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

基本信息

批准号：
8703690
负责人：
Vera Khokhlova
金额：
$ 57.5万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
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/8703690
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

项目摘要

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，也引起了人们的极大兴趣。尽管 HIFU 已成功用于治疗一些良性和恶性肿瘤，但该技术仍得到更广泛的临床认可。目前的障碍包括（a）缺乏确定的计量标准来表征 HIFU 场；（b）对高声强下的热和机械生物效应的机械理解不完整，这阻碍了给定剂量的量化。曝光测量信息；以及（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有限可用性，该提案特别关注高功率水平的治疗。在多年的资助中，我们探索了利用非线性声学的 HIFU 治疗方法，我们开发了用于表征强声场的计量工具，结果表明，冲击形成导致的超声波吸收比相同强度的谐波大 10-100 倍，因此在 100° 的沸腾条件下。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处传递冲击波，在这种治疗方案中，组织消融加速，沸腾的启动有利于图像引导。超声和组织损伤可以被控制以表现出机械损伤、热损伤或两者兼而有之。该提案的具体目标建立在之前的工作基础上，以推进非线性 HIFU 方法的临床应用。在目标 1 中，我们将扩展 HIFU。我们将定义适合临床 HIFU 系统性能评估标准使用的方法，并构建高功率换能器，并将暴露测定与组织（离体）生物效应相关联的方法。为一系列治疗方案（例如纯热治疗、机械治疗或联合治疗）而开发。在目标 3 中，我们将使用健康的猪模型来检查两个靶器官（肝脏和肾脏）的肿瘤治疗。使用代表现代临床系统的二维相控阵的非线性 HIFU 协议这些研究将解决肋骨和呼吸组织运动的干扰，从而可以在临床环境中仔细评估病变形成的精度和控制。治疗并未涉及我们在此提出的详细的基本特征，这项工作将通过提供准确评估 HIFU 暴露的工具，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，从而使公共医疗保健受益。 .该工作将也推动 HIFU 走向更快、更安全的临床治疗。