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生物组织热物理参数的测量方法及实验研究

Measuring Method and Experimental Study of Thermophysical Parameters of Bio-tissue

【作者】 杨昆

【导师】 刘伟;

【作者基本信息】 华中科技大学 , 工程热物理, 2004, 博士

【摘要】 生物组织的热物理参数(如热导率、热扩散率、血液灌注率、代谢产热、动脉血温度等)是生物传热研究的基本参数,它们的准确测定对于研究生物组织中的传热传质机制,对于生物传热模型的构建与验算、对于研究生物组织在各种热源作用下的热响应、对于临床医学和生理学等相关领域的研究均有重要意义。例如,在肿瘤热疗过程中,需要精确控制治疗区域的温度分布,以保证肿瘤组织处于治疗温度而其周围正常组织处于安全温度。为此,需要准确测量肿瘤和及其周围正常组织中的热物理参数分布,以合理组织热源、确定加热剂量,实现对治疗区域温度场的准确预估与控制,从而获得更有效的治疗效果。本文紧扣“生物组织热物理参数的测量”这一主题,对生物组织热物理参数的测量方法进行了深入细致的研究,研制了相关的生物组织热物理参数测量装置,对离体和活体生物组织的热物理参数进行了实验测量。阶跃温升法是一种根据生物组织的热响应来测量生物组织热物理参数的瞬态测量方法。本文对阶跃温升法的测量误差进行了详尽的分析,特别是首次分析了阶跃温升法测量的模型误差及其影响因素,发现了测量时的“最佳测量时间段”,提出了探头参数和测量参数的选择原则,并对前人发现的实验现象给出了新的更合理的解释。在此基础上,研制了阶跃温升法测量装置。设计的柔性生物探针可以方便地测量不同的生理部位,并且有效地实现了热绝缘及电绝缘,使测量更准确。介绍了探头参数的标定方法,并对阶跃温升法的测量精度进行了验证,结果表明:采用该装置,测量热导率的最大误差为1.7%,平均误差为1.09%。利用该阶跃温升法测量装置,研究了水含量和热凝固对生物组织热导率的影响。得到了猪肝热导率与水含量的函数关系式,并由此推导出了蛋白质和脂肪的热导率。热凝固过程主要是由于生物组织中的蛋白质的热致变性引起的,而蛋清的主要成分就是蛋白质和水。因此,本文首先研究了热凝固对蛋清热导率的影响。在此基础上,研究了热凝固对猪肝脏组织热导率的影响。结果表明:由于蛋白质热变性的影响,热凝固后,蛋清热导率略微增加。而热凝固后,虽然猪肝水含量大幅降低,但其热导率减小的幅度不大。这提示我们:热凝固对生物组织热物理参数有重要影响。Chen等人提出的脉冲衰减法也是一种测量生物组织热导率的热瞬态方法,同<WP=4>阶跃温升法相比,脉冲衰减法不需要引入复杂的控制模块对探头温度进行控制,因此其实际测量过程比较简单。本文对脉冲衰减法的测量误差进行了详尽分析。介绍了我们自行设计的脉冲衰减法测量电路,为了适应实际测量的需要,提出了改进的脉冲衰减法。采用脉冲衰减法测量了甘油水溶液的热导率,实际测量结果均表明:由于“点热源”假设的影响,热导率的测量值要比其真实值大。当对活体组织进行测量时,采用脉冲衰减法可以同时测得血液灌注率和热导率。但现有的基于脉冲衰减法的PSM模型在推导时采用了“点热源”假设,没有考虑热敏电阻探头尺寸的影响;而SSM模型在测量时以探头中心温度来代表探头平均温度。这些处理方法与脉冲衰减法测量时的实际物理过程有偏差,是测量时存在模型误差主要原因。本文基于脉冲衰减法提出了一种新的ATM模型,它的主要思想是采用探头的平均温度来测量生物组织的热物理参数。采用数值实验的方法分析了三种模型的测量误差,结果显示:采用ATM模型进行测量,可以显著地提高测量精度。对甘油水溶液的测量也表明,采用ATM模型可以显著地减小热导率测量的误差。为了适应疾病热诊断的需要,减小测量时的组织损伤,防止干扰组织正常的生理状态,需要实现对人体热物理参数的无损测量。本文提出了一种新的无损测量人体组织热物理参数的体表绝热法,推导出了体表绝热情况下组织温度响应的解析解。提出了“有效动脉血温度”的概念,实现了对人体组织血液灌注率和有效动脉血温度的直接无损测量,解决了不能直接测量人体局部组织动脉血温度和代谢产热的难题。并对经典的生物传热方程—Pennes方程进行了简化。本文研究接受国家自然科学基金重点项目(No.59836240)资助。

