Middle East Technical University, Northern Cyprus Campus, Physics Group, Kalkanli, Turkey.
British Columbia Cancer Research Center, Department of Integrative Oncology, Imaging Unit, Vancouver, Canada.
J Biomed Opt. 2021 May;26(5). doi: 10.1117/1.JBO.26.5.055001.
Optical scattering signals obtained from tissue constituents contain a wealth of structural information. Conventional intensity features, however, are mostly dictated by the overall morphology and mean refractive index of these constituents, making it very difficult to exclusively sense internal refractive index fluctuations.
We perform a systematic analysis to elucidate how changes in internal refractive index profile of cell nuclei can best be detected via optical scattering.
We construct stochastically inhomogeneous nuclear models and numerically simulate their azimuth-resolved scattering patterns. We then process these two-dimensional patterns with the goal of identifying features that directly point to subnuclear structure.
Azimuth-dependent intensity variations over the side scattering range provide significant insights into subnuclear refractive index profile. A particular feature we refer to as contrast ratio is observed to be highly sensitive to the length scale and extent of refractive index fluctuations; further, this feature is not susceptible to changes in the overall size and mean refractive index of nuclei, thereby allowing for selective tracking of subnuclear structure that can be linked to chromatin distribution.
Our analysis will potentially pave the way for scattering-based assessment of chromatin reorganization that is considered to be a key hallmark of precancer progression.
从组织成分中获得的光散射信号包含了丰富的结构信息。然而,传统的强度特征主要由这些成分的整体形态和平均折射率决定,因此很难专门感知内部折射率波动。
我们进行了系统的分析,以阐明如何通过光散射最好地检测细胞核内部折射率分布的变化。
我们构建了随机非均匀核模型,并对其进行了数值模拟,以获得它们的方位分辨散射模式。然后,我们处理这些二维模式,以确定直接指向亚核结构的特征。
侧向散射范围内的方位角依赖强度变化为亚核折射率分布提供了重要的见解。我们观察到一个称为对比度比的特定特征对折射率波动的长度尺度和程度非常敏感;此外,这个特征不受核的整体大小和平均折射率变化的影响,从而允许选择性地跟踪与染色质分布相关的亚核结构。
我们的分析将为基于散射的染色质重排评估铺平道路,这被认为是癌症前进展的关键标志之一。