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Two-Dimensional Super-Resolution Visualization of Rat Brain Microvasculature Using Ultrasound Localization Microscopy
Published on: March 28, 2025
980
A Minimally Invasive Framework Reveals Region-Specific Cerebrovascular Remodeling in Aging Using Intravital
Sharon Negri1,2, Adam Nyul-Toth2, Madison Milan1,2
1Vascular Cognitive Impairment and Neurodegeneration Program, Reynolds Oklahoma Center on Aging/Center for Geroscience and Healthy Brain Aging, Dept. of Neurosurgery, OUHSC, Oklahoma City, OK, 73104.
Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|September 14, 2025
Summary
Aging significantly impacts brain blood vessels, affecting cognitive function. This study introduces a novel imaging technique to assess cerebrovascular changes and identify a new biomarker for age-related remodeling, aiding dementia research.
Area of Science:
- Neuroscience
- Biomedical Engineering
- Gerontology
Background:
- Aging cerebrovascular system is linked to cognitive decline and dementia.
- Current imaging methods have limitations in assessing brain vasculature longitudinally and non-invasively.
- Understanding age-related cerebrovascular changes is crucial for developing effective treatments.
Purpose of the Study:
- To develop and validate a novel high-resolution intravital imaging platform for longitudinal assessment of cerebrovascular structure and function.
- To establish a new method for estimating resting cerebral blood flow (CBF) using integrated ultrasound techniques.
- To identify novel biomarkers of age-related cerebrovascular remodeling and assess neurovascular coupling (NVC) in aging models.
Main Methods:
- Development of a combined functional ultrasound (fUS) and ultrasound localization microscopy (ULM) imaging platform.
- Chronic implantation of a transparent polymethylpentene (TPX) cranial window for minimally invasive ultrasound access.
- Integration of microbubble (MB) velocity data with microvascular geometry to estimate CBF.
- Longitudinal assessment of cerebrovascular structure and NVC in aging mice.
Main Results:
- A significant age-related decline in the cortical arteriole-to-venule ratio (AVR) was discovered, serving as a novel biomarker for structural cerebrovascular remodeling.
- The developed platform enables reliable, longitudinal, and minimally invasive assessment of cerebrovascular dynamics.
- Functional ultrasound (fUS) was validated for assessing neurovascular coupling (NVC) responses in aged mice.
Conclusions:
- The novel fUS-ULM imaging platform provides a powerful, non-invasive tool for preclinical cerebrovascular research.
- This technology facilitates the study of vascular contributions to cognitive impairment and neurodegeneration.
- The identified AVR decline offers a new target for therapeutic interventions in aging-related brain diseases.
