Site-specific contrast imaging with locally induced microbubbles from liquid precursors

In studying a site-targeted contrast agent that can be administered as nano-paritcle (liquid droplet) and change its phase from liquid to gas by an external stimulus such as ultrasound to yield microbubbles, we have investigated if the phase shift can be achieved by using short pulses produced by a medical ultrasound scanner and probe. As expected in a preliminary study, we could induce phase shift by using pulsed ultrasound with several MPa negative peak pressure in in vitro experiments by using a linear probe with the frequency range of 3-8 MHz. It was found that the higher the ultrasound frequency, the lower the threshold, which indicated a thermal mechanism in phase shift. However, exposed total energy did not seem to be important to induce the phase shift because increasing wave cycle numbers from 2 to 8 did not lower the threshold significantly. Also it was suggested that negative peak pressure amplitude seemed to play a major role and positive peak did not. In vivo experiments with mice tumor exhibited that microbubble can also be generated in living bodies with ultrasound pulses generated by the ultrasound scanner at the same negative peak pressure amplitude as in in vitro experiments at the frequency of 7.8 MHz.