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: 8371099
• 负责人: Vera Khokhlova
• 金额: $ 59.53万
• 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/8371099
• 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. PUBLIC HEALTH RELEVANCE: High Intensity Ultrasound (HIFU) is gaining acceptance in the clinic as a form of noninvasive or minimally invasive surgery. This proposed work will benefit public health by facilitating development of regulatory guidelines and developing HIFU technology toward faster and safer clinical treatments with ultrasound guidance.

描述（由申请人提供）：高强度聚焦超声（HIFU）是一种新兴的医疗技术，用于在毫米大小的焦点“热点”内热消融目标组织，而不损坏介入组织。在最近的 HIFU 研究中，人们对使用纯机械破坏组织而不进行热凝固（组织解剖）也产生了浓厚的兴趣。尽管 HIFU 成功用于治疗一些良性和恶性肿瘤，但由于安全性和有效性监管标准不完整，该技术更广泛的临床接受度受到阻碍。目前的局限性包括 (a) 缺乏既定的计量标准来表征 HIFU 领域； (b) 对高声强下的热和机械生物效应的机械理解不完整，这阻碍了根据暴露测定信息对剂量进行量化； (c) 临床挑战，例如治疗时间长、肋骨等声学障碍以及具有成本效益的图像引导的可用性有限。该提案解决了这些限制，特别关注高功率水平的治疗。在资助的最初几年，我们探索了利用非线性声学和 开发了用于表征强声场的计量工具。我们表明，冲击形成导致的超声波吸收比相同强度的谐波大 10-100 倍；因此，可以在几毫秒内达到 100°C 的沸腾条件。我们开发了一种治疗方法，使用毫秒长的高压脉冲序列在焦点处传递冲击波。在这样的治疗方案中，组织消融被加速，沸腾的启动促进超声图像引导，并且可以控制组织损伤以表现出机械损伤、热损伤或两者。该提案的具体目标建立在之前的工作基础上，推动非线性 HIFU 方法走向临床应用。在目标 1 中，我们将 HIFU 换能器表征扩展到复杂的阵列源，并且我们将定义适合临床 HIFU 系统性能评估标准使用的方法。在目标 2 中，将建造高功率传感器，并将针对一系列治疗方案（例如纯热、机械或组合）开发将暴露测量与组织（离体）生物效应相关联的方法。在目标 3 中，我们使用健康猪模型检查两个靶器官（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 相控阵来实施一系列非线性 HIFU 协议。这些研究将解决肋骨和呼吸组织运动的干扰，从而能够在临床环境中仔细评估病变形成的精度和控制。之前针对高功率临床治疗的工作并未涉及我们在此提出的详细基本特征。这项工作将通过提供准确评估 HIFU 暴露的工具来有益于公共医疗保健，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 走向更快、更安全的临床治疗。 公共健康相关性：高强度超声 (HIFU) 作为一种无创或微创手术形式正在获得临床认可。这项拟议的工作将通过促进监管指南的制定和开发 HIFU 技术，在超声引导下实现更快、更安全的临床治疗，从而造福公众健康。