Characterization of Microbubble Activity Under Ultra-Short Focused Pulses Delivered by an Imaging Phased Array

Theranostic Ultrasound (ThUS) has been recently developed to combine focused pulses for blood-brain barrier (BBB) opening with Power Cavitation Imaging (PCI) for treatment monitoring in a single repurposed imaging transducer. ThUS employs ultra-short focused pulses for microbubble cavitation, which enables high PCI resolution; however there have not been extensive studies into the nature of microbubble cavitation under these ultra-short pulses. In this study, we investigate the acoustic signal of microbubbles under 1.5 MHz ThUS pulses in an in vitro flow channel, analyzing the types of cavitation present at various pulse lengths and pressures, and assessing the in vivo safety of these pulses in mice. We observe significant spectral broadening in the frequency domain. However, analysis of the time domain signal for multiple pulses reveals a stable cavitation activity at the shortest pulse length of 1.5 cycles. A higher rate of microbubble collapse is observed at longer pulse lengths and higher pressures, as evidenced by a large decrease in acoustic signal amplitude over time. The in vivo study in mice showed no visible damage in mice treated with 1.5- and 5-cycle pulses, and only small erythrocyte extravasation for the mouse treated with 10-cycle pulses at 1.00 MPa. Therefore, this study shows that, despite the dominant broadband activity at ultra-short pulse lengths, there is limited microbubble collapse, which leads to safe BBB opening. This was an initial study to generate the parametric space for safe and efficient ThUS-mediated BBB opening.