A Pivotal Study of Optoacoustic Imaging to Diagnose Benign and Malignant Breast Masses: A New Evaluation Tool for Radiologists

Published Online:https://doi.org/10.1148/radiol.2017172228

Laser optical imaging/US increased specificity in breast mass assessment compared with the grayscale US of the device alone, potentially reducing the number of false-positive examinations and biopsies of benign masses.


To compare the diagnostic utility of an investigational optoacoustic imaging device that fuses laser optical imaging (OA) with grayscale ultrasonography (US) to grayscale US alone in differentiating benign and malignant breast masses.

Materials and Methods

This prospective, 16-site study of 2105 women (study period: 12/21/2012 to 9/9/2015) compared Breast Imaging Reporting and Data System (BI-RADS) categories assigned by seven blinded independent readers to benign and malignant breast masses using OA/US versus US alone. BI-RADS 3, 4, or 5 masses assessed at diagnostic US with biopsy-proven histologic findings and BI-RADS 3 masses stable at 12 months were eligible. Independent readers reviewed US images obtained with the OA/US device, assigned a probability of malignancy (POM) and BI-RADS category, and locked results. The same independent readers then reviewed OA/US images, scored OA features, and assigned OA/US POM and a BI-RADS category. Specificity and sensitivity were calculated for US and OA/US. Benign and malignant mass upgrade and downgrade rates, positive and negative predictive values, and positive and negative likelihood ratios were compared.


Of 2105 consented subjects with 2191 masses, 100 subjects (103 masses) were analyzed separately as a training population and excluded. An additional 202 subjects (210 masses) were excluded due to technical failures or incomplete imaging, 72 subjects (78 masses) due to protocol deviations, and 41 subjects (43 masses) due to high-risk histologic results. Of 1690 subjects with 1757 masses (1079 [61.4%] benign and 678 [38.6%] malignant masses), OA/US downgraded 40.8% (3078/7535) of benign mass reads, with a specificity of 43.0% (3242/7538, 99% confidence interval [CI]: 40.4%, 45.7%) for OA/US versus 28.1% (2120/7543, 99% CI: 25.8%, 30.5%) for the internal US of the OA/US device. OA/US exceeded US in specificity by 14.9% (P < .0001; 99% CI: 12.9, 16.9%). Sensitivity for biopsied malignant masses was 96.0% (4553/4745, 99% CI: 94.5%, 97.0%) for OA/US and 98.6% (4680/4746, 99% CI: 97.8%, 99.1%) for US (P < .0001). The negative likelihood ratio of 0.094 for OA/US indicates a negative examination can reduce a maximum US-assigned pretest probability of 17.8% (low BI-RADS 4B) to a posttest probability of 2% (BI-RADS 3).


OA/US increases the specificity of breast mass assessment compared with the device internal grayscale US alone.

Online supplemental material is available for this article.

