Nonlinear Acoustics in Calibration/Metrology of High Intensity Focused Ultrasound

描述（由申请人提供）：高强度聚焦超声（HIFU）用于无创外科手术，通过使用高振幅聚焦声波在mm大小的焦点“热点”内诱导不可逆的组织损伤。HIFU正在迅速获得广泛的临床应用，并有望达到更广泛的患者群体。然而，在HIFU社区的所有部分中，越来越多的人担心没有标准来测量或报告HIFU领域。人们还认识到，HIFU输出量与产生的生物效应之间的关系尚不清楚。缺乏标准和声学与生物效应的关系是HIFU广泛临床应用的主要障碍。该提案解决了目前在制定此类标准以及理解生物效应机制方面的差距。非线性声学是研究高振幅声音的学科。非线性声波传播导致冲击，不连续性的声波，其中包括一个非常广泛的频率范围。冲击形成和强聚焦使HIFU有别于其他医学超声方法，并使精确测量变得困难。此外，由于产生加热的超声能量损失与频率有关，组织中相对较高的吸收抵消了非线性传播，这意味着没有简单的方法可以直接推断组织中的水分测量值。由于冲击中的频率含量最广，因此在冲击处的吸收是组织加热的关键机制。本项目的具体目标是：(1)利用模拟和测量相结合的方法确定水中高频超声源的高振幅声输出。(2)确定组织幻影和组织中的场，并定义对组织进行水测量的方法。(3)量化非线性声学增强组织加热的机制以及离体组织和体内动物研究中相应的生物效应。(4)将Aims 1-3的结果综合为HIFU设备表征的实用建议，以改善监管监督，了解临床相关HIFU治疗设备的生物效应以及有效性和安全性。我们的方法是数值模拟和实验测量相结合的方法。我们的模型包括非线性声传播效应、衍射、吸收和组织异质性。我们的声学测量工具包括小型宽带水听器和一个新的阶跃震源来校准水听器。我们的热测量技术包括使用高速摄影和主动和被动声学换能器对沸腾进行无创观察。组织模型、切除组织和活体组织将用于实验和建模。这项拟议的工作将通过提供工具和建议来帮助调节和控制HIFU暴露，从而有利于公共卫生，这将提高疗效和安全性，并促进临床更快地接受这种有前途的疗法。公共卫生相关性：高强度超声（HIFU）作为一种无创或微创手术形式在临床中得到越来越广泛的接受。然而，目前尚无商定的HIFU输出校准系统。这项拟议的工作将通过提供工具和建议来帮助调节和控制HIFU暴露，从而有利于公共卫生，这将提高疗效和安全性，并促进临床更快地接受这种有前途的疗法。

DESCRIPTION (provided by applicant): High Intensity Focused Ultrasound (HIFU) is used to perform surgical procedures non-invasively by using high amplitude focused sound waves to induce irreversible tissue damage within a mm-size focal `hot spot.' HIFU is rapidly gaining widespread clinical use and is poised to reach even broader patient populations. However, there has been a rising concern within all parts of the HIFU community that no standards exist for measuring or reporting of HIFU fields. It has been also realized that the relation between HIFU output and the produced bioeffects is poorly understood. This lack of standards and relations of acoustics to bioeffects is a major impediment to broad clinical adoption of HIFU. The proposal addresses this current gap in development of such standards as well as understanding the bioeffect mechanisms. Nonlinear acoustics is the study of high amplitude sound. Nonlinear acoustic propagation leads to shocks, discontinuities in the acoustic wave, which encompass a very broad range of frequencies. Shock formation and strong focusing distinguish HIFU from other medical ultrasound approaches and combine to make accurate measurements difficult. Also, since ultrasound energy losses that create heating are frequency dependent, the relatively high absorption in tissue counteracts nonlinear propagation, which means that no simple way exists to extrapolate water measurements directly to tissue. Since the broadest frequency content is in the shocks, absorption at the shocks is the critical mechanism of tissue heating. The specific aims of this proposed project are: (1) Use combined simulations and measurements to determine the high amplitude acoustic output of HIFU sources in water. (2) Determine the fields in tissue phantoms and tissue and define methods to derate water measurements to tissue. (3) Quantify the mechanism of enhanced tissue heating due to nonlinear acoustics and corresponding bioeffects in ex-vivo tissue and in vivo animal studies (4) Synthesize results of Aims 1-3 into practical recommendations for characterization of HIFU devices to improve regulatory oversight, understanding bioeffects, and efficacy and safety of clinically relevant HIFU therapeutic devices. Our method is a combined approach of numerical simulation and experimental measurement. Our model includes nonlinear acoustic propagation effects, diffraction, absorption, and tissue heterogeneities. Our acoustic measurements tools include small broad bandwidth hydrophones and a new step-shock source to calibrate the hydrophones. Our thermal measurement techniques involve the noninvasive observation of boiling with high speed photography and active and passive acoustic transducers. Tissue phantoms, excised and in vivo tissue will be used in experiments and modeling. This proposed work will benefit public health by providing tools and recommendations to help regulate and control HIFU exposures, which will improve efficacy and safety and facilitate a more rapid clinical acceptance of this promising therapy. PUBLIC HEALTH RELEVANCE: High Intensity Ultrasound (HIFU) is gaining wider acceptance in the clinic as a form of noninvasive or minimally invasive surgery. However, no agreed system for calibration of HIFU output currently exists today. This proposed work will benefit public health by providing tools and recommendations to help regulate and control HIFU exposures which will improve efficacy and safety and facilitate a more rapid clinical acceptance of this promising therapy.