Metrology and Nonlinear Acoustics Bioeffects of High Intensity Focused Ultrasound

高强度聚焦超声的计量学和非线性声学生物效应

• 批准号: 8528581
• 负责人: Vera Khokhlova
• 金额: $ 57.51万
• 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 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8528581
• 关键词: Abdomen; Ablation; Acoustics; Address; Adoption; Architecture; Back; Benchmarking; Benign; Biochemical; Breathing; Clinic; Clinical; Clinical Treatment; Clinical assessments; Coagulation Process; Comparative Study; Complex; Computational algorithm; Custom; Data; Databases; Development; Devices; Dose; Electronics; Elements; Evaluation; Exhibits; Exposure to; Family suidae; Focused Ultrasound Therapy; Furuncles; Grant; Guidelines; Healthcare; Heat-Shock Response; Heating; Holography; Hot Spot; Image; In Situ; Kidney; Kidney Neoplasms; Lesion; Liver; Liver neoplasms; Malignant Neoplasms; Mechanics; Medical Technology; Methods; Modeling; Monitor; Motion; Operative Surgical Procedures; Organ; Output; Performance; Phase; Physiologic pulse; Protocols documentation; Public Health; Pulse Pressure; Readiness; Safety; Shock; Skin; Solutions; Source; System; Technology; Therapeutic; Time; Tissues; Transducers; Treatment Protocols; Ultrasonic Transducer; Ultrasonography; Water; Work; absorption; attenuation; base; clinical application; cost effective; improved; in vivo; interest; irradiation; metrology; millisecond; minimally invasive; novel strategies; pre-clinical; prototype; research study; respiratory; rib bone structure; simulation; tool; treatment site; tumor; vapor

DESCRIPTION (provided by applicant): High Intensity Focused Ultrasound (HIFU) is an emerging medical technology for thermally ablating targeted tissue within a mm-size focal 'hot spot' without damaging intervening tissues. In recent HIFU studies, there has also been significant interest in using purely mechanical destruction of tissue without thermal coagulation (histotripsy). Despite successful use of HIFU for the treatment of some benign and malignant tumors, broader clinical acceptance of this technology is impeded by incomplete regulatory standards for safety and efficacy. Current limitations include (a) a lack of established metrology standards to characterize HIFU fields; (b) an incomplete mechanistic understanding of thermal and mechanical bioeffects at high acoustic intensities, which hinders the quantification of dose given exposimetry information; and (c) clinical challenges such as long treatment times, acoustic obstacles like ribs, and the limited availability of cost-effective image guidance. This proposal addresses these limitations with a particular focus on treatments at high power levels. In the initial years of the grant, we explored HIFU treatments that utilize nonlinear acoustics and developed metrology tools for characterizing intense acoustic fields. We showed that shock formation leads to ultrasound absorption that is 10-100 times greater than for harmonic waves of the same intensity; consequently, boiling conditions at 100¿C can be reached within milliseconds. We developed a treatment method that uses sequences of millisecond-long, high-pressure pulses to deliver shocks waves at the focus. In such treatment regimes, tissue ablation is accelerated, the initiation of boiling facilitates image guidance with ultrasound, and tissue lesions can be controlled to exhibit mechanical damage, thermal damage, or both. The specific aims of this proposal build upon the previous work to advance nonlinear HIFU methods toward clinical adoption. In Aim 1, we will extend HIFU transducer characterization to complex array sources, and we will define methods suitable for standard use in performance assessment of clinical HIFU systems. In Aim 2, high power transducers will be built and the methods for correlating exposimetry with bioeffects in tissue (ex vivo) will be developed for a range of therapeutic regimes such as purely thermal, mechanical, or combined. In Aim 3, we examine tumor treatment in two target organs, the liver and the kidney, using a healthy porcine model. We will implement a range of nonlinear HIFU protocols using a 2D phased array representative of modern clinical systems. These studies will address interference from ribs and respiratory tissue motion, allowing careful assessment of the precision and control of lesion formation in a clinical setting. Previous work targeted at high-power clinical treatments has not involved the detailed fundamental characterizations that we propose here. The work will benefit public health care by providing tools for accurate evaluation of HIFU exposure, thereby aiding the development of regulatory guidelines to facilitate FDA approval of new HIFU therapies while identifying poorly controlled systems. The work will also advance HIFU toward faster and safer clinical treatments.

描述（由适用提供）：高强度聚焦超声（HIFU）是一种新兴的医疗技术，用于在MM大小的焦点“热点”内热消融靶向组织，而不会损害干预组织。在最近的HIFU研究中，也有很大的兴趣使用无热凝血的组织纯机械破坏（组织疗法）。尽管成功使用HIFU来治疗某些良性和恶性肿瘤，但对安全性和效率的不完整监管标准阻碍了对该技术的更广泛的临床接受。当前的局限性包括（a）缺乏表征HIFU字段的既定计量标准； （b）在高声强度下对热和机械生物效应的机械理解不完全理解，这阻碍了给定剂量的量化量； （c）临床挑战，例如长期治疗时间，肋骨等声学障碍以及具有成本效益的图像指导的有限可用性。该提案以高功率水平的治疗方式特别关注这些局限性。在赠款的最初几年中，我们探索了使用非线性声学和 开发的计量工具来表征强烈的声学场。我们表明，冲击形成导致超声滥用比相同强度的谐波波大10-100倍。因此，可以在毫秒内到达100°C处的沸腾条件。我们开发了一种治疗方法，该方法使用毫秒长的高压脉冲序列在焦点下提供冲击波。在这样的治疗方案中，组织消融加速，超声检查沸腾栖息地的启动，可以控制组织病变以暴露于机械损伤，热损伤或两者兼而有之。该提案的具体目的是基于先前的工作，以推动非线性HIFU方法朝着临床采用。在AIM 1中，我们将将HIFU传感器的特征扩展到复杂的阵列源，并将定义适合于临床HIFU系统性能评估的标准使用方法。在AIM 2中，将建立高功率传感器，并将与组织中的生物效应相关联（EX VIVO），以构成一系列治疗方案（例如纯热，机械或合并）。 AIM 3，我们使用健康的猪模型检查了两个靶器官，肝脏和肾脏的肿瘤治疗。我们将使用代表现代临床系统的2D阶段阵列实施一系列非线性HIFU协议。这些研究将解决肋骨和呼吸组织运动的干扰，从而仔细评估临床环境中病变形成的精度和控制。以前针对高功率临床治疗的工作并未涉及我们在这里提出的详细基本特征。这项工作将通过提供准确评估HIFU暴露的工具来使公共保健受益，从而有助于制定监管指南，以促进FDA批准新的HIFU疗法，同时识别控制不良的系统。这项工作还将推动HIFU朝着更快，更安全的临床治疗方向前进。