European Radiology

, Volume 25, Issue 2, pp 410–418 | Cite as

Differentiation of BIRADS-4 small breast lesions via Multimodal Ultrasound Tomography

  • G. Zografos
  • P. Liakou
  • D. Koulocheri
  • I. Liovarou
  • M. Sofras
  • S. Hadjiagapis
  • M. Orme
  • V. MarmarelisEmail author



To demonstrate the use of a new 3D diagnostic imaging technology, termed Multimodal Ultrasonic Tomography (MUT), for the detection of solid breast lesions < 15 mm in maximum dimension.

Methods and materials

3D MUT imaging was performed on 71 volunteers presenting BIRADS-4 nodules, asymmetrical densities, and architectural distortions in X-ray mammograms, who subsequently underwent biopsy. MUT involved D tomographic imaging of the pendulant breast in a water bath using transmission ultrasound and constructed multimodal images corresponding to refractivity and frequency-dependent attenuation (calibrated relative to water). The multimodal images were fused into composite images and a composite index (CI) was calculated and used for diagnostic purposes. The composite images were evaluated against results of histopathology on biopsy specimens.


Histopathology revealed 22 malignant and 49 benign lesions. The pixels of 22 malignant lesions exhibited high values in both refractivity and attenuation, resulting in CI values > 1. In contrast, 99.9 % of benign lesions and normal tissue pixels exhibited lower values of at least one of the attributes measured, corresponding to CI values < 1.


MUT imaging appears to differentiate small malignant solid breast lesions as exhibiting CI values >1, while benign lesions or normal breast tissues exhibit CI values <1.

Key Points

MUT was able to detect all 22 biopsy-confirmed malignant lesions.

MUT was able to differentiate the malignant from the benign lesions.

Additional MUT detections outside the biopsy area must be evaluated prospectively.


Breast cancer detection Ultrasound tomography Multimodal ultrasound Lesion differentiation 3D breast imaging 



Multimodal Ultrasound Tomography


Breast Imaging Reporting and Data System


Invasive ductal carcinoma


Ductal carcinoma in situ




Mediolateral oblique



The scientific guarantor of this publication is Professor George Zografos. The authors of this manuscript declare relationships with the following companies: Mastoscopia SA. The authors state that this work has not received any funding. No complex statistical methods were necessary for this paper. Approval, as required, was obtained by the Research Committee of the Hippokration University Hospital, which acts as the institutional review board. Written informed consent was obtained from all subjects (patients) in this study. Methodology: retrospective, observational, performed at one institution.


