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Imaging of the Mouse Lymphatic Sinus during Early Stage Lymph Node Metastasis Using Intranodal Lymphangiography with X-ray Micro-computed Tomography

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Abstract

Purpose

Lymph node (LN) metastasis is detected prior to distant metastasis in many types of cancer. Detecting early stage LN metastasis can improve treatment outcomes. However, there are few clinical imaging modalities capable of diagnosing metastatic LNs of clinical N0 status (i.e., before their volume increases) with high precision. Here, we report a new method for diagnosing metastatic LNs of clinical N0 status in a mouse model of LN metastasis.

Procedures

The method involved using intranodal lymphangiography with x-ray micro-computed tomography (micro-CT). Contrast agent was injected into an upstream LN to deliver it to a downstream LN, which was then removed and analyzed by micro-CT.

Results

We found that using an intranodal injection rate of 10–60 μl/min filled the lymphatic sinus of the downstream LN with contrast agent, although the accumulation of contrast agent in the upstream LN increased with a faster injection rate. Furthermore, breast cancer cells growing in the lymphatic sinus of the downstream LN (which was of clinical N0 status) impeded the flow of contrast agent from the upstream LN, resulting in areas deficient of contrast agent in the metastatic downstream LN. The formation of defect areas in the downstream LN manifested as a difference in position between the centroid of the entire LN area and the centroid of the region that filled with contrast agent.

Conclusion

The present study indicates that intranodal lymphangiography with micro-CT has the potential to be used as a new method for diagnosing metastatic LNs of clinical N0 status.

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Acknowledgements

The authors would like to thank T. Sato for technical assistance and the Biomedical Research Core of Tohoku University Graduate School of Medicine for technical support.

Funding

The study was supported by JSPS KAKENHI grant numbers 18H03544 (MS), 17K20077 (TK), and 17H00865 (TK).

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Authors and Affiliations

Authors

Contributions

RI, SM, and TK designed the present study. RI, SM, and KT performed the experiments. RI, SM, and TK drafted the manuscript and prepared the figures. RI, MS, SM, and TK interpreted the data. All authors reviewed the manuscript.

Corresponding author

Correspondence to Tetsuya Kodama.

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The authors declare that they have no conflict of interest.

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Electronic supplementary material

PALN metastasis imaged by intranodal lymphangiography at day 14. Contrast agent was observed in the marginal, trabecular and medullary sinuses. (MP4 1724 kb)

PALN metastasis imaged by intranodal lymphangiography at day 21. Contrast agent was observed in the marginal, trabecular and medullary sinuses. (MP4 1756 kb)

PALN metastasis imaged by intranodal lymphangiography at day 28. Defect areas were observed. (MP4 1750 kb)

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Iwamura, R., Sakamoto, M., Mori, S. et al. Imaging of the Mouse Lymphatic Sinus during Early Stage Lymph Node Metastasis Using Intranodal Lymphangiography with X-ray Micro-computed Tomography. Mol Imaging Biol 21, 825–834 (2019). https://doi.org/10.1007/s11307-018-01303-4

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  • DOI: https://doi.org/10.1007/s11307-018-01303-4

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