Non-invasive characterization of pericyte dysfunction in mouse brain using functional ultrasound localization microscopy

Thalgott, J.H.; Zucker, N.; Deffieux, T.; Koopman, M.S.; Dizeux, A.; Avramut, C.M.; Koning, R.I.; Mager, H.J.; Rabelink, T.J.; Tanter, M.; Lebrin, F.

doi:doi:10.1038/s41551-025-01465-x

Early microscopic-scale pericyte dysfunction contributes to the initial stages of many neurological diseases and represents a strong candidate target for therapeutic intervention. A non-invasive imaging modality able to image microvascular alterations induced by pericyte dysfunction is needed. In addition, the development of pericyte-focused therapies remains challenging due to the lack of early biomarkers of disease progression. Here we show that cerebral microvascular alterations induced by pericyte dysfunction can be characterized non-invasively in mice using functional ultrasound localization microscopy (fULM). Depletion of endothelial endoglin in adult mice as a model of hereditary haemorrhagic telangiectasia, leads to pericyte detachment in the arteriole-capillary transition (ACT) zone. Imaging reveals that arteriolar capillaries have irregular shapes, increased diameters, reduced blood speed and neurovascular uncoupling mainly localized in the ACT zone. Transforming growth...Show moreEarly microscopic-scale pericyte dysfunction contributes to the initial stages of many neurological diseases and represents a strong candidate target for therapeutic intervention. A non-invasive imaging modality able to image microvascular alterations induced by pericyte dysfunction is needed. In addition, the development of pericyte-focused therapies remains challenging due to the lack of early biomarkers of disease progression. Here we show that cerebral microvascular alterations induced by pericyte dysfunction can be characterized non-invasively in mice using functional ultrasound localization microscopy (fULM). Depletion of endothelial endoglin in adult mice as a model of hereditary haemorrhagic telangiectasia, leads to pericyte detachment in the arteriole-capillary transition (ACT) zone. Imaging reveals that arteriolar capillaries have irregular shapes, increased diameters, reduced blood speed and neurovascular uncoupling mainly localized in the ACT zone. Transforming growth factor-beta signalling activator C381 restores pericyte coverage and neurovascular response. Our study underscores the potential of fULM in characterizing early microvascular alterations. As super-resolution ultrasound transitions to the clinic, our data support its future use in monitoring pericyte-focused therapies in humans.Show less

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Non-invasive characterization of pericyte dysfunction in mouse brain using functional ultrasound localization microscopy