Stabilized microbubbles show high echogenicity and characteristic non-linear acoustic responses and also works as 'sensitizers' for HIFU therapy. Accordingly, if microbbles were selectively placed in targets inside body, targeted diagnosis and therapy would be possible. However, unfortunately, microbubbles are too large to apply tissues other than in vessels. For tumor detection and therapy, we propose the use of nano-sized liquid precursor of microbubbles, which is small enough to accumulate in tumor tissues and generate microbubbles with ultrasound pulses. We have developed emulsion based precursors containing perfluoropentane and found that microbubbles can be produced with ultrasound pulses produced with a medical ultrasound scanner (modified for this study) at negative peak pressure at about several MPa in water. The pressure threshold for the phase shift decreased with ultrasound frequency, indicating that thermal mechanisms are involved. However, wave numbers in ultrasound pulses did not affect the thresholds, thus not a simple thermal mechanism is dominant. Part of this work was supported by the Japanese Ministry of Education, Culture, Sports, Science and Technology through a grant-in-aid for the creation of innovations through business-academic public sector cooperation.
