摘要
光学相干层析术(Optical Coherence Tomography, OCT)技术是一种全新的成像模式,它可以对生物组织等实现非侵入式、高分辨率、高灵敏度和实时的截面层析成像,因而有希望在生物医学研究及临床诊断方面实现“光学活检”的功能。本论文就OCT系统的设计、成像性能的拓展及其在生物医学领域的应用等方面开展了研究。
首先,设计搭建了一套光纤型OCT成像实验系统,并结合该系统详细分析了OCT技术的成像分辨率、成像时间、探测灵敏度、成像深度等性能参数,同时给出了系统设计时需要注意的相关事项。实际测得该系统的纵向分辨率为16μm,系统灵敏度为-90dB。然后利用该系统对人体多个部位的皮肤进行了活体成像研究。从获得的图像可以清晰的分辨出角质层(掌趾部位)、表皮层、真皮上层等皮肤结构,从而验证了OCT用于表层皮肤形态结构研究的可行性。
其次,提出了一种利用OCT纵向扫描信号的衰减特性提取生物组织的散射特性参数的方案,该方法是利用OCT模型对不同区域内的纵向扫描信号进行曲线拟合来实现的。在定态聚焦情况下,在对已知散射特性的组织模拟液进行OCT成像之后,对比分析了OCT单次散射模型和多次散射模型在描述不同散射强度样品的OCT信号方面的适用性。根据分析结果对OCT模型进行了修正。最后,利用上述方法获得了老鼠肝脏和人体皮肤各组织层的散射系数,实现了OCT技术的功能性扩展。
再次,提出了利用随机相幅矢量和模型分析对数表示下OCT信号的散斑统计特性,并在不同的聚焦状态下对具有不同散射特性的组织模拟液进行了OCT成像的实验。实验结果与理论分析相吻合,采用对数的形式表示OCT信号以及采用较高数值孔径的显微物镜具有抑制散斑噪声的作用。另外,对数形式下的散斑特性与介质的散射特性之间存在一定的相关性,该相关性为提取生物组织的散射特性提供了一种新的途径。
最后,提出了一种基于Fourier变换以及多项式拟合的方法从OCT信号中的色散项获得生物组织结构与功能的信息。该方法通过对OCT的干涉包络进行Fourier变换,再将得到的相位谱进行多项式拟合以实现色散信息的提取。数值模拟以及相关实验均证明了该方法的可行性。该研究结果不仅有助于实现动态的色散补偿,而且可以用来区分不同的生物组织,以及同一生物组织的不同生理状态等。
Optical coherence tomography (OCT) is a fundamentally new type of optical imaging modality, which performs non-invasive, high-resolution, high sensitivity, high speed, cross-sectional tomographic imaging, and enables "optical biopsy". The work is focused on the design of OCT system, the analysis of its performance, and the exploration of OCT application in biomedical areas.
First of all, an experimental OCT system was designed. The fundamental laws governing the resolution, imaging time, sensitivity, and imaging depth of OCT were analyzed in detail, and the related design notes were given out. Finally,16μm axial resolution and-90 dB detection sensitivity was obtained. With the OCT system, we investigated the morphologic structure of in vivo skin in several locations. Structures of the stratum corneum (plamoplantar), the epidermis, and the upper dermis can be distinguished from the obtained cross-sectional images. Therefore, it was demonstrated that OCT is a feasible method for investigation of morphologic structure of superficial layers of human skin.
Second, it was shown that the optical properties of biological tissue can be determined with OCT by fitting a model to the OCT signal from a region of interest. The validity of the single-scattering and multiple-scattering model for both the highly scattering and weakly scattering media was studied using calibrated samples in the fixed focus geometry. According to the experiment results, a proper correction for the confocal properties of the sample arm was presented. Finally, scattering properties of in vitro rat liver and in vivo human skin were obtained.
Third, it was proposed that the statistics properties of the speckle can be discussed theoretically for the OCT signals in the logarithmic scale with the random phasor sum theorem. In the experiments, OCT signals of tissue phantoms with different scattering properties were analyzed under two different focusing conditions. It was found that the effect of the speckle noise can be suppressed by displaying OCT images in the logarithmic scale and using the objective lens with higher numerical aperture. It was also demonstrated that the speckle properties is correlated with the scattering properties of the tested sample, which may provide a new way to characterize the scattering properties of biological tissue.
Finally, it was found that a method based on the Fourier transform and the polynomial fit can be used to extract the information about the structure and function of bio-tissues from the dispersion signal in OCT. The interferogram envelope in OCT was Fourier transformed to the frequency domain, and then the second order dispersion information was obtained by performing a polynomial fit to the phase spectrum. Theoretical simulation and experimental data validated the method. The obtained results in this work not only can be used for the dynamical dispersion compensation, but also provide a way to characterize different tissues, and different physiological conditions.
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