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Mechanical Damage from Cavitation in High Intensity Focused Ultrasound Accelerated Thrombolysis.

机译：高强度聚焦超声加速溶栓作用中空化引起的机械损伤。

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摘要

Stroke is the fourth most common cause of death in the United States (second worldwide), with about 87% of these being ischemic. Recent studies, in vitro and in vivo, have shown that High Intensity Focused Ultrasound (HIFU) accelerates thrombolysis, the dissolution of blood clots, for ischemic stroke. Although the mechanisms are not fully understood, cavitation is thought to play an important role in sonothrombolysis. Acoustic cavitation is typically divided into two categories describing the bubble behavior: stable cavitation describes bubbles undergoing smooth oscillations, while inertial cavitation is characterized by rapid growth followed by violent collapses. Possible mechanisms associated with both stable cavitation (i.e. microstreaming) and inertial cavitation (i.e. microjets) are thought to increase clot lysis by enhancing the delivery of a thrombolytic agent.;The damage to a blood clot's fibrin fiber network from bubble collapses in a HIFU field is studied. The bubble dynamical model used is the Keller-Miksis equation with a linear Kelvin-Voigt viscoelastic material to account for the clot material outside the bubble. The amount of damage to the fiber network caused by a single bubble collapse is estimated by two independent approaches. The first method is based on the stretch of individual fibrin fibers of the blood clot, and estimates the number of broken fibers as a bubble embedded in the blood clot grows to its maximum radius. This method estimates that fibrin fibers (the structural matrix of the blood clot) break as the bubble expands, however the bubble dynamical model does not account for this. To account for the breaking of fibrin fibers (and lysing of red blood cells) a term could be added to the Keller-Miksis equation. This motivates the second method, an independent energy based approach. In this method, the equation for the bubble dynamics, as the bubble grows to its maximum radius, is analyzed in the form of a work-energy statement. The energy method is extended to the more important scenario of a bubble outside a blood clot that collapses asymmetrically creating a jet towards the clot. There is significantly more damage from a bubble growing outside the clot compared to a bubble embedded within the clot structure.;Next, the effects of the physical properties of skull bone when a HIFU wave propagates through it are examined. The dynamics of a test bubble placed at the focus is used in understanding of the pressure field. The sound emitted from the bubble is used to classify the type of cavitation present (stable and/or inertial). The amount of damage in the area surrounding the focus is examined for various initial bubble sizes. The maximum amount of energy available to cause damage to a blood clot increases as the density of the calvaria decreases.;This dissertation is a first step in analyzing potential cavitation mechanisms, which have only been suggested by other authors. The goal is to assess the plausibility of mechanical damage as a mechanism for enhancement of sonothrombolysis with the addition of microbubbles. The methods to estimate mechanical damage derived here offer the first connection between a bubble and the damage it may cause to a blood clot. This work shows that a bubble near but exterior to a blood clot has the potential to cause significant damage. Ultimately, this dissertation contributes to the understanding of how microbubbles can accelerate clot destruction. This understanding will lead to improves design of therapeutic devices.
机译：中风是美国第四大最常见的死亡原因（全球第二），其中约有87％是缺血性的。近期的体内外研究表明，高强度聚焦超声（HIFU）可以促进溶栓作用，从而促进缺血性卒中的血栓溶解。尽管尚未完全了解其机制，但人们认为空化在超声溶栓过程中起着重要作用。声空化通常分为描述气泡行为的两类：稳定的空化描述气泡经历平滑振荡，而惯性的空化以快速增长然后剧烈坍塌为特征。与稳定的空化（即微流）和惯性的空化（即微射流）有关的可能机制被认为通过增强溶栓剂的输送来增加血凝块溶解。HIFU视野中的气泡塌陷对血凝块的纤维蛋白纤维网络的损害被研究。所使用的气泡动力学模型是具有线性Kelvin-Voigt粘弹性材料的Keller-Miksis方程，用以说明气泡外部的凝块材料。由单个气泡破裂导致的对光纤网络的破坏程度可通过两种独立的方法进行估算。第一种方法是基于血凝块中单个纤维蛋白纤维的拉伸，并随着嵌入血凝块中的气泡长到其最大半径来估计断裂纤维的数量。该方法估计纤维蛋白纤维（血凝块的结构基质）会随着气泡的膨胀而破裂，但是气泡动力学模型不能解释这一点。为了说明纤维蛋白纤维的断裂（以及红细胞的溶解），可以在Keller-Miksis方程中添加一个术语。这激发了第二种方法，一种基于能量的独立方法。在这种方法中，当气泡增长到其最大半径时，气泡动力学方程将以功能声明的形式进行分析。能量方法扩展到更重要的情况，即血凝块外部出现气泡，气泡不对称地塌陷，形成朝向血凝块的射流。与嵌入在血块结构内的气泡相比，血块外的气泡生长造成的损害明显更多。其次，研究了HIFU波传播时颅骨的物理特性的影响。放在焦点处的测试气泡的动力学用于了解压力场。从气泡发出的声音用于分类出现的气蚀类型（稳定和/或惯性）。对于各种初始气泡大小，检查焦点周围区域的损坏程度。随着颅盖密度的降低，可用于破坏血凝块的最大能量增加。;本论文是分析潜在空化机制的第一步，只有其他作者提出了这一点。目的是评估机械损伤的合理性，以作为通过添加微泡增强声纳溶栓的一种机制。此处估算出的机械损伤的方法提供了气泡与其可能导致的血块损伤之间的第一联系。这项工作表明，血块附近但外部的气泡有可能造成严重损害。最终，本文有助于理解微气泡如何加速凝块破坏。这种理解将导致改善治疗设备的设计。

著录项

  • 作者

    Weiss, Hope Leigh.;

  • 作者单位

    University of California, Berkeley.;

  • 授予单位 University of California, Berkeley.;
  • 学科 Engineering Biomedical.;Engineering Mechanical.
  • 学位 Ph.D.
  • 年度 2012
  • 页码 80 p.
  • 总页数 80
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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