The way the human brain works remains, to a great extent, a topic of controversy. One reason is our limited ability to study neuronal processes at the level of single cells and capillaries across the entire living brain without employing highly invasive surgical methods. This limitation is now on the brink 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 microcirculation without the need to open the skull or scalp. The technique has been named “diffuse optical localization imaging”, or DOLI in short.
For Razansky, this brings us closer to achieving a long-standing goal in neuroscience: “Visualising biological processes deep in the intact living brain is crucial for understanding both its cognitive functions and neurodegenerative diseases such as Alzheimer’s and Parkinson’s,” he says.
Enhanced fluorescence microscopy
A fluorescent contrast agent is set to glow when administered into the blood stream and irradiated with light of particular wavelength. Fluorescence microscopy makes use of this effect to visualise biological processes at the cellular and molecular level. Until now, researchers using this method on humans or animals have encountered the problem that living tissue scatters and absorbs light extensively, resulting in blurred 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 succeeded in significantly improving this method. “We opted for using a specific spectral region for imaging, the so-called second near-infrared window. This allowed us to greatly reduce the background scattering, absorption and intrinsic fluorescence of the living tissues," explains the professor. In addition, the research team used a recently developed, highly efficient infrared camera and a new quantum dot contrast agent that fluoresces strongly within the selected infrared range.
