Investigating the spectral characteristics of backscattering from heterogeneous spherical nuclei using broadband finite-difference time-domain simulations

Abstract

Abstract. 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 finitedifference time-domain ͑FDTD͒ 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.

Investigating the backscattering characteristics of individual normal and cancerous cells based on experimentally determined three-dimensional refractive index distributions

“…The former was found to be the dominant factor as verified with FDTD simulations. The results of the present study are consistent with the results of former studies [2,[9][10][11][12].…”

“…After obtaining 3D RI distributions of living cells, we utilized a 3D FDTD code developed by our group [9] to investigate the angular and spectral light scattering patterns of cells. A perfectly matching layer (PML) absorbing boundary condition was implemented for suppressing artificial reflections.…”

“…One powerful technique to address the limitations of Mie theory and T-matrix methods is finite-difference time-domain (FDTD) method which provides numerical solutions to Maxwell's equations through discretization of the electric and magnetic fields in both time and spatial domains and which allows arbitrary geometry and RI distributions of the objects to be modeled [2,9]. This technique provides accurate light scattering information of modeled scatterers and has been used to investigate light scattering properties of cells.…”

“…The FDTD method requires three-dimensional (3D) RI of the object. In previous studies the sizes and shapes of cells and nuclei in simulated cell models have been obtained from images measured by conventional 3D microscopy such as confocal microscopy or from images of tissue sections for histopathological examination, and the RI values have been assigned randomly according to prior knowledge on RI values and spatial distributions in cells [2,[9][10][11][12]. Due to lack of appropriate microscopy techniques quantitative 3D RI information of cells was not available in these previous studies and hence the constructed cell models were different from the actual cellular structures.…”

Generalized multiparticle Mie modeling of light scattering by cells

“…For decades, light scattering from single cells has been investigated in many scientific and research literatures [9][10][11][12][13]. Dunn et al [9] employed the finite-difference time-domain (FDTD) method to simulate light scattering from a single uniform cell for the first time.…”