Threshold of fragmentation for ultrasonic contrast agents

TLDR

Ultrasound contrast agents are microbubbles that can be destroyed by low‑MHz acoustic pressure, and their destruction enables estimation of microvascular flow rates. The study aims to characterize contrast‑agent destruction to inform the design of microvascular flow imaging techniques. High‑speed optical imaging was employed to observe contrast agents during acoustic insonation. The results show that resting diameter, pressure, center frequency, and transmission phase significantly affect microbubble fragmentation, and linear models predict the fragmentation threshold as 300 kPa/µm with pressure and –1.2 MHz/µm with frequency when normalized by resting diameter.

Abstract

Ultrasound contrast agents are small microbubbles that can be readily destroyed with sufficient acoustic pressure, typically, at a frequency in the low megaHertz range. Microvascular flow rate may be estimated by destroying the contrast agent in a vascular bed, and estimating the rate of flow of contrast agents back into the vascular bed. Characterization of contrast agent destruction provides important information for the design of this technique. In this paper, high-speed optical observation of an ultrasound contrast agent during acoustic insonation is performed. The resting diameter is shown to be a significant parameter in the prediction of microbubble destruction, with smaller diameters typically correlated with destruction. Pressure, center frequency, and transmission phase are each shown to have a significant effect on the fragmentation threshold. A linear prediction for the fragmentation threshold as a function of pressure, when normalized by the resting diameter, has a rate of change of 300 kPa/microm for the range of pressures from 310 to 1200 kPa, and a two-cycle excitation pulse with a center frequency of 2.25 MHz. A linear prediction for the fragmentation threshold as a function of frequency, when normalized by the resting diameter, has a rate of change of -1.2 MHz/microm for a transmission pressure of 800 kPa, and a two-cycle excitation pulse with a range of frequencies from 1 to 5 MHz.