European Radiology

, Volume 28, Issue 9, pp 3742–3750 | Cite as

Diagnosis of breast cancer based on microcalcifications using grating-based phase contrast CT

  • Xinbin Li
  • Hewei Gao
  • Zhiqiang ChenEmail author
  • Li Zhang
  • Xiaohua Zhu
  • Shengping Wang
  • Weijun Peng



Microcalcifications are an important feature in the diagnosis of breast cancer, especially in the early stages. In this paper, a CT-based method is proposed to potentially distinguish benign and malignant breast diseases based on the distributions of microcalcifications using grating-based phase-contrast imaging on a conventional X-ray tube.


The method presented based on the ratio of dark-field signals to attenuation signals in CT images is compared with the existing method based on the ratio in projections, and the threshold for the classification of microcalcifications in the two types of breast diseases is obtained using our approach. The experiment was operated on paraffin-fixed specimens that originated from 20 female patients ranging from 27–65 years old.


Compared with the method based on projection images (AUC = 0.87), the proposed method is more effective (AUC = 0.95) to distinguish the two types of diseases. The discrimination threshold of microcalcifications for the classification of diseases in CT images is found to be 3.78 based on the Youden index.


The proposed method can be further developed to improve the early diagnosis and diagnostic accuracy and reduce the clinical misdiagnosis rate of breast cancer.

Key Points

Microcalcifications are of special importance to indicate early breast cancer.

Grating-based phase-contrast imaging can improve the diagnosis of breast cancers.

The method described here can better classify benign and malignant breast diseases.


Breast diseases Microcalcifications Grating-based phase-contrast CT ROC curves Youden index 



This study has received funding by the National Natural Science Foundation of China (No. 11235007) and a Tsinghua University Independent Research Project Grant, “Research on Key Technologies and CT Reconstruction methods of multi-energy X-ray imaging”.

Compliance with ethical standards


The scientific guarantor of this publication is Zhiqiang Chen.

Conflict of interest

The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article.

Statistics and biometry

One of the authors, Shengping Wang, has significant statistical expertise.

Ethical approval

Institutional Review Board approval was obtained.

Informed consent

Written informed consent was obtained from all subjects (patients) in this study.


