Evaluation of mechanical properties of the shell materials of ultrasound contrast agent microbubbles by high-speed observation of their radial oscillation.

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Improvement of a high-speed observation systemTo improve spatial and temporal resolutions of high-speed observation, the use of an image intensifier with a high-speed camera and the use of an improved optical condenser for a short-arc flash lamp were examined. The use of these devices resulted in a reduction in minimum exposure time from 200 ns to 20 ns at a 40x objective and an increase in maximum framing rate from 4-million to 16-million fps.Development of a system for measurement of pressure-dependent attenuationA system for measurement of attenuation of microbubble suspensions was developed on the basis of results of our previous study on measurement of attenuation of biological tissues. The system uses a wideband pulse of 10 MHz in center frequency as a probing pulse and measures frequency-dependent attenuation in the frequency range of 3 to 14 MHz. Most of the measurement procedure is automated by computer control to achieve high-precision measurements.Evaluation of shell propert … More ies by high-speed observationA microbubble was exposed to a pulse train of increasing pressure amplitudes, and the shell property of the bubble was evaluated from degree of radial change in the oscillating bubble visualized by the high-speed camera. Nine types of microbubbles, seven ultrasound contrast agents, one type of sub-micron bubbles, and one type of plastic-shelled bubbles were examined. The results showed that microbubbles with lipid shells start radial oscillation from several tens of kPa and oscillation amplitude increases with increase in applied pressure and that Palmitic-acid-or albumin-shelled bubbles start radial oscillation when pressure has exceeded a threshold pressure. The difference in pressure-dependent bubble oscillation is consistent with the ultrasound exposure conditions used for the two shell types of bubbles used in clinical practice.Evaluation of shell properties by attenuation measurementAttenuation of the nine types of bubble suspensions was measured using wideband probing pulses of different pressure amplitudes. Since change in radial oscillation under different pressures causes change in attenuation, we also can estimate shell properties from pressure-dependent attenuation of a bubble suspension. The results of measurements showed that each type of bubble has its own characteristics in pressure-dependent attenuation, and these characteristics are consistent with those found by high-speed observation, suggesting that attenuation measurement is also useful to understand the shell properties of microbubbles. Less