Effects of a mono-disperse bubble population on the cumulative phase delay between second harmonic and fundamental component

A positive cumulative phase delay (CPD) between the second-harmonic and fundamental component of ultrasound waves is a marker specific to ultrasound contrast agents. Dynamic contrast-enhanced ultrasound images generated by using this marker have already been reported in the literature. However, only results obtained with a poly-disperse contrast agent (SonoVue®) have been presented. In this study, we compared CPD values obtained with standard SonoVue® and with a mono-disperse contrast agent (MDCA); the latter consisted of 4-μm microbubbles produced with a MicroSphere Creator®. The same as with SonoVue®, MDCA microbubbles were made of SF6 gas encapsulated in a monolayer phospholipid shell. An ULA-OP research platform equipped with an LA332 linear-array probe was employed to image a dedicated gelatin flow-phantom. Different frequencies (1.5 to 3.5 MHz) with a mechanical index of 0.7 were used. Images were reconstructed in a tomographic fashion, and the contrast to tissue ratio (CTR) evaluated. When imaging at 1.8 MHz (close to the resonance frequency of a 4 μm microbubble), results show significantly stronger CPD values for the mono-disperse microbubbles, resulting in an overall CTR improvement by 5 dB. In conclusion, mono-disperse UCAs can be used to improve imaging performance of cumulative phase delay imaging.