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Japanese Journal of Radiology

, Volume 37, Issue 2, pp 145–153 | Cite as

Perfusion contrast-enhanced ultrasound to predict early lymph-node metastasis in breast cancer

  • Naoko MoriEmail author
  • Shunji Mugikura
  • Minoru Miyashita
  • Yumiko Kudo
  • Mikiko Suzuki
  • Li Li
  • Yu Mori
  • Shoki Takahashi
  • Kei Takase
Original Article
  • 62 Downloads

Abstract

Purpose

To evaluate whether quantitative analysis of perfusion contrast-enhanced ultrasound (CE-US) could predict early lymph-node (LN) metastasis in clinically node-negative breast cancer.

Materials and methods

In this prospective study, 64 breast cancer patients were selected for perfusion CE-US imaging. Regions of interest were placed where the strongest and weakest signal increases were found to obtain peak intensities (PIs; PImax and PImin, respectively) for time–intensity curve analyzes. The PI difference and PI ratio were calculated as follows: PI difference = PImax−PImin; PI ratio = PImax/PImin.

Results

Forty-seven cases were histologically diagnosed as negative for LN metastasis and 17 were positive. There was a significant difference in PImin and the PI ratio between the LN-negative and -positive metastasis groups (p = 0.0053 and 0.0082, respectively). Receiver-operating curve analysis revealed that the area under the curve of PImin and the PI ratio were 0.73 and 0.72, respectively. The most effective threshold for the PI ratio was 1.52, and the sensitivity, specificity, positive predictive value, and negative predictive value were 59% (10/17), 87% (41/47), 63% (10/16), and 85% (41/48), respectively.

Conclusions

Parameters from the quantitative analysis of perfusion CE-US imaging showed significant differences between the LN-negative and -positive metastasis groups in clinically node-negative breast cancer.

Keywords

Breast cancer Lymph-node metastasis Ultrasound Contrast-enhanced ultrasound Microbubble 

Abbreviations

CE-US

Contrast-enhanced ultrasound

LN

Lymph node

PIs

Peak intensities

SLNB

Sentinel LN biopsy

TIC

Time–intensity curve

MVD

Microvessel density

AUC

Area under the curve

ROI

Regions of interest

ICC

Interclass correlation coefficient

ROC

Receiver-operating characteristic

Notes

Acknowledgements

This study was supported by JSPS KAKENHI 26461783 and 15K09913. The authors would like to thank Yumi Fujimoto in Tohoku University Hospital and Shomo Chou in Tohoku University for their kind support. We thank James P. Mahaffey, Ph.D., from Edanz Group (www.edanzediting.com/ac) for editing a draft of this manuscript.

Compliance with ethical standards

Conflict of interest

Naoko Mori has nothing to disclose. Shunji Mugikura has nothing to disclose. Minoru Miyashita has nothing to disclose. Yumiko Kudo has nothing to disclose. Mikiko Suzuki has nothing to disclose. Li Li has nothing to disclose. Yu Mori has nothing to disclose. Shoki Takahashi has nothing to disclose. Kei Takase has nothing to disclose.

