Brain diseases are often associated with specific vascular changes. Now, scientists at Helmholtz Zentrum München, LMU University Hospital Munich and Technical University Munich have introduced a technique to visualize the structures of all the brain’s blood vessels – just below the best capillaries, including any pathological changes.

So far, they have used the technique, which is based on a combination of biochemical methods and artificial intelligence, to capture the entire brain vessel of a mouse.

Changes in blood vessels are a hallmark of many brain disorders – from traumatic brain injury to stroke. Even shows like Alzheimer’s make changes in fine capillaries. In short, analysis of blood vessels is important for understanding both normal and pathological brain functions.

“We have now come very close to achieving that goal”, explains Helmholtz Ali Ertark, director of the Institute for Tissue Engineering and Regenerative Medicine at Zentrum Munchen, and principal investigator in stroke and dementia research at LMU University Hospital Munich.

Make organs transparent

As a first step, Ertark’s team succeeded in visualizing the vascular system of mouse brains with high-resolution fluorescent microscopy without cutting specimens into small volumes.

To do this, they refined the tissue cleaning technique, in which biological tissues are treated with special dyes to make them transparent to the fluorescent canopy. “Previously, this technique could only be used to scan either large vessels or small masses of the brain”, says Mihail Ivilinov Todorov, a doctoral student studying under Ertürk.

So scientists based in Munich adopted a new way of combining the two colors. “It gives us some great images of the cerebral vasculature, including the capillary”, the biologist says.

Vascular networks were captured using artificial intelligence

Applying artificial intelligence, researchers at the Technical University of Munich for team learning in biomedical imaging under the leadership of Professor Björn Menzé used these images to reconnect the entire vascular network of the brain with its finest details.

Such a reconstruction yields more than just images – it also allows a quantitative analysis of vascular structures. “For example, we can statistically record the diameters of different blood vessels or their bifurcations for different areas of the brain”, says Johannes Patzold, a doctoral student in Mainz’s group.

“Over the years, we have developed an intensive learning algorithm that specializes in detecting blood vessels in medical images”, explains Mainz.

“This was the first time we applied it to the entire brain.” The algorithm was able to reliably distinguish between blood vessels and other tissue, even though some areas in the original fluorescence images were not well illuminated and some details were distorted due to light reflections or other errors.

Understanding and diagnosing brain disorders

Mikhail Evilinov Todorov plans to use statistical data to examine vascular changes caused by stroke, while Björn Mainz wants to study the global structures of the vascular system to understand the role of physiological variation in neurological orders. Are, for example. .

Benefit to the patient

The method can also be used in everyday clinical practice: “With our system, we are likely to be able to analyze small tissue samples from human tumors with greater accuracy”, emphasizes Ertark . Cancerous tissues are allowed by blood vessels, and analyzing their structure helps in the staging of tumors.

“This can have an adaptation effect on treatment”, says Ertürk. The biologist also plans to use the new method to realize his vision for the future: the production of human organs on a 3D printer. For this to happen, knowledge of the precise vascular structure of the organ – among many other things – will be important.

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