Imaging of the Mouse Lymphatic Sinus during Early Stage Lymph Node Metastasis Using Intranodal Lymphangiography with X-ray Micro-computed Tomography
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.
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.
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.
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.
Key wordsIntranodal lymphangiography Lymph node Metastasis Clinical N0 CT Micro-CT Sentinel lymph node
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.
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.
The study was supported by JSPS KAKENHI grant numbers 18H03544 (MS), 17K20077 (TK), and 17H00865 (TK).
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
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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