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.

项目摘要/摘要组织疗法是一种非侵入性超声组织消融疗法，依赖于靶向产生用于机械分级和液化组织的空化事件。结果的可量化指标可以预测，可以预测组织疗法的疗法，这对于确保可靠和可重复的治疗方法，但目前不存在。尽管组织肌肉生成的空化和液化组织可以在超声成像中检测到，没有建立的度量来量化诱导的组织损伤与空化的暴露相对，已知随组织特性以及患者之间的变化而变化。和持续组织疗法的临床翻译，建立一个剂量度量至关重要在组织疗法期间沉积在组织中，可以原位监测，以准确预测治疗产生的损伤。在这个项目中，我们建议开发用于监测组织缩影诱导的组织分馏的指标监视由负责的空化事件产生的声气膜发射（ACE）信号组织疗法期间的治疗。 ACE信号编码有关动力学和能量学的信息它们发出的空化事件，取决于机械性能/完整性生成空化事件的媒体。由于在组织疗法期间暴露于空化的结果有针对性的材料被机械破坏，从而改变其机械性能，从而影响空化事件的动态。通过开发监视ACE特征信号的方法可以原位评估生成空化事件的材料的机械状态。我们将进行实验，其中将使用组织肌肉在一系列组织中产生空化模仿具有广泛的机械性能的凝胶幻像和组织。期间治疗，将记录ACE信号。治疗后，将对产生的损害进行光学评估在组织学上，将分析记录的ACE信号，以识别其中的功能与图像或组织学中观察到的诱导损害相关。建立这种相关性将允许 ACE信号用于监测组织摄取过程中诱导材料分馏的度量治疗。为了启用强大的监视，可以使用ACE信号使用除了水管外，阵列还作为接收器。这将确保通往声学的路径生成的空化事件将始终可用以提供对ACE信号的准确监控，但是将需要开发复杂的实时算法才能处理大量数据将生成。一旦ACE信号的特征与凝胶诱发损伤之间的相关性已经鉴定出幻象和离体组织，并进行了用于监测它们的实时算法，它们将在猪模型中在体内进行验证。这项工作的结果对于建立一个组织疗法剂量度量和组织疗法以获得FDA批准以供临床使用。