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J Cancer. 2017 Feb 25;8(5):704-715. doi: 10.7150/jca.18027. eCollection 2017.

Monitoring of Blood Vessel Density Using Contrast-Enhanced High Frequency Ultrasound May Facilitate Early Diagnosis of Lymph Node Metastasis.

Journal of Cancer

Takuma Sato, Tomoaki Takemura, Tomoki Ouchi, Shiro Mori, Maya Sakamoto, Yoichi Arai, Tetsuya Kodama

Affiliations

  1. Graduate School of Biomedical Engineering, Tohoku University, 4-1 Seiryo-machi, Aoba, Sendai, Miyagi 980-8575, Japan;; Department of Urology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba, Sendai, Miyagi 980-8575, Japan.
  2. Graduate School of Biomedical Engineering, Tohoku University, 4-1 Seiryo-machi, Aoba, Sendai, Miyagi 980-8575, Japan.
  3. Graduate School of Biomedical Engineering, Tohoku University, 4-1 Seiryo-machi, Aoba, Sendai, Miyagi 980-8575, Japan;; Department of Oral and Maxillofacial Surgery, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba, Sendai, Miyagi 980-8575, Japan.
  4. Department of Oral Diagnosis, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba, Sendai, Miyagi 980-8575, Japan.
  5. Department of Urology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba, Sendai, Miyagi 980-8575, Japan.

PMID: 28382132 PMCID: PMC5381158 DOI: 10.7150/jca.18027

Abstract

Time-dependent alterations in the ultrasonography characteristics of lymph nodes during early-stage metastasis have not been compared with those of tumor-draining lymph nodes that do not develop tumor; this is partly due to the absence of an appropriate experimental model. In a previous study of lymph nodes with experimental early-stage metastasis, we used contrast-enhanced high-frequency ultrasound to demonstrate that an increase in lymph node blood vessel density preceded any changes in lymph node volume. In the present study, we used an experimental model of lymph node metastasis in which tumor cells metastasized from the subiliac lymph node to the proper axillary lymph node (the tumor-draining lymph node). We utilized contrast-enhanced high-frequency ultrasound to perform a longitudinal analysis of tumor-draining lymph nodes, comparing those at an early-stage of metastasis with those that did not develop detectable metastasis. We found that the normalized blood vessel density of an early-stage metastatic lymph node exhibited a progressive rise, whereas that of a tumor-draining lymph node not containing tumor began to increase later. For both types of lymph nodes, the normalized blood vessel density on the final day of experiments showed a trend towards being higher than that measured in controls. We further found that mice with an initially low value for lymph node blood vessel density subsequently showed a larger increase in the blood vessel density of the metastatic lymph node; this differed significantly from measurements in controls. The present study indicates that a longitudinal analysis of the blood vessel densities of tumor-draining lymph nodes, made using contrast-enhanced high-frequency ultrasound imaging, may be a potentially promising method for detecting early-stage lymph node metastasis in selected patients. Furthermore, our findings suggest that tumor in an upstream lymph node may induce alteration of the vascular structures in draining lymph nodes that do not contain tumor.

Keywords: blood vessel density; contrast-enhanced high frequency ultrasound; early diagnosis; lymph node metastasis

Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

References

  1. Imaging Med. 2014 Feb 1;6(1):41-52 - PubMed
  2. AJR Am J Roentgenol. 2011 Jan;196 (1):W8-12 - PubMed
  3. Nat Rev Cancer. 2012 Feb 24;12(3):210-9 - PubMed
  4. J Natl Cancer Inst. 2015 Jun 10;107(9):null - PubMed
  5. J Exp Med. 1978 Nov 1;148(5):1198-215 - PubMed
  6. J Immunol Methods. 2013 Mar 29;389(1-2):69-78 - PubMed
  7. PLoS One. 2015 Jul 15;10(7):e0133076 - PubMed
  8. J Ultrasound Med. 2004 Jun;23 (6):829-36 - PubMed
  9. J Clin Oncol. 1999 Aug;17(8):2334-40 - PubMed
  10. World J Gastroenterol. 2013 Aug 14;19(30):4850-60 - PubMed
  11. Ultrasound Med Biol. 2014 Jun;40(6):1237-49 - PubMed
  12. AJR Am J Roentgenol. 2005 May;184(5):1691-9 - PubMed
  13. J Physiol Pharmacol. 2008 Dec;59 Suppl 6:791-800 - PubMed
  14. J Ultrasound Med. 2006 Jul;25(7):883-90 - PubMed
  15. Clin Hemorheol Microcirc. 2009;43(1-2):1-9 - PubMed
  16. Pathophysiology. 2010 Sep;17(4):229-51 - PubMed
  17. Br J Surg. 2015 Mar;102(4):399-406 - PubMed
  18. Ultrasound Med Biol. 2008 May;34(5):824-33 - PubMed
  19. Eur Radiol. 2014 Oct;24(10 ):2513-9 - PubMed
  20. AJR Am J Roentgenol. 1997 May;168(5):1311-6 - PubMed
  21. PLoS One. 2013;8(2):e55797 - PubMed
  22. Cancer. 2000 Jun 1;88(11):2534-9 - PubMed
  23. Radiographics. 2013 Oct;33(6):1589-612 - PubMed
  24. Eur J Nucl Med Mol Imaging. 2010 Aug;37 Suppl 1:S138-46 - PubMed
  25. Histopathology. 2000 Apr;36(4):306-12 - PubMed
  26. Cancer Imaging. 2014 Jan 06;13(4):658-69 - PubMed
  27. Adv Drug Deliv Rev. 2001 Aug 23;50(1-2):3-20 - PubMed
  28. Cancer Imaging. 2009 Dec 24;9:104-11 - PubMed
  29. Ultrasound Med Biol. 2000 Sep;26(7):1089-97 - PubMed
  30. Cancer Res. 2013 Apr 1;73(7):2082-92 - PubMed
  31. Histol Histopathol. 2009 Mar;24(3):377-84 - PubMed
  32. Ultrasound Med Biol. 2014 Apr;40(4):747-54 - PubMed
  33. Eur J Radiol. 2010 Feb;73(2):288-93 - PubMed
  34. AJR Am J Roentgenol. 2006 May;186(5):1342-8 - PubMed
  35. Arthritis Rheum. 2003 May;48(5):1445-51 - PubMed
  36. J Natl Cancer Inst. 2000 Mar 15;92(6):486-92 - PubMed
  37. AJR Am J Roentgenol. 2014 Apr;202(4):W400-7 - PubMed
  38. World J Surg Oncol. 2015 Feb 14;13:49 - PubMed
  39. AJR Am J Roentgenol. 2000 May;174(5):1279-84 - PubMed
  40. Cell. 2010 Feb 19;140(4):460-76 - PubMed
  41. PLoS One. 2015 Apr 21;10 (4):e0123619 - PubMed

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