© RSNA, 2017


  • 1. Heywang-Köbrunner SH, Hacker A, Sedlacek S. Magnetic resonance imaging: the evolution of breast imaging. Breast 2013;22(Suppl 2):S77–S82. Crossref, MedlineGoogle Scholar
  • 2. Peters NH, Borel Rinkes IH, Zuithoff NP, Mali WP, Moons KG, Peeters PH. Meta-analysis of MR imaging in the diagnosis of breast lesions. Radiology 2008;246(1):116–124. LinkGoogle Scholar
  • 3. Medeiros LR, Duarte CS, Rosa DD, et al. Accuracy of magnetic resonance in suspicious breast lesions: a systematic quantitative review and meta-analysis. Breast Cancer Res Treat 2011;126(2):273–285. Crossref, MedlineGoogle Scholar
  • 4. Bruening W, Uhl S, Fontanarosa J, Reston J, Treadwell J, Schoelles K. Noninvasive Diagnostic Tests for Breast Abnormalities: Update of a 2006 Review. Rockville, Md: Agency for Healthcare Research and Quality, 2012. Google Scholar
  • 5. Hendrick RE. Radiation doses and cancer risks from breast imaging studies. Radiology 2010;257(1):246–253. LinkGoogle Scholar
  • 6. Valluru KS, Wilson KE, Willmann JK. Photoacoustic Imaging in Oncology: Translational Preclinical and Early Clinical Experience. Radiology 2016;280(2):332–349. LinkGoogle Scholar
  • 7. Manohar S, Vaartjes SE, van Hespen JC, et al. Initial results of in vivo non-invasive cancer imaging in the human breast using near-infrared photoacoustics. Opt Express 2007;15(19):12277–12285. Crossref, MedlineGoogle Scholar
  • 8. Butler R, Tucker FL, Lavin P, Stavros AT. Opto-acoustic breast imaging: imaging-pathology correlation of opto-acoustic features respecting malignancy. ECR 2015. Google Scholar
  • 9. Zhu Q, Cronin EB, Currier AA, et al. Benign versus malignant breast masses: optical differentiation with US-guided optical imaging reconstruction. Radiology 2005;237(1):57–66. LinkGoogle Scholar
  • 10. Zhu Q, You S, Jiang Y, et al. Detecting angiogenesis in breast tumors: comparison of color Doppler flow imaging with ultrasound-guided diffuse optical tomography. Ultrasound Med Biol 2011;37(6):862–869. Crossref, MedlineGoogle Scholar
  • 11. Zhu Q, Ricci A,Jr, Hegde P, et al. Assessment of Functional Differences in Malignant and Benign Breast Lesions and Improvement of Diagnostic Accuracy by Using US-guided Diffuse Optical Tomography in Conjunction with Conventional US. Radiology 2016;280(2):387–397. LinkGoogle Scholar
  • 12. Oraevsky AA. Optoacoustic tomography of the breast. In: Wang LV, ed. Photoacoustic Imaging and Spectroscopy. New York, NY: Taylor & Francis, 2009; 411–430. CrossrefGoogle Scholar
  • 13. Ermilov SA, Khamapirad T, Conjusteau A, et al. Laser optoacoustic imaging system for detection of breast cancer. J Biomed Opt 2009;14(2):024007. Google Scholar
  • 14. Su JL, Wang B, Wilson KE, et al. Advances in Clinical and Biomedical Applications of Photoacoustic Imaging. Expert Opin Med Diagn 2010;4(6):497–510. Crossref, MedlineGoogle Scholar
  • 15. Kruger RA, Lam RB, Reinecke DR, Del Rio SP, Doyle RP. Photoacoustic angiography of the breast. Med Phys 2010;37(11):6096–6100. Crossref, MedlineGoogle Scholar
  • 16. Choi JS, Kim MJ, Youk JH, Moon HJ, Suh HJ, Kim EK. US-guided optical tomography: correlation with clinicopathologic variables in breast cancer. Ultrasound Med Biol 2013;39(2):233–240. Crossref, MedlineGoogle Scholar
  • 17. Kitai T, Torii M, Sugie T, et al. Photoacoustic mammography: initial clinical results. Breast Cancer 2014;21(2):146–153. Crossref, MedlineGoogle Scholar
  • 18. Menke J. Photoacoustic breast tomography prototypes with reported human applications. Eur Radiol 2015;25(8):2205–2213. Crossref, MedlineGoogle Scholar
  • 19. Cicchetti DV. Guidelines, criteria, and rules of thumb for evaluating normed and standardized assessment instruments in psychology. Psychol Assess 1994;6(4):284–290. CrossrefGoogle Scholar
  • 20. Gong X, Xu Q, Xu Z, Xiong P, Yan W, Chen Y. Real-time elastography for the differentiation of benign and malignant breast lesions: a meta-analysis. Breast Cancer Res Treat 2011;130(1):11–18. Crossref, MedlineGoogle Scholar
  • 21. Liu B, Zheng Y, Huang G, et al. Breast Lesions: Quantitative Diagnosis Using Ultrasound Shear Wave Elastography-A Systematic Review and Meta–Analysis. Ultrasound Med Biol 2016;42(4):835–847. Crossref, MedlineGoogle Scholar
  • 22. Hu Q, Wang XY, Zhu SY, et al. Meta-analysis of contrast-enhanced ultrasound for the differentiation of benign and malignant breast lesions. Acta Radiol 2015;56:25–33. Crossref, MedlineGoogle Scholar
  • 23. Berg WA, Cosgrove DO, Dore CJ, et al. Shear-wave elastography improves the specificity of breast US: the BE1 multinational study of 939 masses. Radiology 2012;262(2):435–449. LinkGoogle Scholar

Article History

Received September 25, 2017; revision requested October 16; revision received and final version accepted November 13.
Published online: Nov 27 2017
Published in print: May 2018