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Characterizing perfusion defects in metastatic lymph nodes at an early stage using high-frequency ultrasound and micro-CT imaging

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Abstract

A perfusion defect in a metastatic lymph node (LN) can be visualized as a localized area of low contrast on contrast-enhanced CT, MRI or ultrasound images. Hypotheses for perfusion defects include abnormal hemodynamics in neovascular vessels or a decrease in blood flow in pre-existing blood vessels in the parenchyma due to compression by LN tumor growth. However, the mechanisms underlying perfusion defects in LNs during the early stage of LN metastasis have not been investigated. We show that tumor mass formation with very few microvessels was associated with a perfusion defect in a non-enlarged LN at the early stage of LN metastasis in a LN adenopathy mouse (LN size circa 10 mm). We found in a mouse model of LN metastasis, induced using non-keratinizing tumor cells, that during the formation of the perfusion defect in a non-enlarged LN, the number of blood vessels ≤ 50 μm in diameter decreased, while those of > 50 μm in diameter increased. The methods used were contrast-enhanced high-frequency ultrasound and contrast-enhanced micro-CT imaging systems, with a maximum spatial resolution of > 30 μm. Furthermore, we found no tumor angiogenesis or oxygen partial pressure (pO2) changes in the metastatic LN. Our results demonstrate that the perfusion defect appears to be a specific form of tumorigenesis in the LN, which is a vascular-rich organ. We anticipate that a perfusion defect on ultrasound, CT or MRI images will be used as an indicator of a non-enlarged metastatic LN at an early stage.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Abbreviations

2D:

Two-dimensional

3D:

Three-dimensional

HE:

Hematoxylin and eosin

LDDS:

Lymphatic drug delivery system

LN:

Lymph node

MXH10/Mo/lpr:

MXH10/Mo-lpr/lpr

pO2 :

Partial pressure of oxygen

PALN:

Proper axillary lymph node

SiLN:

Subiliac lymph node

SLN:

Sentinel lymph node

TEV:

Thoracoepigastric vein

UCAD:

Ultrasound contrast agent detection

cN0:

Clinical N0

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Funding

The study was supported by KAKENHI grants from the Japan Society for the Promotion of Science (20K20161 to Ariunbuyan Sukhbaatar; 18H03544 to Maya Sakamoto; and 19K22941, 20H00655, and 21K18319 to Tetsuya Kodama).

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Authors and Affiliations

  1. Graduate School of Biomedical Engineering, Tohoku University, 4-1 Seiryo, Aoba, Sendai, Miyagi, 980-8575, Japan

    Teppei Yamaki, Ariunbuyan Sukhbaatar, Radhika Mishra, Ryoichi Kikuchi, Maya Sakamoto, Shiro Mori & Tetsuya Kodama

  2. Biomedical Engineering Cancer Research Center, Graduate School of Biomedical Engineering, Tohoku University, 4-1 Seiryo, Aoba, Sendai, Miyagi, 980-8575, Japan

    Teppei Yamaki, Ariunbuyan Sukhbaatar, Radhika Mishra, Ryoichi Kikuchi, Maya Sakamoto, Shiro Mori & Tetsuya Kodama

  3. Department of Oral and Maxillofacial Surgery, Tohoku University Hospital, 1-1 Seiryo, Aoba, Sendai, Miyagi, 980-8575, Japan

    Shiro Mori

  4. Department of Electronic Engineering, Graduate School of Engineering, Tohoku University, Aoba, Sendai, Miyagi, 980-8579, Japan

    Tetsuya Kodama

  5. Laboratory of Biomedical Engineering for Cancer, Graduate School of Biomedical Engineering, Tohoku University, 4-1 Seiryo, Aoba Ward, Sendai, Miyagi, 980-8575, Japan

    Tetsuya Kodama

Authors
  1. Teppei Yamaki
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  2. Ariunbuyan Sukhbaatar
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  7. Tetsuya Kodama
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Contributions

Guarantors of the integrity of the entire study, TK; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; approval of the final version of the submitted manuscript, all authors; agrees to ensure any questions related to the work are appropriately resolved, all authors.

Corresponding author

Correspondence to Tetsuya Kodama.

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The authors declare no competing interests.

Ethical approval

Experiments were carried out under established guidelines and approved by the Institutional Animal Care and Use Committee of Tohoku University (2016BeA-019, 2016BeA-005, 2016BeLMo-003).

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Yamaki, T., Sukhbaatar, A., Mishra, R. et al. Characterizing perfusion defects in metastatic lymph nodes at an early stage using high-frequency ultrasound and micro-CT imaging. Clin Exp Metastasis 38, 539–549 (2021). https://doi.org/10.1007/s10585-021-10127-6

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  • DOI: https://doi.org/10.1007/s10585-021-10127-6

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