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Optical Coherence Tomography Detects Necrotic Regions and Volumetrically Quantifies Multicellular Tumor Spheroids.

ABSTRACT: Three-dimensional (3D) tumor spheroid models have gained increased recognition as important tools in cancer research and anticancer drug development. However, currently available imaging approaches used in high-throughput screening drug discovery platforms, for example, bright-field, phase contrast, and fluorescence microscopies, are unable to resolve 3D structures deep inside (>50 ?m) tumor spheroids. In this study, we established a label-free, noninvasive optical coherence tomography (OCT) imaging platform to characterize 3D morphologic and physiologic information of multicellular tumor spheroids (MCTS) growing from approximately 250 to 600 ?m in height over 21 days. In particular, tumor spheroids of two cell lines, glioblastoma (U-87MG) and colorectal carcinoma (HCT116), 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 morphologic and physiologic features of MCTS, showing great potential for high-throughput drug screening. Cancer Res; 77(21); 6011-20. ©2017 AACR.

SUBMITTER: Huang Y

PROVIDER: S-EPMC5866924 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Optical Coherence Tomography Detects Necrotic Regions and Volumetrically Quantifies Multicellular Tumor Spheroids.

Huang Yongyang Y Wang Shunqiang S Guo Qiongyu Q Kessel Sarah S Rubinoff Ian I Chan Leo Li-Ying LL Li Peter P Liu Yaling Y Qiu Jean J Zhou Chao C

Cancer research 20170913 21

Three-dimensional (3D) tumor spheroid models have gained increased recognition as important tools in cancer research and anticancer drug development. However, currently available imaging approaches used in high-throughput screening drug discovery platforms, for example, 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, noninvasive optical coherence tomography (OCT) ima ...[more]

PMID: 28904062

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Project description:Importance:Whether optical coherence tomography angiography (OCT-A) outperforms OCT to detect glaucoma remains inconclusive. Objective:To compare (1) the diagnostic performance for detection of glaucoma and (2) the structure-function association between inner macular vessel density and inner macular thickness. Design, Setting, and Participants:This cross-sectional study included 115 patients with glaucoma and 35 healthy individuals for measurements of retinal thickness and retinal vessel density, segmented between the anterior boundary of internal limiting membrane and the posterior boundary of the inner plexiform layer, over the 3 × 3-mm2 macula using swept-source OCT. All participants were Chinese. Visual sensitivity corresponding to the 3 × 3-mm2 macular region was expressed in unlogged 1/lambert for investigation of the structure-function associations. Diagnostic performance was evaluated with area under the receiver operating characteristic curves (AUCs). The study was conducted between January 12, 2016, and December 12, 2016. Main Outcomes and Measures:Area under the receiver operating characteristic curve and R2 analysis. Results:Of the 115 patients with glaucoma, 42 (36.5%) were women (mean [SD] age, 53.5 [13.4] years); of the 35 individuals with healthy eyes, 25 (71.4%) were women (age, 60.6 [5.9] years). Inner macular vessel density and thickness were 4.3% (95% CI, 2.4%-6.1%) and 21.1 μm (95% CI, 17.4-24.9 μm) smaller, respectively, in eyes with glaucoma compared with healthy eyes. The AUC of mean inner macular thickness for glaucoma detection was greater than that of mean inner macular vessel density (difference, 0.17; 95% CI, 0.01-0.31; P = .03). At 90% specificity, the sensitivity of mean inner macular thicknesses for detection of glaucoma was greater than that of mean inner macular vessel densities (difference, 29.2%; 95% CI, 11.5%-64.6%; P = .02). The strength of the structure-function association was stronger for mean inner macular thickness than mean inner macular vessel density in the linear (difference in R2 = 0.38; 95% CI, 0.22-0.54; P < .001) and nonlinear (difference in R2 = 0.36; 95% CI, 0.21-0.51; P < .001) regression models. Conclusions and Relevance:In this study, OCT measurement of inner macular thickness shows a higher diagnostic performance to detect glaucoma and a stronger structure-function association than the currently used OCT-A measurement of inner macular vessel density. These findings may suggest that OCT-A of the macula has a limited role in the diagnostic evaluation of glaucoma.

Dataset Information

Optical Coherence Tomography Detects Necrotic Regions and Volumetrically Quantifies Multicellular Tumor Spheroids.

Publications

Optical Coherence Tomography Detects Necrotic Regions and Volumetrically Quantifies Multicellular Tumor Spheroids.

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