基于多光子显微技术的乳腺肿瘤早期识别的研究

发布时间：2018-06-07 20:05

本文选题：多光子显微技术 + 二次谐波产生　；参考：《福建师范大学》2016年博士论文

【摘要】：乳腺癌是最常见的女性恶性肿瘤,对女性的健康和生存构成了重大的威胁。“早诊断,早治疗”是降低乳腺癌死亡率、提高患者生活质量的最有效的手段,但目前的临床诊断技术分辨率一般都为“毫米”量级,无法在细胞水平上早期评估乳腺疾病的病理状态。因此,探索面向临床的具有组织病理学的高分辨率的原位无损诊断的新方法新技术,对乳腺肿瘤的早期识别诊断具有重大的意义。近年来,多光子显微技术在早期肿瘤诊疗方面呈现了很强的可行性和广阔的应用前景,该技术具有高空间分辨成像、低细胞损伤、大成像深度等优点,能够在细胞水平上对生物组织进行成像,获得生物组织的形态结构和光谱信息。本论文中,我们主要是进行基于多光子显微技术的乳腺肿瘤早期识别的研究。首先为了实现乳腺肿瘤和非肿瘤性疾病的鉴别诊断,本论文应用多光子显微技术对正常乳腺组织和几种常见乳腺非肿瘤性疾病进行成像研究,结果表明：(1)正常乳腺组织中的脂肪细胞、乳腺导管中的腺上皮细胞和肌上皮细胞、血管等都具有较强的双光子激发荧光信号,而乳腺结缔组织中的胶原纤维和导管基底膜则具有较强的二次谐波信号,这使得多光子显微技术能够高分辨识别乳腺组织中的不同结构成份；(2)多光子显微技术能够区分不同的乳腺非肿瘤性疾病,包括乳腺纤维腺瘤、乳腺增生和乳腺囊肿,并能够提取胶原纤维的密度和方向、腺泡的周长等光学诊断参数,用于定量识别诊断乳腺非肿瘤性疾病。此部分的相关成果发表在Journal of Microscopy,258(1),79-85,2015(SCI收录,IF=2.3)、Proceedings of SPIE,9230, 9230N-1.2014(EI收录)上。其次,本论文应用多光子显微技术对两种常见的乳腺肿瘤(乳腺导管原位癌和浸润性乳腺导管癌)进行成像研究,结果表明：(1)多光子显微技术不仅可以识别这两种常见的乳腺肿瘤,还能区分乳腺导管原位癌的病理类型(包括筛型和实性型)和浸润性乳腺癌的浸润级别(包括低级别浸润性癌和高级别浸润性癌)；(2)多光子显微技术可以提取氧化还原比(NADH与FAD的比值)、细胞核面积和胶原纤维密度等参数指标,用于定量识别诊断乳腺肿瘤性疾病。此部分的相关成果发表在Journal of Physics D:Applied Physics,48,405401,2015(SCI收录,IF=2.7)、Lasers inMedical Science,30,1109-1115,2015(SCI收录,IF=2.5)上。然后,本论文应用多光子显微技术对乳腺肿瘤发展的不同阶段进行深入地研究,结果表明该技术可以监测乳腺导管癌从正常乳腺导管—非浸润性乳腺导管癌—浸润性乳腺导管癌的整个发展过程,同时还能观察到整个发展过程中细胞核面积、胶原含量及导管基底膜周长的增减差异,这些差异可用于定量区分乳腺肿瘤发展的不同阶段。此部分的相关成果发表在Journal of Biomedical Optics,20(9),096007,2015(SCI收录,IF=2.8)、Proceedings of SPIE,9303,93032P,2015(EI收录)上。最后,我们应用多光子显微技术对腋窝淋巴结进行成像研究,对乳腺肿瘤细胞在腋窝淋巴结中的转移情况进行评估,分析阴性淋巴结和阳性淋巴结的不同成像特征,为淋巴结的病理评估提供新技术新方法。此部分的相关论文"Distinction of tissue types in axillary lymph node histology based on multiphoton microscopy"和"Detection of breast cancer axillary lymph node metastases using multiphoton microscopy"正在整理投稿中。总之,通过本论文的研究工作,开拓了基于多光子显微技术的乳腺肿瘤早期识别、乳腺肿瘤发展进程实时监测、乳腺肿瘤细胞淋巴结转移评估的研究,并取得了一些创新性的成果,为多光子显微技术最终发展成为临床上“实时”、“无损”、“原位”诊断乳腺肿瘤和评估肿瘤的发展状态提供可靠的数据基础。
[Abstract]:Breast cancer is the most common malignant tumor in women, which poses a major threat to the health and survival of women. "Early diagnosis and early treatment" is the most effective means to reduce the mortality of breast cancer and improve the quality of life of the patients. However, the resolution of the current clinical diagnostic techniques is generally "millimeter", which can not be evaluated early in the cell level. To estimate the pathological state of the breast disease. Therefore, a new method and new technique for high resolution in situ nondestructive diagnosis of histopathology is explored. It is of great significance for early diagnosis and diagnosis of breast tumors. In recent years, Ta Hikaruko microtechnology has shown strong feasibility and wide application in the early diagnosis and treatment of tumor. This technique has the advantages of high spatial resolution imaging, low cell damage, large imaging depth and so on. It can imaging biological tissues at the cell level and obtain the morphological structure and spectral information of biological tissues. In this paper, we mainly study the early recognition of breast tumor based on multi photon microscopy. The differential diagnosis of breast tumors and non tumor diseases is presented. This paper studies the imaging of normal breast tissue and several common non tumor diseases by multiphoton microscopy. The results