Equivalent-Time-Active-Cavitation-Imaging Enables Vascular-Resolution Blood-Brain-Barrier-Opening-Therapy Planning

Linking cavitation and anatomy was found to be important for predictable outcomes in Focused-Ultrasound Blood-Brain-Barrier-Opening and requires high resolution cavitation mapping. However, cavitation mapping techniques for planning and monitoring of therapeutic procedures either 1) do not leverage the full resolution capabilities of ultrasound imaging or 2) place strong constraints on the length of the therapeutic pulse. This study aimed to develop a high-resolution technique that could resolve vascular anatomy in the cavitation map. Herein, we develop BP-ETACI, derived from bandpass sampling and dual-frequency contrast imaging at 12.5 MHz to produce cavitation maps prior and during blood-brain barrier opening with long therapeutic bursts using a 1.5-MHz focused transducer in the brain of C57BL/6 mice. The BP-ETACI cavitation maps were found to correlate with the vascular anatomy in ultrasound localization microscopy vascular maps and in histological sections. Cavitation maps produced from non-blood-brain-barrier disrupting doses showed the same cavitation-bearing vasculature as maps produced over entire blood-brain-barrier opening procedures, allowing use for 1) monitoring FUS-BBBO, but also for 2) therapy planning and target verification. BP-ETACI is versatile, created high resolution cavitation maps in the mouse brain and is easily translatable to existing FUS-BBBO experiments. As such, it provides a means to further study cavitation phenomena in FUS-BBBO.