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.

中文翻译：

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了解光学反射对比度以实时表征上皮前体病变。

检测早期上皮癌及其前驱病变具有挑战性，因为病变可能很微妙，局灶性或不均匀地分布在大面积的粘膜区域。光学相干断层扫描（OCT）能够对体内表面下微结构进行宽视场成像，是一种很有前景的上皮疾病筛查工具。然而，由于对光学反射对比度知之甚少，其诊断能力尚未得到充分认识。我们使用有限差分时域方法和 OCT 的 1 μm 分辨率形式研究了簇状或堆积的纳米级细胞内散射体的背向散射强度，发现反射对比度与细胞内超微结构簇状或堆积状态之间存在相关性。这些散射体使我们能够解释细胞的生理状态。具体来说，偏振杯状细胞和小凹细胞都表现出不对称的反射对比度，但由于粘蛋白颗粒的超微结构组成不同，它们可以通过粘蛋白杯的光强度来区分；角质形成细胞可以表现出不同的细胞质强度，其细胞质对比度与角蛋白丝的堆积状态密切相关。进一步的初步研究表明，这些对OCT图像对比度的新认识能够对癌前病变进行表征，这可以补充当前基于形态学的标准，实现“虚拟组织学”，并对上皮癌的筛查和监测产生深远的影响。