Optical metabolic imaging quantifies heterogeneous cell populations
Optical metabolic imaging quantifies heterogeneous cell populations
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DOI：
10.1364/boe.6.000559
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发表时间：
2015-02-01
影响因子：
3.4
通讯作者：
Skala, Melissa C.
中科院分区：
文献类型：
--
作者：
Walsh, Alex J.;Skala, Melissa C.
癌症的遗传和表型异质性可能导致肿瘤的侵袭性、侵袭性和对治疗的耐药性。荧光成像由于其高分辨率和分子特异性，在研究肿瘤异质性方面占有独特的地位。通过光学代谢成像和亚群分析（OMI-SPA）相结合，对异质群体进行了鉴定和量化。OMI探测细胞中代谢酶的荧光强度和寿命，提供细胞代谢图像，SPA将细胞群体建模为混合高斯分布，以识别细胞亚群。在本研究中，OMI-SPA通过模拟实验进行了表征，并通过细胞实验进行了验证。为了产生异质群体，以不同比例共培养两种乳腺癌细胞系SKBr3和MDA-MB-231。OMI- spa使用光学氧化还原比（NAD(P) H荧光强度除以FAD强度）、平均NAD(P) H荧光寿命和OMI指数，以最小的平均值和比例误差正确识别两个种群。模拟实验表征了OMI-SPA识别亚种群所需的样本量、数据标准差和亚种群平均分离距离之间的关系。(C) 2015美国光学学会
The genetic and phenotypic heterogeneity of cancers can contribute to tumor aggressiveness, invasion, and resistance to therapy. Fluorescence imaging occupies a unique niche to investigate tumor heterogeneity due to its high resolution and molecular specificity. Here, heterogeneous populations are identified and quantified by combined optical metabolic imaging and subpopulation analysis (OMI-SPA). OMI probes the fluorescence intensities and lifetimes of metabolic enzymes in cells to provide images of cellular metabolism, and SPA models cell populations as mixed Gaussian distributions to identify cell subpopulations. In this study, OMI-SPA is characterized by simulation experiments and validated with cell experiments. To generate heterogeneous populations, two breast cancer cell lines, SKBr3 and MDA-MB-231, were co-cultured at varying proportions. OMI-SPA correctly identifies two populations with minimal mean and proportion error using the optical redox ratio (fluorescence intensity of NAD(P) H divided by the intensity of FAD), mean NAD(P) H fluorescence lifetime, and OMI index. Simulation experiments characterized the relationships between sample size, data standard deviation, and subpopulation mean separation distance required for OMI-SPA to identify subpopulations. (C) 2015 Optical Society of America