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

用于监测组织解剖诱导的原位组织分割的声空化发射 (ACE) 反馈方法

基本信息

批准号：
10670176
负责人：
Jonathan Robert Sukovich
金额：
$ 53.08万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-08-01 至 2026-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10670176
关键词：
Ablation Acoustics Affect Algorithms Animal Model Blood coagulation Brain Clinical Clinical Trials Data Deposition Development Dose Elements Ensure Erythrocytes Europe Event Exposure to Family suidae Feedback Focused Ultrasound Therapy Fractionation Future Gel Generations Heating Histologic Histology Human Hydrogels Image In Situ Kidney Literature Liver Location Measures Mechanics Methods Modality Monitor Operative Surgical Procedures Optics Outcome Pathology Patients Phase Physiologic pulse Prediction of Response to Therapy Procedures Process Property Prostate Radiation Radiation Dose Unit Radiation Toxicity Radiation therapy Radiofrequency Interstitial Ablation Safety Secondary to Secure Signal Transduction Spleen System Techniques Technology Thermometry Time Tissues Treatment Efficacy Ultrasonic Therapy Ultrasonography Visual Work clinical translation cranium efficacy validation experimental study in vivo liver tumor ablation mechanical properties mechanical signal outcome prediction porcine model prediction algorithm rib bone structure risk minimization side effect therapy outcome transmission process ultrasound

项目摘要

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.

项目概要/摘要组织切除术是一种基于超声的非侵入性组织消融疗法，依赖于靶向生成空化事件以机械分级和液化组织。结果的量化指标可以预测组织解剖治疗的效果，因为治疗输入对于确保可靠和可靠至关重要可重复的治疗方法，但目前还不存在。尽管组织解剖产生空化和液化组织可以在超声成像中检测到，但没有既定的指标来量化引起的组织损伤与空化暴露相比，已知空化暴露随组织特性以及患者的不同而变化。和组织解剖学的临床转化正在进行中，建立一个剂量度量至关重要，通过该剂量度量空化能量可以在原位监测组织解剖过程中沉积到组织的物质，以准确预测治疗产生的损伤。在这个项目中，我们建议通过以下方式开发监测组织解剖引起的组织分割的指标：监测由空化事件产生的声空化发射 (ACE) 信号组织解剖期间的治疗。 ACE 信号编码有关物体动力学和能量学的信息它们被发射的空化事件，这取决于机械性能/完整性产生空化事件的介质。由于在组织解剖过程中暴露于空化，目标材料受到机械破坏，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 信号的特征可以在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，其中组织解剖学将用于在一系列组织中产生空化- 模仿具有广泛机械特性的凝胶体模和组织来消融它们。期间治疗时，ACE信号将被记录。治疗后，将对产生的损伤进行光学评估并在组织学上对记录的 ACE 信号进行分析，以确定其中可以进行分析的特征与图像或组织学中观察到的诱导损伤相关。建立这种相关性将允许 ACE 信号用作组织解剖过程中监测诱导材料分级的指标治疗。为了实现稳健的监控，可以使用以下传输元件来监控 ACE 信号：除了水听器之外，该阵列还作为接收器。这将确保有一条可到达的声学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，但由于数据量巨大，需要开发复杂的实时算法来处理将被生成。 ACE 信号特征与凝胶中诱导损伤之间的相关性体模和离体组织已被识别，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解剖剂量度量和组织解剖获得 FDA 批准用于临床。