New potential and applications of contrast-enhanced ultrasound of the breast; own investigations and review of the literature

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. © 2008 Elsevier Ireland Ltd. All rights reserved.

[1]  W. Sauerbrei,et al.  Assessment of breast cancer vascularisation by Doppler ultrasound as a prognostic factor of survival. , 2004, Oncology reports.

[2]  B. Goldberg,et al.  Breast tumor vascularity identified by contrast enhanced ultrasound and pathology: initial results. , 2000, Ultrasonics.

[3]  Helmut Madjar,et al.  Contrast ultrasound in breast tumor characterization: present situation and future tracks , 2001, European Radiology.

[4]  Emilio Quaia,et al.  US characterization of focal hepatic lesions with intermittent high-acoustic-power mode and contrast material. , 2003, Academic radiology.

[5]  M. Mathieu,et al.  Doppler US with perfusion software and contrast medium injection in the early evaluation of radiofrequency in breast cancer recurrences: a prospective phase II study. , 2005, European journal of radiology.

[6]  B. Goldberg,et al.  Sentinel lymph nodes in a swine model with melanoma: contrast-enhanced lymphatic US. , 2004, Radiology.

[7]  P. Phillips,et al.  Contrast–agent detection and quantification , 2004, European radiology.

[8]  M. Blomley.  Can microbubbles be targeted to lymph nodes? , 2004, Radiology.

[9]  W. Berg.  Supplemental screening sonography in dense breasts. , 2004, Radiologic clinics of North America.

[10]  M. Gallegos,et al.  Contrast enhanced harmonic ultrasound for differentiating breast tumors - first results. , 2005, Clinical hemorheology and microcirculation.

[11]  C. Balu-Maestro,et al.  Imaging in evaluation of response to neoadjuvant breast cancer treatment benefits of MRI. , 2005, Breast cancer research and treatment.

[12]  M. Schietzel,et al.  Tumor vascularity of breast lesions: potentials and limits of contrast-enhanced Doppler sonography. , 2000, AJR. American journal of roentgenology.

[13]  S. Kook,et al.  Value of contrast‐enhanced power Doppler sonography using a microbubble echo‐enhancing agent in evaluation of small breast lesions , 2003, Journal of clinical ultrasound : JCU.

[14]  A. Harris,et al.  Distinct Angiogenic patterns are associated with high‐grade in situ ductal carcinomas of the breast , 1997, The Journal of pathology.

[15]  E. Jung,et al.  Tissue Harmonic Imaging (THI) und Contrast Harmonic Imaging (CHI) zur sonographisch gezielten Vakuumstanzbiopsie mammographisch okkulter Brusttumoren , 2004 .

[16]  C. Bustos,et al.  Assessment of breast lesions using Doppler with contrast agents. , 2003, European journal of gynaecological oncology.

[17]  G P Liney,et al.  Differentiation of benign and malignant sub-1 cm breast lesions using dynamic contrast enhanced MRI. , 2004, Breast.

[18]  D O Cosgrove,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. , 2001, Radiology.

[19]  D. Cosgrove,et al.  Enhancement of power Doppler signals from breast lesions with the ultrasound contrast agent EchoGen emulsion: subjective and quantitative assessment. , 1998, Academic radiology.

[20]  Rosa Zabala,et al.  The use of unenhanced Doppler sonography in the evaluation of solid breast lesions. , 2005, AJR. American journal of roentgenology.

[21]  M. Bell,et al.  Immediate and late outcomes after direct stent implantation without balloon predilation. , 2000, Journal of the American College of Cardiology.

[22]  F. Penault-Llorca,et al.  High prognostic significance of residual disease after neoadjuvant chemotherapy: a retrospective study in 710 patients with operable breast cancer , 2005, Breast Cancer Research and Treatment.

[23]  G. Schwartz.  Neoadjuvant induction chemotherapy. , 2005, Minerva ginecologica.

[24]  C. Yücel,et al.  Contrast‐Enhanced Power Doppler Sonography in Breast Lesions , 2004, Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine.

[25]  Christian Greis,et al.  Technology overview: SonoVue (Bracco, Milan). , 2004, European radiology.

[26]  C Del Favero,et al.  A new Doppler signal enhancing agent for flow assessment in breast lesions. , 2000, European journal of ultrasound : official journal of the European Federation of Societies for Ultrasound in Medicine and Biology.

[27]  P. Phillips,et al.  Contrast pulse sequences (CPS): imaging nonlinear microbubbles , 2001, 2001 IEEE Ultrasonics Symposium. Proceedings. An International Symposium (Cat. No.01CH37263).

[28]  Takeo Ishigaki,et al.  The role of contrast-enhanced MR mammography for determining candidates for breast conservation surgery , 2002, Breast cancer.

[29]  M. Rinaldo,et al.  Color-doppler using contrast medium in evaluating the response to neoadjuvant treatment in patients with locally advanced breast carcinoma. , 2005, Anticancer research.

[30]  D. Noh,et al.  Nonpalpable breast lesions: evaluation with power Doppler US and a microbubble contrast agent-initial experience. , 2000, Radiology.

[31]  J. Im,et al.  Differentiation of benign from malignant solid breast masses: conventional US versus spatial compound imaging. , 2005, Radiology.

[32]  R. Warren,et al.  Can breast MRI help in the management of women with breast cancer treated by neoadjuvant chemotherapy? , 2004, British Journal of Cancer.

[33]  D. Cosgrove.  Future Prospects for SonoVue and CPS , 2004, European radiology.

[34]  Roland Felix,et al.  Role of power Doppler techniques and ultrasound contrast enhancement in the differential diagnosis of focal breast lesions , 2002, European Radiology.

[35]  Kazunori Taguchi,et al.  Magnetic resonance imaging for preoperative evaluation of breast cancer: a comparative study with mammography and ultrasonography. , 2004, Journal of the American College of Surgeons.

[36]  A. Broillet,et al.  Assessment of microvascular perfusion changes in a rat breast tumor model using SonoVue to monitor the effects of different anti-angiogenic therapies. , 2005, Academic radiology.

[37]  B. Schneider,et al.  Angiogenesis of breast cancer. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[38]  W. Sauerbrei,et al.  Color Doppler flow criteria of breast lesions. , 1994, Ultrasound in medicine & biology.

[39]  L. Alamo,et al.  Contrast-enhanced color Doppler ultrasound characteristics in hypervascular breast tumors: comparison with MRI , 2001, European Radiology.

[40]  E. van Marck,et al.  Intratumoral hypoxia resulting in the presence of a fibrotic focus is an independent predictor of early distant relapse in lymph node‐negative breast cancer patients , 2001, Histopathology.

[41]  V. R. McCready,et al.  Microbubble contrast agent for color Doppler US: effect on breast masses. Work in progress. , 1996, Radiology.

[42]  R. Bude.  Does contrast-enhanced US have potential for sentinel lymph node detection? , 2004, Radiology.

[43]  K. Holz,et al.  The role of enhanced Doppler Ultrasound in differentiation of benign vs. malignant scar lesion after breast surgery for malignancy , 2000, Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology.

[44]  J. Peterse,et al.  Contrast-enhanced MRI in breast cancer patients eligible for breast-conserving therapy: complementary value for subgroups of patients , 2006, European Radiology.

[45]  J. Jauhiainen,et al.  Dynamics of contrast enhancement in MR imaging and power Doppler ultrasonography of solid breast lesions. , 2002, Acta radiologica.