Objective: Real-time quantitative imaging is becoming highly desirable to study nondestructively the biological behavior of three dimensional cell culture systems. In this work, we investigate the feasibility of quantitative imaging/monitoring of 3D cell culture processes via Electrical Impedance Tomography (EIT), which is capable of generating conductivity images in a non-destructive manner with high temporal resolution. Methods: To this end, a miniature EIT sensor amenable to standard cell culture format is designed. Furthermore, a 3D forward model for the sensor is developed and its sensitivity characteristic is analyzed. Two regularization algorithms, 3D Laplacian regularization and 3D Total Variation, are proposed to perform 3D image reconstruction. To evaluate the designed sensor and the proposed reconstruction methods, phantom simulations and experiments on a rice grain and a high density cancer cell pellet are carried out. Conclusion: Promising results have been attained in both simulation study and experiments, which demonstrate the feasibility of using the designed miniature EIT sensor and proposed image reconstruction methods to visualize three dimensional cell cultures such as spheroids or artificial tissues and organs. Significance: The established work would expedite real-time quantitative imaging of 3D cell culture for assessment of cellular dynamics.
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机译:目的:实时定量成像正变得越来越需要无损研究三维细胞培养系统的生物学行为。在这项工作中,我们研究了通过电阻层析成像(EIT)对3D细胞培养过程进行定量成像/监控的可行性,该技术能够以高破坏力的方式以非破坏性方式生成电导率图像。方法:为此,设计了一种适合标准细胞培养格式的微型EIT传感器。此外,开发了传感器的3D正向模型并分析了其灵敏度特性。提出了两种正则化算法3D Laplacian正则化和3D Total Variation,来执行3D图像重建。为了评估设计的传感器和提出的重建方法,对稻谷和高密度癌细胞团进行了幻像模拟和实验。结论:在仿真研究和实验中均取得了可喜的结果,证明了使用设计的微型EIT传感器和提出的图像重建方法来可视化三维细胞培养物(如球状体或人造组织和器官)的可行性。启示:这项既定的工作将加速3D细胞培养的实时定量成像,以评估细胞动力学。
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