Assessment of internal refractive index profile of stochastically inhomogeneous nuclear models via analysis of two-dimensional optical scattering patterns

Significance: 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. Aim: We perform a systematic analysis to elucidate how changes in internal refractive index profile of cell nuclei can best be detected via optical scattering. Approach: 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. Results: 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. Conclusions: 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.