Acoustic Cavitation Emission (ACE) Feedback Methods for Monitoring Histotripsy-Induced Tissue Fractionation In Situ

项目概要/摘要 组织摧毁术是一种非侵入性的、基于超声的组织消融治疗， 机械性骨折和坏死组织的空化事件。可量化的指标， 组织摧毁治疗的有效性可以预测为治疗输入的函数，对于确保可靠和 可重复的治疗，但目前还不存在。虽然组织分裂症产生的空洞和液化的组织 可以在超声成像中检测到，没有建立量化诱导组织损伤的度量 与空化暴露相比，已知空化暴露随组织特性以及患者而变化。与 组织破坏术的临床翻译正在进行中，关键是要建立一个剂量度量， 可以原位监测在组织摧毁术期间沉积到组织上的放射性物质，以准确地预测治疗产生的损伤。 在这个项目中，我们建议通过以下方法开发用于监测组织分裂诱导的组织分离的指标： 监测由空化事件产生的声空化发射（ACE）信号，所述空化事件负责 在组织解剖过程中进行治疗。ACE信号编码关于微流体的动力学和能量学的信息。 空化事件，它们从这些空化事件中发出，这取决于材料的机械性能/完整性。 介质中产生的空化事件。由于在组织破坏过程中暴露于空化， 目标材料被机械破坏，这改变了它们的机械性能，从而可以影响 空化事件的动力学。通过开发监测ACE信号特征的方法， 可以原位评估产生空化事件的材料的机械状态。 我们将进行实验，其中组织摧毁术将用于在一系列组织中产生空化- 模拟凝胶体模和具有广泛机械性能的组织以消融它们。期间 治疗后，记录ACE信号。治疗后，将对产生的损伤进行光学评估 并对记录的ACE信号进行分析，以确定其中可以 与在图像或组织学中观察到的诱导损伤相关。建立这种相关性将使 ACE信号用作监测组织碎石术期间诱导材料分级的指标 治疗为了实现稳健的监控，可以使用以下发射元件来监控ACE信号： 除了水听器之外，阵列还用作接收器。这将确保一个声学上可访问的路径， 所产生的空化事件将始终可用于提供对ACE信号的准确监测，但是将 需要开发复杂的实时算法来处理， 将被生成。一旦ACE信号的特征与凝胶中诱导的损伤之间存在相关性， 已经鉴定了体模和离体组织，并且开发了用于监测它们的实时算法， 它们将在猪模型中进行体内验证。这项工作的结果对于建立一个 组织破坏剂量度量和组织破坏以获得FDA批准用于临床使用。

PROJECT SUMMARY/ABSTRACT Histotripsy is a non-invasive, ultrasound based tissue ablation therapy which relies on the targeted generation of cavitation events to mechanically fractionate and liquefy tissues. Quantifiable metrics by which the outcomes of histotripsy therapy can be predicted as a function of therapy inputs are essential for ensuring reliable and repeatable treatments, but do not currently exist. Although histotripsy-generated cavitation and liquefied tissue can be detected in ultrasound imaging, there is no established metric to quantify induced tissue damage versus cavitation exposure, which is known to vary with tissue properties, as well as among patients. With clinical translation of histotripsy ongoing, it is critical to establish a dose metric by which cavitation energy deposited to tissue during histotripsy can be monitored in situ to accurately predict therapy-generated damage. In this project we propose to develop metrics for monitoring histotripsy-induced tissue fractionation by monitoring the acoustic cavitation emission (ACE) signals generated by the cavitation events responsible for therapy during histotripsy. The ACE signals encode information about the dynamics and energetics of the cavitation events from which they are emitted, which depend on the mechanical properties/integrity of the media in which the cavitation events were generated. As a result of exposure to cavitation during histotripsy, targeted materials are mechanically disrupted which alters their mechanical properties, which can thus affect the dynamics of the cavitation events. By developing methods to monitor features of the ACE signals the mechanical state of the material in which the cavitation events were generated can be assessed in situ. We will carry out experiments in which histotripsy will be used to generate cavitation in a range of tissue- mimicking gel phantoms and tissues with a wide range of mechanical properties to ablate them. During treatment, the ACE signals will be recorded. Following treatment, generated damage will be assessed optically and histologically and the recorded ACE signals will be analyzed to identify the features in them that can be correlated with the induced damage observed in images or histology. Establishing such correlations will allow the ACE signals to be used as a metric for monitoring induced material fractionation during histotripsy treatment. To enable robust monitoring, the ACE signals can be monitored using the transmitting elements of the array as receivers in addition to hydrophones. This will ensure that an acoustically accessible path to the generated cavitation events will always be available to provide accurate monitoring of the ACE signals, but will require the development of sophisticated real-time algorithms to process owing to the large amount of data that will be generated. Once correlations between features of the ACE signals and induced damage in gel phantoms and ex vivo tissues have been identified, and real-time algorithms for monitoring them developed, they will be validated in vivo in a swine model. The results of this work will be essential for establishing a histotripsy dose metric and for histotripsy to obtain FDA approval for clinical use.