Optimizing Acoustic Activation of Phase Change Contrast Agents with the Activation Pressure Matching Method: A Review.

Sub-micron phase-change contrast agents consist of a liquid perfluorocarbon core that can be vaporized by ultrasound (acoustic droplet vaporization) to generate contrast with excellent spatial and temporal control. When these agents, commonly referred to as nanodroplets, are formulated with cores of low boiling-point perfluorocarbons such as decafluorobutane and octafluoropropane, they can be activated with lowmechanical index imaging pulses for diagnostic applications. Since the utilization of minimum mechanical index is often desirable to avoid unnecessary biological effects, enabling consistent activation of these agents in an acoustic field is a challenge because the energy that must be delivered to achieve the vaporization threshold increases with depth due to attenuation. A novel vaporization approach called Activation Pressure Matching has been developed to deliver the same pressure throughout a field of view in order to produce uniform nanodroplet vaporization and to limit the amount of energy that is delivered. In this manuscript, we discuss the application of this method with a Versasonics V1 Research Ultrasound System to modulate the output pressure from an ATL L11-5 transducer. Vaporization-pulse spacing optimization can be used in addition to matching the activation pressure through depth, and we demonstrate the feasibility of this approach both in vivo and in vitro. The use of optimized vaporization parameters increases the amount of time a single bolus of nanodroplets can generate useful contrast and provides consistent image enhancement in vivo. Therefore, APM is a useful technique for those wishing to maximize the efficacy of phase change contrast agent while minimizing delivered acoustic energy.