References

  1. 1.
    Nemoto T, Vana J, Bedwani RN, Baker HW, McGregor FH, Murphy GP. Management and survival of female breast cancer: results of a national survey by the American College of Surgeons. Cancer. 1980;45(12):2917–24.CrossRefPubMedGoogle Scholar
  2. 2.
    Banerjee M, George J, Song EY, et al. Tree-based model for breast cancer prognostication. J Clin Oncol. 2004;22:2567–75.CrossRefPubMedGoogle Scholar
  3. 3.
    Cianfrocca M, Goldstein LJ. Prognostic and predictive factors in early-stage breast cancer. Oncologist. 2004;9:606–1.CrossRefPubMedGoogle Scholar
  4. 4.
    Swenson KK. Comparison of side effects between sentinel lymph node and axillary lymph node dissection for breast cancer. Ann Surg Oncol. 2002;9:745–53.CrossRefPubMedGoogle Scholar
  5. 5.
    Goldhirsch A, Winer EP, Coates AS, et al. Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013. Ann Oncol. 2013;24:2206–23.CrossRefPubMedGoogle Scholar
  6. 6.
    Giuliano AE. Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial. JAMA. 2011;305:569.CrossRefPubMedGoogle Scholar
  7. 7.
    Esen G, Gurses B, Yilmaz MH, et al. Gray scale and power Doppler US in the preoperative evaluation of axillary metastases in breast cancer patients with no palpable lymph nodes. Eur Radiol. 2005;15:1215–23.CrossRefPubMedGoogle Scholar
  8. 8.
    Abe H, Schmidt RA, Kulkarni K, et al. Axillary lymph nodes suspicious for breast cancer metastasis: sampling with us-guided 14-gauge core-needle biopsy—clinical experience in 100 patients 1. Radiology. 2009;250:41–9.CrossRefPubMedGoogle Scholar
  9. 9.
    Bedi DG, Krishnamurthy R, Krishnamurthy S, et al. Cortical morphologic features of axillary lymph nodes as a predictor of metastasis in breast cancer. in vitro sonographic study. Am J Roentgenol. 2008;191:646–52.CrossRefGoogle Scholar
  10. 10.
    Abe H, Schmidt RA, Sennett CA, et al. US-guided core needle biopsy of axillary lymph nodes in patients with breast cancer: why and how to do it. Radiographics. 2007;27:S91–S99.CrossRefPubMedGoogle Scholar
  11. 11.
    Scaranelo AM, Eiada R, Jacks LM, et al. Accuracy of unenhanced MR imaging in the detection of axillary lymph node metastasis: study of reproducibility and reliability. Radiology. 2012;262:425–34.CrossRefPubMedGoogle Scholar
  12. 12.
    Shien T, Akashi-Tanaka S, Yoshida M, et al. Evaluation of axillary status in patients with breast cancer using thin-section CT. Int J Clin Oncol. 2008;13:314–9.CrossRefPubMedGoogle Scholar
  13. 13.
    Loveless ME, Li X, Huamani J, et al. A method for assessing the microvasculature in a murine tumor model using contrast-enhanced ultrasonography. J Ultrasound Med. 2008;27:1699–709.CrossRefPubMedGoogle Scholar
  14. 14.
    Szabó BK, Saracco A, Tánczos E, et al. Correlation of contrast-enhanced ultrasound kinetics with prognostic factors in invasive breast cancer. Eur Radiol. 2013;23:3228–36.CrossRefPubMedGoogle Scholar
  15. 15.
    Li L, Mori S, Sakamoto M, et al. Mouse model of lymph node metastasis via afferent lymphatic vessels for development of imaging modalities. PLoS One. 2013;8:e55797.CrossRefPubMedGoogle Scholar
  16. 16.
    Li L, Mori S, Kodama M, et al. Enhanced sonographic imaging to diagnose lymph node metastasis: importance of blood vessel volume and density. Cancer Res. 2013;73:2082–9.CrossRefPubMedGoogle Scholar
  17. 17.
    Rubaltelli L, Beltrame V, Tregnaghi A, et al. Contrast-enhanced ultrasound for characterizing lymph nodes with focal cortical thickening in patients with cutaneous melanoma. Am J Roentgenol. 2011;196:W8–W12.CrossRefGoogle Scholar
  18. 18.
    Rubaltelli L, Corradin S, Dorigo A, et al. Automated quantitative evaluation of lymph node perfusion on contrast-enhanced sonography. Am J Roentgenol. 2007;188:977–83.CrossRefGoogle Scholar
  19. 19.
    Wan CF, Du J, Fang H, et al. Enhancement patterns and parameters of breast cancers at contrast-enhanced US: correlation with prognostic factors. Radiology. 2012;262:450–9.CrossRefPubMedGoogle Scholar
  20. 20.
    Pitre-Champagnat S, Leguerney I, Bosq J, et al. Dynamic contrast-enhanced ultrasound parametric maps to evaluate intratumoral vascularization. Investig Radiol. 2015;50:212–7.CrossRefGoogle Scholar
