Patel Arpit, Schoen Scott J, Arvanitis Costas D
IEEE Trans Biomed Eng. 2018 Nov 20. doi: 10.1109/TBME.2018.2882337.
Ultrasonically actuated microbubble oscillations hold great promise for minimally invasive therapeutic interventions. While several preclinical studies have demonstrated the potential of this technology, real-time methods to control the amplitude and type of microbubble oscillations (stable vs inertial acoustic cavitation) and ensure that cavitation occurs within the targeted region are needed for their successful translation to the clinic. In this paper, we propose a real-time nonlinear state controller that uses specific frequency bands of the microbubble acoustic emissions (harmonic, ultra-harmonic, etc.) to control cavitation activity (observer states). To attain both spatial and temporal control of cavitation activity with high signal to noise ratio, we implement a controller using fast frequency-selective passive acoustic mapping (PAM) based on the angular spectrum approach. The controller includes safety states based on the recorded broadband signal level and is able to reduce sensing inaccuracies with the inclusion of multiple frequency bands. In its simplest implementation the controller uses the peak intensity of the passive acoustic maps, reconstructed using the 3rd harmonic (4.896 × 0.019 MHz) of the excitation frequency. Our results show that the proposed real-time nonlinear state controller based on PAM is able to reach the targeted level of observer state (harmonic emissions) in less than 6 seconds and remain within 10 % of tolerance for the duration of the experiment (45 seconds). Similar response was observed using the acoustic emissions from single element passive cavitation detection, albeit with higher susceptibility to background noise and lack of spatial information. Importantly, the proposed PAM-based controller was able to control cavitation activity with spatial selectivity when cavitation existed simultaneously in multiple regions. The robustness of the controller is demonstrated using a range of controller parameters, multiple observer states concurrently (harmonic, ultra-harmonic, and broadband), noise levels (°6 to 12 dB SNR), and bubble concentrations (0.3 to 180 × 103 bubbles per microliter). More research in this direction under preclinical and clinical conditions is warranted.
超声驱动的微泡振荡在微创治疗干预方面具有巨大潜力。虽然多项临床前研究已证明该技术的潜力，但要将其成功应用于临床，仍需要实时方法来控制微泡振荡的幅度和类型（稳定声空化与惯性声空化），并确保空化发生在目标区域内。在本文中，我们提出了一种实时非线性状态控制器，该控制器利用微泡声发射的特定频段（谐波、超谐波等）来控制空化活动（观测器状态）。为了以高信噪比实现空化活动的空间和时间控制，我们基于角谱方法使用快速频率选择性被动声学映射（PAM）实现了一个控制器。该控制器包括基于记录的宽带信号电平的安全状态，并且能够通过包含多个频段来减少传感误差。在其最简单的实现方式中，控制器使用利用激发频率的三次谐波（4.896×0.019 MHz）重建的被动声学图的峰值强度。我们的结果表明，所提出的基于PAM的实时非线性状态控制器能够在不到6秒的时间内达到观测器状态（谐波发射）的目标水平，并在实验持续时间（45秒）内保持在10%的容差范围内。使用单元素被动空化检测的声发射也观察到了类似的响应，尽管对背景噪声更敏感且缺乏空间信息。重要的是，当多个区域同时存在空化时，所提出的基于PAM的控制器能够以空间选择性控制空化活动。使用一系列控制器参数、同时多个观测器状态（谐波、超谐波和宽带）、噪声水平（6至12 dB SNR）和气泡浓度（每微升0.3至180×103个气泡）证明了该控制器的鲁棒性。在临床前和临床条件下朝着这个方向进行更多研究是有必要的。
