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mm大小的焦点“热点”内热消融目标组织，而不会损伤中间组织。在最近的HIFU研究中，人们对使用不经热凝固的纯机械破坏组织（组织切片）也很感兴趣。尽管HIFU成功地用于治疗一些良性和恶性肿瘤，但由于安全性和有效性的监管标准不完善，阻碍了该技术在临床的广泛接受。目前的限制包括(a)缺乏确定的计量标准来描述HIFU领域；(b)对高声强下的热生物效应和机械生物效应的机制理解不完整，这妨碍了给定暴露学信息的剂量量化；(c)临床挑战，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有限可用性。本提案解决了这些限制，特别关注高功率水平下的处理。在拨款的最初几年，我们探索了利用非线性声学和