Pharmaceutical delivery can be noninvasively targeted on-demand by microbubble (MB) assisted focused ultrasound (FUS). Passive cavitation detection (PCD) has become a useful method to obtain real-time feedback on MB activity due to a FUS pulse. Previous work has demonstrated the acoustic PCD response of MBs at a variety of acoustic parameters, but few have explored variations in microbubble parameters. The goal of this study was to determine the acoustic response of different MB size populations and concentrations. Four MB size distributions were prepared (2, 3, 5 µm diameter and polydisperse) and pulled through a 2% agar wall-less vessel phantom. FUS was applied by a 1.515 MHz geometrically focused transducer for 1 ms pulses at 1 Hz PRF and seven distinct mechanical indices (MI) ranging from 0.01 to 1.0 (0.0123 to 1.23 MPa PNP). We found that the onset of harmonic (HCD) and broadband cavitation dose (BCD) depends on the mechanical index, MB size and MB concentration. When matched for MI, the HCD and BCD rise, plateau, and decline as microbubble concentration is increased. Importantly, when microbubble size and concentration are combined into gas volume fraction, all four microbubble size distributions align to similar onset and peak; these results may help guide the planning and control of MB + FUS therapeutic procedures.
Keywords: focused ultrasound; inertial cavitation; passive cavitation detection; size-isolated microbubbles; stable cavitation.