Endogenous optical biomarkers of ovarian cancer evaluated with multiphoton microscopy

Endogenous optical biomarkers of ovarian cancer evaluated with multiphoton microscopy
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DOI:
10.1158/1055-9965.epi-07-0009
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发表时间:
2007-10-01
影响因子:
3.8
通讯作者:
Utzinger, Urs
Utzinger, Urs
中科院分区:
医学3区
文献类型:
--
作者:
Kirkpatrick, Nathaniel D.;Brewer, Molly A.;Utzinger, Urs

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目的:在妇科肿瘤中,卵巢癌居第二位,死亡率最高。目前,尚无准确的卵巢癌早期诊断技术。此外,对这种疾病的早期进展知之甚少。我们成像了来自正常和异常卵巢活检的内源性组织成分的多光子相互作用,这些组织成分在从手术室和显微镜运送过程中保持存活。实验设计:用双光子激发荧光(2PEF)和二次谐波产生(SHG)来评估卵巢表面和基质。高分辨率光学切片图像分析基于2PEF的上皮形态和基于SHG的胶原密度和结构完整性。结果:正常组织表现为均匀的上皮层,间质中胶原结构高度规整,而异常组织表现为不同的上皮细胞,细胞体积较大,胶原结构有明显的定量改变。来自卵巢癌高危患者的样本(基于他们的个人/家族癌症病史)显示出高度不同的细胞氧化还原比率和倾向于癌症样本的胶原结构的变化。结论:这项研究强调了基于定量的胶原结构变化和氧化还原比率估计的可行卵巢活检中内源性信号的差异,这可能有助于提高卵巢癌的检测和进一步的洞察力,特别是在疾病的早期阶段。
Purpose: Among gynecologic cancers, ovarian cancer is the second most common and has the highest mortality. Currently, there is no accurate early diagnostic technique for ovarian cancer. Furthermore, little is understood regarding the early progression of this disease. We have imaged multiphoton interactions of endogenous tissue constituents from normal and abnormal ovarian biopsies that were kept viable during transport from the operating room and microscopy.Experimental Design: The ovarian surface and underlying stroma were assessed with two-photon excited fluorescence (2PEF) and second harmonic generation (SHG). High-resolution, optically sectioned images were analyzed for epithelial morphology based on 2PEF and collagen density and structural integrity based on SHG. Additionally, multiwavelength 2PEF provided an estimation of the cellular redox ratio of epithelial cells.Results: Normal tissue exhibited a uniform epithelial layer with highly structured collagen in the stroma, whereas abnormal tissue exhibited varied epithelium with large cells and substantial quantitative changes to the collagen structure. Samples from patients at high risk for developing ovarian cancer (based on their personal/family history of cancer) exhibited highly variable cellular redox ratios and changes in collagen structure that trended toward cancer samples.Conclusion: This study highlights differences in endogenous signals in viable ovarian biopsies based on quantitative collagen structural changes and redox ratio estimates that may lead to improved detection and further insights in ovarian cancer, particularly in the early stages of the disease.