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Whole-Brain 3D Activation and Functional Connectivity Mapping in Mice using Transcranial Functional Ultrasound Imaging
Published on: February 24, 2021
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Non-invasive characterization of pericyte dysfunction in mouse brain using functional ultrasound localization
Jérémy H Thalgott1, Nicolas Zucker2, Thomas Deffieux2
1Einthoven Laboratory for Vascular and Regenerative Medicine, Department of Internal Medicine (Nephrology), Leiden University Medical Centre, Leiden, the Netherlands.
Nature Biomedical Engineering
|July 30, 2025
Summary
Functional ultrasound localization microscopy (fULM) non-invasively images early pericyte dysfunction in neurological disease models. This technique can monitor therapeutic interventions targeting microvascular changes.
Area of Science:
- Neuroscience
- Medical Imaging
- Vascular Biology
Background:
- Pericyte dysfunction is an early event in neurological diseases.
- Non-invasive imaging and early biomarkers for pericyte-focused therapies are needed.
- Cerebral microvascular alterations are key indicators of disease progression.
Purpose of the Study:
- To characterize cerebral microvascular alterations caused by pericyte dysfunction using functional ultrasound localization microscopy (fULM).
- To assess the potential of fULM as a non-invasive imaging modality for early disease detection and therapeutic monitoring.
- To evaluate the efficacy of a transforming growth factor-β activator in restoring pericyte function and neurovascular coupling.
Main Methods:
- Utilized functional ultrasound localization microscopy (fULM) for non-invasive imaging of mouse cerebral microvasculature.
- Induced pericyte dysfunction by depleting endothelial endoglin in adult mice, modeling hereditary hemorrhagic telangiectasia.
- Analyzed microvascular parameters including shape, diameter, blood speed, and neurovascular coupling in the arteriole-capillary transition (ACT) zone.
Main Results:
- fULM successfully characterized cerebral microvascular alterations in a mouse model of pericyte dysfunction.
- Observed irregular arteriolar capillaries, increased diameters, reduced blood speed, and neurovascular uncoupling localized to the ACT zone.
- Treatment with transforming growth factor-β activator C381 restored pericyte coverage and normalized neurovascular response.
Conclusions:
- fULM is a powerful tool for non-invasively characterizing early microvascular changes associated with pericyte dysfunction.
- The study provides a foundation for using super-resolution ultrasound in clinical settings for monitoring neurological diseases and pericyte-targeted therapies.
- fULM demonstrates potential as a biomarker for assessing treatment efficacy in neurological disorders.