show that: (1) the fat cells in normal mammary tissues, the gland epithelial cells and myoepithelial cells in the mammary ducts, and the blood vessels are all strong. The two-photon excitation of the fluorescence signal, while the collagen fiber and the catheter base membrane in the connective tissue of the mammary gland have a strong two harmonic signal, which makes the multi photon microscopy can distinguish the different structural components in the breast tissue high resolution; (2) multi photon microscopy can distinguish different non tumor diseases of the breast, including the mammary gland. Journal of Microscopy, 258 (1), 79-852015 (SCI, IF=2.3), Proceedings of SPIE, Proceedings of SPIE, 9230, 9230N-1.2, and 9230N-1.2, which can be used to identify the density and direction of collagen fibers, and the perimeter of the acinus. 014 (EI). Secondly, this paper uses multi photon microscopy to study two common breast tumors (breast ductal carcinoma in situ and invasive ductal carcinoma). The results show that: (1) multiphoton microscopy can not only identify the two common breast tumors, but also distinguish the pathological types of breast ductal carcinoma in situ (package). Infiltration grade (including low-grade invasive cancer and high grade invasive cancer) in invasive and invasive breast cancer (including low grade invasive and high grade invasive cancer); (2) multiphoton microscopy can extract the redox ratio (ratio of NADH to FAD), nuclear area and collagen fiber density, for quantitative identification and diagnosis of breast cancer disease. The results are published on Journal of Physics D:Applied Physics, 484054012015 (SCI, IF=2.7), Lasers inMedical Science, 301109-11152015 (SCI, IF=2.5). Then, this paper uses multiphoton microscopy to study the different stages of breast cancer development. The results show that this technique can monitor mammary gland conduction. The difference in cell nuclear area, collagen content and the perimeter of the basilar membrane during the whole development process can be used to distinguish the different stages of the development of breast tumor. The results were published on Journal of Biomedical Optics, 20 (9), 0960072015 (SCI, IF=2.8), Proceedings of SPIE, 930393032P, 2015 (EI). Finally, we applied multiphoton microscopy to imaging axillary lymph nodes, assessing the metastasis of breast tumor cells in the axillary lymph nodes, and analyzing negative lymph nodes. Distinction of tissue types in axillary lymph node histology based on multiphoton. Copy "is in the process of finishing the contribution. In a word, through the research work of this paper, we have opened up the early recognition of breast tumor based on multi photon microscopy, real-time monitoring of the development process of breast tumor, the evaluation of lymph node metastasis of breast tumor cells, and achieved some innovative results, which will be the final development of multiphoton microscopy. The bed provides a reliable data base for real-time, non-destructive, in situ diagnosis of breast tumors and evaluation of tumor development.
【学位授予单位】：福建师范大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R737.9

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