New high-resolution 3D maps show how the brain’s blood vessels changes with age

New high-resolution 3D maps show how the brain’s blood vessels changes with age

According to Kim, aging is one of the primary factors involved in neurodegenerative disorders.

“Yet, we really don’t have a good baseline understanding of how normal aging itself changes the brain, particularly the brain’s vasculature,” Kim said. And with the aging population in the United States growing, he said it’s critical to understand these changes, especially within the network of blood vessels.

Blood vessels, especially micro-vessels, regulate oxygen and energy supply and waste removal to and from neurons. Despite their importance, Kim said, most existing research focuses on how neuron structure and function degenerates over time, rather than the vasculature. When researchers do study the brain’s vasculature, they’ve primarily examined larger blood vessels or focused on a single, easy-to-access region of the brain, the somatosensory cortex. More importantly, typical neuroimaging techniques, like MRI, don’t provide high enough resolution to see what’s happening in the tiny blood vessels, which make up 80% to 85% of the brain’s vasculature, according to Kim.

Kim and the research team produced a detailed map of the vascular network of the whole mouse brain using two high-resolution 3D mapping techniques: serial two-photon tomography — a technique that creates a series of stacked 2D images — and light sheet fluorescence microscopy, which images intact 3D samples to visualize the whole brain at a single cell-resolution. They imaged the brains of young and old mice to chart vasculature changes across the brain with normal aging.

“Because we’re doing high-resolution mapping with the sufficient resolution, we can reconstruct the whole vascular structure and scan the entire brain to pinpoint areas that undergo selective degeneration with age,” Kim said. “What we found is that the area that most people study showed the least amount of change, whereas profound change happens in areas in the deep areas of the brain. This suggests that we’ve been looking at the wrong area when it comes to aging studies.”

The images showed that changes in the vascular network don’t occur equally across the brain. Rather, they were concentrated in the basal forebrain, deep cortical layers and hippocampal network, suggesting these areas are more vulnerable to vascular degeneration. These regions play a role in attention, sleep, memory processing and storage, among other functions.

As brains age, vascular length and branching density decreases approximately 10%, indicating that there’s a sparser network to distribute blood. Arteries in older brains also appear more twisted compared to those in younger brains, which can impede blood flow, especially to areas further away from the main arteries like the deep cortical layers, Kim explained.

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