National Taiwan University, Graduate Institute of Biomedical Electronics and Bioinformatics, Taipei, Taiwan.
J Biomed Opt. 2010 Jan-Feb;15(1):015007. doi: 10.1117/1.3324838.
Reflectance spectra measured from epithelial tissue have been used to extract size distribution and refractive index of cell nuclei for noninvasive detection of precancerous changes. Despite many in vitro and in vivo experimental results, the underlying mechanism of sizing nuclei based on modeling nuclei as homogeneous spheres and fitting the measured data with Mie theory has not been fully explored. We describe the implementation of a three-dimensional finite-difference time-domain (FDTD) simulation tool using a Gaussian pulse as the light source to investigate the wavelength-dependent characteristics of backscattered light from a nuclear model consisting of a nucleolus and clumps of chromatin embedded in homogeneous nucleoplasm. The results show that small-sized heterogeneities within the nuclei generate about five times higher backscattering than homogeneous spheres. More interestingly, backscattering spectra from heterogeneous spherical nuclei show periodic oscillations similar to those from homogeneous spheres, leading to high accuracy of estimating the nuclear diameter by comparison with Mie theory. In addition to the application in light scattering spectroscopy, the reported FDTD method could be adapted to study the relations between measured spectral data and nuclear structures in other optical imaging and spectroscopic techniques for in vivo diagnosis.
从上皮组织测量的反射光谱被用于提取细胞核的大小分布和折射率，以进行癌前病变的非侵入性检测。尽管有许多体外和体内实验结果，但基于将细胞核建模为均匀球体并使用 Mie 理论拟合测量数据来确定细胞核大小的基本原理尚未得到充分探索。我们描述了一种使用高斯脉冲作为光源的三维有限差分时域（FDTD）模拟工具的实现，以研究由嵌入在均匀核质中的核仁核和染色质团组成的核模型的光后向散射的波长依赖性特征。结果表明，核内的小尺寸非均匀性会产生比均匀球体高约五倍的后向散射。更有趣的是，来自非均匀球形核的后向散射光谱显示出类似于均匀球体的周期性振荡，从而导致通过与 Mie 理论比较来估计核直径的高度准确性。除了在光散射光谱学中的应用外，所报道的 FDTD 方法还可以适应于研究在其他光学成像和光谱技术中测量的光谱数据与核结构之间的关系，用于体内诊断。
