title: Impact of Filling Gas on Subharmonic Emissions of Phospholipid Ultrasound Contrast Agents.
abstract: Subharmonic signals backscattered from gas-filled lipid-shelled microbubbles have generated significant research interest because they can improve the detection and sensitivity of contrast-enhanced ultrasound imaging. However, the emission of subharmonic signals is strongly characterized by a temporal dependence, the origins of which have not been sufficiently elucidated. The features that influence subharmonic emissions need to be identified not only to better develop next-generation microbubble contrast agents, but also to develop more efficient subharmonic imaging (SHI) modes and therapeutic strategies. We examined the effect of microbubble filling gas on subharmonic emissions. Phospholipid shelled-microbubbles with different gaseous compositions such as sulfur hexafluoride (SF6), octafluoropropane (C3F8) or decafluorobutane (C4F10), nitrogen (N2)/C4F10or air were insonated using a driving frequency of 10 MHz and peak negative pressure of 450 kPa, and their acoustic responses were tracked by monitoring both second harmonic and subharmonic emissions. Microbubbles were first acoustically characterized with their original gas and then re-characterized after substitution of the original gas with air, SF6or C4F10. A measureable change in intensity of the subharmonic emissions with a 20- to 40-min delayed onset and increasing subharmonic emissions of the order 12-18 dB was recorded for microbubbles filled with C4F10. Substitution of C4F10with air eliminated the earlier observed delay in subharmonic emissions. Significantly, substitution of SF6for C4F10successfully triggered a delay in the subharmonic emissions of the resultant agents, whereas substitution of C4F10for SF6eliminated the earlier observed suppression of subharmonic emissions, clearly suggesting that the type of filling gas contained in the microbubble agent influences subharmonic emissions in a time-dependent manner. Because our agents were dispersed in air-stabilized phosphate-buffered saline, these results suggest that the diffusivity of the gas from the agent to the surrounding medium is correlated with the time-dependent evolution of subharmonic emissions.
authors.affiliation: Imagerie et Cerveau, Inserm UMR U930, Université François Rabelais, Tours, France.
authors.forename: Emma
authors.initials: E
authors.lastname: Kanbar
authors.affiliation: Imagerie et Cerveau, Inserm UMR U930, Université François Rabelais, Tours, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Fouan
authors.affiliation: Imagerie et Cerveau, Inserm UMR U930, Université François Rabelais, Tours, France.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Sennoga
authors.affiliation: Imagerie et Cerveau, Inserm UMR U930, Université François Rabelais, Tours, France.
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Doinikov
authors.affiliation: Imagerie et Cerveau, Inserm UMR U930, Université François Rabelais, Tours, France. Electronic address: Ayache.bouakaz@univ-tours.fr.
authors.forename: Ayache
authors.initials: A
authors.lastname: Bouakaz
mesh_terms: D003287:Contrast Media; D005740:Gases; D045423:Microbubbles; D010743:Phospholipids; D000069453:Ultrasonic Waves
chemical_list: D003287:Contrast Media; D005740:Gases; D010743:Phospholipids
keywords: Gas diffusion; Microbubbles; Non-linear imaging; Subharmonic; Ultrasound contrast agents