New potential and applications of contrast-enhanced ultrasound of the breast: Own investigations and review of the literature

https://doi.org/10.1016/j.ejrad.2008.07.037Get rights and content

Abstract

Imaging of angiogenesis is a challenge for modern imaging. Velocimetry in malignant breast lesions and density of malignant vessels are very low. In breast imaging, first results of contrast-enhanced ultrasound (CEUS) were disappointing. Microbubbles are fragile when examined with high frequency US, commonly used in breast imaging. Second-generation contrast agents increase intensively the signal level of breast lesions and new sequences like CPS (Coherence Pulse Sequencing) might be accurate to detect malignant vessels in breast lesions for characterization, to assess the extent of infiltrative breast carcinoma or to evaluate the tumor response after chemotherapy. Another interesting clinical application is the differentiation between post-operative changes and recurrences.

In this review, we detail the main results obtained with contrast ultrasonography in a characterization study. In malignant lesions, enhancement was fast, starting with less than 20 s. Compared to MR, enhancement appeared faster. Malignant vessels were predominant in the external ring of the nodule, conversely vessels were seen in the center of the lesion in benign nodules. Malignant vessels were also seen outside the lesion. This knowledge could lead the surgeon to perform a larger lumpectomy in these cases, to obtain sane margins and to reduce recurrences.

Section snippets

Principles of tumor vascularization and hypothetical clinical applications of contrast-enhanced ultrasound of the breast

US contrast agents with microbubbles are used to increase vascular signals at Doppler US and have been shown to improve color Doppler US assessment of tumoral vessels in breast lesions, despite typical motion and blooming artifacts and early signal saturation. Contrast-enhanced ultrasonography (CEUS) of the breast is less commonly performed than abdominal CEUS. Nevertheless, several authors had focussed on the possible application of sonographic contrast media to breast imaging [1], [2]. Main

Main features of vascularization and Doppler imaging in breast lesions

Angiogenesis plays a major role in the development of breast cancer. Both tumor growth and metastatic seeding are strongly related with the angiogenetic process [3]. It is also recognized that borderline lesions, considered as potentially malignant like atypical hyperplasia or the lobular carcinoma in situ have an overall vascularization more prominent than that of truly benign lesions. Among hypervascularized lesions, there is also a relationship between the density of the vessels and the

What are the clinical applications?

It is possible to evaluate the vascularization of breast masses with MRI using intravenous injection of Gadolinium chelate, and with CT using intravenous injection of iodine. As a statement, EUS could claim the same role than contrast-enhanced MRI which are the following:

  • -

    Characterization of an inconclusive mass on mammography and/or breast sonography and improvement for the differentiation between benign and malignant breast masses.

  • -

    Staging of ductal infiltrative cancers, especially in patients

Detection modes

Non-harmonic [10] and harmonic [11] US imaging techniques with air-filled contrast agents may overcome the limitations of color Doppler US and allow effective characterization of ambiguous breast lesions. Pulse-inversion harmonic imaging (PIHI) is a contrast-enhanced harmonic technique that works by sending two out-of-phase pulses and summing returning echoes. During low acoustic power imaging, microbubbles present a much higher non-linear behaviour than native tissues, expanding from a

Characterization of breast masses

Due to angiogenesis, vascularization of malignant lesions is more prominent than that of benign masses [17], [18]. Vessels morphology is also different: malignant vessels are tortuous and somewhat irregular; there is no muscular layer in these vessels, and the arterial wall is not elastic; vessels are more prominent in the peripheral part of the tumor than in the middle [19]. Resistive and pulsatility indices measured with Pulsed Doppler are higher than that of benign tumors. Resistive index

Discussion

From the literature, specificity is greatly improved using contrast media [28]. Nevertheless, of these higher specificity could be associated with a weaker sensitivity [29]. In this study, the authors have tried to determine the added value of contrast media in addition to regular sonography and Doppler imaging. They tried to classify the lesions according to the BIRADS classification for the B mode imaging, power Doppler imaging and contrast US with Levovist®. Among 69 cases (28 malignant, 41

Evaluation of tumor response after neoadjuvant chemotherapy

Early assessment of tumor response after chemotherapy is critical. It is one of the major prognostic factors in breast cancer [33]. Large tumors (>3 cm) or high grade tumors are usually treated with chemotherapy as a first-line treatment. The aim is to decrease the tumor size, to facilitate a conservative treatment when possible and to limit the possibility of metastatic spreading [34]. Mammography and plain sonography are not sufficient to evaluate the tumor size in response to treatment

Conclusion

The role of CEUS remains to be defined in many aspects. Its position in the strategy for the detection staging and follow-up of breast lesions is still unclear. The characteristics of tumor enhancement remain to be clarified with series using state-of-the-art equipment and second-generation contrast media, because previous series were too heterogeneous. Software allowing a more robust analysis of the enhancement curve characteristics should also facilitate the reproducibility. Acquisition

References (47)

  • W.A. Berg

    Supplemental screening sonography in dense breasts

    Radiol Clin North Am

    (2004)
  • R.P. Kedar et al.