【Abstract】 The thermophysical parameters of biological tissue, including the thermal conductivity, the thermal diffusivity, the blood perfusion, the metabolic heat rate and the arterial blood temperature, are the basic parameters for bio-heat transfer research. The estimation of the thermophysical parameters of biological tissue is important for the research of biological heat and mass transfer, for the establishment and validation of bio-heat transfer equation, for the understanding of the thermal response of the biological tissue under outer-supplied heating energy, for the related study of physiology and medical engineering. Particularly during the thermal therapy of cancer, the temperature of the therapy region should be exactly controlled in order to make the temperature of the tumor in the therapy temperature and the temperature of the normal tissue in the safe temperature. Therefore, the thermophysical parameters of the tumor and its surrounding normal tissue should be accurately estimated. Thus the heat source can be well controlled to construct a required temperature field, and an effective treatment can be achieved.In this paper, the measuring methods of the thermophysical parameters of biological tissue were studied. The related measuring devices were developed. And some thermophysical parameters of living and dead tissue were measured.The step-temperature technique is a transient thermal technique to measure tissue thermophysical parameters according to the thermal response of tissue. In this paper, a sensitivity analysis of the step-temperature technique was performed. Particularly, the model error of the step-temperature technique was discussed by using numerical experiment method. An optimal measurement time window was found. The choose principles of the bead parameters and the measuring parameters were put forward. A new reasonable interpretation for the previous experiment phenomena was found. On the bases of the sensitivity analysis, a measuring device for the step temperature technique was developed. A supple thermistor probe was designed, in which the thermal insulation and electricity insulation were achieved. The calibration method of the thermistor bead was introduced. The measurement precision was validated by measuring the thermal conductivity of the mixture of glycerol and agar-gelled water. The results showed that the maximum measuring error was 1.7%, and the average measuring error was 1.09%. The measuring device was used to study the effects of water content and thermal <WP=6>coagulation on the thermal conductivity of biological tissue. The formula about the water content and the thermal conductivity of pig liver was found. The thermal conductivity of protein and lipid was derived from the formula. The thermal coagulation is caused by the tissue structural protein thermal denaturation. The major compositions of egg albumen are protein and water. Therefore, egg albumen was used as a medium for studying the effect of thermal coagulation. And then, pig liver was used. The results showed that the thermal conductivity of egg albumen increased slightly after undergo a thermal coagulation process. However, the thermal conductivity of pig liver just decreased a little in spite of the water content of pig liver decreased so much. These phenomena demonstrated that thermal coagulation has a considerable influence on the thermophysical parameters of biological tissue.The pulse decay method developed by Chen et al is also a transient thermal technique for measuring of tissue thermal conductivity. Comparing with the step temperature technique, the pulse decay method needn’t to control the probe bead temperature by using a complicate controlling modular, thus is easier to achieve. In this paper, a sensitivity analysis of the pulse decay method was performed. A measuring device for the step temperature technique was developed. In order to meet the requirement of practical measurement, an improved thermal pulse decay method was presented. The thermal conductivity of the mixture of glycerol and agar-gelled

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