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First-in-human liver-tumour surgery guided by multispectral fluorescence imaging in the visible and near-infrared-I/II windows

Abstract

The second near-infrared wavelength window (NIR-II, 1,000–1,700 nm) enables fluorescence imaging of tissue with enhanced contrast at depths of millimetres and at micrometre-scale resolution. However, the lack of clinically viable NIR-II equipment has hindered the clinical translation of NIR-II imaging. Here, we describe an optical-imaging instrument that integrates a visible multispectral imaging system with the detection of NIR-II and NIR-I (700–900 nm in wavelength) fluorescence (by using the dye indocyanine green) for aiding the fluorescence-guided surgical resection of primary and metastatic liver tumours in 23 patients. We found that, compared with NIR-I imaging, intraoperative NIR-II imaging provided a higher tumour-detection sensitivity (100% versus 90.6%; with 95% confidence intervals of 89.1%–100% and 75.0%–98.0%, respectively), a higher tumour-to-normal-liver-tissue signal ratio (5.33 versus 1.45) and an enhanced tumour-detection rate (56.41% versus 46.15%). We infer that combining the NIR-I/II spectral windows and suitable fluorescence probes might improve image-guided surgery in the clinic.

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Fig. 1: Description of the study plan and the visible and NIR-Ι/II multispectral imaging instrument for clinical applications.
Fig. 2: Comparison of the penetration and resolution of NIR-II and NIR-I imaging and the NIR-Ι/II image-guided tumour resection of subcutaneous HepG2 tumour-bearing mice.
Fig. 3: Intraoperative NIR-ΙI/I imaging of patients with primary HCC, intrahepatic metastasis or extrahepatic metastasis.
Fig. 4: Intraoperative NIR-I/II fluorescence image-guided tumour resection.
Fig. 5: Comparison of TNR or TBR for NIR-II and NIR-I imaging.
Fig. 6: Comparison of tumour-detection ability of NIR-I/II imaging.

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Data availability

The main data supporting the results in this study are available within the paper and its Supplementary Information. The raw and analysed datasets are available in figshare with the identifier https://doi.org/10.6084/m9.figshare.10316318 (ref. 39).

Code availability

Custom-developed code was applied to overlay the fluorescence signals on photographs. The raw MATLAB codes are available from the corresponding author upon request.

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Acknowledgements

This study was supported by the National Key Research and Development Program of China (2017YFA0205200, 2016YFC0102600), National Natural Science Foundation of China (NSFC) (81930053, 61622117, 81671759, 81227901), the Chinese Academy of Sciences (GJJSTD20170004), Beijing Natural Science Foundation (JQ19027), Beijing Nova Program (Z181100006218046), the Scientific Instrument Developing Project of the Chinese Academy of Sciences (YZ201672), the innovative research team of high-level local universities in Shanghai, and the Zhuhai High-level Health Personnel Team Project (Zhuhai HLHPTP201703). We acknowledge the instrumental and technical support of the multi-modal biomedical imaging experimental platform, Institute of Automation, Chinese Academy of Sciences.

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J.T., Z.C. and Z.H. conceived the idea of the project. Z.H. wrote the manuscript in addition to designing, performing and analysing all experiments. Z.H., C.F., B.L. and Z.Z. performed the experiments. S.S., P.H. and X.X. collected the information on patients with liver cancer. X. Sun., T.Z. and Y.Z. assisted with histology. Y.C. assisted with PET/CT imaging. C. Cao., M.C., X. Shi., C.L. and C. Chi. assisted with data analysis. Z.C. and S.S.G. assisted with experimental design, manuscript preparation and data/image analysis. J.T. designed, supervised and analysed all experiments, in addition to assisting with manuscript preparation.

Corresponding authors

Correspondence to Sanjiv Sam Gambhir, Zhen Cheng or Jie Tian.

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Hu, Z., Fang, C., Li, B. et al. First-in-human liver-tumour surgery guided by multispectral fluorescence imaging in the visible and near-infrared-I/II windows. Nat Biomed Eng 4, 259–271 (2020). https://doi.org/10.1038/s41551-019-0494-0

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