Applications of second-harmonic generation imaging microscopy in ovarian and breast cancer.
Applications of second-harmonic generation imaging microscopy in ovarian and breast cancer.
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DOI：
10.4137/pmc.s13214
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发表时间：
2015
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影响因子：
--
通讯作者：
Campagnola PJ
中科院分区：
文献类型：
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作者：
Tilbury K;Campagnola PJ
从这个角度来看，我们讨论了如何使用二次谐波产生（SHG）显微镜的非线性光学技术，大大提高了我们对乳腺癌和卵巢癌的肿瘤微环境（TME）的理解。胶原结构的显著变化与这些上皮癌相关，SHG可以以亚微米分辨率对这些变化进行高灵敏度和特异性成像。这些信息在历史上没有被病理学家利用，但有可能提高诊断和预后能力。我们总结了实用的图像处理工具，分析纤维形态的SHG图像的乳腺癌和卵巢癌在人体组织和动物模型。我们还描述了利用SHG物理基础的方法，这些物理基础在描绘正常和恶性组织中是有效的。首先，我们描述了使用偏振分辨二次谐波产生相关的大分子和超分子结构的指标。二次谐波的相干性和相应的相位匹配过程导致发射方向性（前向到后向），这与亚分辨率纤维组装有关。这些分析比纯粹基于形态学的分析更一般，适用范围更广;然而，它们的计算量更大。将所有这些定量分析结合起来的活体成像技术也正在出现。现在，所有这些技术都可以与快速发展的成像系统小型化相结合，以提供其在临床情况中的应用，包括增强病理分析以及辅助实时手术确定肿瘤边缘。
In this perspective, we discuss how the nonlinear optical technique of second-harmonic generation (SHG) microscopy has been used to greatly enhance our understanding of the tumor microenvironment (TME) of breast and ovarian cancer. Striking changes in collagen architecture are associated with these epithelial cancers, and SHG can image these changes with great sensitivity and specificity with submicrometer resolution. This information has not historically been exploited by pathologists but has the potential to enhance diagnostic and prognostic capabilities. We summarize the utility of image processing tools that analyze fiber morphology in SHG images of breast and ovarian cancer in human tissues and animal models. We also describe methods that exploit the SHG physical underpinnings that are effective in delineating normal and malignant tissues. First we describe the use of polarization-resolved SHG that yields metrics related to macromolecular and supramolecular structures. The coherence and corresponding phase-matching process of SHG results in emission directionality (forward to backward), which is related to sub-resolution fibrillar assembly. These analyses are more general and more broadly applicable than purely morphology-based analyses; however, they are more computationally intensive. Intravital imaging techniques are also emerging that incorporate all of these quantitative analyses. Now, all these techniques can be coupled with rapidly advancing miniaturization of imaging systems to afford their use in clinical situations including enhancing pathology analysis and also in assisting in real-time surgical determination of tumor margins.