Label-free imaging approaches seek to simplify and augment histopathologic assessment by replacing the current practice of staining by dyes to visualize tissue morphology with quantitative optical measurements. Quantitative phase imaging (QPI) operates with visible/UV light and thus provides a resolution matched to current practice. Here we introduce and demonstrate confocal QPI for label-free imaging of tissue sections and assess its utility for manual histopathologic inspection. Imaging cancerous and normal adjacent human breast and prostate, we show that tissue structural organization can be resolved with high spatial detail comparable to conventional hematoxylin and eosin (H&E) stains. Our confocal QPI images are found to be free of halo, solving this common problem in QPI. We further describe a virtual imaging system based on finite-difference time-domain (FDTD) calculations and combine it with numerical tissue phantoms to quantitatively show the absence of halo and the improved clarity in resolving subcellular features with confocal QPI compared to wide-field QPI. Confocal QPI bears the potential to become a common tool for label-free disease diagnosis, while the presented FDTD method provides a flexible platform to evaluate the diagnostic potential of QPI methods.

中文翻译：

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共聚焦相显微镜对组织形态的高分辨率无标记成像

无标记成像方法试图通过替代当前的染料染色方法，以定量光学测量可视化组织形态，从而简化和增强组织病理学评估。定量相位成像（QPI）在可见/紫外光下运行，因此提供了与当前实践相匹配的分辨率。在这里，我们介绍并演示了用于组织切片无标签成像的共聚焦QPI，并评估了其用于手动组织病理学检查的效用。成像癌和正常人的乳房和前列腺癌，我们显示组织结构组织可以与传统的苏木精和曙红（H＆E）染色相媲美的高空间细节得以解决。发现我们的共焦QPI图像没有光晕，从而解决了QPI中的这一常见问题。我们进一步描述了基于有限差分时域（FDTD）计算的虚拟成像系统，并将其与数字组织体模相结合以定量显示不存在光晕，并且与宽场QPI相比，共聚焦QPI解决亚细胞特征的清晰度更高。共聚焦QPI有望成为无标签疾病诊断的通用工具，而本文提出的FDTD方法提供了灵活的平台来评估QPI方法的诊断潜力。