Two-photon microscope enables faster, less harmful brain imaging

The newly designed microscope, featuring adaptive line illumination, allows for real-time observation of neural networks. According to Weijian Yang, the research team leader, “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.” This technology enables researchers to capture brain activity much faster than traditional methods, paving the way for deeper insights into how neurons communicate during processes like learning. 

Published in Optica, the study details the incorporation of a new adaptive sampling scheme that replaces traditional point illumination with line illumination. This breakthrough enables in vivo imaging of neuronal activity in a mouse cortex at speeds ten times faster than conventional two-photon microscopy, while also reducing the required laser power by more than tenfold. 

Traditional two-photon microscopy, while effective for imaging deep tissue, is often slow and can potentially harm brain tissue due to the high laser power used. To address these challenges, the research team implemented a novel strategy that uses a short line of light to illuminate areas of active neural tissue. This approach not only speeds up the imaging process but also minimizes the laser exposure to non-essential areas, significantly reducing the risk of tissue damage. 

• Adaptive sampling: This new technique allows the microscope to selectively illuminate active neurons rather than the entire sample area. This precision reduces the energy deposited into brain tissue, further lowering the potential for damage. 

• Digital micromirror device (DMD): A DMD chip, containing thousands of controllable mirrors, dynamically shapes and steers the light beam. This allows the system to target neurons with high precision. 

• High-speed, high-resolution imaging: By using the DMD, the researchers can mimic point scanning at high resolution, enabling fast identification of regions of interest. This technique makes it possible to isolate individual neurons, facilitating more accurate interpretations of neural interactions. 

The research team successfully demonstrated the capabilities of the new microscope by imaging calcium signals in the brains of living mice at 198 Hz, a speed significantly faster than traditional two-photon systems. This enables the monitoring of rapid neural events that slower methods might miss. The team plans to further enhance the system by incorporating voltage imaging capabilities, which will allow for even faster monitoring of neural activity. 

In addition, the researchers are working on making the microscope more user-friendly and portable, which will increase its applicability in real-world neuroscience research. 

MEDICA-tradefair.com; Source: Optica