• prospective

• experimental

• performed at one institution


  1. 1.
    WHO | Cancer, WHO 2016Google Scholar
  2. 2.
    Fasching PA, Ekici AB, Adamietz BR, et al (2011) Breast Cancer Risk - Genes, Environment and Clinics. Geburtshilfe Frauenheilkd 71:1056–1066CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Hilleren DJ, Andersson IT, Lindholm K, Linnell FS (1991) Invasive lobular carcinoma: mammographic findings in a 10-year experience. Radiology 178:149–154CrossRefPubMedGoogle Scholar
  4. 4.
    Brenner RJ, Pfaff JM (1996) Mammographic features after conservation therapy for malignant breast disease: Serial findings standardized by regression analysis. Am J Roentgenol 167:171–178CrossRefGoogle Scholar
  5. 5.
    Sickles EA (2000) Breast Imaging: From 1965 to the Present1. Radiology 215:1–16CrossRefPubMedGoogle Scholar
  6. 6.
    Anton G, Bayer F, Beckmann MW, et al (2013) Grating-based darkfield imaging of human breast tissue. Z Med Phys 23:228–235CrossRefPubMedGoogle Scholar
  7. 7.
    Radi MJ (1989) Calcium oxalate crystals in breast biopsies. An overlooked form of microcalcification associated with benign breast disease. Arch Pathol Lab Med 113:1367–1369PubMedGoogle Scholar
  8. 8.
    Johnson JM (1999) Histological Correlation of Microcalcifications in Breast Biopsy Specimens. Arch Surg 134:712CrossRefPubMedGoogle Scholar
  9. 9.
    Haka AS, Shafer-Peltier KE, Fitzmaurice M, Crowe J, Dasari RR, Feld MS (2002) Identifying microcalcifications in benign and malignant breast lesions by probing differences in their chemical composition using raman spectroscopy. Cancer Res. 62:5375–5380PubMedGoogle Scholar
  10. 10.
    Dahlstrom JE, Jain S (2001) Histological correlation of mammographically detected microcalcifications in stereotactic core biopsies. Pathology 33:444–448CrossRefPubMedGoogle Scholar
  11. 11.
    Ellis IO, Humphreys S, Michell M, Pinder SE, Wells CA, Zakhour HD (2004) Best Practice No 179. Guidelines for breast needle core biopsy handling and reporting in breast screening assessment. J Clin Pathol 57:897–902CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Cai W, Ning R (2009) Dose efficiency consideration for volume-of-interest breast imaging using x-ray differential phase-contrast CT. Proc SPIE 7258:72584D–72584D–9CrossRefGoogle Scholar
  13. 13.
    Stampanoni M, Wang Z, Thüring T, et al (2011) The first analysis and clinical evaluation of native breast tissue using differential phase-contrast mammography. Invest Radiol 46:801–806CrossRefPubMedGoogle Scholar
  14. 14.
    Hauser N, Wang Z, Kubik-Huch RA, et al (2014) A study on mastectomy samples to evaluate breast imaging quality and potential clinical relevance of differential phase contrast mammography. Invest Radiol 49:131–137CrossRefPubMedGoogle Scholar
  15. 15.
    Sztrókay A, Herzen J, Auweter SD, et al (2013) Assessment of grating-based X-ray phase-contrast CT for differentiation of invasive ductal carcinoma and ductal carcinoma in situ in an experimental ex vivo set-up. Eur Radiol 23:381–387CrossRefPubMedGoogle Scholar
  16. 16.
    Willner M, Herzen J, Grandl S, et al (2014) Quantitative breast tissue characterization using grating-based x-ray phase-contrast imaging. Phys Med Biol 59:1557–1571CrossRefPubMedGoogle Scholar
  17. 17.
    Michette A, Buckley C (1993) X-ray science and technologyGoogle Scholar
  18. 18.
    Keyrilainen J, Bravin A, Fernandez M, Tenhunen M, Virkkunen P, Suortti P (2010) Phase-contrast X-ray imaging of breast. Acta Radiol 51:866–884CrossRefPubMedGoogle Scholar
  19. 19.
    Bonse U, Hart M (1965) An X-ray interferometer. Appl Phys Lett 6:155–156CrossRefGoogle Scholar
  20. 20.
    Takeda M, Ina H, Kobayashi S (1982) Fourier-transform method of fringe-pattern analysis for computer-based topography and interferometry. J Opt Soc Am 72:156CrossRefGoogle Scholar
  21. 21.
    Momose A, Fukuda J (1995) Phase-contrast radiographs of nonstained rat cerebellar specimen. Med Phys 22:375–379CrossRefPubMedGoogle Scholar
  22. 22.
    Davis TJ, Gao D, Gureyev TE, Stevenson AW, Wilkins SW (1995) Phase-contrast imaging of weakly absorbing materials using hard X-rays. Nature 373:595–598CrossRefGoogle Scholar
