Posted on behalf of Janelle Weaver.
A new optical imaging tool that doesn’t damage tissue could help doctors to diagnose brain disorders and perform surgeries.
The noninvasive technique relies on a tweaked version of two-photon laser-scanning miscroscopy, which produces high-resolution images of living tissue by beaming photons that penetrate through cell layers. But unlike the traditional approach, which enhances image contrast with toxic fluorescent dyes, the new one, called third-harmonic generation (THG), creates sharp images by matching the laser focus with the physical features of the tissue.
The method is ideal for picturing lipid-rich structures, such as the long projections that connect neurons, rather than tiny compartments within cell bodies. Because abnormal lipid metabolism characterizes Alzheimer’s disease and brain cancer, the tool could detect these medical conditions. It could also guide recording electrodes and surgical instruments into the brain.
The team, led by Huibert Mansvelder and Marie Louise Groot of VU University in Amsterdam, took pictures of slices of mouse brains, and also of the brains of live anesthetized mice via craniotomy. You can see a selection of their results below.
The work was published today in Proceedings of the National Academy of Sciences.
Top image: How the technique works. By changing the focus of the laser beam, researchers can visualize neuronal projections without fluorescent dyes.
(A) THG image of live brain tissue in the mouse. Cell bodies look like dark shadows. (B) Standard 2-photon fluorescence from Nile Red-stained lipid structures at the same location as A. (D) Bundle of nerve fibers in a mouse brain slice. (F) Blood vessels in a live, anesthetized mouse.
(A-C) Images of live, anesthetized mouse brain taken at different depths (100, 200 and 300 µm). The contrast stays high, despite a decrease in the signal at deeper locations.
(B, C) Pipette inserted into mouse brain slice to record neuronal signals. The laser beam does not disrupt the functioning of neurons.