Supercontinuum-tailoring multicolor imaging reveals spatiotemporal dynamics of heterogeneous tumor evolution

Xiujuan Gao, Xinyuan Huang, Zhongyun Chen, Liu Yang, Yifu Zhou, Zhenxuan Hou, Jie Yang, Shuhong Qi, Zheng Liu, Zhihong Zhang, Qian Liu, Qingming Luo () and Ling Fu ()
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Xiujuan Gao: Huazhong University of Science and Technology
Xinyuan Huang: Huazhong University of Science and Technology
Zhongyun Chen: Huazhong University of Science and Technology
Liu Yang: Huazhong University of Science and Technology
Yifu Zhou: Huazhong University of Science and Technology
Zhenxuan Hou: Huazhong University of Science and Technology
Jie Yang: Huazhong University of Science and Technology
Shuhong Qi: Huazhong University of Science and Technology
Zheng Liu: Hainan University
Zhihong Zhang: Huazhong University of Science and Technology
Qian Liu: Hainan University
Qingming Luo: Hainan University
Ling Fu: Huazhong University of Science and Technology

Nature Communications, 2024, vol. 15, issue 1, 1-14

Abstract: Abstract Tumor heterogeneity and tumor evolution contribute to cancer treatment failure. To understand how selective pressures drive heterogeneous tumor evolution, it would be useful to image multiple important components and tumor subclones in vivo. We propose a supercontinuum-tailoring two-photon microscope (SCT-TPM) and realize simultaneous observation of nine fluorophores with a single light beam, breaking through the ‘color barrier’ of intravital two-photon fluorescence imaging. It achieves excitation multiplexing only by modulating the phase of fiber supercontinuum (SC), allowing to capture rapid events of multiple targets with maintaining precise spatial alignment. We employ SCT-TPM to visualize the spatiotemporal dynamics of heterogeneous tumor evolution under host immune surveillance, particularly the behaviors and interactions of six tumor subclones, immune cells and vascular network, and thus infer the trajectories of tumor progression and clonal competition. SCT-TPM opens up the possibility of tumor lineage tracking and mechanism exploration in living biological systems.

Date: 2024
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DOI: 10.1038/s41467-024-53697-1

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