Effect of Hydrostatic Pressure, Boundary Constraints and Viscosity on the Vaporization Threshold of Low-Boiling-Point Phase-Change Contrast Agents.

The vaporization of low-boiling-point phase-change contrast agents (PCCAs) using ultrasound has been explored in vitro and in vivo. However, it has been reported that the pressure required for activation is higher in vivo, even after attenuation is accounted for. In this study, the effect of boundary constraints, hydrostatic pressure and viscosity on PCCA vaporization pressure threshold are evaluated to explore possible mechanisms for variations in in vivo vaporization behavior. Vaporization was measured in microtubes of varying inner diameter and a pressurized chamber under different hydrostatic pressures using a range of ultrasound pressures. Furthermore, the activation threshold was evaluated in the kidneys of rats. The results confirm that the vaporization threshold is higher in vivo and reveal an increasing activation threshold inversely proportional to constraining tube size and inversely proportional to surrounding viscosity in constrained environments. Counterintuitively, increased hydrostatic pressure had no significant effect experimentally on the PCCA vaporization threshold, although it was confirmed that this result was supported by homogeneous nucleation theory for liquid perfluorocarbon vaporization. These factors suggest that constraints caused by the surrounding tissue and capillary walls, as well as increased viscosity in vivo, contribute to the increased vaporization threshold compared with in vitro experiments, although more work is required to confirm all relevant factors.