EXPRESS: Microvasculature- and Layer-Resolved Neurovascular Signatures of Peri-Infarct Depolarizations Revealed by Functional Ultrasound Imaging

Peri-infarct depolarizations (PIDs) critically influence neurovascular dysfunction and lesion expansion after ischemic stroke, yet their hemodynamic signatures across cortical layers and vascular compartments remain poorly defined. Using functional ultrasound (fUS), a technique based on ultrafast Doppler imaging that enables high-sensitivity and high-resolution mapping of individual vessels, we characterized the spatiotemporal dynamics of cerebral blood volume (CBV) during PIDs in rats subjected to photothrombotic ischemia. PIDs arose at the ischemic core and propagated through the ipsi-lesional cortex, exhibiting a characteristic sequence of hypoperfusion, peak hyperemia, and post-depolarization depression. Analysis of penetrating arterioles and venules revealed marked hemispheric differences, while comparable CBV modulation between arterioles and venules was observed within the infarcted hemisphere. Laminar profiling further demonstrated that deeper cortical layers displayed greater hyperemic responses and more pronounced CBV depression than superficial layers during PID. Together, these findings establish functional ultrasound as a powerful in vivo approach for resolving microvascular and laminar hemodynamic dynamics during PIDs and for defining PID-associated CBV signatures that reflect early neurovascular dysfunction in acute ischemic stroke.