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Researchers tout two-photon fluorescence microscope for brain imaging

by Gus Iversen, Editor in Chief | August 19, 2024
Alzheimers/Neurology
Weijian Yang (right) with graduate students Shu Guo (left) and Yunyang Li (middle) in front of the new two-photon microscope. Photo: Molly M Bechtel, UC Davis
Researchers from the University of California, Davis, have unveiled an innovative two-photon fluorescence microscope that promises to significantly enhance brain imaging.

This new microscope, detailed in Optica, features a faster imaging process while minimizing damage to brain tissue, making it a valuable tool for studying neural dynamics and neurological diseases in real time.

Led by Weijian Yang, the research team developed the microscope with a focus on observing neural networks at cellular resolution. Unlike traditional two-photon microscopy, which can be slow and harmful to tissue, this new method uses adaptive sampling and line illumination instead of the standard point illumination. This allows the microscope to image at speeds ten times faster than previous techniques, with a tenfold reduction in laser power, thereby reducing potential harm to brain tissue.

Yang highlighted the microscope's potential for real-time observation of neural activity, which is critical for understanding brain functions like learning and memory. "Our new microscope is ideally suited for studying the dynamics of neural networks in real time," Yang said.

Illustration shows adaptive sampling scheme, in which a laser beam patterned by a digital micromirror device selectively illuminates neurons in the brain tissue to image their activity Image: Wei Wei and Mei Xueting, LINGO.AI LLC
The system's adaptive sampling technique targets only active neurons, reducing background noise and speeding up the process. A digital micromirror device (DMD) helps achieve this by dynamically shaping and steering the light beam. This innovation allows for precise imaging of neuronal structures, enabling the microscope to capture rapid neural events that slower methods might miss.

The team demonstrated the microscope's capabilities by imaging calcium signals in living mouse brain tissue, achieving a speed of 198 Hz. This speed and precision in capturing neural activity can provide valuable insights into brain function and disease.

Future developments aim to integrate voltage imaging for even faster neural activity readouts and to improve the microscope’s usability for broader neuroscience applications.

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