Abstract
Focused ultrasound (FUS) represents an innovative, non-invasive method for modulating the permeability of the blood-brain barrier (BBB), allowing transient openings for therapeutic delivery. Yet, excessive BBB disruption risks cerebral damage and neurological symptoms. Current imaging techniques typically lack the ability to provide detailed hemodynamic data in tandem with BBB integrity assessments across whole brain regions. Here, we introduce a FUS-compatible, deep learning enhanced multi-parametric photoacoustic/ultrasound localization (PAUL) imaging method employing a clinical ultrasound linear array. This dual-modality technique enables comprehensive whole brain imaging through the intact skull, capturing brain microvasculature, changes in blood flow and oxygenation, as well as mapping the distribution of BBB permeability tracers. Our technology enables visualization of microvascular structures down to 22 µm and provides detailed tracking of blood flow dynamics at the single microvasculature level. Our results demonstrate that BBB modulation results in decreased blood flow and flow rate, especially in regions with high BBB permeable tracer retention. This indicates PAUL imaging can non-invasively monitor BBB disruption caused by FUS, offering a potential advancement in the management and understanding of BBB dynamics.