A model for the oscillation of gas bubbles encapsulated in a thin shell has been developed. The model depends on viscous and elastic properties of the shell, described by thickness, shear modulus, and shear viscosity. This theory was used to describe an experimental ultrasound contrast agent from Nycomed, composed of air bubbles encapsulated in a polymer shell. Theoretical calculations were compared with measurements of acoustic attenuation at amplitudes where bubble oscillations are linear. A good fit between measured and calculated results was obtained. The results were used to estimate the viscoelastic properties of the shell material. The shell shear modulus was estimated to between 10.6 and 12.9 MPa, the shell viscosity was estimated to between 0.39 and 0.49 Pas. The shell thickness was 5% of the particle radius. These results imply that the particles are around 20 times more rigid than free air bubbles, and that the oscillations are heavily damped, corresponding to Q-values around 1. We conclude that the shell strongly alters the acoustic behavior of the bubbles: The stiffness and viscosity of the particles are mainly determined by the encapsulating shell, not by the air inside.

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Nycomed’s ultrasound contrast agent NC100100 has been investigated by in vitro acoustic measurements. Acoustic attenuation spectra were used to determine resonance frequencies of the particles. The spectra were correlated with size distributions, and it was found that the shell-encapsulated gas bubbles can be described as viscoelastic particles with bulk modulus 700 kPa. When exposed to hydrostatic overpressures mimicking those found in vivo during the systolic heart cycle, the resonance frequency increased, as expected by the particles’ increased stiffness. This effect was reversible: After the pressure was released, the particles went back to giving the original attenuation spectrum. This shows that the particles are not destroyed or otherwise changed by the pressure. Acoustic backscatter measured as a function of distance through a contrast agent was used to estimate the backscatter efficiency of the particles, that is, the ratio between scattered and absorbed ultrasound. Results from these measurements agree with theoretical estimates based on the attenuation spectra. Measurements on NC100100 were compared with earlier results from measurements on Albunex® and measurements on an experimental polymer-encapsulated contrast agent, showing how different shell materials cause differences in particle stability and stiffness.

The acoustic properties of NC100100 are dependent on microbubble size. The observed batch-to-batch variance in the acoustic properties of the product may be fully explained by variation in concentration and size. Microbubble volume is a more precise predictor of in vitro/in vivo efficacy than microbubble number and consequently was chosen as the assay/dosage parameter for NC100100.

Myocardial ischaemia can be detected with epicardial three-axis accelerometers. The accelerometer had the ability to distinguish ischaemia from interventions altering global myocardial function. This novel technique may be used for continuous real-time monitoring of myocardial ischaemia during and after cardiac surgery.

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