title: Fluid Viscosity Affects the Fragmentation and Inertial Cavitation Threshold of Lipid-Encapsulated Microbubbles.
abstract: Ultrasound and microbubble optimization studies for therapeutic applications are often conducted in water/saline, with a fluid viscosity of 1 cP. In an in vivo context, microbubbles are situated in blood, a more viscous fluid (∼4 cP). In this study, ultrahigh-speed microscopy and passive cavitation approaches were employed to investigate the effect of fluid viscosity on microbubble behavior at 1 MHz subject to high pressures (0.25-2 MPa). The propensity for individual microbubble (n = 220) fragmentation was found to significantly decrease in 4-cP fluid compared with 1-cP fluid, despite achieving similar maximum radial excursions. Microbubble populations diluted in 4-cP fluid exhibited decreased wideband emissions (up to 10.2 times), and increasingly distinct harmonic emission peaks (e.g., ultraharmonic) with increasing pressure, compared with those in 1-cP fluid. These results suggest that in vitro studies should consider an evaluation using physiologic viscosity perfusate before transitioning to in vivo evaluations.
authors.affiliation: Center for Ultrasound Molecular Imaging and Therapeutics, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
authors.forename: Brandon
authors.initials: B
authors.lastname: Helfield
authors.affiliation: Center for Ultrasound Molecular Imaging and Therapeutics, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: Black
authors.affiliation: Center for Ultrasound Molecular Imaging and Therapeutics, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Qin
authors.affiliation: Center for Ultrasound Molecular Imaging and Therapeutics, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
authors.forename: John
authors.initials: J
authors.lastname: Pacella
authors.affiliation: Center for Ultrasound Molecular Imaging and Therapeutics, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, 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, Pennsylvania, USA. Electronic address: villanuevafs@upmc.edu.
authors.forename: Flordeliza S
authors.initials: FS
authors.lastname: Villanueva
mesh_terms: D002214:Capsules / Q000737:chemistry* / Q000528:radiation effects; D003287:Contrast Media / Q000737:chemistry / Q000528:radiation effects; D005740:Gases / Q000138:chemical synthesis*; D019220:High-Energy Shock Waves; D008055:Lipids / Q000737:chemistry* / Q000528:radiation effects; D008422:Materials Testing; D045423:Microbubbles; D011829:Radiation Dosage; D012212:Rheology / Q000379:methods; D012996:Solutions / Q000737:chemistry / Q000528:radiation effects; D013010:Sonication / Q000379:methods*; D014783:Viscosity
chemical_list: D002214:Capsules; D003287:Contrast Media; D005740:Gases; D008055:Lipids; D012996:Solutions
keywords: Fluid viscosity; Fragmentation; High-speed imaging; Inertial cavitation; Microbubbles; Stable cavitation; Ultrasound