The effect of resonance on transient microbubble acoustic response: Experimental observations and numerical simulations.

A large number of acoustic signals from single lipid-shelled Definity® (Lantheus Medical Imaging, N. Billerica, MA) microbubbles have been measured using a calibrated microacoustic system, and a unique transient characteristic of resonance has been identified in the onset of scatter. Comparison of the numerically obtained response of microbubbles with acoustic measurements provides good agreement for a soft shell that is characterized by small area dilatation modulus and strain softening behavior, and identifies time to maximum radial excursion and scatter as a robust marker of resonance during transient response. As the sound amplitude increases a two-population pattern emerges in the time delay vs the fundamental acoustic scatter plots, consisting of an initial part pertaining to microbubbles with less than resonant rest radii, which corresponds to the weaker second harmonic resonance, and the dominant resonant envelope pertaining to microbubbles with resonant and greater than resonant rest radii, which corresponds to the primary and subharmonic resonances. Consequently, a wider resonant spectrum is observed. It is a result of the strain softening nature of soft lipid shells, based on which the microbubble sizes corresponding to the above resonances decrease as the sound amplitude increases. This bares an impact on the selection of an optimal microbubble size pertaining to subharmonic imaging.

The acoustic scatter from single biSphere microbubbles.

Single microbubble acoustic acquisitions provide information on the behaviour of microbubble populations by enabling the generation of large amounts of data. Acoustic signals from single polylactide-shelled and albumin coated biSphere™ microbubbles have been acquired. The responses observed from a range of incident frequencies and acoustic pressures varied in duration. Partial echoes shorter than the incident pulse duration have been observed for low frequency pulses of sufficient amplitude, suggesting release of gas from bubbles. The results presented suggest that the mechanism of scatter from hard shelled agents may be shell disruption and gas release, or partly from gas leaking from defected shell sites, which has previously not been observed optically. These results can provide the basis for improved imaging through optimization of incident pulse parameters, with potential benefits to both diagnostic and therapeutic techniques.

Single microbubble response using pulse sequences: initial results.

The study of acoustic scattering by single microbubbles has the potential to offer improved signal processing techniques. A microacoustic system that employs a hydrodynamically-focused flow was used to detect radiofrequency (RF) backscatter from single microbubbles. RF data were collected using a commercial scanner. Results are presented for two agents, namely Definity (Lantheus Medical Imaging, N. Billerica, MA, USA) and biSphere (Point Biomedical Corp, San Carlos, CA, USA). The agents were insonified with amplitude-modulated pulses, and it was observed in both agents that a subpopulation of microbubbles did not produce a measurable echo from the first-half amplitude pulse, but did produce a response from the full amplitude pulse and from a subsequent half amplitude pulse. The number of microbubbles in this subpopulation was seen to increase with increasing transmit amplitude. These results do not bear out the simple theory of microbubble-pulse sequence interaction and invite a reassessment of signal processing approaches.