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Research Article

Diagnostic power of diffuse reflectance spectroscopy for targeted detection of breast lesions with microcalcifications

Jaqueline S. Soares, Ishan Barman, Narahara Chari Dingari, Zoya Volynskaya, Wendy Liu, Nina Klein, Donna Plecha, Ramachandra R. Dasari, and Maryann Fitzmaurice
  1. aGeorge R. Harrison Spectroscopy Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139;
  2. bDepartments of Pathology and Radiology, Case Western Reserve University, Cleveland, OH 44106; and
  3. cDepartments of Pathology and Radiology, University Hospitals Case Medical Center, Cleveland, OH 44106

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PNAS first published December 24, 2012; https://doi.org/10.1073/pnas.1215473110
Jaqueline S. Soares
aGeorge R. Harrison Spectroscopy Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139;
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Ishan Barman
aGeorge R. Harrison Spectroscopy Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139;
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Narahara Chari Dingari
aGeorge R. Harrison Spectroscopy Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139;
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Zoya Volynskaya
aGeorge R. Harrison Spectroscopy Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139;
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Wendy Liu
bDepartments of Pathology and Radiology, Case Western Reserve University, Cleveland, OH 44106; and
cDepartments of Pathology and Radiology, University Hospitals Case Medical Center, Cleveland, OH 44106
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Nina Klein
bDepartments of Pathology and Radiology, Case Western Reserve University, Cleveland, OH 44106; and
cDepartments of Pathology and Radiology, University Hospitals Case Medical Center, Cleveland, OH 44106
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Donna Plecha
bDepartments of Pathology and Radiology, Case Western Reserve University, Cleveland, OH 44106; and
cDepartments of Pathology and Radiology, University Hospitals Case Medical Center, Cleveland, OH 44106
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Ramachandra R. Dasari
aGeorge R. Harrison Spectroscopy Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139;
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Maryann Fitzmaurice
bDepartments of Pathology and Radiology, Case Western Reserve University, Cleveland, OH 44106; and
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  • For correspondence: maryann.fitzmaurice@case.edu
  1. Edited* by Mildred S. Dresselhaus, Massachusetts Institute of Technology, Cambridge, MA, and approved November 14, 2012 (received for review September 5, 2012)

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Abstract

Microcalcifications geographically target the location of abnormalities within the breast and are of critical importance in breast cancer diagnosis. However, despite stereotactic guidance, core needle biopsy fails to retrieve microcalcifications in up to 15% of patients. Here, we introduce an approach based on diffuse reflectance spectroscopy for detection of microcalcifications that focuses on variations in optical absorption stemming from the calcified clusters and the associated cross-linking molecules. In this study, diffuse reflectance spectra are acquired ex vivo from 203 sites in fresh biopsy tissue cores from 23 patients undergoing stereotactic breast needle biopsies. By correlating the spectra with the corresponding radiographic and histologic assessment, we have developed a support vector machine-derived decision algorithm, which shows high diagnostic power (positive predictive value and negative predictive value of 97% and 88%, respectively) for diagnosis of lesions with microcalcifications. We further show that these results are robust and not due to any spurious correlations. We attribute our findings to the presence of proteins (such as elastin), and desmosine and isodesmosine cross-linkers in the microcalcifications. It is important to note that the performance of the diffuse reflectance decision algorithm is comparable to one derived from the corresponding Raman spectra, and the considerably higher intensity of the reflectance signal enables the detection of the targeted lesions in a fraction of the spectral acquisition time. Our findings create a unique landscape for spectroscopic validation of breast core needle biopsy for detection of microcalcifications that can substantially improve the likelihood of an adequate, diagnostic biopsy in the first attempt.

  • histopathology
  • mammography
  • real-time guidance

Footnotes

  • ↵1J.S.S., I.B., and N.C.D. contributed equally to this work.

  • ↵2Present address: Aperio Technologies, Inc., Vista, CA, 92081.

  • ↵3To whom correspondence should be addressed. E-mail: maryann.fitzmaurice{at}case.edu.
  • Author contributions: J.S.S., I.B., N.C.D., Z.V., R.R.D., and M.F. designed research; J.S.S., I.B., N.C.D., Z.V., W.L., N.K., D.P., and M.F. performed research; J.S.S., I.B., and N.C.D. analyzed data; and J.S.S., I.B., N.C.D., and M.F. wrote the paper.

  • The authors declare no conflict of interest.

  • ↵*This Direct Submission article had a prearranged editor.

  • This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1215473110/-/DCSupplemental.

Freely available online through the PNAS open access option.

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Reflectance spectra detect breast calcifications
Jaqueline S. Soares, Ishan Barman, Narahara Chari Dingari, Zoya Volynskaya, Wendy Liu, Nina Klein, Donna Plecha, Ramachandra R. Dasari, Maryann Fitzmaurice
Proceedings of the National Academy of Sciences Dec 2012, 201215473; DOI: 10.1073/pnas.1215473110

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Reflectance spectra detect breast calcifications
Jaqueline S. Soares, Ishan Barman, Narahara Chari Dingari, Zoya Volynskaya, Wendy Liu, Nina Klein, Donna Plecha, Ramachandra R. Dasari, Maryann Fitzmaurice
Proceedings of the National Academy of Sciences Dec 2012, 201215473; DOI: 10.1073/pnas.1215473110
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