激光照射下生物组织热效应的数值分析与实验研究
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摘要
本文结合数值分析和实验手段，致力于提供激光诱导生物组织热效应全参数预测平台，探索激光医学中的生物传热原理，提高激光应用的安全性和有效性。
首先从生物组织中的光分布和热传输规律的分析出发，改进了热传导方程中激光热源项的表达式，并给出多层结构模型。全面总结了传热方程的求解条件：组织的光学特性参数、热物性参数、血液灌注率及边界条件和初始条件，激光的特性参数也是可选择、可控制的重要参量。
其次进行了生物传热方程的数值求解，在轴对称柱坐标下将计算区域合理划分为二维，采用Matlab软件实现有限元方法求解生物热传输的非线性偏微分方程，计算了组织温度场的分布，温度可作三维动态显示。模拟了多种典型热效应激光应用模型中组织的温度响应，如典型散射型Nd:YAG激光凝结肝脏组织的激光间质疗法模型，Nd:YAG激光照射大鼠皮肤组织模型，典型吸收型CO2激光照射离体猪肉组织模型，CO2激光照射大鼠皮肤组织模型，He-Ne激光照射人体皮肤组织的三层结构模型。从模拟结果可以清楚地看到在不同条件下组织温度空间分布及时间行为，分析了光源项、灌注项和多层模型等对计算结果的影响，讨论了活体组织在低功率长时间激光照射下温度的动态平衡现象。
最后为了验证理论模型及计算的准确性，构建了可用于激光医学中无损/微创温度测量的实验系统，采用微型热电偶与红外辐射测温仪同时监测生物组织内部和表面温度，该系统适合于高精度、大范围、微小点快速响应的温度测量。通过改变激光参数（激光功率、连续/脉冲、照射时间），设计了临床应用范围的多组实验，实时测量了两种典型热效应激光（CO2和Nd:YAG激光）辐照下各种组织（离体猪肝脏、猪脂肪、猪肌肉和活体大鼠皮肤）的温度，首次进行了脉冲CO2和脉冲Nd:YAG照射活体大鼠皮肤的温度实验，得到激光辐照开始、过程及照射后生物组织温度场的变化规律，总结分析了一些主要影响因素。
结果表明预测和实验具有较好的一致性，修正后的模型更合理，该方法可以用于多种热效应激光应用的预测，并且随组织参数的无损测量技术的发展而获得持久的生命力。
本文工作得到了天津市自然科学基金(激光-组织热损伤的实时监测和预示技术研究，No. 023602611)支持。
This dissertation is devoted to provide full parameters prediction method of laser induced bio-tissue thermal effect by combining numerical analysis and experimental means. This research is in the interest of exploring bio-heat transfer theory in the laser medicine and enhancing the security and validity of laser application.
At first laser heat source term expression was modified in the heat conduction equation from analyzing the light distribution and thermal transferring in the bio-tissue, and multilayer model was presented. Solution conditions of heat transfer equation were summarized entirely, which include tissue optical properties, tissue thermal properties, blood perfusion rate, boundary conditions and initial conditions. Laser characteristics are also important parameters adapt to choosing and controlling.
Then the bio-heat transfer equation was solved numerically. The compute area was divided reasonably to two dimensions in the axial symmetry cylinder coordinate. The Finite Element Method(FEM) realized by Matlab software is used to solve the bio-heat transfer nonlinear Partial Differential Equation(PDE). The tissue temperature distribution was calculated and can display in three dimensions dynamically. The temperature response of several typical thermal laser applications were simulated, such as the typical scatter dominating Nd:YAG laser coagulating the liver in the Laser Interstitial Thermotherapy (LITT), Nd:YAG laser irradiating the in vivo murine skin, typical absorption dominating CO2 laser irradiating in vitro porcine tissue, CO2 laser irradiating in vivo murine skin and the three layers model of HeNe laser irradiating in vivo human skin. The temperature of space distribution and time behavior on different conditions can be shown clearly from the simulation results. The influence of light source, perfusion and multilayer to the calculation results was analysed. And the temperature dynamical balance phenomena of in vivo tissue under low power and long time laser irradiation was discussed.
Finally, in order to validate the veracity of theory model and calculation an experiment system which can be used in noninvasive or minimally invasive temperature measuring in laser medicine was constructed. This system used miniature thermocouple and infrared radiation thermometer to monitor the inner and surface temperature synchronously. Such a system is suitable to high precision, large range, minute point and rapid response temperature measuring.
Several group experiments were designed in the clinic application range by changing the laser parameters(laser power, continue/pulse, irradiate time). Temperature of Two typical thermal effect laser, CO2 and Nd:YAG laser, irradiating several tissue, in vitro porcine liver, fat, muscle and in vivo murine skin were measured on line. The temperature experiments of pulse CO2 and Nd:YAG laser irradiating in vivo murine skin were done at the first time. The temperature changing rule before, during and after laser irradiating were recorded, some main influencing factors were summarized and analysed.
The results proved the prediction and experiments have well coherence. The modified model is more reasonable. This method can be applied in several thermal laser application prediction and can obtain permanent life with the development of noninvasive measurement techniques of tissue properties.
