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Journal of Medical Ultrasonics

Open Access 20-04-2024 | Metastasis | Special Feature: Review Article

Prospects of perfusion contrast-enhanced ultrasound (CE-US) in diagnosing axillary lymph node metastases in breast cancer: a comparison with lymphatic CE-US

Authors: Naoko Mori, Li Li, Masazumi Matsuda, Yu Mori, Shunji Mugikura

Published in: Journal of Medical Ultrasonics

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Abstract

Accurate diagnosis of lymph node (LN) metastasis is vital for prognosis and treatment in patients with breast cancer. Imaging 1modalities such as ultrasound (US), MRI, CT, and 18F-FDG PET/CT are used for preoperative assessment. While conventional US is commonly recommended due to its resolution and sensitivity, it has limitations such as operator subjectivity and difficulty detecting small metastases. This review shows the microanatomy of axillary LNs to enhance accurate diagnosis and the characteristics of contrast-enhanced US (CE-US), which utilizes intravascular microbubble contrast agents, making it ideal for vascular imaging. A significant focus of this review is on distinguishing between two types of CE-US techniques for axillary LN evaluation: perfusion CE-US and lymphatic CE-US. Perfusion CE-US is used to assess LN metastasis via transvenous contrast agent administration, while lymphatic CE-US is used to identify sentinel LNs and diagnose LN metastasis through percutaneous contrast agent administration. This review also highlights the need for future research to clarify the distinction between studies involving “apparently enlarged LNs” and “clinical node-negative” cases in perfusion CE-US research. Such research standardization is essential to ensure accurate diagnostic performance in various clinical studies. Future studies should aim to standardize CE-US methods for improved LN metastasis diagnosis, not only in breast cancer but also across various malignancies.
Literature
1.
Fisher B, Bauer M, Wickerham DL, et al. Relation of number of positive axillary nodes to the prognosis of patients with primary breast cancer. NSABP Update Cancer. 1983;52:1551–7.PubMed
2.
Nemoto T. Management and survival of female breast cancer: results of a national survey by the American College of Surgeons. Cancer. 1980;15:2917–24.CrossRef
3.
Chang JM, Leung JWT, Moy L, et al. Axillary Nodal Evaluation in Breast Cancer: State of the Art. Radiology. 2020;295:500–15.PubMedCrossRef
4.
Chung HL, Le-Petross HT, Leung JWT. Imaging Updates to Breast Cancer Lymph Node Management. Radiographics. 2021;41:1283–99.PubMedCrossRef
5.
Sun SX, Moseley TW, Kuerer HM, et al. Imaging-Based Approach to Axillary Lymph Node Staging and Sentinel Lymph Node Biopsy in Patients With Breast Cancer. Am J Roentgenol. 2020;214:249–58.CrossRef
6.
7.
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.PubMedCrossRef
8.
Shimizu H, Mori N, Mugikura S, et al. (2023) Application of Texture and Volume Model Analysis to Dedicated Axillary High-resolution 3D T2-weighted MR Imaging: A Novel Method for Diagnosing Lymph Node Metastasis in Patients with Clinically Node-negative Breast Cancer. MRMS mp.2022–0091
9.
Patani N, Mokbel K. The clinical significance of sentinel lymph node micrometastasis in breast cancer. Breast Cancer Res Treat. 2009;114:393–402.PubMedCrossRef
10.
Barr RG, Huang P, Luo Y, et al. Contrast-enhanced ultrasound imaging of the liver: a review of the clinical evidence for SonoVue and Sonazoid. Abdom Radiol (NY). 2020;45:3779–88.PubMedCrossRef
11.
Fujimitsu R, Shimakura M, Urakawa H, et al. Homogeneously enhancing breast lesions on contrast enhanced US: differential diagnosis by conventional and contrast enhanced US findings. Jpn J Radiol. 2016;34:508–14.PubMedCrossRef
12.
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.PubMedPubMedCentralCrossRef
13.
