Abstract

Detecting early‐stage epithelial cancers and their precursor lesions are challenging as lesions could be subtle and focally or heterogeneously distributed over large mucosal areas. Optical coherence tomography (OCT) that enables wide‐field imaging of subsurface microstructures in vivo is a promising screening tool for epithelial diseases. However, its diagnostic capability has not been fully appreciated since the optical reflectance contrast is poorly understood. We investigated the back‐scattered intensities from clustered or packed nanometer scale intracellular scatterers using finite‐difference time‐domain method and 1‐μm resolution form of OCT, and uncovered that there existed correlations between the reflectance contrasts and the ultrastructural clustering or packing states of these scatterers, which allows us to interpret the physiological state of the cells. Specifically, both polarized goblet cells and foveolar cells exhibited asymmetric reflectance contrast, but they could be differentiated by the optical intensity of the mucin cup due to the different ultrastructural make‐ups of the mucin granules; keratinocytes could demonstrate varied cytoplasmic intensity and their cytoplasmic contrast was closely correlated with the packing state of keratin filaments. Further preliminary study demonstrated that these new understandings of OCT image contrast enables the characterization of precancerous lesions, which could complement the current morphology‐based criteria in realizing “virtual histology” and would have a profound impact for the screening and surveillance of epithelial cancers.

Highlights

  • Epithelial cancers rank in the leading causes of mortality worldwide.[1,2,3] detecting cancers at their early or precancerous stages is associated with favorable prognosis, it remains a major challenge in routine clinical practice

  • We firstly developed back-scattering models of mucin granules (Supporting Information Figure 1), microvilli (Supporting Information Figure 2), and keratin filaments (Supporting Information Figure 3) using the finite-difference time-domain (FDTD) method according to transmission electron microscopic (TEM) images and previously published data (Table 1)

  • In μOCT images of swine squamous epithelia (SSE) with different degree of keratinization, we found that the cytoplasmic optical intensity of keratinocytes was associated with the packing states of intracellular keratin filaments: cells presenting bright cytoplasm had filaments that were closely packed into bundles; those demonstrating relatively low intensity contained filaments that were loosely dispersed within cytoplasm (Figures 5–7)

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Summary

| INTRODUCTION

Epithelial cancers rank in the leading causes of mortality worldwide.[1,2,3] detecting cancers at their early or precancerous stages is associated with favorable prognosis, it remains a major challenge in routine clinical practice In most cases, these early-stage lesions are difficult to be recognized by the eye[4,5,6,7] and can be focally and heterogeneously distributed over a large mucosal area.[5,6,8,9] biopsies often have to be randomly performed on multiple portions of the mucosa, with the hope of sampling changes of particular clinical relevance, which is frequently missed.[5,6,10] Histological analysis of stained, thin sections from resected materials remains the gold standard for a definitive diagnosis, where contrast agents are adopted to highlight structures of interest with clear understandings on the underlying mechanistic chemistry of staining. We further validate the feasibility of the improved understandings on the optical reflectance contrast of epithelial cells for real-time characterization of epithelial cancers and their precursors

| RESULTS
| DISCUSSION
| MATERIALS AND METHODS
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