This work has been supported by Tianjin Natural Science Funds(Research on real time monitoring and prediction technique of Laser-Tissue Thermal Damage, No. 023602611).
首先从生物组织中的光分布和热传输规律的分析出发，改进了热传导方程中激光热源项的表达式，并给出多层结构模型。全面总结了传热方程的求解条件：组织的光学特性参数、热物性参数、血液灌注率及边界条件和初始条件，激光的特性参数也是可选择、可控制的重要参量。
其次进行了生物传热方程的数值求解，在轴对称柱坐标下将计算区域合理划分为二维，采用Matlab软件实现有限元方法求解生物热传输的非线性偏微分方程，计算了组织温度场的分布，温度可作三维动态显示。模拟了多种典型热效应激光应用模型中组织的温度响应，如典型散射型Nd:YAG激光凝结肝脏组织的激光间质疗法模型，Nd:YAG激光照射大鼠皮肤组织模型，典型吸收型CO2激光照射离体猪肉组织模型，CO2激光照射大鼠皮肤组织模型，He-Ne激光照射人体皮肤组织的三层结构模型。从模拟结果可以清楚地看到在不同条件下组织温度空间分布及时间行为，分析了光源项、灌注项和多层模型等对计算结果的影响，讨论了活体组织在低功率长时间激光照射下温度的动态平衡现象。
最后为了验证理论模型及计算的准确性，构建了可用于激光医学中无损/微创温度测量的实验系统，采用微型热电偶与红外辐射测温仪同时监测生物组织内部和表面温度，该系统适合于高精度、大范围、微小点快速响应的温度测量。通过改变激光参数（激光功率、连续/脉冲、照射时间），设计了临床应用范围的多组实验，实时测量了两种典型热效应激光（CO2和Nd:YAG激光）辐照下各种组织（离体猪肝脏、猪脂肪、猪肌肉和活体大鼠皮肤）的温度，首次进行了脉冲CO2和脉冲Nd:YAG照射活体大鼠皮肤的温度实验，得到激光辐照开始、过程及照射后生物组织温度场的变化规律，总结分析了一些主要影响因素。
结果表明预测和实验具有较好的一致性，修正后的模型更合理，该方法可以用于多种热效应激光应用的预测，并且随组织参数的无损测量技术的发展而获得持久的生命力。
本文工作得到了天津市自然科学基金(激光-组织热损伤的实时监测和预示技术研究，No. 023602611)支持。
This dissertation is devoted to provide full parameters prediction method of laser induced bio-tissue thermal effect by combining numerical analysis and experimental means. This research is in the interest of exploring bio-heat transfer theory in the laser medicine and enhancing the security and validity of laser application.
At first laser heat source term expression was modified in the heat conduction equation from analyzing the light distribution and thermal transferring in the bio-tissue, and multilayer model was presented. Solution conditions of heat transfer equation were summarized entirely, which include tissue optical properties, tissue thermal properties, blood perfusion rate, boundary conditions and initial conditions. Laser characteristics are also important parameters adapt to choosing and controlling.
Then the bio-heat transfer equation was solved numerically. The compute area was divided reasonably to two dimensions in the axial symmetry cylinder coordinate. The Finite Element Method(FEM) realized by Matlab software is used to solve the bio-heat transfer nonlinear Partial Differential Equation(PDE). The tissue temperature distribution was calculated and can display in three dimensions dynamically. The temperature response of several typical thermal laser applications were simulated, such as the typical scatter dominating Nd:YAG laser coagulating the liver in the Laser Interstitial Thermotherapy (LITT), Nd:YAG laser irradiating the in vivo murine skin, typical absorption dominating CO2 laser irradiating in vitro porcine tissue, CO2 laser irradiating in vivo murine skin and the three layers model of HeNe laser irradiating in vivo human skin. The temperature of space distribution and time behavior on different conditions can be shown clearly from the simulation results. The influence of light source, perfusion and multilayer to the calculation results was analysed. And the temperature dynamical balance phenomena of in vivo tissue under low power and long time laser irradiation was discussed.
Finally, in order to validate the veracity of theory model and calculation an experiment system which can be used in noninvasive or minimally invasive temperature measuring in laser medicine was constructed. This system used miniature thermocouple and infrared radiation thermometer to monitor the inner and surface temperature synchronously. Such a system is suitable to high precision, large range, minute point and rapid response temperature measuring.
Several group experiments were designed in the clinic application range by changing the laser parameters(laser power, continue/pulse, irradiate time). Temperature of Two typical thermal effect laser, CO2 and Nd:YAG laser, irradiating several tissue, in vitro porcine liver, fat, muscle and in vivo murine skin were measured on line. The temperature experiments of pulse CO2 and Nd:YAG laser irradiating in vivo murine skin were done at the first time. The temperature changing rule before, during and after laser irradiating were recorded, some main influencing factors were summarized and analysed.
The results proved the prediction and experiments have well coherence. The modified model is more reasonable. This method can be applied in several thermal laser application prediction and can obtain permanent life with the development of noninvasive measurement techniques of tissue properties.
This work has been supported by Tianjin Natural Science Funds(Research on real time monitoring and prediction technique of Laser-Tissue Thermal Damage, No. 023602611).
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