Researchers use new technique to visualize brain tissue non-invasively
The functioning of the human brain remains, to a large extent, a subject of controversy. One reason is our limited ability to study neural processes at the level of individual cells and capillaries throughout the living brain without using highly invasive surgical methods. This limitation is now on the verge of change.
Researchers led by Daniel Razansky, professor of biomedical imaging at ETH Zurich and the University of Zurich, have developed a fluorescence microscopy technique that facilitates high-resolution images of the microcirculation without the need for open the skull or scalp. The technique has been named “diffuse optical localization imaging”, or DOLI for short.
For Razansky, this brings us closer to achieving a long-held goal in neuroscience: “Visualizing biological processes deep within the intact living brain is crucial to understanding both its cognitive functions and neurodegenerative diseases such as the disease. Alzheimer’s and Parkinson’s disease, ”he says.
Enhanced fluorescence microscopy
A fluorescent contrast agent is set to glow when delivered into the bloodstream and irradiated with light of a particular wavelength. Fluorescence microscopy uses this effect to visualize biological processes at the cellular and molecular level. Until now, researchers using this method on humans or animals have faced the problem that living tissue widely scatter and absorb light, resulting in blurry images and the inability to identify the exact location of the fluorescent agent inside the brain.
By introducing several new techniques, Razansky and his team have now managed to significantly improve this method.
“We opted to use a specific spectral region for imaging, the so-called second near infrared window. This allowed us to considerably reduce the background scattering, absorption and intrinsic fluorescence of living tissues, ”explains the professor. In addition, the research team used a recently developed, highly efficient infrared camera and a novel quantum dot contrast agent that fluoresces strongly in the selected infrared range.
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 microscopy approaches. with conventional fluorescence. Razansky and his team then injected living mice with microdroplets encapsulating fluorescent quantum dots as a contrast agent. They were then able to locate these droplets individually in the living brain using the new technique.
For the first time, we were able to clearly visualize the microvascularization and blood flow deep in the mouse brain in a completely non-invasive manner. “
Daniel Razansky, Professor of Biomedical Imaging at ETH Zurich and University of Zurich
In addition, researchers at ETH Zurich and the University of Zurich observed that the size of the imaged microdroplets depends on their depth in the brain. This makes the DOLI technique capable of three-dimensional imaging.
Compared to other biological imaging techniques, such as optoacoustic imaging, also developed by Razansky, the DOLI technique takes advantage of the great versatility and straightforward nature of established fluorescence imaging approaches. “You basically need a relatively simple and affordable camera setup without any pulsed lasers or fancy optics. This facilitates distribution in laboratories, ”explains Razansky.
A basis for new perspectives
Neurological disorders, ranging from epilepsy, strokes to various types of dementia, affect up to a billion people worldwide. Therefore, it is of the utmost importance to better understand the biological causes of neurodegenerative and other brain diseases and to detect them at an early stage.
According to Razansky, improved fluorescence microscopy based on the DOLI method provides a good basis for this: “We assume that this technique will also lead to new knowledge about how the brain works and, in the longer term, will facilitate the development of new options. therapeutic. ” Until then, however, he and his team will likely have to monitor the brains of a few more mice.