| Ultrasound can produce selective, accurately localized biological effects and is potentially useful in numerous therapeutic applications. For "non-invasive" (incision-free, extra-corporeal) ultrasound surgery, predominantly thermally-based methods have been used to destroy diseased tissue volumes. Thermal ablation, however, has limited applicability because intervening tissue heating is difficult to prevent and precise treatment of deep-seated tissues is often not possible. Cavitation, with disruptive effects capable of destroying large tissue volumes at depth without undesired tissue heating, can be a highly effective mechanism for ultrasound surgery. Cavitation-based methods have potentially significant advantages over conventional thermal methods but have been avoided primarily because cavitation can be unpredictable and cavitational bioeffects hard to adequately control.; Ways to make cavitation predictable and controllable, thus practical, for non-invasive ultrasound surgery were explored in this research. The underlying principle is that pre-existing gas bodies or "nuclei" are essential for therapeutically effective cavitation during ultrasound insonation. The presence of these nuclei makes cavitation much easier to initiate, while their absence can lead to unpredictable and uncontrolled cavitational effects. Approaches for cavitational ultrasound therapy utilizing exogenous and endogenous nuclei were developed. In the exogenous approach, stabilized, gas-filled microbubbles, i.e. ultrasound contrast agents (UCA), were introduced into the circulatory system prior to ultrasound therapy. The significant increase in the availability and uniformity of cavitation nuclei made tissue destruction easier to achieve. In the endogenous approach, pulsed ultrasound methods were developed that initiated cavitation and generated localized microbubble populations that enhanced tissue destruction.; Approaches using the combination of UCA and pulsed therapy may make cavitation a highly effective mechanism for ultrasound surgery. The sensitivity of cavitation to nuclei and acoustic parameters presents opportunities to optimize therapy for precise surgical results. With real-time indicators of gas bubble dynamics to guide therapy delivery, cavitational tissue destruction may be predictable and controllable. Controlled non-thermal approaches will make numerous non-invasive ultrasound therapies possible. |
