A research team from Washington University in St. Louis and Northwestern University has developed a new imaging technique that enables scientists to visualize blood flow and oxygenation at the level of individual cells within the brain's microvasculature. The method, called super-resolution functional photoacoustic microscopy (SR-fPAM), was led by Song Hu, professor of biomedical engineering at the McKelvey School of Engineering.
The technology works by tracking red blood cells as they move through brain vessels and observing changes in their color based on oxygenation levels. SR-fPAM uses short laser pulses to cause hemoglobin in red blood cells to generate ultrasound waves, a process known as the photoacoustic effect. This allows researchers to reconstruct three-dimensional images of microvascular structures with single-cell detail.
Traditional imaging methods have allowed scientists to observe neuronal activity but have not provided enough spatial resolution to study microvascular function at the same scale. This limitation has made it difficult to fully understand diseases like cerebral small vessel disease, which is linked to cognitive impairment and dementia.
In experiments using mouse brains, SR-fPAM revealed how blood flow and oxygen distribution changed after a stroke was induced. When one vessel was blocked, neighboring vessels quickly adapted their flow patterns so that red blood cells could continue delivering oxygen.
"When one vessel is blocked, red blood cells take alternative routes to continue the flow and oxygen supply," said Hu. "Using SR-fPAM, we can observe not only structural changes in the 3D microvasculature, but also how fast red blood cells move, how their flow directions change, and how they release oxygen into the surrounding tissue in response to stroke-induced ischemia."
Hu's team plans to combine SR-fPAM with two-photon microscopy in future work so that both neurons and red blood cells can be imaged simultaneously at single-cell resolution.
"This would allow us to study how neurons and microvessels are spatiotemporally coordinated with each other and how their dynamic coupling gets disrupted in disease," Hu said. "It may also help us better interpret clinical neuroimaging techniques, such as functional MRI, which infers brain activity from vascular signals."
Hu believes this technology could eventually lead to improved early detection strategies for diseases affecting small brain vessels.
"Cerebral small vessel disease is increasingly recognized as a leading cause of cognitive impairment and dementia, and WashU is at the frontier of this in both basic and clinical research," Hu said. "If we can better understand how microvascular oxygenation and flow change in the early stages of disease, it may help guide the development of early detection strategies and therapeutic interventions."
The findings were published on March 3, 2026 in Light: Science & Applications.
