New Microscopy System Improves In Vivo Brain Imaging

Neuroscientists have long sought to capture the brain's remarkable ability to reshape its neural connections, a phenomenon known as plasticity. However, conventional microscopy techniques have struggled to keep pace with these rapid changes, hindered by slow imaging speeds and the brain's light-scattering properties. A new collaboration between MIT engineers and neuroscientists has yielded a microscopy system that will help improve our understanding of brain plasticity.

The multiline orthogonal scanning temporal focusing (mosTF) system scans brain tissue with perpendicular lines of light, exciting fluorescent neurons engineered to glow when stimulated. By employing advanced algorithms to reassign scattered photons to their origin, mosTF achieves an eight-fold increase in imaging speed and a four-fold improvement in signal-to-background ratio compared to traditional two-photon microscopy.

“While two-photon microscopy is the only method that allows high resolution visualization of synapses deep in scattering tissue, such as the brain, the required point by point scanning is mechanically slow. The mosTF system significantly reduces scan time without sacrificing resolution,” said Elly Nedivi, co-author of the paper published in Scientific Reports.

In head-to-head tests, mosTF outperformed conventional microscopes, producing images with a 36-times better signal-to-background ratio in simulated tissue conditions. Crucially, it could resolve the fine dendritic spines where synapses form and remodel, a feat essential for monitoring plasticity across entire neurons.

While mosTF represents a significant leap forward, the researchers are already planning further improvements. "We're continuing to work toward the goal of developing even more efficient microscopes to look at plasticity even more efficiently," said corresponding author Peter T.C. So.