Abstract
Localized measurements of scattering in biological tissue provide sensitivity to microstructural morphology but have limited utility to wide-field applications, such as surgical guidance. This study introduces sub-diffusive spatial frequency domain imaging (sd-SFDI), which uses high spatial frequency illumination to achieve wide-field sampling of localized reflectances. Model-based inversion recovers macroscopic variations in the reduced scattering coefficient [Formula: see text] and the phase function backscatter parameter (γ). Measurements in optical phantoms show quantitative imaging of user-tuned phase-function-based contrast with accurate decoupling of parameters that define both the density and the size-scale distribution of scatterers. Measurements of fresh ex vivo breast tissue samples revealed, for the first time, unique clustering of sub-diffusive scattering properties for different tissue types. The results support that sd-SFDI provides maps of microscopic structural biomarkers that cannot be obtained with diffuse wide-field imaging and characterizes spatial variations not resolved by point-based optical sampling.
Highlights
Measurements of light scattering are known to be sensitive to the composition and orientation of cells, intracellular constituents, and the extracellular matrix [1]
This study focuses on a novel alternative that applies subdiffusive spatial frequency domain imaging to achieve localized reflectance sampling over a wide field of view quickly
While γ has been shown to be linearly proportional to the fractal dimension of scatterers in a turbid medium, a deterministic link between the two parameters is complicated by other physical parameters that influence the exact form of the scattering phase function [27]; a concise description of γ may best be as a metric proportional to the length scale of biological scattering features
Summary
Measurements of light scattering are known to be sensitive to the composition and orientation of cells, intracellular constituents, and the extracellular matrix [1]. Diffuse wide-field imaging of tissue exploits a signal dominated by multiply scattered light where the remission at each pixel is representative of an average of long and tortuous photon path lengths covering relatively large volumes (cubic millimeters to cubic centimeters). Reflectance remissions that are collected near the source location are dominated by low-ordered scattered photons, which are sensitive to both the frequency of scattering events and the anisotropic character of the scatterers [2,3,4,5,6]. Under these conditions, the light-transport regime has been termed sub-diffuse. The resulting sub-diffusive parameter maps show clear discrimination of tissue types based on scattering parameters that reflect their microstructural differences
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