Design of Noninvasive Therapies Utilizing Nonlinear Focused Ultrasound With Shocks

利用非线性聚焦超声和冲击的无创治疗设计

• 批准号: 9308466
• 负责人: Vera Khokhlova
• 金额: $ 60.31万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-15 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9308466
• 关键词: Abdomen; Ablation; Accounting; Acoustics; Acute; Address; Blood Vessels; Breathing; Calibration; Cessation of life; Clinical; Clinical Treatment; Clinical Trials; Cold Therapy; Conduct Clinical Trials; Development; Diffusion; Dose; Early Diagnosis; Elements; Family suidae; Focused Ultrasound; Focused Ultrasound Therapy; Generations; Histology; Human; Image; Imaging Techniques; In Situ; Individual; Kidney; Lesion; Liver; Malignant Neoplasms; Measurement; Mechanics; Medical; Methodology; Methods; Modality; Modeling; Monitor; Motion; Organ; Performance; Perfusion; Phase; Physiologic pulse; Physiological; Pilot Projects; Power Sources; Primary carcinoma of the liver cells; Property; Protocols documentation; Public Health; Radiofrequency Interstitial Ablation; Renal carcinoma; Respiration; Safety; Sampling; Shock; Site; Solid; Sonication; Structure; System; Technology; Testing; Thermal Ablation Therapy; Time; Tissues; Transducers; Ultrasonography; Uncertainty; United States National Institutes of Health; Work; absorption; base; clinical application; clinically relevant; design; experimental study; image guided; imaging capabilities; improved; in vivo; in vivo Model; metrology; minimally invasive; novel; preclinical study; prototype; rib bone structure; simulation; therapy design; tool; treatment planning; treatment strategy; tumor

PROJECT SUMMARY Renal carcinoma (RCC) and hepatocellular carcinoma (HCC) are two of the most common abdominal solid organ malignancies in the US, accounting for nearly 100,000 combined new cases and nearly 40,000 deaths in 2015 [Siegel 2015]. With recent imaging advances leading to early diagnosis, medical practice is shifting toward the use of minimally invasive focal therapies (e.g., radiofrequency ablation, cryotherapy) for treating tumors. However, these treatments possess limitations: They require invasive deployment and rely on thermal effects that are poorly controlled, especially near vascular structures that can act as heat sinks. In addition, real-time treatment monitoring capabilities are minimal because thermal lesions are not easily visualized on standard imaging techniques. High intensity focused ultrasound (HIFU) offers an alternative focal therapy that can be delivered noninvasively. At present, clinical HIFU treatments involve thermal ablations that are subject to these same limitations; however, boiling histotripsy (BH) is a noninvasive HIFU modality recently invented by our group that can potentially overcome these limitations by delivering high-amplitude shock waves to mechanically ablate tissue. BH has many potential clinical advantages over existing focal therapies, including thermal HIFU: 1) generation of precise, controllable lesions with sharp margins while sparing critical structures; 2) targeting and real-time monitoring of treatments through ultrasound-based imaging, which utilizes the strong acoustic reflectivity of bubbles; and 3) potentially faster resorption of liquefied BH lesions. In previous years of NIH support, we have developed metrology tools for characterizing HIFU fields with shocks, invented the BH method and elucidated its physical mechanisms, identified effective pulse sequences, implemented real-time B-mode imaging of treatments, and designed a HIFU array optimized for abdominal BH applications. However, two scientific challenges remain in order to reliably deliver safe and effective BH treatments in humans: First, the impact of tissue inhomogeneities on shock formation is not yet quantitatively understood. Second, dose metrics and corresponding treatment strategies have not been defined and validated for ablating tissue volumes comprising multiple target sites. The first two aims in this project seek to address these challenges by 1) extending our nonlinear metrology tools to include modeling in heterogeneous tissues to predict in situ shock formation, and 2) conducting experimental studies in ex vivo liver and kidney tissue to determine dose metrics for use in designing volumetric BH treatments. The third aim involves the performance of rigorous pre-clinical studies using a prototype system to treat in pig kidney and liver in vivo. Successful completion of these aims will aid the design and execution of BH treatments, providing the framework needed to conduct clinical trials for RCC and HCC. Beyond the specific clinical targets, these studies will facilitate the advancement of BH for other clinical applications as well as the development of novel ultrasound-based therapies that utilize shocks.

项目概要 肾癌（RCC）和肝细胞癌（HCC）是两种最常见的腹部实体瘤 美国的器官恶性肿瘤，合计新增病例近 10 万例，死亡人数近 4 万例 2015 [西格尔 2015]。随着最新成像技术的进步带来早期诊断，医疗实践正在发生变化 倾向于使用微创局部疗法（例如射频消融、冷冻疗法）来治疗 肿瘤。然而，这些治疗方法具有局限性：它们需要侵入性部署并依赖于热 效果控制不佳，尤其是在可充当散热器的血管结构附近。此外， 实时治疗监测能力很小，因为热损伤不容易在 标准成像技术。高强度聚焦超声 (HIFU) 提供另一种聚焦治疗 可以无创地传递。目前，临床HIFU治疗主要采用热消融治疗， 受这些相同的限制；然而，沸腾组织解剖 (BH) 最近是一种无创 HIFU 模式 我们的团队发明的，可以通过提供高振幅冲击来克服这些限制 波以机械方式消融组织。与现有的局部治疗相比，BH 具有许多潜在的临床优势 治疗，包括热 HIFU：1）产生具有锐利边缘的精确、可控病变，同时 保护关键结构； 2）通过超声进行治疗的靶向和实时监测 成像，利用气泡的强声反射率； 3）可能更快地吸收液化 BH 病变。在 NIH 前几年的支持中，我们开发了用于表征 HIFU 场的计量工具 发明了BH法并阐明了其物理机制，识别了有效脉冲 序列，实现了治疗的实时 B 模式成像，并设计了优化的 HIFU 阵列 腹部 BH 应用。然而，为了可靠地提供安全和可靠的服务，仍然存在两个科学挑战 对人类有效的 BH 治疗：首先，组织不均匀性对休克形成的影响尚不清楚 定量地理解。其次，剂量指标和相应的治疗策略尚未制定 定义并验证用于消融包含多个目标部位的组织体积。本次活动的前两个目标 项目寻求通过以下方式解决这些挑战：1）扩展我们的非线性计量工具，将建模纳入其中 异质组织来预测原位休克形成，2) 进行离体实验研究 肝脏和肾脏组织，以确定用于设计体积 BH 治疗的剂量指标。第三个目标 涉及使用原型系统进行严格的临床前研究来治疗猪肾和 肝脏在体内。成功完成这些目标将有助于 BH 治疗的设计和执行， 提供进行 RCC 和 HCC 临床试验所需的框架。超出具体 临床目标，这些研究将促进 BH 在其他临床应用中的进步 以及利用电击的新型超声波疗法的开发。