Ultrasound contrast agents consisting of gas microbubbles stabilised by a polymer or surfactant coating have been in clinical use for several decades. Research into the biomedical uses of microbubbles, however, remains a highly active and growing field. This is largely due to their considerable versatility and the wide range of applications for which they have demonstrated potential benefits. In addition to contrast enhancement, diagnostic applications include: perfusion mapping and quantification and molecular imaging. In drug and gene therapy microbubbles can be used as vehicles which are inherently traceable in vivo and can provide both targeted and controlled release. In addition, the dynamic behaviour of the microbubbles in response to ultrasound excitation contributes to the therapeutic process. At low intensities microbubbles have been shown to mediate reversible enhancement of cell and endothelial permeability, including temporary opening of the blood brain barrier. At higher intensities they have been used as means of increasing the efficiency of thrombolysis, high-intensity focused ultrasound (HIFU) surgery and lithotripsy. The aim of this review is to describe the key physical principles which determine how microbubbles and ultrasound interact and the implications for their design, preparation and exploitation in diagnostic and therapeutic applications.
Surfactant-coated microbubbles are utilized in a wide variety of applications, from wastewater purification to contrast agents in medical ultrasound imaging. In many of these applications, the stability of the microbubbles is crucial to their effectiveness. Controlling this, however, represents a considerable challenge. In this study, the potential for stabilizing microbubbles using solid nanoparticles adsorbed onto their surfaces was explored. A new theoretical model has been developed to describe the influence of interfacially adsorbed solid particles upon the dissolution of a gas bubble in a liquid. The aim of this work was to test experimentally the prediction of the model that the presence of the nanoparticles would inhibit gas diffusion and coalescence/disproportionation, thus increasing the life span of the bubbles. Near-monodisperse microbubbles (~100 μm diameter) were prepared using a microfluidic device and coated with a surfactant, with and without the addition of a suspension of spherical gold nanoparticles (~15 nm diameter). The experimental results confirmed the theoretical predictions that as the surface concentration of gold nanoparticles increased the bubbles underwent negligible changes in their size and size distribution over a period of 30 days at the ambient temperature and pressure. Under the same conditions, bubbles coated with the same surfactant but no nanoparticles survived only a matter of hours.
Recent work has shown that incorporating solid nanoparticles into the coatings of contrast agent microbubbles can be used to control their stability and to provide other functional characteristics for example in multimodality imaging. The aim of this study was to investigate the influence of nanoparticle characteristics and concentration on the response of the microbubbles to ultrasound excitation. Theoretical models were first derived to simulate the effects of adsorbing different types and concentrations of nanoparticle on to the surface of a bubble in both a monolayer and a layer of finite thickness. The results indicate that the particles modify the symmetry of the microbubble oscillations and enhance their nonlinear character. Experimentally, microbubbles coated with a surfactant and varying concentrations of gold nanoparticles of different sizes and surface properties were produced using either sonication or microfluidics. The attenuation and backscattering coefficients from the bubble suspensions and the scattered response from individual bubbles were measured for a range of frequencies (1-7.5MHz) and pressures (50-500kPa). The nanoparticles were found to enhance the nonlinear character of the bubble response in qualitative agreement with the theoretical results. Both the degree of enhancement and stability of the microbubbles was dependent upon the nanoparticle surface chemistry.
Recent work has shown that incorporating solid nanoparticles into the coatings of contrast agent microbubbles can be used to control their stability and to provide other functional characteristics for example in multimodality imaging. The aim of this study was to investigate the influence of nanoparticle characteristics and concentration on the response of the microbubbles to ultrasound excitation. Theoretical models were first derived to simulate the effects of adsorbing different types and concentrations of nanoparticle on to the surface of a bubble in both a monolayer and a layer of finite thickness. The results indicate that the particles modify the symmetry of the microbubble oscillations and enhance their nonlinear character. Experimentally, microbubbles coated with a surfactant and varying concentrations of gold nanoparticles of different sizes and surface properties were produced using either sonication or microfluidics. The attenuation and backscattering coefficients from the bubble suspensions and the scattered response from individual bubbles were measured for a range of frequencies (1–7.5 MHz) and pressures (50–500 kPa). The nanoparticles were found to enhance the nonlinear character of the bubble response in agreement with the theoretical results. Both the degree of enhancement and stability of the microbubbles was dependent upon the nanoparticle surface chemistry.
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