UC Davis devises laser-based microscope for brain scanning

29 Aug 2024

Faster, hi-res imaging achieved thanks to novel adaptive sampling scheme and line illumination.

From Ford Burkhart in Tucson

Researchers at University of California Davis (UC Davis) have designed a new laser-scanning approach to microscopy that is expected to open doors to brain-imaging in mouse models with improved speed and resolution.

The Davis team, led by Weijian Yang in the Department of Electrical and Computer Engineering, uses a two-photon fluorescence microscope to create high-speed images of neural activity at the level of individual cells.

The new microscope is expected to cause less harm to brain tissue than traditional two-photon microscopy and will provide a clearer view of how neurons communicate. That, in turn, is expected to lead to new insights into brain function and neurological diseases.

The development is described in Optica.

Yang commented, “The work was driven by the need to overcome limitations in current brain imaging techniques.” He sees considerable commercialization possibilities down the road. Traditional two-photon microscopy, while powerful for viewing deep into the brain with great detail, is inherently slow and has a risk of damaging brain tissues due to excessive light exposure, Yang said.

He added: “One could increase the imaging speed by using multiple beams at once, i.e. by shining and scanning multiple points over different parts of the sample at once, but this further increases the laser power on the tissue and thus increases the risk of thermal damage. Thus, the conventional multi-beam approach to increase the speed poses a significant challenge, especially when trying to capture rapid neuronal activities without harming the sensitive brain tissues.”

Avoiding thermal damage

The main problem the Davis team targeted was how to quickly and safely observe the activity of many neurons without the usual negative effects of heating and damaging the brain tissue that accompany traditional methods.

“Our approach allows researchers to monitor neural activity more extensively and in real-time,” Yang said, “which is crucial for understanding complex brain functions and disorders.”

Funding for the project came from the U.S. National Science Foundation as well as the Burroughs Wellcome Fund, the National Institute of Neurological Disorders and Stroke and the National Eye Institute.

“There is certainly a potential market to commercialize this technology,” Yang said. “At the very beginning, the target market would be research institutes.”

The new microscope offers a number of benefits over the existing brain-imaging technologies, including greater sensitivity, safety, storage size of images and power usage. Specifically, the new system significantly increases the imaging speed of neuronal activity. And it significantly reduces the level of laser power deposited on the brain tissue.

Yang added that the team’s microscope could be built based on a conventional two-photon microscope, with an added module of beam shaping – that is, turning a circular beam profile into a short-line profile – and an added module of beam patterning through a digital mirror device or DMD.

“It only slightly increases the cost of a conventional two-photon microscope.” Yang added. He said they have not patented the device, “But there is definitely a commercialization potential.”

“Increasing the imaging throughput in two-photon microscopy to monitor the brain activity has great significance in neuroscience,” Yang said. “Increasing throughput typically means increasing laser power and thus thermal damage in the brain. Our work overcomes this issue, and our technique is compatible with and could be easily adopted in typical laser-scanning two-photon microscopy that uses a galvo-resonant or galvo-galvo scanning system.”

Applications

Yang told the journal Optica: “Our new microscope is ideally suited for studying the dynamics of neural networks in real time, which is crucial for understanding fundamental brain functions such as learning, memory and decision-making. For example, researchers could use it to observe neural activity during learning to better understand communication and interaction among different neurons during this process.”

Yang’s team describes the two-photon fluorescence microscope as incorporating a new adaptive sampling scheme that replaces traditional point illumination with line illumination. It reports that the new method enables in vivo imaging of neuronal activity in a mouse cortex and can image at speeds ten times faster than traditional two-photon microscopy while also reducing the laser impact on the brain more than tenfold.

“By providing a tool that can observe neuronal activity in real time, our technology could be used to study the pathology of diseases at the earliest stages,” said Davis team member Yunyang Li, “This could help researchers better understand and more effectively treat neurological diseases such as Alzheimer’s, Parkinson’s and epilepsy.”