Abstract
The three-dimensional (3D) tumor spheroid model is a critical tool for high-throughput ovarian cancer research and anticancer drug development in vitro. However, the 3D structure prevents high-resolution imaging of the inner side of the spheroids. We aim to visualize and characterize 3D morphological and physiological information of the contact multicellular ovarian tumor spheroids growing over time. We intend to further evaluate the distinctive evolutions of the tumor spheroid and necrotic tissue volumes in different cell numbers and determine the most appropriate mathematical model for fitting the growth of tumor spheroids and necrotic tissues. A label-free and noninvasive swept-source optical coherence tomography (SS-OCT) imaging platform was applied to obtain two-dimensional (2D) and 3D morphologies of ovarian tumor spheroids over 18 days. Ovarian tumor spheroids of two different initial cell numbers (5,000- and 50,000- cells) were cultured and imaged (each day) over the time of growth in 18 days. Four mathematical models (Exponential-Linear, Gompertz, logistic, and Boltzmann) were employed to describe the growth kinetics of the tumor spheroids volume and necrotic tissues. Ovarian tumor spheroids have different growth curves with different initial cell numbers and their growths contain different stages with various growth rates over 18 days. The volumes of 50,000-cells spheroids and the corresponding necrotic tissues are larger than that of the 5,000-cells spheroids. The formation of necrotic tissue in 5,000-cells numbers is slower than that in the 50,000-cells ones. Moreover, the Boltzmann model exhibits the best fitting performance for the growth of tumor spheroids and necrotic tissues. Optical coherence tomography (OCT) can serve as a promising imaging modality to visualize and characterize morphological and physiological features of multicellular ovarian tumor spheroids. The Boltzmann model integrating with 3D OCT data of ovarian tumor spheroids provides great potential for high-throughput cancer research in vitro and aiding in drug development.
Highlights
Cell culture in vitro is a widely used tool to evaluate the biological performance of bioactive molecules, tissue morphology, drug action, protein production, and mechanism of diseases out of the living organism [1,2,3]
Our results demonstrated that Optical coherence tomography (OCT) was a promising imaging modality for characterization and quantification of multicellular ovarian tumor spheroid in morphology, growth kinetics, and the formation of the necrotic core
We found that the best fitting result for the normal tissue was at peak-1 (P1 = 0.34/mm) and the necrotic region was at peak-2 (P2 = 0.56/mm) for all tumor spheroids detected in this study with R2 > 0.95
Summary
Cell culture in vitro is a widely used tool to evaluate the biological performance of bioactive molecules, tissue morphology, drug action, protein production, and mechanism of diseases out of the living organism [1,2,3]. To study 3D tumor spheroids characteristics, fluorescence imaging techniques including confocal microscopy and multiphoton microscopy (MPM), are widely employed to characterize the morphology of tumor spheroids [30,31,32,33,34]. Light sheet fluorescence microscopy (LSFM) and single plane illumination microscopy (SPIM) are proposed as novel alternatives to provide a high-resolution 3D structural imaging of entire tumor spheroids [35,36,37,38]. Whereas these techniques require extensive steps for samples preparation including transferring, staining, mounting, and/or clearing of tumor spheroids, which impede longitudinal imaging and high-throughput screening [36]
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