Department of Instrument Science and Engineering, Shanghai Jiao Tong University, Shanghai, China.
Department of Medical Ultrasound, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China.
Ultrason Sonochem. 2019 Apr;52:512-521. doi: 10.1016/j.ultsonch.2018.12.031. Epub 2018 Dec 21.
Acoustic cavitation from ultrasound-driven microbubbles can induce diverse bioeffects that are useful in clinical therapy. However, lack of control over the cavitation activity of flowing microbubbles results in unwanted treatment regions in the targeted tissue, which influences the therapeutic efficacy and bio-safety. The aim of this study is to understand the relationship between the ultrasound pulse parameters and cavitation properties of flowing microbubbles, including the type (and transition between types), threshold, intensity and temporal distribution of cavitation. An in vitro physiological-flow phantom was fabricated, in which the microbubbles had a constant velocity, and were sonicated to a 1-MHz focused transducer at a wide range of peak negative pressures (PNPs) (0.10-1.28 MPa), pulse repetition frequencies (PRFs) (1-200 Hz) and pulse lengths (PLs) (10-400 μs). The signals from the flowing bubbles were passively detected by another 7.5-MHz plane transducer. From detailed time- and frequency-domain analysis, we found 1). The occurrence of stable cavitation (SC) and inertial cavitation (IC) depended on PNP and PL when the PRF was below a critical value (PRF threshold) that related to the fluid velocity and PNP full width at half maximum diameter of the transducer. 2) Below the PRF threshold, the PL had no influence on the temporal distribution of SC intensity; however, above the PRF threshold, the SC properties depended on the PL because of acoustically-driven diffusion. Specifically, at shorter PLs, the SC intensity had a uniform temporal distribution and was independent of the PRF; at longer PLs, the SC intensity correlated negatively with the PRF. 3) Below the PRF threshold, the IC properties were independent of the PRF. Increasing the PRF above the PRF threshold caused the IC intensity to decrease with a non-uniform temporal distribution. These results indicate that the fluid velocity and a pulsed acoustic field influence the number and properties of the replenished bubbles into the targeted region, resulting in the change of cavitation properties. In future therapeutic applications, the physiological fluid conditions must be taken into consideration to design reasonable pulse parameters and achieve desirable cavitation properties.
超声驱动微泡的声空化可诱导多种生物效应，这些效应在临床治疗中很有用。然而，由于无法控制流动微泡的空化活性，导致在目标组织中出现不需要的治疗区域，这会影响治疗效果和生物安全性。本研究旨在了解超声脉冲参数与流动微泡的空化特性之间的关系，包括空化的类型（及其类型之间的转换）、阈值、强度和时间分布。我们制作了一个体外生理流动仿体，其中微泡具有恒定速度，并在很宽的峰值负压（PNP）（0.10-1.28 MPa）、脉冲重复频率（PRF）（1-200 Hz）和脉冲长度（PL）（10-400 μs）范围内用 1 MHz 聚焦换能器进行声处理。流动气泡的信号通过另一个 7.5 MHz 平面换能器被动检测。通过详细的时频域分析，我们发现：1）当 PRF 低于与流体速度和换能器半最大值直径有关的临界值（PRF 阈值）时，稳定空化（SC）和惯性空化（IC）的发生取决于 PNP 和 PL；2）在 PRF 阈值以下，PL 对 SC 强度的时间分布没有影响；然而，在 PRF 阈值以上，由于声驱动扩散，SC 特性取决于 PL。具体而言，在较短的 PL 下，SC 强度具有均匀的时间分布且与 PRF 无关；在较长的 PL 下，SC 强度与 PRF 呈负相关；3）在 PRF 阈值以下，IC 特性与 PRF 无关。将 PRF 增加到 PRF 阈值以上会导致 IC 强度随时间的非均匀分布而降低。这些结果表明，流体速度和脉冲声场会影响补充到目标区域的气泡数量和性质，从而改变空化性质。在未来的治疗应用中，必须考虑生理流体条件，以设计合理的脉冲参数并实现理想的空化特性。
