiny slivers 20-micrometers thick. (Courtesy of Amunts, Zilles, Evans et al.)

The scientists would like to understand the relationship within the structure of the brain, its function and behavior.

"It is necessary to have all the reference brains, which have this very high microscopic resolution and therefore we created such [a] reference brain,” said Amunts.

The BigBrain model on Amunts’ computer screen belonged to a 65-year-old woman who had no neurological problems.

To create it, the researchers first cut the brain into 7,400 slices, each 20 micrometers thick, then stained each slice with a special dye so all the cell bodies were visible. After that, the slices were digitized and carefully realigned.

“This involved us in both manual activity in shifting broken pieces of the data into the right spatial location and then a large amount of computational analysis," said Alan Evans at McGill University, who was in charge of digital reconstruction, "which allowed us to overcome the distortions, both the geometric and optical, to reassemble the data into a coherent three-dimensional form.”

The resolution on the reference brain is 50 times greater than the standard brain scans currently available. Its images allow scientists to better visualize what’s happening in certain areas of the brain. BigBrain paves the way to understanding how the brain’s anatomy contributes to language, learning and other processes, or how its shape relates to chemical signaling or gene expression.

Amunts says BigBrain offers, for example, a platform to measure the thickness of the cerebral cortex, which changes as one ages and has been associated with neurodegenerative disorders like Alzheimer's.

“So having a gold standard, reliable data, on how thick the cortex indeed is will help to perform such studies in humans, in living human subjects, where the cortical thickness is also measured,” she said.

Access to BigBrain is free online and will be available to the public. Her team is now at work on two more model brains that capture even more details of individual cells.