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: 7873962
• 负责人: Mark F Hamilton
• 金额: $ 17.52万
• 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 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7873962
• 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; Hand; 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; 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）：有两种主要机制，高强度聚焦超声（HIFU）可以消除组织。一个是机械的，并且由于空化。另一种是热疗和沸腾的热量，这是由于超声吸收迅速升高。基于空化的组织消融，称为组织疗法，为肿瘤无创治疗以及患有左心脏疾病综合征（HLHS）的新生儿提供了有希望的机会。当前可用于新生儿的唯一治疗方法是心脏导管插入术和气囊房屋隔膜造口术，必须在出生后2周内进行。与此过程相关的发病率和死亡率高达50％。组织疗法的优势在于它具有鲜明划界边界的组织消融的能力。查尔斯·凯恩（Charles Cain）博士和同事在密歇根大学对受控超声组织消融的最新研究表明，可以根据HLHS治疗需要精确切除组织片段，以塑造心房隔膜。面临的挑战是保持空化，从而控制组织消融。空化是一种复杂的现象，取决于许多因素，例如超声强度，脉搏持续时间和重复频率，周围培养基的性质以及气泡核的存在。了解这一复杂过程对于基于空化的超声方法的实际和临床应用是必要的。但是，不仅目前没有使用模型来描述组织疗法涉及的空化簇动力学，而且还不清楚在组织消融过程中如何与空化竞争。 Vera Khokhlova博士和同事在华盛顿大学进行的最新实验表明，凝胶中的组织消融仅在沸腾而不是通过空化来创建气泡后才发生。无论组织侵蚀是由于空化还是沸腾，涉及复杂的气泡动力学。拟议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，用于冲击波岩石疗法中的空化集群动力学。我们的模型允许分析相互作用的气泡动力学，这些动力学考虑了脉动，翻译，合并和整流扩散的分析。将使用描述气泡生长并在组织界面附近塌陷的模型的修饰来分析与组织的气泡相互作用。估计由冲击波和喷气机引起的组织中的应力估计。组织加热并最终由于与休克增强吸收相关的高温引起的最终沸腾，以确定热作用在组织疗法中的作用。该模型的各个方面将通过与我们顾问Khokhlova博士提供的正在进行的实验中的测量值进行比较。该项目的长期目标是提供一个数学模型，该模型阐明基于空化和高温的消融性超声技术的基本物理，从而有助于修改协议以改善这些新程序的功效。 公共卫生相关性：组织疗法是通过用于产生局部气泡活性的高强度超声来清除组织的名称。它被认为是一种新的烧烤技术，可用于患有肿瘤左心脏综合征的肿瘤和新生儿的无创治疗。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。