Schneider M, Arditi M, Barrau MB, et al. BR1: a new ultrasonographic contrast agent based on sulfur hexafluoride-filled microbubbles. Invest Radiol. 1995;30:451–7.PubMedCrossRef
14.
Dietrich CF, Nolsøe CP, Barr RG, et al. Guidelines and Good Clinical Practice Recommendations for Contrast Enhanced Ultrasound (CEUS) in the Liver – Update 2020 – WFUMB in Cooperation with EFSUMB, AFSUMB, AIUM, and FLAUS. Ultraschall Med. 2020;41:562–85.PubMedCrossRef
15.
Sidhu P, Cantisani V, Dietrich C, et al. The EFSUMB Guidelines and Recommendations for the Clinical Practice of Contrast-Enhanced Ultrasound (CEUS) in Non-Hepatic Applications: Update 2017 (Long Version). Ultraschall Med. 2018;39:e2-44.PubMedCrossRef
16.
Miyamoto Y, Ito T, Takada E, et al. Efficacy of Sonazoid (Perflubutane) for Contrast-Enhanced Ultrasound in the Differentiation of Focal Breast Lesions: Phase 3 Multicenter Clinical Trial. AJR Am J Roentgenol. 2014;202:W400–7.PubMedCrossRef
17.
Zhang YX, Wang XM, Kang S, et al. Contrast-enhanced ultrasonography in qualitative diagnosis of sentinel lymph node metastasis in breast cancer: A meta-analysis. J Cancer Res Ther. 2015;11:697–703.PubMedCrossRef
18.
Fowler JC, Solanki CK, Guenther I, et al. A pilot study of dual-isotope lymphoscintigraphy for breast sentinel node biopsy comparing intradermal and intraparenchymal injection. Eur J Surg Oncol. 2009;35:1041–7.PubMedCrossRef
19.
20.
Tanis PJ, Nieweg OE, Olmos RAV, et al. Anatomy and physiology of lymphatic drainage of the breast from the perspective of sentinel node biopsy. J Am Coll Surg. 2001;192:399–409.PubMedCrossRef
21.
Morton MJ, Charboneau JW, Banks PM. Inguinal lymphadenopathy simulating a false aneurysm on color-flow Doppler sonography. AJR Am J Roentgenol. 1988;151:115–6.PubMedCrossRef
22.
23.
Tschammler A, Ott G, Schang T, et al. Lymphadenopathy: differentiation of benign from malignant disease–color Doppler US assessment of intranodal angioarchitecture. Radiology. 1998;208:117–23.PubMedCrossRef
24.
Vermeulen PB, Sardari Nia P, Colpaert C, et al. Lack of angiogenesis in lymph node metastases of carcinomas is growth pattern-dependent. Histopathology. 2002;40:105–7.PubMedCrossRef
25.
Naresh KN, Nerurkar AY, Borges AM. Angiogenesis is redundant for tumour growth in lymph node metastases. Histopathology. 2001;38:466–70.PubMedCrossRef
26.
27.
Li L, Mori S, Kodama M, et al. Enhanced Sonographic Imaging to Diagnose Lymph Node Metastasis: Importance of Blood Vessel Volume and Density. Can Res. 2013;73:2082–92.CrossRef
28.
Sontum PC. Physicochemical characteristics of Sonazoid, a new contrast agent for ultrasound imaging. Ultrasound Med Biol. 2008;34:824–33.PubMedCrossRef
29.
Ito T. Let us utilize breast contrast-enhanced ultrasound more. J Med Ultrason. 2018;45:543–4.CrossRef
30.
Miyamoto Y, Ito T, Takada E, et al. Phase II clinical study of DD-723 (perflubutane): dose–response study in patients with breast tumors. J Med Ultrason. 2012;39:79–86.CrossRef
31.
Li L, Mori S, Sakamoto M, et al. Mouse Model of Lymph Node Metastasis via Afferent Lymphatic Vessels for Development of Imaging Modalities. Takabe K, editor. PLoS ONE. 2013;8:e55797.PubMedPubMedCentralCrossRef
32.