  23. 23.
    Chapman D, Thomlinson W, Johnston RE, et al (1997) Diffraction enhanced x-ray imaging. Phys Med Biol 42:2015–2025CrossRefPubMedGoogle Scholar
  24. 24.
    Snigirev A, Snigireva I, Kohn V, Kuznetsov S, Schelokov I (1995) On the possibilities of x-ray phase contrast microimaging by coherent high-energy synchrotron radiation. Rev Sci Instrum 66:5486–5492CrossRefGoogle Scholar
  25. 25.
    Wilkins SW, Gureyev TE, Gao D, Pogany A, Stevenson AW (1996) Phase-contrast imaging using polychromatic hard X-rays. Nature 384:335–338CrossRefGoogle Scholar
  26. 26.
    Chen R, Liu P, Xiao T, Xu LX (2014) X-ray imaging for non-destructive microstructure analysis at SSRF. Adv Mater 26:7688–7691CrossRefPubMedGoogle Scholar
  27. 27.
    David C, Nöhammer B, Solak HH, Ziegler E (2002) Differential x-ray phase contrast imaging using a shearing interferometer. Appl Phys Lett 81:3287–3289CrossRefGoogle Scholar
  28. 28.
    Momose A (2003) Phase-sensitive imaging and phase tomography using X-ray interferometers. Opt Express 11:2303–2314CrossRefPubMedGoogle Scholar
  29. 29.
    Pfeiffer F, Weitkamp T, Bunk O, David C (2006) Phase retrieval and differential phase-contrast imaging with low-brilliance X-ray sources. Nat Phys 2:258–261CrossRefGoogle Scholar
  30. 30.
    David C, Weitkamp T, Pfeiffer F, et al (2007) Hard X-ray phase imaging and tomography using a grating interferometer. Spectrochim Acta B At Spectrosc 62:626–630CrossRefGoogle Scholar
  31. 31.
    Pfeiffer F (2012) Milestones and basic principles of grating-based x-ray and neutron phase-contrast imaging. AIP Conf Proc 1466:2–11CrossRefGoogle Scholar
  32. 32.
    Coan P, Bravin A, Tromba G (2013) Phase-contrast x-ray imaging of the breast: recent developments towards clinics. J Phys D Appl Phys 46:494007CrossRefGoogle Scholar
  33. 33.
    Roessl E, Daerr H, Koehler T, Martens G, van Stevendaal U (2014) Clinical boundary conditions for grating-based differential phase-contrast mammography. Philos Trans R Soc A Math Phys Eng Sci 372:1–7CrossRefGoogle Scholar
  34. 34.
    Fredenberg E, Danielsson M, Stayman JW, Siewerdsen JH, Aslund M, Åslund M (2012) Ideal-observer detectability in photon-counting differential phase-contrast imaging using a linear-systems approach. Med Phys 39:5317–5335CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Olivo A, Gkoumas S, Endrizzi M, et al (2013) Low-dose phase contrast mammography with conventional x-ray sources. Med Phys 40:90701CrossRefGoogle Scholar
  36. 36.
    Morita T, Yamada M, Kano A, Nagatsuka S, Honda C, Endo T (2008) A comparison between film-screen mammography and full-field digital mammography utilizing phase contrast technology in breast cancer screening programs. Digital Mammography 2008:48–54Google Scholar
  37. 37.
    Tanaka T, Honda C, Matsuo S, et al (2005) The first trial of phase contrast imaging for digital full-field mammography using a practical molybdenum x-ray tube. Invest Radiol 40:385–396CrossRefPubMedGoogle Scholar
  38. 38.
    Michel T, Rieger J, Anton G, et al (2013) On a dark-field signal generated by micrometer-sized calcifications in phase-contrast mammography. Phys Med Biol 58:2713–2732CrossRefPubMedGoogle Scholar
  39. 39.
    Wang Z, Hauser N, Singer G, et al (2014) Non-invasive classification of microcalcifications with phase-contrast X-ray mammography. Nat Commun 5:3797CrossRefPubMedGoogle Scholar
  40. 40.
    Scherer KH (2016) Grating-Based X-Ray Phase-Contrast Mammography. Technical University of Munich, GermanyCrossRefGoogle Scholar
  41. 41.
    Wang ZT, Kang KJ, Huang ZF, Chen ZQ (2009) Quantitative grating-based x-ray dark-field computed tomography. Appl Phys Lett 95:94105CrossRefGoogle Scholar
  42. 42.
    Maier A, Hofmann HG, Berger M, et al (2013) CONRAD--a software framework for cone-beam imaging in radiology. Med Phys 40:111914CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Fawcett T (2006) An introduction to ROC analysis. Pattern Recognit Lett 27:861–874CrossRefGoogle Scholar
  44. 44.
    Hanley JA, McNeil BJ (1982) The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiol Illinois 143:29–36CrossRefGoogle Scholar
