TY - JOUR
T1 - Optical coherence tomography detects necrotic regions and volumetrically quantifies multicellular tumor spheroids
AU - Huang, Yongyang
AU - Wang, Shunqiang
AU - Guo, Qiongyu
AU - Kessel, Sarah
AU - Rubinoff, Ian
AU - Chan, Leo Li Ying
AU - Li, Peter
AU - Liu, Yaling
AU - Qiu, Jean
AU - Zhou, Chao
N1 - Funding Information:
This work was supported by NSF IDBR grant 1455613, PFI:AIR-TT grant 1640707, NIH grants R21EY026380 and R15EB019704, and Lehigh University startup fund.
Publisher Copyright:
©2017 AACR.
PY - 2017/11/1
Y1 - 2017/11/1
N2 - 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 mm) 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 mm 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.
AB - 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 mm) 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 mm 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.
UR - http://www.scopus.com/inward/record.url?scp=85033799095&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-17-0821
DO - 10.1158/0008-5472.CAN-17-0821
M3 - Article
C2 - 28904062
AN - SCOPUS:85033799095
SN - 0008-5472
VL - 77
SP - 6011
EP - 6020
JO - Cancer research
JF - Cancer research
IS - 21
ER -