Kurihara T, Matsuda S, Nakamura Y, et al. Establishment of a model of sentinel lymph node metastasis using immunodeficient swine. Sci Rep. 2019;9:7923.PubMedPubMedCentralCrossRef
33.
Zhu J, Rowland EM, Harput S, et al. 3D Super-Resolution US Imaging of Rabbit Lymph Node Vasculature in Vivo by Using Microbubbles. Radiology. 2019;291:642–50.PubMedCrossRef
34.
Omoto K, Mizunuma H, Ogura S, et al. New method of sentinel node identification with ultrasonography using albumin as contrast agent: a study in pigs. Ultrasound Med Biol. 2002;28:1115–22.PubMedCrossRef
35.
Goldberg BB, Merton DA, Liu J-B, et al. Sentinel Lymph Nodes in a Swine Model with Melanoma: Contrast-enhanced Lymphatic US. Radiology. 2004;230:727–34.PubMedCrossRef
36.
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.PubMedCrossRef
37.
Cui Q, Dai L, Li J, et al. Accuracy of CEUS-guided sentinel lymph node biopsy in early-stage breast cancer: a study review and meta-analysis. World J Surg Oncol. 2020;18:112.PubMedPubMedCentralCrossRef
38.
Omoto K, Futsuhara K, Sekine O, et al. Sentinel Node Identification Method Using Contrast-Enhanced Ultrasonography with Sonazoid Injected Subareolarly in Breast Cancer: A Multicenter Study. Ultrasound Med Biol. 2011;37:S102.CrossRef
39.
Shimazu K, Ito T, Uji K, et al. Identification of sentinel lymph nodes by contrast-enhanced ultrasonography with Sonazoid in patients with breast cancer: a feasibility study in three hospitals. Cancer Med. 2017;6:1915–22.PubMedPubMedCentralCrossRef
40.
Liu X, Wang M, Wang Q, et al. Diagnostic value of contrast-enhanced ultrasound for sentinel lymph node metastasis in breast cancer: an updated meta-analysis. Breast Cancer Res Treat. 2023;202:221–31.PubMedCrossRef
41.
42.
Xu H, Xu GL, Li XD, et al. Correlation between the contrast-enhanced ultrasound image features and axillary lymph node metastasis of primary breast cancer and its diagnostic value. Clin Transl Oncol. 2021;23:155–63.PubMedCrossRef
43.
Agliata G, Valeri G, Argalia G, et al. Role of Contrast-Enhanced Sonography in the Evaluation of Axillary Lymph Nodes in Breast Carcinoma: A Monocentric Study. J Ultrasound Med. 2017;36:505–11.PubMedCrossRef
44.
Du LW, Liu HL, Gong HY, 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;94:20200874.PubMedCrossRef
45.
Zhuang L, Ming X, Liu J, et al. Comparison of lymphatic contrast-enhanced ultrasound and intravenous contrast-enhanced ultrasound in the preoperative diagnosis of axillary sentinel lymph node metastasis in patients with breast cancer. Br J Radiol. 2022;95:20210897.PubMedCrossRef
46.
Zhu AQ, Li XL, An LW, et al. Predicting Axillary Lymph Node Metastasis in Patients With Breast Invasive Ductal Carcinoma With Negative Axillary Ultrasound Results Using Conventional Ultrasound and Contrast-Enhanced Ultrasound. J Ultrasound Med. 2020;39:2059–70.PubMedCrossRef
47.
Lassau N, Chebil M, Chami L, et al. Dynamic contrast-enhanced ultrasonography (DCE-US): a new tool for the early evaluation of antiangiogenic treatment. Target Oncol. 2010;5:53–8.PubMedCrossRef
48.
Lyshchik A, Fleischer AC, Huamani J, et al. Molecular imaging of vascular endothelial growth factor receptor 2 expression using targeted contrast-enhanced high-frequency ultrasonography. J Ultrasound Med. 2007;26:1575–86.PubMedPubMedCentralCrossRef
49.
