生物组织光学断层成像与光学参数提取方法研究
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摘要
生物组织光学参数与组织成份、结构和健康状态直接相关,对组织光学参数进行非接触、快速、准确的在体测量具有重要的意义。光学相干层析成像(OCT)技术具有非侵入、高分辨、高动态范围的优点,在组织光学参数检测应用中具有很高的研究价值。本文对OCT系统特性进行了理论分析、数值模拟和实验验证,并在此基础上探讨了光学参数提取的可行性和具体方法。
首先讨论了OCT系统的原理和信号特征,分析了快速扫描延迟线的光学系统结构和色散特性；使用扩展惠更斯-菲涅耳原理对OCT系统进行了噪声分析,并对具有不连续层状结构的样本最大探测深度进行了讨论；实验中利用组织模拟液对理论方法进行了验证。
建立了基于快速扫描延迟线的时域OCT系统,可以实现100线/s以上的扫描频率和2 mm以上的扫描光程。系统采用光纤迈克尔逊干涉结构,使用1550 nm光源,纵向分辨率14 gm,并成功对实际生物组织进行了层析成像实验。对于系统可能存在的色散问题,研究并设计了通过数值变换进行色散补偿的方法,对于水或者快速扫描延迟线产生的色散成功进行了二阶和三阶色散补偿。使用OCT系统实现了透明和浑浊物质折射率的精确测量。
系统的讨论了光在生物组织中的传输特性,考虑到OCT系统的光学结构,我们进行了有针对性的理论分析。第一步,建立了聚焦光束的数学模型,使用单页双曲线模拟入射光束分布,精确地模拟了入射光的初始状态；第二步,使用蒙特卡洛方法对OCT信号进行了数值模拟。对光子传输光程过程、出射位置、能量状态以及在干涉平面上的分布进行了追踪统计,实现了OCT系统的数值模拟。在此基础上研究了OCT信号与散射系数、吸收系数以及散射相函数(各向异性因子)之间的依赖关系。对各种参数样品的模拟结果进行了系统分析,确定了吸收系数、散射系数和各向异性因子对纵向干涉信号衰减方式的影响。在此基础上,提出了基于比例缩放的压缩算法,有效提高了数值模拟的效率,并在此基础上实现了快速反向蒙特卡洛运算。
应用最优化理论,结合最小二乘法和快速蒙特卡洛运算实现了从OCT信号中提取样品散射和吸收系数。在积累大量蒙特卡洛模拟数据的基础上,使用前馈人工神经网络同样实现了光学参数的拟合求解。实验中,主要使用组织模拟液IntralipidTM(英脱利匹特,脂肪乳注射剂)和印度墨水配置不同光学参数样品。在进行OCT干涉测量后,拟合求解了光学参数。对含糖模拟液和牛奶制品也进行了相同的实验测量,结果验证了参数提取方法的可行性。实验验证了NaCK、KCl以及葡萄糖浓度对折射率的影响,通过实验验证了葡萄糖浓度的变化对溶液散射和吸收系数会产生影响,这对于血糖的无损测量具有重要意义。论文最后讨论了进一步完善理论和实验方法的设想。
The optical properties of biomedical tissues clearly relate with ingredients, structure and status of human health. Optical Coherence Tomography (OCT) is an imaging technologies with noninvasive property, high resolution and high dynamic range. This technology is of great value for measuring optical parameters of turbid materials, such as tissues. In this thesis, the basic theories of OCT have been researched. The signal of OCT system is simulated by Monte Carlo numerical algorithm. The paper also discusses the possibility of reconstruction of optical parameter of turbid samples by OCT system. Verification based on experiment has been presented. This thesis makes research on the following aspects.
First and foremost, the principle and signal characteristics were explained and discussed. Derivative process for the dispersion properties of rapid scanning optical delay line (RSOD) was given out in detail. The extended Huygens-Fresnel principle is quoted for analyzing signal to noise ratio and maximum probing depth in turbid samples. Theoretical conclusions have been verified by experiments in phantom liquid sample.
A time-domain OCT system has been build up with RSOD for tissue measurement with 1550 nm optical source. The system could execute depth scanning at speed of 100 times per second with resolution of 14μm and maximum probing depth of 2 mm. We performed numerical dispersion compensation for water and RSOD up to the second order. The refractive index of transparent and turbid liquid was measured by OCT accurately.
We analyzed transformation of photon in a systematic way with consideration of optical scheme. The geometry model of focused optical beam was established by describing with myriads of hyperboloids of one sheet. The initial status of photons can be determined in accordance to Gaussian distribution the way a focused beam performs. OCT signals were simulated by means of Monte Carlo and the propagating trajectory, weight and position on correlate plane of each photon will be recorded. With assistant of Monte Carlo simulation, the relationship of OCT signal and optical parameters was revealed by adding up effects of a large number of photons. Numerical results have presented relation of signal intensity and depth of target layer with different scattering coefficient, absorption coefficient and anisotropy parameter. A condensed method based on scaling path and weight of photons was introduced to accelerating simulation procedure, which makes the fast inverse Monte Carlo reality.
A new algorithm of measuring optical parameters of turbid material was put forward by OCT system and depth dependent signals. The method is a inverse process of Monte Carlo and reconstruction of parameters by optimization methods or artificial neural networks. Liquid mixture of IntralipidTM and India ink was measured and analyzed by inverse Monte Carlo. IntralipidTM with glucose and milk were also used as samples. The influence of NaCl, KCl and glucose on refractive index of liquid is measured by OCT system. Results of experiments show that the degrading speed of OCT signal is sensitive with concentration of fat, color agent and glucose. These ingredients change scattering or absorption properties of turbid phantoms. Some suggestions about theory and experiment were put forward at the end of this thesis.
