Formation of Perfusion Defects in Lymph Nodes During the Early Stage of Metastasis 

Abstract

A perfusion defect in metastatic lymph nodes (LNs) can be visualized as a localized area of low contrast on contrast-enhanced CT, MRI or ultrasound images. Hypotheses for perfusion defect include abnormal hemodynamics in neovascular vessels and decrease in blood flow in pre-existing blood vessels in the parenchyma due to compression of tumor growth in the LNs. However, the mechanism of perfusion defects in LNs during the early stage of LN metastasis has not yet been investigated. Here we show that the formation of a tumor mass with very few microvessels was associated with the development of a perfusion defect in the non-enlarged LN at the early stage of LN metastasis. We found in a mouse model of LN metastasis induced using non-keratinizing tumor cells that during formation of the perfusion defect in non-enlarged LN, the number of blood vessels £ 50 mm in diameter decreased, while the volume of existing blood vessels >50 mm in diameter increased using contrast-enhanced high-frequency ultrasound and contrast-enhanced micro-CT imaging systems with a maximum spatial resolution of > 30 mm. Furthermore, we found that tumor angiogenesis and pO2 changes in the metastatic LN were not observed. Our results demonstrate that the perfusion defect appear to be a specific form of tumorigenesis in the LN as vascular-rich organ at the early stage of metastasis. We anticipate a perfusion defect on ultrasound, CT or MRI images to be used as an indicator in the non-enlarged LN at the early stage of LN metastasis.