Heat Induced Changes in the Mechanics of Soft Tissue

激光，微波，射频和类似技术的进步继续促进热治疗各种病理的新应用。 然而，大多数临床研究的动机是设备技术的进步，而不是对基本的热生物力学的基本理解，而目前对热生物力学的理解仍然很少。 因此，开发热疗法的潜力将需要量化临床可控参数的影响，例如温度水平、加热历史和加热期间的机械负载状态。 一般来说，热处理有两种主要的不可逆效应，即细胞坏死和结构蛋白变性。 因此，为了设计并最终优化热疗法，必须能够预测（空间和时间）给定加热装置对细胞活力和结缔组织完整性的伴随不可逆效应。 这项工作的总体目标不是研究具体的临床应用，而是建立一个理论基础，用于量化软组织非线性各向异性行为中不可逆的热诱导变化-我们的具体目标是开发和验证将暴露于宽温度范围的三种不同组织的现象学热机械损伤关系（从45到85 ℃），等温和非等温），听觉周期（从几秒到几小时），以及加热过程中的机械负荷状态（等长、等张和循环拉伸）。 拟定组织为牛腱索、心外膜和内膜。 除了凝胶基质之外，腱索主要由单轴取向的胶原蛋白、胶原蛋白的2- D网络的心外膜以及胶原蛋白和弹性蛋白的2-D网络的内膜组成。 选择这三种组织是因为它们具有越来越多的成分和微观结构复杂性，并且它们允许严格执行和解释单轴或平面内双轴测试-这将允许开发1-D和2- D关系，从而增加复杂性。 在文献中没有可比的数据或热损伤的本构关系。 PI最近表明，温度水平和加热时间的影响在热诱导胶原蛋白变性中是耦合的：在腱索的无牵引等温收缩试验中，存在指数关系形式的“时间-温度等效性”。 类似的关系也存在于热诱导的细胞死亡中。 PI假设在更一般的条件下（例如，多轴、非等温加载），这将简化关于负载和温度相关的缩放加热时间的量化。 从有限应变损伤力学和不可逆连续热力学的概念将被扩展到确定的亥姆霍兹自由能和损伤演化方程对当前的有限应变和先前的热损伤，后者可能取决于一个累积的缩放加热时间的依赖。 这样的量化将允许潜在的热疗法的组织水平的工程分析，并希望其优化。 ***

9634109 Humphrey Advances in laser, microwave, radio-frequency, and similar technologies continue to promote new applications of heat to treat various pathologies. yet, most clinical studies are motivated by the advances in device technology, not a fundamental understanding of the underlying thermo- biomechanics, which at present remains poorly understood. Exploiting the potential of heat-therapy will, therefore, require quantification of the effects of clinically controllable parameters such as the temperature level, heating history, and the mechanical load state during heating. In general, there are two primary irreversible effects of heat treatment, cell necrosis and denaturation of structural proteins. Thus, to design and eventually optimize a heat-therapy, one must be able to predict (spatially and temporally) the concomitant irreversible effects on cell viability and connective tissue integrity for a given heating device. Rather than studying a specific clinical application, the overall goal of this work is to establish a theoretical basis for quantifying irreversible heat-induced changes in the nonlinear, anistropic behavior of soft tissue -- our specific aim is to develop and validate phenomenological thermomechanical damage relations for three different tissues that will be exposed to a broad range of temperatures (from 45 to 85oC), both isothermally and non-isothermally), hearing periods (from seconds to hours), and mechanical load states during heating (isometric, isotonic, and cyclic stretching). The proposed tissues are bovine chordae tendineae, epicardium, and endocardium. In addition to a gel matrix, chordae consists primarily of uniaxially oriented collagen, epicardium of a 2- D network of collagen, and endocardium of a 2-D network of collagen and elastin. These three tissues were selected because they have increasingly more constituents and microstructural complexity, and they admit rigorously performed and interpreted uniaxial or in-pl ane biaxial testing -- this will allow the development of 1-D and then 2- D relations of increasing complexity. There are no comparable data or constitutive relations for thermal-damage in the literature. The PIs recently showed that the effects of temperature level and heating period are coupled in heat-induced collagen denaturation: there exists a "time-temperature equivalency" in the form of an exponential relation in traction free, isothermal shrinkage tests on chordae. A similar relation exists in heat-induced cell death. The PIs hypothesize that an analogous equivalency exists in tissues under more general conditions (e.g., multiaxial, non- isothermal loading), which will simplify quantification in terms of a load and temperature-dependent scaled heating time. Concepts from finite strain damage mechanics and irreversible continuum thermodynamics will be extended to determine the dependence of the Helmholtz free energy and the damage evolution equation on the current finite strain and prior thermal-damage, the latter of which likely depends on an accumulative scaled heating time. Such quantification will allow tissue-level engineering analysis of potential heat-therapies, and hopefully optimization thereof. ***