See into living brain with lasers and nanotubes

"The NIR-IIa light can pass through intact scalp skin and skull and penetrate millimeters into the brain, allowing us to see vasculature in an almost noninvasive way," says Guosong Hong. "All we have to remove is some hair." (Credit: Mario D'Amore/Flickr)

By injecting carbon nanotubes into the bloodstream, scientists can use near-infrared lasers to see blood flow in a living animal’s brain.

The new technique, which is almost completely noninvasive, was developed for mice, but could offer insight into human ailments, such as strokes, migraines, and possibly Alzheimer’s and Parkinson’s diseases.

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Some of the most damaging brain diseases can be traced to irregular blood delivery in the brain. Current procedures for viewing blood flow are either overly invasive or less effective.

Surgically removing part of the skull offers a clear view of activity at the cellular level. But the trauma can alter the function or activity of the brain or even stimulate an immune response.

Meanwhile, noninvasive techniques such as CT scans or MRI visualize function best at the whole-organ level, but can’t visualize individual vessels or groups of neurons.

The first step of the new technique, called near infrared-IIa imaging, or NIR-IIa, involves injecting water-soluble carbon nanotubes into a live mouse’s bloodstream. The researchers then shine a near-infrared laser over the rodent’s skull.

See under the scalp

The light causes the specially designed nanotubes to fluoresce at wavelengths of 1,300-1,400 nanometers; this range represents a sweet spot for optimal penetration with very little light scattering. The fluorescing nanotubes can then be detected to visualize the blood vessels’ structure.

Amazingly, the technique allows scientists to view about three millimeters underneath the scalp and is fine enough to visualize blood coursing through single capillaries only a few microns across, says senior author Hongjie Dai, professor of chemistry at Stanford University.

Furthermore, it does not appear to have any adverse affect on innate brain functions.

“The NIR-IIa light can pass through intact scalp skin and skull and penetrate millimeters into the brain, allowing us to see vasculature in an almost non-invasive way,” says first author Guosong Hong, who conducted the research as a graduate student in Dai’s lab and is now a postdoctoral fellow at Harvard University. “All we have to remove is some hair.”

Strokes and migraines

The technique, reported in Nature Photonics, could eventually be used in human clinical trials, Hong says, but will need to be tweaked. First, the light penetration depth needs to be increased to pass deep into the human brain. Second, injecting carbon nanotubes needs approval for clinical application; the scientists are currently investigating alternative fluorescent agents.

For now, though, the technique provides a new technique for studying human cerebral-vascular diseases, such as stroke and migraines, in animal models.

Other research has shown that Alzheimer’s and Parkinson’s diseases might elicit—or be caused in part by—changes in blood flow to certain parts of the brain. NIR-IIa imaging might offer a means of better understanding the role of healthy vasculature in those diseases, Hong says.

“We could also label different neuron types in the brain with bio-markers and use this to monitor how each neuron performs. Eventually, we might be able to use NIR-IIa to learn how each neuron functions inside of the brain.”

Other coauthors of the study are from Stanford, Massachusetts General Hospital, and Harvard Medical School.

Source: Stanford University