Flash-Replenishment Passive Acoustic Mapping for Robust Monitoring of Transvertebral Focused Ultrasound

Microbubble (MB)-mediated focused ultrasound (FUS) therapy targeting the spinal cord requires reliable, intra-operative treatment monitoring of cavitation activity within the spinal canal. Prefocal cavitation during transvertebral focused ultrasound can hinder assessment of intracanal cavitation events. Due to reflection and subsequent refocusing of sound by the vertebral bones, circulating MBs in the prelaminar space can generate strong acoustic signals that interfere with attenuated emissions from MBs in the canal, pushing the latter below the noise floor of prefocal cavitation activity in reconstructed images. By pairing transvertebral FUS sequencing with 'Flash-Replenishment' style pulse sequencing common in contrast ultrasound, we suppressed cavitation at its source in the prelaminar, pre-vertebral regions, and performed transvertebral passive acoustic mapping through ex vivo human vertebrae. We show ex vivo that, on average, interleaving 'flash' pulses during FUS sequencing can raise the canal-prefocal source strength ratio in reconstructed images by approximately 1.75 times compared to conventional pulse sequencing. We further show that the maximum pressure in the canal during 'flash' pulses is much lower than the subsequent 'therapeutic' pulses, suggesting the 'flash' pulse will have limited potential to induce bioeffects in the spinal cord. We then performed in vivo 'flash-replenishment' ultrasound in porcine dorsal musculature and determined reperfusion rates are on the order of 2-3 seconds in the largest vessels supplying the muscles after MB destruction allowing for flexibility in FUS sequence design. In summary, this work exemplifies that a spatial and temporal window of bubblefree prefocal space can provide an unobscured sightline for monitoring intracanal cavitation reliably.