Imaging the Activation of Low-Boiling-Point Phase-Change Contrast Agents in the Presence of Tissue Motion Using Ultrafast Inter-frame Activation Ultrasound Imaging.

Nanoscale phase-change contrast agents (PCCAs) have been found to have great potential in non-invasive extravascular imaging and therapeutic delivery. However, the contrast-to-tissue ratio (CTR) of PCCA images is usually limited because of either physiological motion or incomplete cancelation of tissue signal. Therefore, to improve the CTR of PCCA images in the presence of physiological motion, a new imaging technique, ultrafast inter-frame activation ultrasound (UIAU) imaging, is proposed and validated. Results of studies with controlled motion in tissue-mimicking phantoms indicate UIAU could provide significantly higher CTRs (maximum: 17.3 ± 0.9 dB) relative to conventional pulse inversion imaging (maximum CTR: 3.4 ± 1.4 dB). UIAU has CTRs up to 16.1 ± 1.0 dB relative to 3.9 ± 2.3 dB for differential imaging in the presence of physiological motion at 20 mm/s. In vivo imaging of PCCAs in the rat liver also reveals the ability of UIAU to enhance PCCA image contrast in the presence of physiological motion.