本文選題：多光子顯微技術(shù) + 二次諧波產(chǎn)生�。� 參考：《福建師范大學(xué)》2016年博士論文

【摘要】：乳腺癌是最常見(jiàn)的女性惡性腫瘤,對(duì)女性的健康和生存構(gòu)成了重大的威脅�！霸缭\斷,早治療”是降低乳腺癌死亡率、提高患者生活質(zhì)量的最有效的手段,但目前的臨床診斷技術(shù)分辨率一般都為“毫米”量級(jí),無(wú)法在細(xì)胞水平上早期評(píng)估乳腺疾病的病理狀態(tài)。因此,探索面向臨床的具有組織病理學(xué)的高分辨率的原位無(wú)損診斷的新方法新技術(shù),對(duì)乳腺腫瘤的早期識(shí)別診斷具有重大的意義。近年來(lái),多光子顯微技術(shù)在早期腫瘤診療方面呈現(xiàn)了很強(qiáng)的可行性和廣闊的應(yīng)用前景,該技術(shù)具有高空間分辨成像、低細(xì)胞損傷、大成像深度等優(yōu)點(diǎn),能夠在細(xì)胞水平上對(duì)生物組織進(jìn)行成像,獲得生物組織的形態(tài)結(jié)構(gòu)和光譜信息。本論文中,我們主要是進(jìn)行基于多光子顯微技術(shù)的乳腺腫瘤早期識(shí)別的研究。首先為了實(shí)現(xiàn)乳腺腫瘤和非腫瘤性疾病的鑒別診斷,本論文應(yīng)用多光子顯微技術(shù)對(duì)正常乳腺組織和幾種常見(jiàn)乳腺非腫瘤性疾病進(jìn)行成像研究,結(jié)果表明：(1)正常乳腺組織中的脂肪細(xì)胞、乳腺導(dǎo)管中的腺上皮細(xì)胞和肌上皮細(xì)胞、血管等都具有較強(qiáng)的雙光子激發(fā)熒光信號(hào),而乳腺結(jié)締組織中的膠原纖維和導(dǎo)管基底膜則具有較強(qiáng)的二次諧波信號(hào),這使得多光子顯微技術(shù)能夠高分辨識(shí)別乳腺組織中的不同結(jié)構(gòu)成份；(2)多光子顯微技術(shù)能夠區(qū)分不同的乳腺非腫瘤性疾病,包括乳腺纖維腺瘤、乳腺增生和乳腺囊腫,并能夠提取膠原纖維的密度和方向、腺泡的周長(zhǎng)等光學(xué)診斷參數(shù),用于定量識(shí)別診斷乳腺非腫瘤性疾病。此部分的相關(guān)成果發(fā)表在Journal of Microscopy,258(1),79-85,2015(SCI收錄,IF=2.3)、Proceedings of SPIE,9230, 9230N-1.2014(EI收錄)上。其次,本論文應(yīng)用多光子顯微技術(shù)對(duì)兩種常見(jiàn)的乳腺腫瘤(乳腺導(dǎo)管原位癌和浸潤(rùn)性乳腺導(dǎo)管癌)進(jìn)行成像研究,結(jié)果表明：(1)多光子顯微技術(shù)不僅可以識(shí)別這兩種常見(jiàn)的乳腺腫瘤,還能區(qū)分乳腺導(dǎo)管原位癌的病理類(lèi)型(包括篩型和實(shí)性型)和浸潤(rùn)性乳腺癌的浸潤(rùn)級(jí)別(包括低級(jí)別浸潤(rùn)性癌和高級(jí)別浸潤(rùn)性癌)；(2)多光子顯微技術(shù)可以提取氧化還原比(NADH與FAD的比值)、細(xì)胞核面積和膠原纖維密度等參數(shù)指標(biāo),用于定量識(shí)別診斷乳腺腫瘤性疾病。此部分的相關(guān)成果發(fā)表在Journal of Physics D:Applied Physics,48,405401,2015(SCI收錄,IF=2.7)、Lasers inMedical Science,30,1109-1115,2015(SCI收錄,IF=2.5)上。然后,本論文應(yīng)用多光子顯微技術(shù)對(duì)乳腺腫瘤發(fā)展的不同階段進(jìn)行深入地研究,結(jié)果表明該技術(shù)可以監(jiān)測(cè)乳腺導(dǎo)管癌從正常乳腺導(dǎo)管—非浸潤(rùn)性乳腺導(dǎo)管癌—浸潤(rùn)性乳腺導(dǎo)管癌的整個(gè)發(fā)展過(guò)程,同時(shí)還能觀察到整個(gè)發(fā)展過(guò)程中細(xì)胞核面積、膠原含量及導(dǎo)管基底膜周長(zhǎng)的增減差異,這些差異可用于定量區(qū)分乳腺腫瘤發(fā)展的不同階段。此部分的相關(guān)成果發(fā)表在Journal of Biomedical Optics,20(9),096007,2015(SCI收錄,IF=2.8)、Proceedings of SPIE,9303,93032P,2015(EI收錄)上。最后,我們應(yīng)用多光子顯微技術(shù)對(duì)腋窩淋巴結(jié)進(jìn)行成像研究,對(duì)乳腺腫瘤細(xì)胞在腋窩淋巴結(jié)中的轉(zhuǎn)移情況進(jìn)行評(píng)估,分析陰性淋巴結(jié)和陽(yáng)性淋巴結(jié)的不同成像特征,為淋巴結(jié)的病理評(píng)估提供新技術(shù)新方法。此部分的相關(guān)論文"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�？傊�,通過(guò)本論文的研究工作,開(kāi)拓了基于多光子顯微技術(shù)的乳腺腫瘤早期識(shí)別、乳腺腫瘤發(fā)展進(jìn)程實(shí)時(shí)監(jiān)測(cè)、乳腺腫瘤細(xì)胞淋巴結(jié)轉(zhuǎn)移評(píng)估的研究,并取得了一些創(chuàng)新性的成果,為多光子顯微技術(shù)最終發(fā)展成為臨床上“實(shí)時(shí)”、“無(wú)損”、“原位”診斷乳腺腫瘤和評(píng)估腫瘤的發(fā)展?fàn)顟B(tài)提供可靠的數(shù)據(jù)基礎(chǔ)。
[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.
【學(xué)位授予單位】：福建師范大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2016
【分類(lèi)號(hào)】：R737.9

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