应用近红外光谱分析技术进行人体血糖浓度无创检测有着很高的应用价值。 对于人体，选择合适的测量部位会使近红外测量的精度明显提高。由于耳垂部位 有血流丰富、便于探头固定等优点，易用性较强，本文针对耳垂作为测量部位进 行近红外无创血糖检测的可行性开展了相关研究。 报告在阐述近红外血糖检测中常用的指尖、手掌、前臂，以及本文拟研究的 耳垂的生理结构基础上，从各部位皮肤的分层厚度角度以及各部分之间血糖浓度 相关性进行了分析；其次，开展了人体口服葡萄糖耐受实验，实验结果表明，耳 垂毛细血管中的血糖浓度变化与前臂静脉全血及指尖毛细血管中的葡萄糖浓度 变化趋势基本相同，相关系数均在 0.8 之上；由此可以认为，从生理学角度，耳 垂作为血糖检测的测量部位是可行的。 采用蒙特卡洛模拟方法，分别开展了基于耳垂五层皮肤模型在大浓度下和人 体血糖浓度下的仿真，结果表明，此模型下，位置浮动基准点存在，且在大浓度 下受个体差异比在人体血糖浓度下影响较大，该结果可用于指导无创血糖检测探 头设计中源光纤与探测光纤之间的距离；同时，针对耳垂的结构特性，基于仿真 结果分析了其透射光的分布规律及受个体差异的影响，并在径向上和耳垂的漫反 射光进行了比较，表明耳垂透射光有较大的应用潜力。 最后，基于耳垂五层模型的仿真数据，以及利用双光纤空间分辨漫反射测量 系统进行的仿体实验数据，分别用基准位置 1.9 mm 的原始光谱数据、在扣背景 处理后和基于浮动基准方法的光谱修正后建立糖浓度预测的多变量模型，得到的 预测精度呈现递增趋势；针对 1.9 mm 径向位置处的透射光进行糖浓度预测的多 变量模型，其预测精度与基于浮动基准方法进行光谱修正后的模型结果相当。由 此表明在近红外光谱进行无创血糖浓度测量时，选取耳垂作为测量部位是可行的， 具有较大的应用前景。 关键词，近红外光谱，无创血糖测量，耳垂，浮动基准方法，口服糖耐量实验ABSTRACT The application of near infrared spectroscopy analysis in human blood glucose sensing is of great measurement potential and practical significance. For human body, choosing an appropriate measurement site can enhance the accuracy on near-infrared sensing. The earlobe has many advantages for its affluent blood flow, and its convenience for the attachment of the optical sensing probe. So the earlobe site is convenient to use. In this dissertation, the feasibility of the earlobe as the measurement site on near-infrared blood glucose sensing is studied. Based on the physiological structures of the intended studying site earlobe and other common measurement sites such as the fingertip, palm and the forearm, analysis is done from the skin layer thickness aspect and the correlation of the blood glucose concentration of each site. Then OGTT experiments are conducted. The results show that the change of the blood glucose level in earlobe capillary is in general the same as the changing trend of it in the forearm venous whole blood and the fingertip capillary whole blood. The correlation coefficients are both above 0.8. It is indicated that from the physiological perspective the earlobe is feasible to be a measurement site in blood glucose sensing. Using the Monte-Carlo simulation method, the simulations based on the earlobe five-layered skin model in both high glucose concentration level and in human body glucose level are done. The results show that the positional floating reference point existsin this model, and it is affected by individual variances more significantly under the high glucose concentration level than in human body glucose level.The results could guide the specification of the range of the light source fiber and the detector fiber. The distribution of the earlobe transmission light and the influence of the individual variance on earlobe transmission light are analyzed based on the simulation results according to the earlobe structural features. And the intensity of transmission light and the diffuse reflected light is compared in radial direction. It is demonstrated that the earlobe transmission light has a great application potential. Finally, based on the Monte-Carlo simulation data of the earlobe five-layered skin model and the phantom experiments’ data on a two-fiber spatial resolution diffuse reflected light detection system, a series of PLS modeling are conducted. The results show that using the earlobe transmission light at radial position 1.9 mm can achieve the same modeling results using the spectrum correction method. Thus preliminarily verify the feasibility of choosing earlobe as the measurement site for non-invasive blood glucose sensing and its bright application prospect. KEY WORDS: Near Infrared Spectroscopy, Non-invasive Blood Glucose Sensing Earlobe, Floating Reference Point, OGTT目录 第一章 绪论..........................................................................................1 1.1 人体近红外无创血糖检测的背景意义 ..............................................................1 1.2 人体近红外无创血糖检测的研究进展 ..............................................................2 1.3 人体近红外无创血糖检测中存在的难题 .........................................................3 1.4 人体近红外无创血糖应用的测量部位概述 .....................................................5 1.5 本报告的研究内容和主要工作安排 .................................................................6 第二章 近红外无创血糖检测的理论基础..............................................8 2.1 描述光在生物组织中传播用到的光学参数 ......................................................8 2.2 生物组织中光传播的蒙特卡洛模拟方法 ........................................................11 2.3 近红外无创血糖测量的基本原理 ...................................................................15 2.4 浮动基准方法理论及原理 ...............................................................................17 2.5 近红外无创血糖检测中常用的化学计量学方法 ............................................19 2.6 小结 ....................................................................................................................21 第三章 在生理上选取耳垂部位进行血糖测量的可行性研究 ...........22 3.1 耳垂和指尖、手掌、前臂测量部位的生理特征比较 ...................................22 3.1.1 人体皮肤分层及皮下组织的解剖结构介绍......................................22 3.1.2 指尖、手掌、前臂和耳垂的皮肤分层结构......................................23 3.2 耳垂内毛细血管全血和前臂内静脉全血的葡萄糖浓度关系 .......................27 3.3 OGTT 中耳垂和指尖测量部位的血糖浓度的变化过程比较.........................28 3.4 OGTT 中耳垂和前臂内侧测量部位的血糖浓度的变化过程比较.................29 3.5 对耳垂测量部位进行血糖测量的可行性评价 ...............................................30 3.6 小结 ...................................................................................................................30 第四章 基于蒙特卡洛模拟方法的对耳垂的近红外光谱特性的仿真研 究 ..............................................................................................................31 4.1 耳垂位置浮动基准点的存在特性研究 ...........................................................31 4.1.1 耳垂皮肤五层模型下对漫反射光强的蒙特卡洛模拟......................31 4.1.2 耳垂部位的个体差异对浮动基准点的影响模拟..............................32 4.2 耳垂部位对透射光强的蒙特卡洛模拟 ............................................................34 4.2.1 耳垂的透射光强的分布规律...............................................................34 4.2.2 耳垂的透射光强与漫反射光强的比较...............................................35 4.2.3 耳垂部位个体差异对透射光强的影响...............................................36 4.3 耳垂部位在人体血糖浓度范围内的蒙特卡洛模拟 .......................................37 4.4 小结 ....................................................................................................................38第五章 基于耳垂测量部位无创血糖检测精度的模拟分析及实验研究 ..................................................................................................................39 5.1 耳垂测量部位基于位置浮动基准点的光谱修正方法 ....................................39 5.2 利用耳垂透射光对葡萄糖浓度的预测精度的影响评价 ................................41 5.3 耳垂测量部位基于位置浮动基准点光谱修正方法的实验研究 ....................43 5.4 小结 .............................