title: Dynamic Behavior of Microbubbles during Long Ultrasound Tone-Burst Excitation: Mechanistic Insights into Ultrasound-Microbubble Mediated Therapeutics Using High-Speed Imaging and Cavitation Detection.
abstract: Ultrasound (US)-microbubble (MB)-mediated therapies have been found to restore perfusion and enhance drug/gene delivery. On the presumption that MBs do not persist during long US exposure under high acoustic pressures, most schemes use short US pulses when a high US pressure is employed. However, we recently observed an enhanced thrombolytic effect using long US pulses at high acoustic pressures. Therefore, we explored the fate of MBs during long tone-burst exposures (5 ms) at various acoustic pressures and MB concentrations via direct high-speed optical observation and passive cavitation detection. MBs first underwent stable or inertial cavitation depending on the acoustic pressure and then formed gas-filled clusters that continued to oscillate, break up and form new clusters. Cavitation detection confirmed continued, albeit diminishing, acoustic activity throughout the 5-ms US excitation. These data suggest that persisting cavitation activity during long tone bursts may confer additional therapeutic effects.
authors.affiliation: Center for Ultrasound Molecular Imaging and Therapeutics, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.
authors.forename: Xucai
authors.initials: X
authors.lastname: Chen
authors.affiliation: Center for Ultrasound Molecular Imaging and Therapeutics, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Center for Ultrasound Molecular Imaging and Therapeutics, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: Pacella
authors.affiliation: Center for Ultrasound Molecular Imaging and Therapeutics, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.
authors.forename: Flordeliza S
authors.initials: FS
authors.lastname: Villanueva
mesh_terms: D003287:Contrast Media / Q000737:chemistry / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D018274:Electroporation / Q000379:methods; D005466:Fluorocarbons / Q000737:chemistry* / Q000528:radiation effects*; D005740:Gases / Q000138:chemical synthesis* / Q000528:radiation effects; D045423:Microbubbles / Q000627:therapeutic use*; D011829:Radiation Dosage; D013010:Sonication / Q000379:methods*; D014464:Ultrasonic Therapy / Q000379:methods*
chemical_list: D003287:Contrast Media; D005466:Fluorocarbons; D005740:Gases; C108042:perfluorobutane
keywords: Cavitation; High-speed imaging; Microbubble dynamics; Sonothrombolysis; Ultrasound contrast agents; Ultrasound therapy