Researchers are using new technology to visualize brain tissue non-invasively

The way the human brain works is, to a large extent, controversial. One reason is the limited ability to study neural processes at the level of single cells and capillaries throughout the living brain without the use of highly invasive surgical techniques. This limit is currently on the verge of change.

Researchers led by ETH Zurich and Daniel Razansky, a professor of biomedical imaging at the University of Zurich, have developed fluorescence microscopy technology that facilitates high-resolution images of microcirculation without opening the skull or skull. This technique is called “diffusion optical positioning imaging”, or DOLI for short.

For Razansky, this approaches achieving the long-standing goal of neuroscience. “Visualizing the biological processes deep inside an intact living brain is important for understanding both its cognitive function and neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease,” he says. I will.

Enhanced fluorescence microscope

Fluorescent contrast media are administered into the bloodstream and are set to emit light when exposed to light of a specific wavelength. Fluorescence microscopy takes advantage of this effect to visualize biological processes at the cellular and molecular levels. So far, researchers using this method for humans and animals have found that living tissues scatter and absorb light extensively, blurring images and making it impossible to pinpoint the exact location of fluorescent agents in the brain. I was facing the problem.

Razansky and his team have succeeded in significantly improving this method by introducing several new technologies.

“We chose to use a specific spectral region for imaging, the so-called second near-infrared window, which significantly reduced background scattering, absorption, and intrinsic fluorescence of living tissue,” he said. Explains. In addition, the research team used a recently developed high-efficiency infrared camera and a new quantum dot contrast agent that fluoresces strongly within the selected infrared range.

High resolution image of the brain

Researchers first tested the new technique using a synthetic tissue model that simulates the properties of brain tissue, demonstrating that microscopic images can be obtained with four times the penetration depth of traditional fluorescence microscopy approaches. .. Razansky and his team then injected microdroplets encapsulating fluorescent quantum dots as a contrast agent into living mice. They were then able to use new technology to individually localize these droplets in the living brain.

For the first time, we were able to clearly visualize the microvascular system and blood circulation deep in the mouse brain in a completely non-invasive manner. “

Daniel Razansky, Professor of Biomedical Imaging at ETH Zurich and the University of Zurich

In addition, researchers at the ETH Zurich and the University of Zurich have observed that the size of the imaged microdroplets depends on how deep they are located in the brain. This enables DOLI technology for 3D imaging.

Compared to other biological imaging techniques, such as photoacoustic imaging, also developed by Razansky, DOLI technology takes advantage of the versatility and simplicity of an established fluorescence imaging approach. “Basically, we need a relatively simple and affordable camera setup without the use of pulsed lasers or advanced optics, which makes it easier to reach in the lab,” Razansky explains. To do.

The basis of new insights

Neurological disorders ranging from epilepsy and stroke to various types of dementia affect up to 1 billion people worldwide. Therefore, it is of utmost importance to better understand the biological causes of neurodegeneration and other brain disorders and to detect them early.

According to Razansky, an improved fluorescence microscope based on the DOLI method provides a good basis for this. “We believe this technology will also lead to new insights into brain function and, in the long run, will facilitate the development of new treatment options.” But until then, he and his team probably had a few more. The mouse brain should be monitored.