Ultrasound imaging from vaporization signals emitted by phase change contrast agents

Phase change contrast agents (PCCAs) exhibit a unique acoustic signature during the transition from a liquid droplet to a gas microbubble. Here, we demonstrate that this event can be used to generate an ultrasound image, and that the signal can be separated from that of a conventional microbubble. This presents a new opportunity to monitor PCCA activation in both diagnostic and therapeutic applications. A confocal, dual-frequency transducer was used to transmit 2 cycle, Gaussian enveloped sinusoids at 8 MHz and passively receive at 1 MHz. PCCAs were continuously infused through a microcellulose tube (250 μm diameter). At low pressures, vaporization signals from PCCAs were of significantly higher energy than signals emitted from the equivalent microbubble formulation. Specifically, when a peak negative pressure (PNP) of 0.51 MPa was transmitted, the contrast-to-noise ratio (CNR) was 18.94 dB for PCCAs and 2.28 dB for control microbubbles. As the PNP was increased to 0.76 MPa, these values changed to 22.1 dB and 9.73 dB, respectively. Time-domain averaging (TDA) helped to increase the separation of PCCA and microbubble signals. After TDA, the CNR at 0.76 MPa was 23.79 dB for PCCAs and 1.72 dB for microbubbles. The lateral resolution of the system was pressure dependent. With increasing pressure, the apparent diameter of the tube increased from 0.74 mm at 0.51 MPa to 1.14 mm at 0.76 MPa. This is due to the fact that the focal zone capable of activating PCCAs expands with increasing pressure.