Abstract

.Phase and polarization of coherent light are highly perturbed by interaction with microstructural changes in premalignant tissue, holding promise for label-free detection of early tumors in endoscopically accessible tissues such as the gastrointestinal tract. Flexible optical multicore fiber (MCF) bundles used in conventional diagnostic endoscopy and endomicroscopy scramble phase and polarization, restricting clinicians instead to low-contrast amplitude-only imaging. We apply a transmission matrix characterization approach to produce full-field en-face images of amplitude, quantitative phase, and resolved polarimetric properties through an MCF. We first demonstrate imaging and quantification of biologically relevant amounts of optical scattering and birefringence in tissue-mimicking phantoms. We present an entropy metric that enables imaging of phase heterogeneity, indicative of disordered tissue microstructure associated with early tumors. Finally, we demonstrate that the spatial distribution of phase and polarization information enables label-free visualization of early tumors in esophageal mouse tissues, which are not identifiable using conventional amplitude-only information.

Highlights

  • White-light endoscopy is the standard-of-care for inspecting large areas of the gastrointestinal (GI) tract and lung for premalignant change and cancer.[1]

  • Applying a recently reported[27] transmission matrix (TM) characterization architecture for multicore fiber (MCF), we show that quantitative phase- and polarization-resolved images can be obtained in transmission mode from tissue-mimicking phantoms that, respectively, contain physiologically relevant concentrations of optical scatterers and birefringent materials

  • We exploited a novel TM characterization architecture to enable wide-field imaging of quantitative phase- and polarizationresolved properties of biological samples through a flexible MCF bundle (FIGH-06-350G, Fujikura; length of 2 m, 6000 cores, core diameter of ∼2.9 μm, core spacing of 4.4 μm, and outer diameter of 350 Æ 20 μm)

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Summary

Introduction

White-light endoscopy is the standard-of-care for inspecting large areas of the gastrointestinal (GI) tract and lung for premalignant change (dysplasia) and cancer.[1] For example, Barrett’s esophagus is an acquired metaplastic condition that predisposes patients to the development of esophageal adenocarcinoma. The cancer risk for Barrett’s patients increases significantly in the presence of premalignant transformation (dysplasia), up to more than 30% per year.[1] Early identification of dysplasia enables curative intervention through simple endoscopic resection or radiofrequency ablation.[2] the current surveillance procedure uses white-light endoscopy combined with random biopsy, which together show only 40% to 64% sensitivity for dysplasia, leading to high miss rates.[3] The 5-year survival rate for esophageal cancer is only 15%, yet can be as high as 80% when patients are diagnosed with early-stage disease,[3] improvements in endoscopic early detection methodologies are urgently needed.

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