High-resolution images of the brain
The researchers first tested the new technique using synthetic tissue models that simulate the properties of brain tissue, demonstrating that it is possible to acquire microscopic images at four times the penetration depth of conventional fluorescence microscopy approaches. Razansky and his team then injected living mice with microdroplets encapsulating fluorescent quantum dots as a contrast agent. They were then able to localize these droplets individually in the living brain using the new technique.
“For the first time, we were able to clearly visualise the microvasculature and blood circulation deep in the mouse brain entirely noninvasively,” says Razansky. In addition, the researchers from ETH Zurich and the University of Zurich observed that the size of the imaged microdroplets depends on how deep they are located in the brain. This makes the DOLI technique capable of three-dimensional imaging.
Compared with other biological imaging techniques, such as optoacoustic imaging, also developed by Razansky, the DOLI technique takes advantage of the high versatility and uncomplicated nature of established fluorescence imaging approaches. “You basically need a relatively simple and affordable camera setup without any pulsed lasers or sophisticated optics. This facilitates the dissemination in labs,” explains Razansky.
A basis for new insights
Neurological disorders, ranging from epilepsy, strokes to various types of dementia, affect up to one billion people worldwide. Therefore, it is of paramount importance to better understand the biological causes of neurodegenerative and other brain diseases and to detect them at an early stage.
According to Razansky, the improved fluorescence microscopy based on the DOLI method offers a good basis for this: “We assume that this technique will also lead to new insights into brain function and, in the longer term, facilitate development of new therapeutic options.” Until then, however, he and his team will most likely have to watch the brains of mice for a while longer.