Researchers at the Mark and Mary Stevens Neuroimaging and Informatics Institute (Stevens INI) at the Keck School of Medicine of USC have developed a pioneering brain imaging technique that tracks the pulsing of the brain’s smallest blood vessels in rhythm with each heartbeat. This breakthrough method offers new insights into the aging brain and may illuminate mechanisms underlying Alzheimer’s disease.
Published in Nature Cardiovascular Research, the study introduces the first noninvasive approach to measure “microvascular volumetric pulsatility”—the cyclical expansion and contraction of tiny blood vessels in living humans.
Using ultra-high field 7T magnetic resonance imaging (MRI), the team observed that these microvascular pulses intensify with age, particularly in the brain’s deep white matter, a region essential for inter-brain network communication but vulnerable to reduced blood flow from distal arteries. Increased microvascular pulsation may disrupt brain function, contributing to memory decline and potentially accelerating Alzheimer’s progression.
“Arterial pulsation functions like the brain’s natural pump, aiding fluid movement and waste clearance,” explained Danny JJ Wang, PhD, professor of neurology and radiology at the Keck School of Medicine and senior author of the study. “Our method allows us, for the first time in humans, to monitor microvessel volume changes associated with aging and vascular risk factors, paving the way for new studies into brain health, dementia, and small vessel disease.”
While prior research has linked arterial stiffness and heightened pulsation in larger vessels to stroke, dementia, and small vessel disease, measuring these changes in the brain’s tiniest vessels has been challenging, often restricted to animal models.
To overcome this, the USC team combined vascular space occupancy (VASO) and arterial spin labeling (ASL) MRI techniques to capture subtle microvessel volume fluctuations throughout the cardiac cycle. Their findings revealed that older adults exhibit pronounced microvascular pulsations in deep white matter, with hypertension amplifying these effects.
“These results establish a critical connection between large vessel imaging observations and the microvascular damage seen in aging and Alzheimer’s disease,” said lead author Fanhua Guo, PhD, a postdoctoral researcher in Wang’s laboratory.
Excessive microvascular pulsation may also impair the brain’s glymphatic system, a network responsible for clearing waste, including beta-amyloid—a protein that accumulates in Alzheimer’s disease. Disruption of this clearance system could accelerate cognitive decline over time.
“Measuring these tiny vascular pulses in vivo represents a major advancement,” noted Arthur W. Toga, PhD, director of Stevens INI. “This technique not only deepens our understanding of brain aging but also holds promise for early diagnosis and monitoring of neurodegenerative disorders.”
The team is now exploring adaptation of this imaging method for broader clinical use, including on standard 3T MRI scanners. Future research will investigate whether microvascular volumetric pulsatility can serve as a predictive biomarker for cognitive decline and inform early intervention strategies for Alzheimer’s disease and related conditions.
“This is just the beginning,” Wang concluded. “Our goal is to translate this innovation from research to clinical practice, potentially guiding diagnosis, prevention, and treatment strategies for millions at risk of dementia.”
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