Scientists expect a new microscopy technique to offer a more comprehensive picture of deep brain activity.

Imaging the brain is hard. Not only is it composed of millions of neurons and host to fast-moving signals, but also much of the activity is buried deep within tissue. So far, most brain imaging technologies focus on either speed or resolution, but struggle to do both together well.

For example, many imaging techniques capture high-resolution brain scans, but can't track neural activity in real time. The few techniques that do combine resolution and speed only can focus on small portions of the brain, imaging just a few cells at a time.

"This is in part because the limits that govern these tradeoffs have not been explored or pushed in a systematic and integrated manner," Alipasha Vaziri, head of the Laboratory of Neurotechnology and Biophysics at Rockefeller University, said in a news release.

To create a better brain imaging technique, researchers decided to build on a method called two-photon microscopy, or 2p microscopy. The technique uses a laser to light-up different parts of the brain.

Because 2p microscopy involves point-by-point scanning of a specific neural targets, the technique is rather slow. Vaziri and his colleagues tweaked the technology to allow the targeting of multiple brain regions in parallel.

Another problem with 2p microscopy is that it can normally only be used to image the brain's surface, the cortex.

"One of the biggest challenges in neuroscience is developing imaging techniques that measure the activity of deep brain regions while maintaining high resolution," Vaziri said.

By combining 2p microscopy with 3p microscopy, a technology much better suited to deep brain imaging, scientists were able to combine accuracy and speed. Researchers dubbed their new technique hybrid multiplexed sculpted light microscopy, or HyMS.

The new method isn't limited to tiny targets. It can be used to track 12,000 neurons within an large tissue sample, and can track neural activity in real time. The method also can track brain activity at different depths simultaneously.

The technology will allow researchers to better understand the complex neural patterns responsible for sophisticated cognition.

"Before, people hadn't even been able to look at the activity of neurons over the entire depth of the cortex, which has multiple layers, all at the same time," Vaziri said. "With this technology, you can actually see what the information flow looks like within the cortex, and between cortical and subcortical structures."

In proof-of-concept tests, scientists used the new technique to image the activity of thousands mice neurons as the animals walked on a treadmill or listened to sounds. The test results suggest researchers can use HyMS to monitor complex neural activities in animals.

Vaziri and his colleagues described the new technology in a paper published this week in the journal Cell.

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