Pysz MA, Foygel K, Panje CM, et al. Assessment and monitoring tumor vascularity with contrast-enhanced ultrasound maximum intensity persistence imaging. Invest Radiol. 2011;46:187–95.PubMedPubMedCentralCrossRef
50.
Wilson SR, Jang HJ, Kim TK, et al. Real-Time Temporal Maximum-Intensity-Projection Imaging of Hepatic Lesions with Contrast-Enhanced Sonography. Am J Roentgenol. 2008;190:691–5.CrossRef
51.
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.PubMedCrossRef
52.
Ito K, Noro K, Yanagisawa Y, et al. High-Accuracy Ultrasound Contrast Agent Detection Method for Diagnostic Ultrasound Imaging Systems. Ultrasound Med Biol. 2015;41:3120–30.PubMedCrossRef
53.
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;27:821–31.PubMedCrossRef
54.
Pitre-Champagnat S, Leguerney I, Bosq J, et al. Dynamic Contrast-Enhanced Ultrasound Parametric Maps to Evaluate Intratumoral Vascularization. Invest Radiol. 2015;50:212–7.PubMedCrossRef
55.
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.PubMedCrossRef
56.
Mori N, Mugikura S, Miyashita M, et al. Perfusion contrast-enhanced ultrasound to predict early lymph-node metastasis in breast cancer. J Jpn J Radiol. 2019;37:145–53.PubMedCrossRef
57.
Shimizu H, Mori N, Ren H, et al. Multimodal imaging findings including high-resolution 3D T2-weighted imaging for COVID-19 vaccine-associated axillary lymphadenopathy in a patient with breast cancer. Radiol Case Rep. 2022;17:2831–6.PubMedPubMedCentralCrossRef
58.
Fang F, Gong Y, Liao L, et al. Value of Contrast-Enhanced Ultrasound for Evaluation of Cervical Lymph Node Metastasis in Papillary Thyroid Carcinoma. Front Endocrinol (Lausanne). 2022;13: 812475.PubMedCrossRef
59.
Luo ZY, Hong YR, Yan CX, et al. Utility of quantitative contrast-enhanced ultrasound for the prediction of lymph node metastasis in patients with papillary thyroid carcinoma. Clin Hemorheol Microcirc. 2022;80:37–48.PubMedCrossRef
60.
Ding Z, Deng C, Wang Z, et al. Comparison of contrast-enhanced ultrasound and contrast-enhanced computed tomography for the diagnosis of cervical lymph node metastasis in squamous cell carcinoma of the oral cavity. Int J Oral Maxillofac Surg. 2021;50:294–301.PubMedCrossRef
61.
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:W8-12.CrossRef
62.
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.CrossRef
63.
Rubaltelli L, Khadivi Y, Tregnaghi A, et al. Evaluation of lymph node perfusion using continuous mode harmonic ultrasonography with a second-generation contrast agent. J Ultrasound Med. 2004;23:829–36.PubMedCrossRef
64.
Toki A, Niikura H, Mori N, et al. Establishment of a Diagnostic Method for Pelvic Sentinel Lymph Node Metastasis by Contrast-Enhanced Ultrasound in Uterine Cancer. Ultrasound Med Biol. 2021;47:2107–16.PubMedCrossRef
65.
Kitano M, Sakamoto H, Kudo M. Contrast-enhanced endoscopic ultrasound. Dig Endosc. 2014;26(Suppl 1):79–85.PubMedCrossRef
Metadata
Title
Prospects of perfusion contrast-enhanced ultrasound (CE-US) in diagnosing axillary lymph node metastases in breast cancer: a comparison with lymphatic CE-US
Authors
Naoko Mori
Li Li
Masazumi Matsuda
Yu Mori
Shunji Mugikura
Publication date
20-04-2024
Publisher
Springer Nature Singapore
Published in
Journal of Medical Ultrasonics
Print ISSN: 1346-4523
Electronic ISSN: 1613-2254
DOI
https://doi.org/10.1007/s10396-024-01444-w