In vitrocharacterization of the subharmonic ultrasound signal from Definity microbubbles at high frequencies

Abstract

Ultrasound microbubble contrast agents have been demonstrated to scatter subharmonic energy at one-half the driving frequency. At ultrasound frequencies in the 20-40 MHz range, the subharmonic offers the potential to differentiate the blood in the microcirculation from the surrounding tissue. It is unknown whether current contrast agents, manufactured to be resonant between 2 and 12 MHz, are ideal for subharmonic imaging at higher frequencies. We performed numerical simulations of the Keller-Miksis model for the behavior of a single bubble and experimental investigations of Definity microbubbles in water. The results supported the hypothesis that off-resonant bubbles, excited at their second harmonic, may be primarily responsible for the observed subharmonic energy. For frequencies between 20 and 32 MHz and 32 and 40 MHz, the optimal bubble diameters for the generation of subharmonics in vitro were determined experimentally to be 1.2-5 microm and less than 1.2 microm, respectively. Definity may be a suitable ultrasound contrast agent for subharmonic imaging at 20 MHz with peak-negative pressures between 380 and 590 kPa and pulses greater than or equal to four cycles in duration.

Nonlinear response to ultrasound of encapsulated microbubbles

“…However, it has some limitations because the harmonics generated may be reflected by the surrounding tissue with the subsequent reduction of resolution. To overcome these restrictions the use of harmonics of higher order [37], or subharmonic ultrasound signals has been proposed [38,39]. Consequently, the analysis given here could be extended in order to determine the range of governing parameters where subharmonic and superharmonic imaging are optimized.…”

The effect of amplitude modulation on subharmonic imaging with chirp excitation

“…The excitation center frequency was selected as 7.6 MHz, since it was double the resonance frequency of the microbubbles used in this study. Instead of comparing the peak subharmonic power or subharmonic-to-fundamental ratio, which are commonly used for characterizing microbubbles and for measuring their nonlinear behaviors [48], [50], [51], the total subharmonic power was calculated to evaluate the subharmonic behavior of UCAs to different excitation signals. The reason for using this method was due to the variation in bandwidths of the LFM and NLFM chirps used in this study.…”

Size-isolation of ultrasound-mediated phase change perfluorocarbon droplets using differential centrifugation

“…Microfluidic production, 9 microfluidic sorting, 10,11 and pore-filtration 12,13 have been used to generate specific size ranges of microbubbles and droplets. Microfluidic techniques have been effective in controlling particle size.…”