There is strong evidence that the morphological parameters of multicellular tumor spheroids (MCTS), particularly size, sphericity, and growth pattern, play a role in their cytochemical responses. Because tumor spheroids accurately represent the three-dimensional (3D) structure of in vivo tumors, they may also mimic in vivo cytochemical responses, thus lending them relevance to cancer research. Knowledge of MCTS attributes, including oxygen and nutrient gradients, hypoxia resistance, and drug response, assist specialists seeking the most efficient ways to treat cancer. Structural information on tumor spheroids can provide insight into these attributes, and become a valuable asset for treatment in vivo. Currently, high-resolution bioimaging modalities, most notably bright field imaging, phase contrast imaging, fluorescent microscopy, and confocal imaging, are being employed for this purpose. However, these modalities lack sufficient penetration depth to resolve the entire geometry of large spheroids (>200um). In response to this deficiency, we propose a potential high-throughput imaging platform using optical coherence tomography (OCT) to quantify MCTS morphology. OCT’s high resolution and depth penetration allow us to obtain complete, high-detailed, 3D tumor reconstructions with accurate diameter measurements. Furthermore, a computer-based voxel counting method is used to quantify tumor volume, which is significantly more accurate than the estimations required by 2D-projection modalities. Thus, this imaging platform provides one of the most complete and robust evaluations of tumor spheroid morphology, and shows great potential for contribution to the study of cancer treatment and drug discovery.
We have demonstrated the capability of spectral domain optical coherence tomography (SDOCT) system to image full development of mouse embryonic cardiovascular system. Monitoring morphological changes of mouse embryonic heart occurred in different embryonic stages helps identify structural or functional cardiac anomalies and understand how these anomalies lead to congenital heart diseases (CHD) present at birth. In this study, mouse embryo hearts ranging from E9.5 to E15.5 were prepared and imaged in vitro. A customized spectral domain OCT system was used for imaging, with a central wavelength of 1310nm, spectral bandwidth of ~100nm and imaging speed of 47kHz A-scans/s. Axial resolution of this system was 8.3µm in air, and transverse resolution was 6.2 µm with 5X objective. Key features of mouse embryonic cardiovascular development such as vasculature remodeling into circulatory system, separation of atria and ventricles and emergence of valves could be clearly seen in three-dimensional OCT images. Optical clearing was applied to overcome the penetration limit of OCT system. With high resolution, fast imaging speed, 3D imaging capability, OCT proves to be a promising biomedical imaging modality for developmental biology studies, rivaling histology and micro-CT.