  1. 1.
    US Preventive Services Task Force (2009) Screening for breast cancer: U.S. preventive task force recommendation statement. Ann Intern Med 151:716–726CrossRefGoogle Scholar
  2. 2.
    Gabe R, Duffy SW (2005) Evaluation of service screening mammography in practice: the impact on breast cancer mortality. Ann Oncol 16:153–162CrossRefGoogle Scholar
  3. 3.
    Schopper D, de Wolf C (2009) How effective are breast cancer screening programmes by mammography? Review of the current evidence. Eur J Cancer 45:1916–1923PubMedCrossRefGoogle Scholar
  4. 4.
    Baines CJ (1999) A tangled web: factors likely to affect the efficacy of screening mammography. J Natl Cancer Inst 91:833–838PubMedCrossRefGoogle Scholar
  5. 5.
    Kerlikowske K, Grady D, Barclay J, Sickles EA, Ernster V (1996) Effect of age, breast density, and family history on the sensitivity of first screening mammography. JAMA 276:33–38PubMedCrossRefGoogle Scholar
  6. 6.
    Helbich TH (2000) Contrast-enhanced MRI of the breast. Eur J Radiol 34:208–219PubMedCrossRefGoogle Scholar
  7. 7.
    Eby PR, DeMartini WB, Peacock S, Rosen EL, Lauro B, Lehman CD (2007) Cancer yield of probably benign breast MR examinations. J Magn Reson Imaging 26:950–955PubMedCrossRefGoogle Scholar
  8. 8.
    Kuhl CK, Schrading S, Leutner CC et al (2005) Mammography, breast ultrasound and MRI for surveillance of women at high familial risk for breast cancer. J Clin Oncol 23:8469–8476PubMedCrossRefGoogle Scholar
  9. 9.
    Flobbe K, Bosch AM, Kessels AG et al (2003) The additional diagnostic value of ultrasonography in the diagnosis of breast cancer. Arch Intern Med 163:1194–1199PubMedCrossRefGoogle Scholar
  10. 10.
    Nothacker M, Duda V, Hahn M, Warm M, Degenhardt F, Madjar H et al (2009) Early detection of breast cancer: benefits and risks of supplemental breast ultrasound in asymptomatic women with mammographically dense breast tissue. A systematic review. BMC Cancer 9:335–343PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Golub RM, Parsons RE, Sigel B et al (1993) Differentiation of breast tumors by ultrasound tissue characterization. J Ultrasound Med 12:601–608PubMedGoogle Scholar
  12. 12.
    Stavros AT, Thickman D, Rapp CL et al (1995) Solid breast nodules: use of sonography to distinguish between benign and malignant lesions. Radiology 196:123–134PubMedCrossRefGoogle Scholar
  13. 13.
    Gefen S, Tretiak OJ, Piccoli CW et al (2003) ROC analysis of ultrasound tissue characterization classifiers for breast cancer diagnosis. IEEE Trans Med Imaging 22:170–177PubMedCrossRefGoogle Scholar
  14. 14.
    Chen CM, Chou YH, Han KC et al (2003) Breast lesions on sonograms: computer-aided diagnosis with nearly setting independent features and artificial neural networks. Radiology 226:504–514PubMedCrossRefGoogle Scholar
  15. 15.
    Smith A (2005) Full-field breast tomosynthesis. Radiol Manag 27:25–31Google Scholar
  16. 16.
    Kelly KM, Dean J, Comulada WS, Lee SJ (2010) Breast cancer detection using automated whole breast ultrasound and mammography in radiographically dense breast. Eur Radiol 20:734–742PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Garra BS, Cespedes EI, Ophir J, Spratt SR, Zuurbier RA, Magnant CM et al (1997) Elastography of breast lesions: initial clinical results. Radiology 202:79–86PubMedCrossRefGoogle Scholar
  18. 18.
    Thomas A, Fischer T, Frey H, Ohlinger R, Grunwald S, Blohmer J-U et al (2006) Real-time elastography — an advanced method of ultrasound: first results in 108 patients with breast lesions. Ultrasound Obstet Gynecol 28:335–340PubMedCrossRefGoogle Scholar
  19. 19.
    Marmarelis VZ, Kim TS, Shehada REN (2003) High resolution ultrasonic transmission tomography. Proc SPIE Med Imaging 5035:33–40CrossRefGoogle Scholar
  20. 20.
    Jeong JW, Kim TS, Do SH, Shin DC, Singh M, Marmarelis VZ (2005) Soft tissue differentiation using multi-band signatures of high resolution ultrasonic transmission tomography. IEEE Trans Med Imaging 24:399–408PubMedCrossRefGoogle Scholar
  21. 21.
    Marmarelis VZ, Jeong JW, Shin DC, Do SH (2007) High-resolution 3-D imaging and tissue differentiation with ultrasound transmission tomography. In: Andre ME (ed) Acoustical imaging, vol 28. Springer, Dordrecht, pp 195–206CrossRefGoogle Scholar
  22. 22.
    Jeong JW, Shin DC, Do SH, Klipfel NE, Holmes DR, Hovanessian-Larsen LJ et al (2008) Differentiation of cancerous lesions in excised human breast specimens using multi-band attenuation profiles from ultrasonic transmission tomography. J Ultrasound Med 27:435–451PubMedGoogle Scholar
  23. 23.
    Zografos G, Koulocheri D, Liakou P, Sofras M, Hadjiagapis S, Orme M, Marmarelis V (2011) Detection of breast cancer via 3D multimodal ultrasound tomography. European Congress of Radiology, Poster No. 5349Google Scholar
  24. 24.
    Marmarelis V, Sofras M, Orme M, Hadjiagapis S, Koulocheri D, Liakou P, Zografos G (2011) Novel diagnostic imaging technology for detection of breast cancer via 3D transmission ultrasound tomography. European Congress of Radiology, Poster No. 5357Google Scholar
  25. 25.
    Marmarelis V, Sofras M, Orme M, Hadjiagapis S, Koulocheri D, Liakou P, Zografos (2011) Detection and differentiation of mm-size lesions in the breast using the new technology of 3D Multimodal Ultrasonic Tomography. RSNA Conference, Poster No. 11034449Google Scholar
  26. 26.
    Zografos G, Koulocheri D, Liakou P, Grigoropoulos P, Sofras M, Hadjiagapis S, Orme M, Forte S, Marmarelis V (2012) Non-invasive differentiation of small breast lesions via 3D MUT imaging. European Congress of Radiology, Paper No. B0218Google Scholar
  27. 27.
    Zografos G, Koulocheri D, Liakou P, Liovarou I, Sofras M, Hadjiagapis S, Orme M, Marmarelis V (2014) Can transmission-ultrasound tomography detect small lesions in dense breasts? European Congress of Radiology, Paper No. B0465Google Scholar
  28. 28.
    Greenleaf JF, Bahn RC (1981) Clinical imaging with transmissive ultrasonic computerized tomography. IEEE Trans Biomed Eng 28:177–185PubMedCrossRefGoogle Scholar
  29. 29.
    Carson PL, Meyer CR, Scherzinger AL, Oughton TV (1981) Breast imaging in coronal planes with simultaneous pulse echo and transmission ultrasound. Science 214:1141–1143PubMedCrossRefGoogle Scholar
  30. 30.
    Schreiman JS, Gisvold JJ, Greenleaf JF, Bahn RC (1984) Ultrasound transmission computed tomography of the breast. Radiology 150:523–530PubMedCrossRefGoogle Scholar
  31. 31.
    Duric N, Littrup P, Poulo L, Babkin A, Holsapple E, Rama O et al (2007) Detection of breast cancer with ultrasound tomography: first results with the computed ultrasound risk evaluation (CURE) prototype. Med Phys 2:773–785CrossRefGoogle Scholar
  32. 32.
    Zografos G, Koulocheri D, Liakou P, Sofras M, Hadjiagapis S, Orme M et al (2013) Novel technology of Multimodal Ultrasound Tomography detects breast lesions. Eur Radiol 23:673–683PubMedCrossRefGoogle Scholar

Copyright information

© European Society of Radiology 2014

Authors and Affiliations

  • G. Zografos
    • 1
  • P. Liakou
    • 1
  • D. Koulocheri
    • 2
  • I. Liovarou
    • 3
  • M. Sofras
    • 3
  • S. Hadjiagapis
    • 3
  • M. Orme
    • 3
  • V. Marmarelis
    • 3
    • 4
    Email author
  1. 1.Breast UnitUniversity of Athens School of MedicineAthensGreece
  2. 2.Department of RadiologyHippokration HospitalAthensGreece
  3. 3.Mastoscopia S.A.AthensGreece
  4. 4.Department of Biomedical EngineeringUniversity of Southern CaliforniaLos AngelesUSA

Personalised recommendations