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

项目摘要/摘要 组织电切术是一种非侵入性的、基于超声波的组织消融疗法，它依赖于靶向生成 空化事件对机械分离和液化组织的影响。结果所依据的可量化指标 组织摩擦学治疗的可能性可以预测为治疗投入的一种功能，对于确保可靠和 可重复治疗，但目前还不存在。尽管组织摩擦学产生的空化和液化组织 在超声成像中可以检测到，目前还没有建立量化所致组织损伤的指标 与空化暴露相比，空化暴露已知会随着组织属性的不同以及患者之间的不同而不同。使用 组织摩擦学的临床翻译正在进行中，关键是建立空化能量所依据的剂量度量 在组织摩擦检查过程中沉积到组织中的物质可以被原位监测，以准确地预测治疗引起的损害。 在这个项目中，我们建议开发监测组织碎屑病引起的组织分离的指标，方法是 监测由空化事件产生的声空化发射(ACE)信号 组织诊断学期间的治疗。ACE信号编码了关于动力学和能量学的信息 从哪个空化事件发射，这取决于机械性能/完整性 产生空化事件的介质。由于在组织摩擦检查过程中暴露于空化， 目标材料被机械破坏，从而改变其机械性能，从而影响 空化事件的动力学。通过开发方法来监控ACE信号的特征 产生空化事件的材料的力学状态可以在现场进行评估。 我们将进行实验，利用组织摩擦学在一系列组织中产生空化- 模仿凝胶模体和组织，具有广泛的机械性能，以消除它们。在.期间 处理后，将记录ACE信号。在治疗之后，将对产生的损害进行光学评估 并对组织学和记录的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。建立这种关联将允许 血管紧张素转换酶信号可作为组织学过程中监测诱导物质分级的指标 治疗。为了实现可靠的监控，可以使用以下传输元件来监控ACE信号 该阵列除了作为水听器外，还作为接收器。这将确保声学上可到达的路径 生成的空化事件将始终可用于提供对ACE信号的准确监控，但将 由于需要处理大量数据，因此需要开发复杂的实时算法进行处理 将会被生成。血管紧张素转换酶信号特征与凝胶损伤的一次相关性 已经识别了幻影和体外组织，并开发了实时算法来监测它们， 它们将在活体猪模型中得到验证。这项工作的结果将是建立一个 组织检查剂量测量和组织检查以获得FDA批准用于临床。

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.