Pressure-Dependent Attenuation and Scattering of Phospholipid-Coated Microbubbles at Low Acoustic Pressures

Previous optical studies have shown threshold behavior of single-contrast agent microbubbles. Below the acoustic pressure threshold, phospholipid-coated microbubbles with sizes <5.0 μm in diameter oscillate significantly less than above the threshold pressure. Previous studies also revealed an acoustic pressure-dependent attenuation of ultrasound by microbubble contrast agents. In this study, we investigated whether pressure-dependent acoustic behavior may be explained by threshold behavior. For this purpose, pressure-dependent attenuation and scattering of a phospholipid-coated contrast agent were measured. Transmit frequencies between 1.5 and 6.0 MHz and acoustic pressures between 5 and 200 kPa were applied. Unlike the galactose-based contrast agent Levovist, the phospholipid-coated contrast agent BR14 showed a pressure-dependent attenuation. In addition, it was found that filtered suspensions with only microbubbles <3.0 μm in diameter show more pressure-dependent attenuation behavior than native suspensions of phospholipid-coated microbubbles. For the scattering measurements conducted at 3.0 MHz, the native suspension did not show any pressure-dependent behavior. However, the filtered suspension responded highly nonlinearly. Between 30 and 150 kPa, 16 dB additional scattered power was obtained. We concluded that threshold behavior of phospholipid-coated microbubbles results in pressure-dependent attenuation and scattering.