IEEE Trans Ultrason Ferroelectr Freq Control. 2021 Sep;68(9):2884-2895. doi: 10.1109/TUFFC.2021.3073347. Epub 2021 Aug 27.
Inertial cavitation induced by pulsed high-intensity focused ultrasound (pHIFU) has previously been shown to successfully permeabilize tumor tissue and enhance chemotherapeutic drug uptake. In addition to HIFU frequency, peak rarefactional pressure ( p ), and pulse duration, the threshold for cavitation-induced bioeffects has recently been correlated with asymmetric distortion caused by nonlinear propagation, diffraction and formation of shocks in the focal waveform, and therefore with the transducer F -number. To connect previously observed bioeffects with bubble dynamics and their attendant physical mechanisms, the dependence of inertial cavitation behavior on shock formation was investigated in transparent agarose gel phantoms using high-speed photography and passive cavitation detection (PCD). Agarose phantoms with concentrations ranging from 1.5% to 5% were exposed to 1-ms pulses using three transducers of the same aperture but different focal distances ( F -numbers of 0.77, 1.02, and 1.52). Pulses had central frequencies of 1, 1.5, or 1.9 MHz and a range of p at the focus varying within 1-18 MPa. Three distinct categories of bubble behavior were observed as the acoustic power increased: stationary near-spherical oscillation of individual bubbles, proliferation of multiple bubbles along the pHIFU beam axis, and fanned-out proliferation toward the transducer. Proliferating bubbles were only observed under strongly nonlinear or shock-forming conditions regardless of frequency, and only where the bubbles reached a certain threshold size range. In stiffer gels with higher agarose concentrations, the same pattern of cavitation behavior was observed, but the dimensions of proliferating clouds were smaller. These observations suggest mechanisms that may be involved in bubble proliferation: enhanced growth of bubbles under shock-forming conditions, subsequent shock scattering from the gel-bubble interface, causing an increase in the repetitive tension created by the acoustic wave, and the appearance of a new growing bubble in the proximal direction. Different behaviors corresponded to specific spectral characteristics in the PCD signals: broadband noise in all cases, narrow peaks of backscattered harmonics in the case of stationary bubbles, and broadened, shifted harmonic peaks in the case of proliferating bubbles. The shift in harmonic peaks can be interpreted as a Doppler shift from targets moving at speeds of up to 2 m/s, which correspond to the observed bubble proliferation speeds.
先前的研究表明，脉冲高强度聚焦超声（pHIFU）诱导的惯性空化可成功地使肿瘤组织穿孔，并增强化疗药物的摄取。除了 HIFU 频率、峰值稀疏压（p）和脉冲持续时间外，最近已经将空化诱导生物效应的阈值与非线性传播引起的不对称失真相关联，与焦点波形中的衍射和冲击波的形成相关联，因此与换能器 F-数相关联。为了将先前观察到的生物效应与气泡动力学及其伴随的物理机制联系起来，使用高速摄影和被动空化检测（PCD）在透明琼脂糖凝胶仿体中研究了惯性空化行为对冲击波形成的依赖性。使用三个孔径相同但焦距不同的换能器（F-数分别为 0.77、1.02 和 1.52），将浓度为 1.5%至 5%的琼脂糖仿体暴露于 1ms 脉冲下。脉冲的中心频率为 1、1.5 或 1.9MHz，焦点处的 p 范围在 1-18MPa 内变化。随着声功率的增加，观察到三种不同的气泡行为类别：单个气泡的近球形稳定振荡、沿 pHIFU 光束轴的多个气泡增殖以及向换能器扇形增殖。无论频率如何，只有在强烈非线性或形成冲击波的条件下才会观察到增殖气泡，并且只有在气泡达到一定的阈值尺寸范围时才会观察到增殖气泡。在琼脂糖浓度较高的较硬凝胶中，观察到相同的空化行为模式，但增殖云的尺寸较小。这些观察结果表明可能涉及气泡增殖的机制：在形成冲击波的条件下增强气泡的生长，随后从凝胶-气泡界面散射冲击波，导致由声波产生的重复张力增加，并在近侧方向出现新的生长气泡。不同的行为对应于 PCD 信号中的特定谱特征：所有情况下均为宽带噪声，静止气泡情况下为反向散射谐波的窄峰，增殖气泡情况下为展宽、移位的谐波峰。谐波峰的位移可以解释为速度高达 2m/s 的目标的多普勒位移，这与观察到的气泡增殖速度相对应。
