title: Acoustic Behavior of Halobacterium salinarum Gas Vesicles in the High-Frequency Range: Experiments and Modeling.
abstract: Gas vesicles (GVs) are a new and unique class of biologically derived ultrasound contrast agents with sub-micron size whose acoustic properties have not been fully elucidated. In this study, we investigated the acoustic collapse pressure and behavior of Halobacterium salinarum gas vesicles at transmit center frequencies ranging from 12.5 to 27.5 MHz. The acoustic collapse pressure was found to be above 550 kPa at all frequencies, nine-fold higher than the critical pressure observed under hydrostatic conditions. We illustrate that gas vesicles behave non-linearly when exposed to ultrasound at incident pressure ranging from 160 kPa to the collapse pressure and generate second harmonic amplitudes of -2 to -6 dB below the fundamental in media with viscosities ranging from 0.89 to 8 mPa·s. Simulations performed using a Rayleigh-Plesset-type model accounting for buckling and a dynamic finite-element analysis suggest that buckling is the mechanism behind the generation of harmonics. We found good agreement between the level of second harmonic relative to the fundamental measured at 20 MHz and the Rayleigh-Plesset model predictions. Finite-element simulations extended these findings to a non-spherical geometry, confirmed that the acoustic buckling pressure corresponds to the critical pressure under hydrostatic conditions and support the hypothesis of limited gas flow across the GV shell during the compression phase in the frequency range investigated. From simulations, estimates of GV bandwidth-limited scattering indicate that a single GV has a scattering cross section comparable to that of a red blood cell. These findings will inform the development of GV-based contrast agents and pulse sequences to optimize their detection with ultrasound.
authors.affiliation: Sunnybrook Research Institute, Physical Sciences, Toronto, Ontario, Canada. Electronic address: emmanuel.cherin@sri.utoronto.ca.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Cherin
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California, USA.
authors.forename: Johan M
authors.initials: JM
authors.lastname: Melis
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California, USA.
authors.forename: Raymond W
authors.initials: RW
authors.lastname: Bourdeau
authors.affiliation: Sunnybrook Research Institute, Physical Sciences, Toronto, Ontario, Canada.
authors.forename: Melissa
authors.initials: M
authors.lastname: Yin
authors.affiliation: Division of Engineering and Applied Science, California Institute of Technology, Pasadena, California, USA.
authors.forename: Dennis M
authors.initials: DM
authors.lastname: Kochmann
authors.affiliation: Sunnybrook Research Institute, Physical Sciences, Toronto, Ontario, Canada; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: F Stuart
authors.initials: FS
authors.lastname: Foster
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California, USA.
authors.forename: Mikhail G
authors.initials: MG
authors.lastname: Shapiro
mesh_terms: D003198:Computer Simulation; D003287:Contrast Media; D019617:Halobacterium salinarum; D045423:Microbubbles; D008962:Models, Theoretical; D011312:Pressure; D000069453:Ultrasonic Waves
chemical_list: D003287:Contrast Media
keywords: Buckling; Contrast agent; High-frequency ultrasound; Modeling; Submicron gas vesicles