Studying the human brain with non-invasive fluorescence microscopy

Researchers have established a novel non-invasive method for studying the human brain using fluorescence microscopy, possibly advancing treatments for neurodegenerative diseases.

The research, conducted by scientists at ETH Zurich and the University of Zurich, has developed a new technique named diffuse optical localisation imaging (DOLI), proficient in attaining high-resolution images of microcirculation without evasive procedures. This groundbreaking development could potentially enhance knowledge of the human brain, which can aid in research for neurodegenerative diseases like Alzheimer’s and Parkinson’s.

Currently, our capacity to analyse how the human brain works is extremely limited, requiring highly invasive surgical methods to examine neuronal processes at the level of capillaries and single cells; nevertheless, this new method achieves that feat without the need to open the skull or scalp.

Daniel Razansky, a Professor of Biomedical Imaging and leader of the study, said: “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.”

Fluorescence microscopy works by administering a fluorescent contrast agent to the bloodstream, which is irradiated with light of a particular wavelength; this allows biological processes at the molecular and cellular level to be analysed. Where this process becomes problematic is that the body’s tissue can scatter and absorb the light, producing blurred images that make locating the fluorescent agent in the human brain extremely challenging. Nevertheless, the new method looks to bypass this problem.

Razansky said: “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. We also used a highly efficient infrared camera and a new quantum dot contrast agent that fluoresces strongly within the selected infrared range.”

Firstly, the novel technique was experimented with using synthetic tissue models to simulate human brain tissue, which indicated that the method could achieve microscopic images at four times the penetration depth of conventional fluorescence microscopy. Next, the team inoculated living mice with microdroplets encapsulating fluorescent quantum dots as a contrast agent, with the new technique proven to be adept at distinguishing these droplets in the brain tissue.

Razansky explained: “For the first time, we were able to clearly visualise the microvasculature and blood circulation deep in the mouse brain entirely noninvasively. You basically need a relatively simple and affordable camera setup without any pulsed lasers or sophisticated optics. This facilitates the dissemination in labs. We assume that this technique will also lead to new insights into brain function and, in the longer term, facilitate the development of new therapeutic options.”

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