New Revelations from 3D Map of Blood Vessels in Cerebral Cortex

Dr. David Kleinfeld, professor of physics and neurobiology at the University of California, San Diego (UCSD; USA), and colleagues mapped blood vessels in an area of the mouse brain that receives sensory signals from the whiskers.

The organization of neural cells in this brain region has been well understood, as was a pattern of blood vessels that plummet from the surface and return from deep of the brain, but the network in between was unexplored. Nevertheless, these tiny arterioles and venules deliver oxygen and nutrients to energy-hungry brain cells and carry away wastes.

The investigators traced this precise network by filling the vessels with a fluorescent gel. Then, using an automated system developed by coauthor Dr. Philbert Tsai, which removes thin layers of tissue with a laser while taking a series of images to reconstructed the three-dimensional (3D) network of tiny vessels. The project centered on a region of the cerebral cortex in which the nerve cells are so well known that they can be traced to individual whiskers. These neurons gather in “barrels,” one per whisker, an organizational pattern evidenced in other sensory areas as well.

The scientists expected each whisker barrel to correlate with its own blood supply, but that was not the case. The blood vessels do not line up with the functional structure of the neurons they feed. “This was a surprise, because the blood vessels develop in tandem with neural tissue,” Dr. Kleinfeld said. Instead, microvessels beneath the surface loop and connect in patterns that do not obviously correspond to the barrels.

To search for patterns, the researchers employed a type of mathematics called graph theory, which describes systems as interconnected nodes. Using this strategy, no concealed subunits arose, revealing that the mesh undeniably forms a continuous network they call the “angiome.”

The vascular maps traced in this study raise a question of what the researchers are in reality visualizing in a widely used brain imaging modality called functional magnetic resonance imaging (MRI), which in one form measures brain activity by recording changes in oxygen levels in the blood. The idea is that activity will locally deplete oxygen. Therefore, the researchers shook whiskers on individual mice and discovered that optical signals linked with depleted oxygen centered on the barrels, where electrical recordings confirmed neural activity. Hence, brain mapping does not depend on a modular arrangement of blood vessels.

The researchers also calculated patterns of blood flow based on the diameters and connections of the vessels and questioned how this would change if a feeder arteriole were blocked. The map allowed them to detect “perfusion domains,” which predict the volumes of lesions that result when a clot occludes a vessel. Significantly, they were able to build a physical model of how these lesions form, as may occur in cases of human dementia.

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