  21. 21.
    Du J, Li F-H, Fang H, et al. Correlation of real-time gray scale contrast-enhanced ultrasonography with microvessel density and vascular endothelial growth factor expression for assessment of angiogenesis in breast lesions. J Ultrasound Med. 2008;27:821–3.CrossRefPubMedGoogle Scholar
  22. 22.
    Mori N, Mugikura S, Takahashi S, et al. Quantitative analysis of contrast-enhanced ultrasound imaging in invasive breast cancer: a novel technique to obtain histopathologic information of microvessel density. Ultrasound Med Biol. 2017;43:607–14.CrossRefPubMedGoogle Scholar
  23. 23.
    Ecanow JS, Abe H, Newstead GM, et al. Axillary staging of breast cancer: what the radiologist should know. Radiographics. 2013;33:1589–612.CrossRefPubMedGoogle Scholar
  24. 24.
    Murphy CD, Jones JL, Javid SH, et al. Do sentinel node micrometastases predict recurrence risk in ductal carcinoma in situ and ductal carcinoma in situ with microinvasion? Am J Surg. 2008;196:566–8.CrossRefPubMedGoogle Scholar
  25. 25.
    American College of Radiology. Breast imaging reporting and data system (BI-RADS). 5th ed. Reston: Reston American College of Radiology; 2013.Google Scholar
  26. 26.
    Schneider CA, Rasband WS, Eliceiri KW, et al. NIH Image to ImageJ: 25 years of image analysis. Nat Methods. 2012;9:671–5.CrossRefPubMedGoogle Scholar
  27. 27.
    Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics. 1977;33:159.CrossRefPubMedGoogle Scholar
  28. 28.
    Ignee A, Jedrejczyk M, Schuessler G, et al. Quantitative contrast enhanced ultrasound of the liver for time intensity curves—reliability and potential sources of errors. Eur J Radiol. 2010;73:153–8.CrossRefPubMedGoogle Scholar
  29. 29.
    Gadre A, Briner W, O’Leary M. A scanning electron microscope study of the human cervical lymph node. Acta Otolaryngol (Stockh.). 1994;114:87–90.CrossRefGoogle Scholar
  30. 30.
    Herman PG, Kim C-S, de Sousa MA, et al. Microcirculation of the lymph node with metastases. Am J Pathol. 1976;85:333.PubMedGoogle Scholar
  31. 31.
    Ohta T, Nishioka M, Nakata N, et al. Five cases of axillary lymph node metastatic breast cancer on contrast-enhanced sonography. J Ultrasound Med. 2015;34:1131–7.CrossRefPubMedGoogle Scholar
  32. 32.
    Goldberg BB, Merton DA, Liu J-B, et al. Contrast-enhanced sonographic imaging of lymphatic channels and sentinel lymph nodes. J Ultrasound Med. 2005;24:953–65.CrossRefPubMedGoogle Scholar
  33. 33.
    Omoto K, Matsunaga H, Take N, et al. Sentinel node detection method using contrast-enhanced ultrasonography with sonazoid in breast cancer: preliminary clinical study. Ultrasound Med Biol. 2009;35:1249–56.CrossRefPubMedGoogle Scholar
  34. 34.
    Cox K, Taylor-Phillips S, Sharma N, et al. Enhanced pre-operative axillary staging using intradermal microbubbles and contrast-enhanced ultrasound to detect and biopsy sentinel lymph nodes in breast cancer: a potential replacement for axillary surgery. Br J Radiol. 2018;91(1082):20170626.PubMedGoogle Scholar
  35. 35.
    Zhao J, Zhang J, Zhu Q-L, et al. The value of contrast-enhanced ultrasound for sentinel lymph node identification and characterisation in pre-operative breast cancer patients: a prospective study. Eur Radiol. 2018;28(4):1654–61.CrossRefPubMedGoogle Scholar
  36. 36.
    Veronesi U, De Cicco C, Galimberti V, et al. A comparative study on the value of FDG-PET and sentinel node biopsy to identify occult axillary metastases. Ann Oncol. 2006;18:473–8.CrossRefPubMedGoogle Scholar

Copyright information

© Japan Radiological Society 2018

Authors and Affiliations

  1. 1.Department of Diagnostic RadiologyTohoku University Graduate School of MedicineSendaiJapan
  2. 2.Department of Surgical OncologyTohoku University Graduate School of MedicineSendaiJapan
  3. 3.Department of Physiological Laboratory CenterTohoku University HospitalSendaiJapan
  4. 4.Department of Orthopedic SurgeryTohoku University Graduate School of MedicineSendaiJapan

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