Two tissue ablation mechanisms: acoustic cavitation and shock-induced boiling

两种组织消融机制：声空化和冲击引起的沸腾

• 批准号: 8039977
• 负责人: Mark F Hamilton
• 金额: $ 16.84万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2012-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8039977
• 关键词: Ablation; Accounting; Acoustics; Administrative Supplement; Affect; Area; Birth; Calibration; Cardiac Catheterization Procedures; Cell Nucleus; Clinical; Code; Collaborations; Complex; Contrast Media; Coupled; Data; Dependence; Diagnosis; Diagnostic; Diffusion; Drug Delivery Systems; Elasticity; Equation; Excision; Fever; Focused Ultrasound Therapy; Foundations; Frequencies; Furuncles; Gases; Gel; Goals; Grant; Growth; Heart Atrium; Heating; Hemostatic function; High Frequency Waves; High temperature of physical object; Hypoplastic Left Heart Syndrome; In Vitro; Induced Hyperthermia; Investigation; Liquid substance; Literature; Lithotripsy; Location; Measurement; Mechanics; Medicine; Methods; Michigan; Microbubbles; Modeling; Modification; Morbidity - disease rate; Motion; Names; Phase; Physics; Physiologic pulse; Potential Energy; Procedures; Process; Property; Proteins; Protocols documentation; Radial; Research; Research Personnel; Role; Rupture; Shock; Solutions; Speed; Stress; Surface; Techniques; Technology; Temperature; Terminology; Theoretical Studies; Therapeutic; Thermal Conductivity; Time; Tissues; Translations; Ultrasonics; Ultrasonography; United States National Institutes of Health; Universities; Violence; Viscosity; Washington; Work; absorption; base; clinical application; improved; in vivo; interest; mathematical model; metrology; minimally invasive; mortality; neonate; practical application; public health relevance; research study; shear stress; simulation; soft tissue; tissue processing; tumor

DESCRIPTION (provided by applicant): There are two primary mechanisms by which high intensity focused ultrasound (HIFU) can ablate tissue. One is mechanical and due to cavitation. The other is thermal, via hyperthermia and boiling, due to the rapid temperature increase from absorption of ultrasound. Cavitation-based tissue ablation, referred to as histotripsy, offers promising opportunities for noninvasive treatment of tumors, as well as neonates with hypoplastic left heart syndrome (HLHS). The only treatment currently available for neonates is cardiac catheterization and balloon atrial septostomy, which must be performed within 2 weeks of birth. The morbidity and mortality rate associated with this procedure is as high as 50%. The advantage of histotripsy is its ability to provide tissue ablation with sharply demarcated boundaries. Recent investigations of controlled ultrasonic tissue ablation performed at the University of Michigan by Dr. Charles Cain and coworkers showed that tissue segments can be excised precisely, as required for HLHS treatment to perforate the atrial septum. The challenge is to keep the cavitation and therefore tissue ablation under control. Cavitation is a complicated phenomenon that depends on many factors such as ultrasound intensity, pulse duration and repetition frequency, properties of the surrounding medium, and presence of bubble nuclei. Understanding this complex process is necessary for practical and clinical applications of cavitation-based ultrasound methods. However, not only is there no model currently being used to describe cavitation cluster dynamics involved in histotripsy, but it is also not clear how boiling competes with cavitation in the process of tissue ablation. Recent experiments at the University of Washington by Dr. Vera Khokhlova and coworkers suggest that tissue ablation in gel occurs only following the creation of bubbles by boiling, rather than by cavitation. Whether tissue erosion is due to cavitation or boiling, complicated bubble dynamics are involved. The principal objective of the proposed research is to develop a mathematical model starting with the investigators' existing formalism for cavitation cluster dynamics in shock-wave lithotripsy. Our model permits analysis of interacting bubble dynamics accounting for pulsation, translation, coalescence, and rectified diffusion. Bubble interaction with tissue will be analyzed using a modification of the model that describes bubble growth and collapse near a tissue interface. Stresses in the tissue caused by shock waves and jets emitted during collapse will be estimated. Tissue heating and ultimately boiling due to hyperthermia associated with shock-enhanced absorption will be modeled to determine the role of thermal effects in histotripsy. Aspects of the model will be checked via comparison with measurements in ongoing experiments made available to us by our consultant Dr. Khokhlova. The long-term goal of the project is to provide a mathematical model that clarifies the underlying physics of ablative ultrasound technologies based on cavitation and also hyperthermia, and thus aids in modifying protocols for improving the efficacy of these new procedures. PUBLIC HEALTH RELEVANCE: Histotripsy is the name given to sharply demarcated fragmentation and removal of tissue by high intensity ultrasound used to produce localized cavitation bubble activity. It has been proposed as a new ablative technology that can be applied to noninvasive treatment of tumors and neonates with hypoplastic left heart syndrome. Our project will develop the mathematical foundation required to model this process and aid in increasing its efficacy through control of the cavitation and other physical mechanisms contributing to tissue ablation.

描述（由申请人提供）：高强度聚焦超声（HIFU）消融组织的主要机制有两种。一种是机械性的，由于空化。另一种是热的，通过热疗和沸腾，由于吸收超声波导致温度快速升高。基于空化的组织消融，称为组织摧毁术，为肿瘤的无创治疗以及患有左心发育不良综合征（HLHS）的新生儿提供了有希望的机会。目前唯一可用于新生儿的治疗方法是心导管插入术和球囊房间隔造口术，必须在出生后2周内进行。与该手术相关的发病率和死亡率高达50%。组织摧毁术的优点是其能够提供具有清晰分界线的组织消融。最近由Charles Cain博士及其同事在密歇根大学进行的受控超声组织消融研究表明，可以精确切除组织段，如HLHS治疗所需，以修复房间隔。挑战在于保持空化并因此控制组织消融。空化是一种复杂的现象，取决于许多因素，如超声强度，脉冲持续时间和重复频率，周围介质的性质，以及气泡核的存在。了解这个复杂的过程是必要的实际和基于空化的超声方法的临床应用。然而，目前不仅没有模型用于描述组织破坏中涉及的空化簇动力学，而且也不清楚沸腾如何在组织消融过程中与空化竞争。Vera Khokhlova博士及其同事最近在华盛顿大学进行的实验表明，凝胶中的组织消融仅发生在沸腾产生气泡之后，而不是空化。无论组织侵蚀是由于空化还是沸腾，都涉及复杂的气泡动力学。所提出的研究的主要目标是开发一个数学模型，从研究人员现有的形式主义的冲击波碎石空化集群动力学。我们的模型允许分析相互作用的气泡动力学占脉动，平移，合并，整流扩散。将使用描述组织界面附近气泡生长和塌陷的模型修改来分析气泡与组织的相互作用。将估计塌陷期间发出的冲击波和射流引起的组织应力。组织加热，并最终沸腾，由于高温与冲击增强吸收将被建模，以确定热效应在组织破坏中的作用。模型的各个方面将通过与我们的顾问Khokhlova博士提供给我们的正在进行的实验中的测量结果进行比较来检查。该项目的长期目标是提供一个数学模型，阐明基于空化和热疗的消融超声技术的基本物理学，从而有助于修改协议，以提高这些新程序的疗效。 公共卫生关系：组织破坏术是指通过高强度超声产生局部空化气泡活动，对组织进行清晰划分的破碎和切除。它被认为是一种新的消融技术，可应用于肿瘤和新生儿左心发育不良综合征的无创治疗。我们的项目将开发建模这一过程所需的数学基础，并通过控制空化和其他有助于组织消融的物理机制来帮助提高其功效。