The potential of multiparametric contrast-enhanced ultrasound to detect and predict sentinel lymph node status in invasive breast cancer

Axillary mapping and assessment of axillary lymph node status remains a key staging issue for determining treatment strategies and algorithms for patients with invasive breast cancer. Various ultrasound techniques (elastography, color Doppler, and SMI) are used to improve diagnostic accuracy. In recent years, ultrasound contrast agents have been widely adopted, increasing the diagnostic capabilities of ultrasound.

The aim: to evaluate the diagnostic efficiency of CEUS and multiparametric ultrasound with the inclusion of the ultrasound contrast technique in preoperative detection and prediction of metastases in the SLN.

Materials and methods. This study included a comprehensive analysis of data from 120 up-front patients with invasive breast cancer to evaluate the diagnostic value of qualitative (contrast patterns), quantitative, combined and multiparametric (combined CEUS parameters + B-mode) models.

Results. Axillary lymph node metastases were detected in 29.2% of cases; the proportion of pN+ patients increased from patterns I–II to IV–V (up to 71–100%; p<0.001); combining patterns III–VI versus I–II yielded an OR of 6.0. B-mode showed a leading role in predicting metastasis based on cortical thickening of more than 3 mm (p < 0.001; AUC 0.84), transverse size and blood flow type in the color Doppler imaging mode had moderate information content (p = 0.02 and p = 0.077, respectively). Integration of features improved accuracy: combined model – AUC 0.686, sensitivity – 60%, specificity – 81.2%, and multiparametric (combined with the addition of B-mode and color Doppler imaging) – the highest values (AUC 0.78; sensitivity 65.8%, specificity 80%).

Conclusion. Intradermal paraareolar ultrasound injection of contrast agent provides a high rate of lymph node (SLN) identification and predict the status and metastatic burden of axillary lymph nodes. Multiparametric ultrasound, combining B-mode, color Doppler, and CEUS improves the diagnostic accuracy of axillary staging in patients with breast cancer.

1. Nartokova A.S.-Kh., Koychuev A.A., Marchenko A.G., Nartokov D.N. On clinical aspects of sentinel lymph node biopsy in breast cancer: a literature review. International Research Journal. 2021; 5 (107): 53. https://doi.org/10.23670/IRJ.2021.107.5.053 (In Russian)

2. Semiglazov V.F., Krivorotko P.V., Zhiltsova E.K. et al. Twenty-year experience of examining biopsies of signal lymph nodes in breast cancer. Tumors of Female Reproductive System. 2020; 16 (1): 12–20. https://doi.org/10.17650/1994-4098-2020-16-1-12-20 (In Russian)

3. Ecanow J.S., Abe H., Newstead G.M. et al. Axillary staging of breast cancer: what the radiologist should know. Radiographics. 2013; 33 (6): 1589–1612. https://doi.org/10.1148/rg.336125060

4. Goldberg B.B., Merton D.A., Liu J.B. et al. Sentinel lymph nodes in a swine model with melanoma: contrast-enhanced lymphatic US. Radiology. 2004; 230 (3): 727–734. https://doi.org/10.1148/radiol.2303021440

5. Jin L., Wang R., Zhuang L. et al. Evaluation of whole axillary status with lymphatic contrast-enhanced ultrasound in patients with breast cancer. Eur. Radiol. 2022; 32 (1): 630–638. https://doi.org/10.1007/s00330-021-08100-8

6. Gkegkes I.D., Iavazzo C. Advantages by using the intradermal microbubbles for sentinel lymph node detection in penile cancer. Hell. J. Nucl. Med. 2016; 19 (3): 289. https://doi.org/10.1967/s0024499100414

7. Lahtinen O., Eloranta M., Anttila M. et al. Preoperative sentinel lymph node localization in vulvar cancer: preliminary experience with inguinal intradermal contrast-enhanced ultrasound. Eur. Radiol. 2018; 28 (5): 2089–2095. https://doi.org/10.1007/s00330-017-5155-7

8. Pang W., Zhou F., Zhu Y. et al. The value of percutaneous contrast-enhanced ultrasound in sentinel lymph node identification, metastatic status and burden diagnosis in early breast cancer. J. Ultrasound Med. 2024; 43: 293–303. https://doi.org/10.1002/jum.16359

9. Wakisaka N., Endo K., Kitazawa T. et al. Detection of sentinel lymph node using contrast-enhanced agent, Sonazoid™, and evaluation of its metastasis with superb microvascular imaging in oral and oropharyngeal cancers: a preliminary clinical study. Acta Otolaryngol. 2019; 139 (1): 94–99. https://doi.org/10.1080/00016489.2018.1535193

10. Du L.W., Liu H.L., Gong H.Y. et al. Adding contrast-enhanced ultrasound markers to conventional axillary ultrasound improves specificity for predicting axillary lymph node metastasis in patients with breast cancer. Br. J. Radiol. 2021; 94 (1118): 20200874. https://doi.org/10.1259/bjr.20200874

11. Boughey J.C., Yu H., Dugan C.L. et al. Changes in surgical management of the axilla over 11 years – report on more than 1500 breast cancer patients treated with neoadjuvant chemotherapy on the prospective I-SPY2 trial. Ann. Surg. Oncol. 2023; 30 (11): 6401–6410. https://doi.org/10.1245/s10434-023-13759-y