首先讨论了OCT系统的原理和信号特征,分析了快速扫描延迟线的光学系统结构和色散特性；使用扩展惠更斯-菲涅耳原理对OCT系统进行了噪声分析,并对具有不连续层状结构的样本最大探测深度进行了讨论；实验中利用组织模拟液对理论方法进行了验证。
建立了基于快速扫描延迟线的时域OCT系统,可以实现100线/s以上的扫描频率和2 mm以上的扫描光程。系统采用光纤迈克尔逊干涉结构,使用1550 nm光源,纵向分辨率14 gm,并成功对实际生物组织进行了层析成像实验。对于系统可能存在的色散问题,研究并设计了通过数值变换进行色散补偿的方法,对于水或者快速扫描延迟线产生的色散成功进行了二阶和三阶色散补偿。使用OCT系统实现了透明和浑浊物质折射率的精确测量。
系统的讨论了光在生物组织中的传输特性,考虑到OCT系统的光学结构,我们进行了有针对性的理论分析。第一步,建立了聚焦光束的数学模型,使用单页双曲线模拟入射光束分布,精确地模拟了入射光的初始状态；第二步,使用蒙特卡洛方法对OCT信号进行了数值模拟。对光子传输光程过程、出射位置、能量状态以及在干涉平面上的分布进行了追踪统计,实现了OCT系统的数值模拟。在此基础上研究了OCT信号与散射系数、吸收系数以及散射相函数(各向异性因子)之间的依赖关系。对各种参数样品的模拟结果进行了系统分析,确定了吸收系数、散射系数和各向异性因子对纵向干涉信号衰减方式的影响。在此基础上,提出了基于比例缩放的压缩算法,有效提高了数值模拟的效率,并在此基础上实现了快速反向蒙特卡洛运算。
应用最优化理论,结合最小二乘法和快速蒙特卡洛运算实现了从OCT信号中提取样品散射和吸收系数。在积累大量蒙特卡洛模拟数据的基础上,使用前馈人工神经网络同样实现了光学参数的拟合求解。实验中,主要使用组织模拟液IntralipidTM(英脱利匹特,脂肪乳注射剂)和印度墨水配置不同光学参数样品。在进行OCT干涉测量后,拟合求解了光学参数。对含糖模拟液和牛奶制品也进行了相同的实验测量,结果验证了参数提取方法的可行性。实验验证了NaCK、KCl以及葡萄糖浓度对折射率的影响,通过实验验证了葡萄糖浓度的变化对溶液散射和吸收系数会产生影响,这对于血糖的无损测量具有重要意义。论文最后讨论了进一步完善理论和实验方法的设想。
The optical properties of biomedical tissues clearly relate with ingredients, structure and status of human health. Optical Coherence Tomography (OCT) is an imaging technologies with noninvasive property, high resolution and high dynamic range. This technology is of great value for measuring optical parameters of turbid materials, such as tissues. In this thesis, the basic theories of OCT have been researched. The signal of OCT system is simulated by Monte Carlo numerical algorithm. The paper also discusses the possibility of reconstruction of optical parameter of turbid samples by OCT system. Verification based on experiment has been presented. This thesis makes research on the following aspects.
First and foremost, the principle and signal characteristics were explained and discussed. Derivative process for the dispersion properties of rapid scanning optical delay line (RSOD) was given out in detail. The extended Huygens-Fresnel principle is quoted for analyzing signal to noise ratio and maximum probing depth in turbid samples. Theoretical conclusions have been verified by experiments in phantom liquid sample.
A time-domain OCT system has been build up with RSOD for tissue measurement with 1550 nm optical source. The system could execute depth scanning at speed of 100 times per second with resolution of 14μm and maximum probing depth of 2 mm. We performed numerical dispersion compensation for water and RSOD up to the second order. The refractive index of transparent and turbid liquid was measured by OCT accurately.
We analyzed transformation of photon in a systematic way with consideration of optical scheme. The geometry model of focused optical beam was established by describing with myriads of hyperboloids of one sheet. The initial status of photons can be determined in accordance to Gaussian distribution the way a focused beam performs. OCT signals were simulated by means of Monte Carlo and the propagating trajectory, weight and position on correlate plane of each photon will be recorded. With assistant of Monte Carlo simulation, the relationship of OCT signal and optical parameters was revealed by adding up effects of a large number of photons. Numerical results have presented relation of signal intensity and depth of target layer with different scattering coefficient, absorption coefficient and anisotropy parameter. A condensed method based on scaling path and weight of photons was introduced to accelerating simulation procedure, which makes the fast inverse Monte Carlo reality.
A new algorithm of measuring optical parameters of turbid material was put forward by OCT system and depth dependent signals. The method is a inverse process of Monte Carlo and reconstruction of parameters by optimization methods or artificial neural networks. Liquid mixture of IntralipidTM and India ink was measured and analyzed by inverse Monte Carlo. IntralipidTM with glucose and milk were also used as samples. The influence of NaCl, KCl and glucose on refractive index of liquid is measured by OCT system. Results of experiments show that the degrading speed of OCT signal is sensitive with concentration of fat, color agent and glucose. These ingredients change scattering or absorption properties of turbid phantoms. Some suggestions about theory and experiment were put forward at the end of this thesis.
引文
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