An Open Access Chamber Designed for the Acoustic Characterisation of Microbubbles

Elliott Smith,Thomas Carpenter,David Cowell,Stephen Evans,Steven Freear,Alejandro F Frangi,Luzhen Nie,James Mclaughlan,Harry Clegg

doi:10.3390/app12041818

Abstract

Microbubbles are used as contrast agents in clinical ultrasound for Left Ventricular Opacification (LVO) and perfusion imaging. They are also the subject of promising research in therapeutics as a drug delivery mechanism or for sonoporation and co-administration. For maximum efficacy in these applications, it is important to understand the acoustic characteristics of the administered microbubbles. Despite this, there is significant variation in the experimental procedures and equipment used to measure the acoustic properties of microbubble populations. A chamber was designed to facilitate acoustic characterisation experiments and was manufactured using additive manufacturing techniques. The design has been released to allow wider uptake in the research community. The efficacy of the chamber for acoustic characterisation has been explored with an experiment to measure the scattering of SonoVue® microbubbles at the fundamental frequency and second harmonic under interrogation from emissions in the frequency range of 1.6 to 6.4 MHz. The highest overall scattering values were measured at 1.6 MHz and decreased as the frequency increased, a result which is in agreement with previously published measurements. Statistical analysis of the acoustic scattering measurements have been performed and a significant difference, at the 5% significance level, was found between the samples containing contrast agent and the control sample containing only deionised water. These findings validate the proposed design for measuring the acoustic scattering characteristics of ultrasound contrast agents.

Highlights

For every acoustic scattering measurement presented a two-tailed t-test was performed between the average root mean square (RMS) amplitude component of the received data corresponding to a scattering measurement and a reference measurement in which no microbubbles were present
The null hypothesis that “the introduction of microbubbles into the acoustic path has no effect on the amplitude component at frequency f s ” was rejected at the 5% significance level for all of the amplitude components used to determine the scattering characteristics in the remainder of this section
Whilst the transducers chosen in this study offer the ability to investigate a broad range of frequencies around those typically required for microbubble characterisation, they are interchangeable, and transducers covering different frequency ranges may be used

Summary

Introduction

Microbubbles are gas-filled bubbles encapsulated in a shell and are typically 1–10 μm in diameter. Microbubbles are used as Ultrasound Contrast Agents (UCAs) because they oscillate in the presence of an acoustic field. This oscillation is due to the stiffness of the enclosed gas and the inertia of the liquid surrounding the microbubble [1,2]. Microbubbles act as resonant systems during insonification [3]. The resonant frequency is dependent on the physical properties of the encapsulating shell, the gas core, and the surrounding medium [2,4,5]. An oscillating microbubble dissipates energy through re-radiation, viscous dissipation, and thermal dissipation [3,6]

Methods

Results

Discussion

Conclusion