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. 2015 Apr 30:5:9907.
doi: 10.1038/srep09907.

Raman spectroscopic sensing of carbonate intercalation in breast microcalcifications at stereotactic biopsy

R Sathyavathi  1 , Anushree Saha  2 , Jaqueline S Soares  3 , Nicolas Spegazzini  4 , Sasha McGee  5 , Ramachandra Rao Dasari  4 , Maryann Fitzmaurice  2 , Ishan Barman  6
Affiliations

Raman spectroscopic sensing of carbonate intercalation in breast microcalcifications at stereotactic biopsy

R Sathyavathi et al. Sci Rep. .

Abstract

Microcalcifications are an early mammographic sign of breast cancer and frequent target for stereotactic biopsy. Despite their indisputable value, microcalcifications, particularly of the type II variety that are comprised of calcium hydroxyapatite deposits, remain one of the least understood disease markers. Here we employed Raman spectroscopy to elucidate the relationship between pathogenicity of breast lesions in fresh biopsy cores and composition of type II microcalcifications. Using a chemometric model of chemical-morphological constituents, acquired Raman spectra were translated to characterize chemical makeup of the lesions. We find that increase in carbonate intercalation in the hydroxyapatite lattice can be reliably employed to differentiate benign from malignant lesions, with algorithms based only on carbonate and cytoplasmic protein content exhibiting excellent negative predictive value (93-98%). Our findings highlight the importance of calcium carbonate, an underrated constituent of microcalcifications, as a spectroscopic marker in breast pathology evaluation and pave the way for improved biopsy guidance.

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Figures

Figure 1
Figure 1
Representative Raman spectra of (a) a benign breast lesion (FCC) and (b) a malignant breast lesion (DCIS) with type II microcalcifications, with model fits and residuals; (c) Raman spectra of pure calcium hydroxyapatite (CaHa) and calcium carbonate (CaCa); and (d) 960 cm−1 Raman feature, characteristic of apatite structures, acquired from a benign lesion with type II microcalcifications. The overlaid Lorentzian fit is used to compute the FWHM of the band and, thus, to provide a measure of the carbonate intercalation in the apatite structure.
Figure 2
Figure 2
Box plots summarizing the Raman spectra-derived data for the different breast lesions with type II microcalcifications: (a) the FWHM of the 960 cm−1 band, (b) the FC of calcium carbonate (CaCa) and (c) the FC of cytoplasmic protein content.
Figure 3
Figure 3
Two-parameter Raman decision algorithm developed to distinguish malignant from benign breast lesions with type II microcalcifications. DCIS/IDC sites are depicted by red squares, while the FCC and FA lesions are marked by blue stars and blue circles, respectively.
Figure 4
Figure 4
Photomicrograph of an H&E-stained breast biopsy tissue core harboring type II microcalcifications within a benign breast lesion (fibrocystic change)(4X). The box highlights the lesion interrogation volume. The microcalcifications (arrows) occupy only a small fraction of the overall tissue volume sampled by the Raman spectroscopy fiber-probe.
See this image and copyright information in PMC

References

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