Characterization and quantification of necrotic tissues and morphology in multicellular ovarian cancer tumor spheroids using optical coherence tomography

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.

Peptide aggregation-induced immunogenic cell death in a breast cancer spheroid model

“…Drug resistance is often associated with the formation of a hypoxic core (necrotic core) 38 . Therefore, we aimed to form large spheroids (>500 μm in diameter) since those larger than 500 μm in diameter exhibit gradient and zone formation 39,40 . In this study, we cultivated and analyzed spheroid growth, utilizing them on day 7 post-formation when they reached approximately 800 mm in diameter (Figure 2A and 2B) .…”

Dimension‐based quantification of aging‐associated cerebral microvasculature determined by optical coherence tomography and two‐photon microscopy

“…A swept-source OCT imaging system (VEG220, Thorlabs) with a swept-source laser of 1310 nm center wavelength and 100 nm spectral bandwidth was employed to provide an axial resolution of 14 μm in the air (10 μm in mouse brain) and lateral resolution of 20 μm. The wavelengthswept frequency and sensitivity in this system were 200 kHz and 98 dB, respectively [27][28][29][30][31][32][33][34][35][36][37]. The OCT-based optical microangiography (OMAG) algorithm was utilized to acquire in vivo volumetric angiography in mouse cerebral cortex by coherently analyzing the intrinsic scattering property of moving red blood cells (RBCs) in blood vessels [15,25].…”

Recent Advances in Multicellular Tumor Spheroid Generation for Drug Screening

“…This study demonstrated the spheroid imaging of hypoxia that could be a future target for the drug-screening analysis. In other cell lines, ovarian cancer cell (OVCAR-8) was applied to visualize 3D structures and monitor necrotic zones within the MCTs (Figure 7F) [146]. In this study, a swept-source optical coherence tomography platform was fabricated, and OCT images were obtained.…”

“…Copyright 2020, Wiley Online Library; Reprinted with permission from [121]. Copyright 2020, American Chemical Society; Reprinted with permission from [146]. Copyright 2021, Optical Society of America; Reprinted with permission from [110].…”