12. Zhang Q., Agyekum E.A., Zhu L. et al. Clinical value of three combined ultrasonography modalities in predicting axillary lymph node metastasis risk in breast IDC. Front. Oncol. 2021; 11: 715097. https://doi.org/10.3389/fonc.2021.715097

13. Yuan X.W., Cao C.L., Li W.X. et al. Diagnostic value of different CEUS methods for SLN metastasis in breast neoplasms: meta-analysis and indirect comparison. Quant. Imaging Med. Surg. 2025; 15 (6): 5660–5673. https://doi.org/10.21037/qims-24-317

14. Huang C., Luo J., Shan Z. et al. The value of the improved percutaneous and intravenous contrast-enhanced ultrasound diagnostic classification in sentinel lymph nodes of breast cancer. Quant. Imaging Med. Surg. 2024; 14 (3): 2391–2404. https://doi.org/10.21037/qims-23-1210

15. Omoto K., Futsuhara K., Watanabe T. Sentinel lymph node identification using contrast-enhanced ultrasound in breast cancer: review of the literature. J. Med. Ultrason. 2024; 51 (4): 581–585. https://doi.org/10.1007/s10396-023-01313-y. Erratum in: J. Med. Ultrason. 2024; 51 (4): 693. https://doi.org/10.1007/s10396-024-01493-1

16. Zhu Y., Jia Y., Pang W. et al. Ultrasound contrast-enhanced patterns of sentinel lymph nodes: predictive value for nodal status and metastatic burden in early breast cancer. Quant. Imaging Med. Surg. 13 (1): 160–170. https://doi.org/10.21037/qims-22-234

17. Cui Q., Dai L., Li J. et al. Contrast-enhanced ultrasound-guided sentinel lymph node biopsy in early-stage breast cancer: a prospective cohort study. Wld J. Surg. Oncol. 2023; 21: 143. https://doi.org/10.1186/s12957-023-03024-7

18. Liu J., Liu X., He J. et al. Percutaneous contrast-enhanced ultrasound for localization and diagnosis of sentinel lymph node in early breast cancer. Sci. Rep. 2019; 9 (1): 13545. https://doi.org/10.1038/s41598-019-49736-3

19. Dong Y., Liu J., Jia W. et al. Factors affecting preoperative sentinel lymph nodes contrast-enhanced ultrasound in breast cancer. Quant. Imaging Med. Surg. 2025; 15 (9): 8125–8136. https://doi.org/10.21037/qims-2024-2879

20. Dobruch-Sobczak K., Szlenk A., Gumowska M. et al. Multiparametric ultrasound assessment of axillary lymph nodes in patients with breast cancer. Sci Rep. 2024; 14 (1), 23072. https://doi.org/10.1038/s41598-024-73376-x

21. Barentsz M.W., Verkooijen H.M., Pijnappel R.M. et al. Sentinel lymph node localization with contrast-enhanced ultrasound and an I-125 seed: an ideal prospective development study. Int. J. Surg. 2015; 14: 1–6. https://doi.org/10.1016/j.ijsu.2014.12.019

22. Matsuzawa F., Einama T., Abe H. et al. Accurate diagnosis of axillary lymph node metastasis using contrast-enhanced ultrasonography with Sonazoid. Mol. Clin. Oncol. 2015; 3 (2): 299–302. https://doi.org/10.3892/mco.2014.483

23. Zhong J., Sun D.S., Wei W. et al. Contrast-Enhanced Ultrasound-Guided Fine-Needle Aspiration for Sentinel Lymph Node Biopsy in Early-Stage Breast Cancer. Ultrasound Med. Biol. 2018; 44 (7): 1371–1378. https://doi.org/10.1016/j.ultrasmedbio.2018.03.005

24. Busko E.A. Multiparametric ultrasound examination in early diagnosis and monitoring of treatment of breast cancer: Dis. ... Doctor of Medicine. St. Petersburg: Federal State Budgetary Institution “N.N. Petrov National Medical Research Center of Oncology” of the Ministry of Health of the Russian Federation, 2021. 328 p. (In Russian)

25. Yuan X.W., Cao C.L., Li W.X. et al. Diagnostic value of different contrast-enhanced ultrasound (CEUS) methods for sentinel lymph node metastasis in patients with breast neoplasms: a meta-analysis and indirect comparison. Quant. Imaging Med. Surg. 2025; 15 (6): 5660–5673. https://doi.org/10.21037/qims-24-317

26. Fan Y., Luo J., Lu Y. et al. The application of contrast-enhanced ultrasound for sentinel lymph node evaluation and mapping in breast cancer patients. Quant. Imaging Med. Surg. 2023; 13 (7): 4392–4404. https://doi.org/10.21037/qims-22-901

27. Giuliano A.E., Ballman K.V., McCall L. et al. Effect of axillary dissection vs no axillary dissection on 10-year overall survival among women with invasive breast cancer and sentinel node metastasis: the ACOSOG Z0011 randomized trial. JAMA. 2017; 318: 918–926. https://doi.org/10.1001/jama.2017.11470

28.