Nonlinear Optics with Near-Infrared Excitation Enable Real-Time Quantitative Diagnosis of Human Cervical Cancers
Nonlinear Optics with Near-Infrared Excitation Enable Real-Time Quantitative Diagnosis of Human Cervical Cancers
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DOI：
10.1158/0008-5472.can-20-0348
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发表时间：
2020-09-01
期刊：
影响因子：
11.2
通讯作者：
Ishii, Masaru
中科院分区：
文献类型：
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作者：
Matsui, Takahiro;Tamoto, Ryo;Ishii, Masaru
通过活组织检查进行组织学分析是评估恶性肿瘤的最有用的方法之一。然而，分析的某些方面，如侵入性，评估范围，从活检到报告的周转时间可以改进。在这里，我们报告了一种新的方法，可视化人类宫颈组织的三维，没有活检，固定，或染色，并具有足够的质量为组织学诊断。采用近红外激发和非线性光学技术，通过三次谐波产生（THG）和二次谐波产生（SHG）构建图像来可视化未染色的人子宫颈上皮组织。在使用深度学习进行图像分析后，THG图像能够以六个参数的定量方式评估核形态。还可以基于SHG图像和另一种深度学习分析来定量评估上皮内纤维化变化。单独使用每种分析方法，以AUC>= 0.92对正常和癌组织进行定量分类。此外，利用机器学习算法对THG和SHG图像进行组合分析，可以对正常组织、上皮内瘤变和浸润性癌的三维图像文件进行准确分类，加权kappa系数为0.86。我们的方法使实时非侵入性诊断宫颈病变，从而构成一个潜在的工具，大大改变早期detection.Significance：这项研究提出了一种新的方法，用于诊断癌症使用非线性光学，这使得可视化的活组织的组织学特征，而不需要任何活检或染色染料。
Histopathologic analysis through biopsy has been one of the most useful methods for the assessment of malignant neoplasms. However, some aspects of the analysis such as invasiveness, evaluation range, and turnaround time from biopsy to report could be improved. Here, we report a novel method for visualizing human cervical tissue three-dimensionally, without biopsy, fixation, or staining, and with sufficient quality for histologic diagnosis. Near-infrared excitation and nonlinear optics were employed to visualize unstained human epithelial tissues of the cervix uteri by constructing images with third-harmonic generation (THG) and second-harmonic generation (SHG). THG images enabled evaluation of nuclear morphology in a quantitative manner with six parameters after image analysis using deep learning. It was also possible to quantitatively assess intraepithelial fibrotic changes based on SHG images and another deep learning analysis. Using each analytical procedure alone, normal and cancerous tissue were classified quantitatively with an AUC >= 0.92. Moreover, a combinatory analysis of THG and SHG images with a machine learning algorithm allowed accurate classification of three-dimensional image files of normal tissue, intraepithelial neoplasia, and invasive carcinoma with a weighted kappa coefficient of 0.86. Our method enables real-time noninvasive diagnosis of cervical lesions, thus constituting a potential tool to dramatically change early detection.Significance: This study proposes a novel method for diagnosing cancer using nonlinear optics, which enables visualization of histologic features of living tissues without the need for any biopsy or staining dye.