Optical Coherence Tomography Detects Necrotic Regions and Volumetrically Quantifies Multicellular Tumor Spheroids.
Optical Coherence Tomography Detects Necrotic Regions and Volumetrically Quantifies Multicellular Tumor Spheroids.
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DOI：
10.1158/0008-5472.can-17-0821
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发表时间：
2017-11-01
期刊：
影响因子：
11.2
通讯作者：
Zhou C
中科院分区：
文献类型：
--
作者：
Huang Y;Wang S;Guo Q;Kessel S;Rubinoff I;Chan LL;Li P;Liu Y;Qiu J;Zhou C
三维(3D)肿瘤球体模型作为癌症研究和抗癌药物开发的重要工具得到了越来越多的认可。然而，目前在高通量筛选药物发现平台中使用的现有成像方法，如亮场、相位对比度和荧光显微镜，无法解析(>；50微米)肿瘤球体内部的3D结构。在这项研究中，我们建立了一个无标记、非侵入性的光学相干断层扫描(OCT)成像平台，以表征21天内从~250微米到~600微米高的多细胞肿瘤球体(MCT)的三维形态和生理信息。尤其是胶质母细胞瘤(U-87 MG)和结直肠癌(HCT 116)两种细胞系的肿瘤球体在生长后期的几何形状上表现出明显的演化。MCT的体积使用基于体素的方法准确地定量，而不需要假设它们的几何形状。相比之下，传统的基于直径的体积计算假设完美的球状形状，导致了很大的量化误差。此外，我们基于增加的固有光衰减，成功地检测到这些肿瘤球体内的坏死区，这表明在肿瘤球体中进行无标记生存测试是一种很有前途的替代方法。因此，OCT可以作为一种有前景的成像手段来表征MCTS的形态和生理特征，在高通量药物筛选方面显示出巨大的潜力。
Three-dimensional (3D) tumor spheroid models have gained increased recognition as important tools in cancer research and anti-cancer drug development. However, currently available imaging approaches employed in high-throughput screening drug discovery platforms e.g. bright field, phase contrast, and fluorescence microscopies, are unable to resolve 3D structures deep inside (>50 µm) tumor spheroids. In this study, we established a label-free, non-invasive optical coherence tomography (OCT) imaging platform to characterize 3D morphological and physiological information of multicellular tumor spheroids (MCTS) growing from ~250 µm up to ~600 µm in height over 21 days. In particular, tumor spheroids of two cell lines glioblastoma (U-87 MG) and colorectal carcinoma (HCT 116) exhibited distinctive evolutions in their geometric shapes at late growth stages. Volumes of MCTS were accurately quantified using a voxel-based approach without presumptions of their geometries. In contrast, conventional diameter-based volume calculations assuming perfect spherical shape resulted in large quantification errors. Furthermore, we successfully detected necrotic regions within these tumor spheroids based on increased intrinsic optical attenuation, suggesting a promising alternative of label-free viability tests in tumor spheroids. Therefore, OCT can serve as a promising imaging modality to characterize morphological and physiological features of MCTS, showing great potential for high-throughput drug screening.