title: Spatiotemporal evolution of cavitation dynamics exhibited by flowing microbubbles during ultrasound exposure.
abstract: Ultrasound and microbubble-based therapies utilize cavitation to generate bioeffects, yet cavitation dynamics during individual pulses and across consecutive pulses remain poorly understood under physiologically relevant flow conditions. SonoVue(®) microbubbles were made to flow (fluid velocity: 10-40 mm/s) through a vessel in a tissue-mimicking material and were exposed to ultrasound [frequency: 0.5 MHz, peak-rarefactional pressure (PRP): 150-1200 kPa, pulse length: 1-100,000 cycles, pulse repetition frequency (PRF): 1-50 Hz, number of pulses: 10-250]. Radiated emissions were captured on a linear array, and passive acoustic mapping was used to spatiotemporally resolve cavitation events. At low PRPs, stable cavitation was maintained throughout several pulses, thus generating a steady rise in energy with low upstream spatial bias within the focal volume. At high PRPs, inertial cavitation was concentrated in the first 6.3 ± 1.3 ms of a pulse, followed by an energy reduction and high upstream bias. Multiple pulses at PRFs below a flow-dependent critical rate (PRF(crit)) produced predictable and consistent cavitation dynamics. Above the PRF(crit), energy generated was unpredictable and spatially biased. In conclusion, key parameters in microbubble-seeded flow conditions were matched with specific types, magnitudes, distributions, and durations of cavitation; this may help in understanding empirically observed in vivo phenomena and guide future pulse sequence designs.
authors.affiliation: Biomedical Ultrasonics, Biotherapy, and Biopharmaceuticals Laboratory, Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Oxford, Oxfordshire OX3 7DQ, United Kingdom. james.choi@eng.ox.ac.uk
authors.forename: James J
authors.initials: JJ
authors.lastname: Choi
authors.forename: Constantin-C
authors.initials: CC
authors.lastname: Coussios
mesh_terms: D003287:Contrast Media; D004867:Equipment Design; D045423:Microbubbles; D008962:Models, Theoretical; D010743:Phospholipids; D011312:Pressure; D013459:Sulfur Hexafluoride; D013997:Time Factors; D014160:Transducers, Pressure; D014465:Ultrasonics / Q000295:instrumentation / Q000379:methods*
chemical_list: D003287:Contrast Media; D010743:Phospholipids; C420843:contrast agent BR1; D013459:Sulfur Hexafluoride