An Ultrasound Enhancing Agent with Nonlinear Acoustic Activity that Depends on the Presence of an Electric Field

Abstract

The nonlinear acoustic properties of microbubble ultrasound enhancing agents have allowed for the development of subharmonic, second harmonic, and contrast-pulse sequence ultrasound imaging modes, which enhance the quality, reduce the noise, and improve the diagnostic capabilities of clinical ultrasound. This study details acoustic scattering responses of perfluorobutane (PFB) microbubbles, an un-nested perfluoropentane (PFP) nanoemulsion, and two nested PFP nanoemulsions-one comprising a negatively charged phospholipid bilayer and another comprising a zwitterionic phospholipid bilayer-when excited at 1 or 2.25 MHz over a peak negative pressure range of 200 kPa to 4 MPa in the absence and presence of a 1-Hz, 1-V/cm electric field. The only sample that exhibited an increase in nonlinear activity in the presence of an electric field at both excitation frequencies was the negatively charged nested PFP nanoemulsion; the most pronounced effect was observed at an excitation of 2.25 MHz. Interestingly, the application of an electric field not only increased the nonlinear acoustic activity of the negatively charged nested PFP nanoemulsion but increased it beyond that seen when the nanoemulsion is un-nested and on the same scale as PFB microbubbles.

Keywords: Electric field; Harmonics; Nesting; Perfluorocarbon; Scattering; Ultrasound.