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）：高强度聚焦超声（HIFU）消融组织有两种主要机制。一种是机械性的，由空化引起。另一种是热的，通过热疗和煮沸，由于吸收超声波导致温度迅速升高。以空腔为基础的组织消融，即组织切片，为肿瘤和新生儿左心发育不全综合征（HLHS）的无创治疗提供了有希望的机会。目前唯一可用于新生儿的治疗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。与此相关的发病率和死亡率高达50%。组织切片的优点是它能够提供清晰的组织消融边界。最近由密歇根大学Charles Cain博士及其同事进行的受控超声组织消融研究表明，可以精确切除组织段，这是HLHS治疗房间隔穿孔所需要的。难点在于如何控制空化和组织消融。空化是一种复杂的现象，它与超声强度、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等因素有关。了解这一复杂的过程对于空化超声方法的实际和临床应用是必要的。然而，目前不仅没有模型用于描述组织切片中涉及的空化簇动力学，而且也不清楚在组织消融过程中沸腾与空化是如何竞争的。华盛顿大学Vera Khokhlova博士及其同事最近的实验表明，凝胶中的组织消融只发生在沸腾产生气泡之后，而不是通过空化。无论组织侵蚀是由空化还是沸腾引起的，都涉及到复杂的气泡动力学。提出的研究的主要目的是建立一个数学模型，从研究人员现有的形式开始，用于冲击波碎石中的空化团动力学。我们的模型允许分析相互作用的气泡动力学计算脉动，平移，合并，和纠正扩散。气泡与组织的相互作用将使用模型的修改来分析，该模型描述了气泡在组织界面附近的生长和崩溃。在坍塌过程中，由冲击波和喷射产生的组织应力将被估计出来。将对与冲击增强吸收相关的高温引起的组织加热和最终沸腾进行建模，以确定热效应在组织学中的作用。该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，以澄清基于空化和热疗的烧蚀超声技术的潜在物理原理，从而有助于修改方案，提高这些新程序的疗效。