    Microbubble contrast agent for color Doppler US: effect on breast masses. Work in progress

    Radiology

    (1996)
  • B.P. Schneider et al.

    Angiogenesis of breast cancer

    J Clin Oncol

    (2005)
  • D. Watermann et al.

    Assessment of breast cancer vascularisation by Doppler ultrasound as a prognostic factor of survival

    Oncol Rep

    (2004)
  • R.J. Schroeder et al.

    Role of power Doppler techniques and ultrasound contrast enhancement in the differential diagnosis of focal breast lesions

    Eur Radiol

    (2003)
  • H. Reinikainen et al.

    Dynamics of contrast enhancement in MR imaging and power Doppler ultrasonography of solid breast lesions

    Acta Radiol

    (2002)
  • L. Alamo et al.

    Contrast-enhanced color Doppler ultrasound characteristics in hypervascular breast tumors: comparison with MRI

    Eur Radiol

    (2001)
  • M. Stuhrmann et al.

    Breast cancer recurrence versus scar. Ultrasonographic differentiation using Levovist as the contrast medium

    Ultraschall Med

    (2001)
  • M.J.K. Blomley et al.

    Do different types of liver lesions differ in their uptake of the microbubble contrast agent SH U 508A in the late liver phase? Early experience

    Radiology

    (2001)
  • D. Cosgrove

    Future prospects for SonoVue and CPS

    Eur Radiol

    (2004)
  • C. Greis

    Technology overview: SonoVue (Bracco, Milan)

    Eur Radiol

    (2004)
  • P. Philips et al.

    Contrast-agent detection and quantification

    Eur Radiol

    (2004)
  • Cited by (79)

    • Meta-Analysis: Contrast-Enhanced Ultrasound Versus Conventional Ultrasound for Differentiation of Benign and Malignant Breast Lesions

      2018, Ultrasound in Medicine and Biology
      Citation Excerpt :

      It has been demonstrated that angiogenesis plays an important role in the development of breast cancer in terms of tumor growth and metastasis (Drudi et al. 2012), including most of the advanced breast cancers, and some others at early stages, such as atypical hyperplasia or lobular carcinoma in situ (Drudi et al. 2012). Researchers have found that internal and surrounding vascularity on US are characteristic of malignancy (Ferrara et al. 2000; Sehgal et al. 2000), and vascular density is associated with tumor aggressiveness (Balleyguier et al. 2009). Together these sonographic features of conventional US offer relatively high accuracy in distinguishing between benign and malignant breast lesions.

    • Ultrasound Imaging Technologies for Breast Cancer Detection and Management: A Review

      2018, Ultrasound in Medicine and Biology
      Citation Excerpt :

      Enhancement patterns in the early phase and contrast medium persistence in the late phase differ in benign and malignant breast lesions. The features of malignancy include early and fast enhancement in the early phase, centripetal filling, claw-shaped enhancement, higher maximum intensity and contrast medium accumulation in the late phase (see Fig. 5), whereas the features of benign tissue include delayed, centrifugal filling, homogeneous enhancement and seldomly contrast medium present in the late phase (see Fig. 6) (Balleyguier et al. 2009; del Cura et al. 2005; Jung et al. 2005; Zhao et al. 2010). Since 2011, the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) guidelines for CEUS of the breast remain an important topic for research, but have not been recommended for routine clinical use (Piscaglia et al. 2012).

    • Modulation of mammary tumor vascularization by mast cells: Ultrasonographic and histopathological approaches

      2017, Life Sciences
      Citation Excerpt :

      Although CEUS has some advantages when compared with Doppler, it is not a perfect method and present some disadvantages such as the placement of the ROI and the analysis of only one plane of the mammary tumor and not the entire lesion [57]. According to previous studies, malignant lesions showed higher maximum signal intensity (PI), fast wash-in, the wash-out is observed immediately after the peak (probably due to the presence of arteriovenous shunts and higher microvascular density) and shorter TTP; the opposite can be observed in benign lesions [52,58–60]. Due to a lack of studies on CEUS in rat models, it is not possible to establish comparisons of the data from this study with other previously obtained by other researchers.

    View all citing articles on Scopus
    View full text