  45. 45.
    Zweig MH, Campbell G (1993) Receiver-operating characteristic (ROC) plots: A fundamental evaluation tool in clinical medicine. Clin. Chem. 39:561–577PubMedGoogle Scholar
  46. 46.
    Youden WJ (1950) Index for rating diagnostic tests. Cancer 3:32–35CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Schisterman EF, Perkins NJ, Liu A, Bondell H (2005) Optimal cut-point and its corresponding Youden Index to discriminate individuals using pooled blood samples. Epidemiology 16:73–81CrossRefPubMedGoogle Scholar
  48. 48.
    Ruopp MD, Perkins NJ, Whitcomb BW, Schisterman EF (2008) Youden Index and optimal cut-point estimated from observations affected by a lower limit of detection. Biometrical J. 50:419–430CrossRefGoogle Scholar
  49. 49.
    Scherer K, Willer K, Gromann L, et al (2015) Toward Clinically Compatible Phase-Contrast Mammography. PLoS One 10:e0130776CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Grandl S, Scherer K, Sztrokay-Gaul A, et al (2015) Improved visualization of breast cancer features in multifocal carcinoma using phase-contrast and dark-field mammography: an ex vivo study. Eur Radiol 25:3659–3668CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Scherer K, Birnbacher L, Chabior M, et al (2014) Bi-directional x-ray phase-contrast mammography. PLoS One 9:e93502CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Liu J, Cai W, Ning R (2016) Evaluation of differential phase contrast cone beam CT imaging system. J Xray Sci Technol 25:357–372Google Scholar
  53. 53.
    Ge Y, Li K, Garrett J, Chen GH (2014) Grating based x-ray differential phase contrast imaging without mechanical phase stepping. Opt Express 22:14246–14252CrossRefPubMedGoogle Scholar
  54. 54.
    Kagias M, Wang Z, Villanueva-Perez P, Jefimovs K, Stampanoni M (2016) 2D-Omnidirectional Hard-X-Ray Scattering Sensitivity in a Single Shot. Phys Rev Lett 116:93902CrossRefGoogle Scholar
  55. 55.
    Momose A, Yashiro W, Harasse S, Kuwabara H (2011) Four-dimensional X-ray phase tomography with Talbot interferometry and white synchrotron radiation: dynamic observation of a living worm. Opt Express 19:8423–8432CrossRefPubMedGoogle Scholar
  56. 56.
    Wang Z, Huang Z, Zhang L, et al (2011) Low dose reconstruction algorithm for differential phase contrast imaging. J Xray Sci Technol 19:403–415PubMedGoogle Scholar
  57. 57.
    Stutman D, Finkenthal M (2012) Glancing angle Talbot-Lau grating interferometers for phase contrast imaging at high x-ray energy. Appl. Phys. Lett. 101:1–6CrossRefGoogle Scholar
  58. 58.
    Zanette I, Bech M, Rack A, et al (2012) Trimodal low-dose X-ray tomography. Proc Natl Acad Sci U S A 109:10199–10204CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Miao H, Chen L, Bennett EE, et al (2013) Motionless phase stepping in X-ray phase contrast imaging with a compact source. Proc Natl Acad Sci 110:19268–19272CrossRefPubMedGoogle Scholar
  60. 60.
    Bevins N, Zambelli J, Li K, Qi Z, Chen G-H (2012) Multicontrast x-ray computed tomography imaging using Talbot-Lau interferometry without phase stepping. Med Phys 39:424CrossRefPubMedGoogle Scholar
  61. 61.
    Marschner M, Willner M, Potdevin G, et al (2016) Helical X-ray phase-contrast computed tomography without phase stepping. Sci Rep 6:23953CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Xie H, Cai W, Yang L, Mao H, Tang X (2016) Reducing radiation dose in grating based x-ray phase contrast CT with twin-peaks in its phase stepping curves. Med Phys 43:5942–5950CrossRefPubMedGoogle Scholar

Copyright information

© European Society of Radiology 2018

Authors and Affiliations

  • Xinbin Li
    • 1
    • 2
  • Hewei Gao
    • 3
  • Zhiqiang Chen
    • 1
    • 2
    Email author
  • Li Zhang
    • 1
    • 2
  • Xiaohua Zhu
    • 1
    • 2
  • Shengping Wang
    • 4
  • Weijun Peng
    • 4
  1. 1.Department of Engineering PhysicsTsinghua UniversityBeijingChina
  2. 2.Key Laboratory of Particle and Radiation Imaging (Tsinghua University) of Ministry of EducationBeijingChina
  3. 3.RefleXion MedicalHaywardUSA
  4. 4.Fudan University Shanghai Cancer CenterShanghaiChina

Personalised recommendations