Abstract

This study investigates the hypothesis that structured light reflectance imaging with high spatial frequency patterns [Formula: see text] can be used to quantitatively map the anisotropic scattering phase function distribution [Formula: see text] in turbid media. Monte Carlo simulations were used in part to establish a semi-empirical model of demodulated reflectance ([Formula: see text]) in terms of dimensionless scattering [Formula: see text] and [Formula: see text], a metric of the first two moments of the [Formula: see text] distribution. Experiments completed in tissue-simulating phantoms showed that simultaneous analysis of [Formula: see text] spectra sampled at multiple [Formula: see text] in the frequency range [0.05-0.5] [Formula: see text] allowed accurate estimation of both [Formula: see text] in the relevant tissue range [0.4-1.8] [Formula: see text], and [Formula: see text] in the range [1.4-1.75]. Pilot measurements of a healthy volunteer exhibited [Formula: see text]-based contrast between scar tissue and surrounding normal skin, which was not as apparent in wide field diffuse imaging. These results represent the first wide-field maps to quantify sub-diffuse scattering parameters, which are sensitive to sub-microscopic tissue structures and composition, and therefore, offer potential for fast diagnostic imaging of ultrastructure on a size scale that is relevant to surgical applications.

Highlights

  • Light scattering in biological tissue is a complex process that occurs as photons traverse index of refraction mismatches along their propagation path

  • The index mismatches are associated with tissue morphology and cellular ultrastructure

  • While scatter remission spectra are sensitive to biological structure and morphology, the biological information that is encoded in collected spectra is dependent on the light transport regime that is sampled

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Summary

Introduction

Light scattering in biological tissue is a complex process that occurs as photons traverse index of refraction mismatches along their propagation path. The index mismatches are associated with tissue morphology (e.g. cytoskeletal arrangement) and cellular ultrastructure (e.g. size and shape of nucleus, mitochondria, other cytoplasmic organelles). Measurements of scattering remission spectra have shown sensitivity to sub-cellular morphological changes in biological tissue [1,2,3,4,5,6,7,8]; these observations support the use of scattering as an endogenous and label-free contrast mechanism to differentiate between tissue types [8, 9]. While scatter remission spectra are sensitive to biological structure and morphology, the biological information that is encoded in collected spectra is dependent on the light transport regime that is sampled. Scattering interactions between photons and tissue can be described by a basic set of parameters including the frequency of scattering events, given by the scattering coefficient (μs ) , the probability of scattering angles, defined by the scattering phase function ( P (θs )) , and the average scatter direction, given by the first moment of the

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