Abstract
Diffuse reflectance spectroscopy (DRS) is a promising new technique for breast cancer diagnosis. However, inter-patient variation due to breast tissue heterogeneity may interfere with the accuracy of this technique. To tackle this issue, we aim to determine the diagnostic accuracy of DRS in individual patients. With this approach, DRS measurements of normal breast tissue in every individual patient are directly compared with measurements of the suspected malignant tissue. Breast tissue from 47 female patients was analysed ex vivo by DRS. A total of 1,073 optical spectra were collected. These spectra were analyzed for each patient individually as well as for all patients collectively and results were compared to the pathology analyses. Collective patient data analysis for discrimination between normal and malignant breast tissue resulted in a sensitivity of 90 %, a specificity of 88 %, and an overall accuracy of 89 %. In the individual analyses all measurements per patient were categorized as either benign or malignant. The discriminative accuracy of these individual analyses was nearly 100 %. The diagnosis was classified as uncertain in only one patient. Based on the results presented in this study, we conclude that the analysis of optical characteristics of different tissue classes within the breast of a single patient is superior to an analysis using the results of a cohort data analysis. When integrated into a biopsy device, our results demonstrate that DRS may have the potential to improve the diagnostic workflow in breast cancer.
Similar content being viewed by others
References
Gioux S, Choi H, Frangioni J (2010) Image-guided surgery using invisible near-infrared light: fundamentals of clinical translation. Mol Imaging 9(5):237–255
Keereweer S, Kerrebijn J, van Driel P, Xie B, Kaijzel E, Snoeks T, Que I, Hutteman M, van der Vorst J, Mieog J, Vahrmeijer A, van de Velde C, Baatenburg de Jong R, Löwik C (2011) Optical image-guided surgery—where do we stand? Mol Imaging Biol 13(2):199–207
Brown J, Vishwanath K, Palmer G, Ramanujam N (2009) Advances in quantitative UV-visible spectroscopy for clinical and pre-clinical application in cancer. Curr Opin Biotechnol 20(1):119–131
Sćepanović O, Volynskaya Z, Kong C, Galindo L, Dasari R, Feld M (2009) A multimodal spectroscopy system for real-time disease diagnosis. Rev Sci Instrum 80(4):043103
Zhu C, Palmer G, Breslin T, Harter J, Ramanujam N (2008) Diagnosis of breast cancer using fluorescence and diffuse reflectance spectroscopy: a Monte-Carlo-model-based approach. J Biomed Opt 13(3):034015
Ariga R, Bloom K, Reddy V, Kluskens L, Francescatti D, Dowlat K, Siziopikou P, Gattuso P (2002) Fine-needle aspiration of clinically suspicious palpable breast masses with histopathologic correlation. Am J Surg 184(5):410–413
Burns R, Brown J, Roe S, Sprouse L, Yancey A, Witherspoon L (2000) Stereotactic core-needle breast biopsy by surgeons: minimum 2-year follow-up of benign lesions. Ann Surg 232(4):542–548
Chaiwun B, Settakorn J, Ya-In C, Wisedmongkol W, Rangdaeng S, Thorner P (2002) Effectiveness of fine-needle aspiration cytology of breast: analysis of 2,375 cases from northern Thailand. Diagn Cytopathol 26(3):201–205
Youk J, Kim E, Kim M, Lee J, Oh K (2007) Missed breast cancers at US-guided core needle biopsy: how to reduce them. Radiographics 27(1):79–94
Kennedy S, Geradts J, Bydlon T, Brown J, Gallagher J, Junker M, Barry W, Ramanujam N, Wilke L (2010) Optical breast cancer margin assessment: an observational study of the effects of tissue heterogeneity on optical contrast. Breast Cancer Res Treat 12(6):R91
Vishwanath K, Yuan H, Barry W, Dewhirst M, Ramanujam N (2009) Using optical spectroscopy to longitudinally monitor physiological changes within solid tumors. Neoplasia 11(9):889–900
Volynskaya Z, Haka A, Bechtel K, Fitzmaurice M, Shenk R, Wang N, Nazemi J, Dasari R, Feld M (2008) Diagnosing breast cancer using diffuse reflectance spectroscopy and intrinsic fluorescence spectroscopy. J Biomed Opt 13(2):024012
Keller M, Majumder S, Kelley M, Meszoely I, Boulos F, Olivares G, Mahadevan-Jansen A (2010) Autofluorescence and diffuse reflectance spectroscopy and spectral imaging for breast surgical margin analysis. Lasers Surg Med 42(1):15–23
Brown J, Wilke L, Geradts J, Kennedy S, Palmer G, Ramanujam N (2009) Quantitative optical spectroscopy: a robust tool for direct measurement of breast cancer vascular oxygenation and total hemoglobin content in vivo. Cancer Res 69(7):2919–2926
Zhu C, Palmer G, Breslin T, Harter J, Ramanujam N (2006) Diagnosis of breast cancer using diffuse reflectance spectroscopy: comparison of a Monte Carlo versus partial least squares analysis based feature extraction technique. Lasers Surg Med 38(7):714–724
Bigio I, Bown S, Briggs G, Kelley C, Lakhani S, Pickard D, Ripley P, Rose I, Saunders C (2000) Diagnosis of breast cancer using elastic-scattering spectroscopy: preliminary clinical results. J Biomed Opt 5(2):221–228
Breslin T, Xu F, Palmer G, Zhu C, Gilchrist K, Ramanujam N (2004) Autofluorescence and diffuse reflectance properties of malignant and benign breast tissues. Ann Surg Oncol 11(1):65–70
Nachabé R, Hendriks B, van der Voort M, Desjardins A, Sterenborg H (2010) Estimation of biological chromophores using diffuse optical spectroscopy: benefit of extending the UV–VIS wavelength range to include 1000 to 1600 nm. Biomed Optics Express 18(24):1432–1442
Nachabé R, Hendriks B, Desjardins A, van der Voort M, van der Mark M, Sterenborg H (2010) Estimation of lipid and water concentrations in scattering media with diffuse optical spectroscopy from 900 to 1,600 nm. J Biomed Opt 15(3):037015
Nachabé R, Evers D, Hendriks B, Lucassen G, van der Voort M, Rutgers E, Vrancken Peeters M, van der Hage J, Oldenburg H, Wesseling J, Ruers T (2011) Diagnosis of breast cancer using diffuse optical spectroscopy from 500 to 1600 nm: a comparison of classification methods. J Biomed Opt 16(8):087010
Nachabé R, Evers D, Hendriks B, Lucassen G, van der Voort M, Wesseling J, Ruers T (2011) Effect of bile absorption coefficients on the estimation of liver tissue optical properties and related complications in discriminating healthy and tumorous samples. Biomed Optics Express 2(3):600–614
Zonios G, Perelman L, Backman V, Manoharan R, Fitzmaurice M, Van Dam J, Feld M (1999) Diffuse reflectance spectroscopy of human adenomatous colon polyps in vivo. Appl Opt 38(31):6628–6637
Farrell T, Patterson M, Wilson B (1992) A diffusion theory model of spatially resolved, steady-state diffuse reflectance for the noninvasive determination of tissue optical properties in vivo. Med Phys 19(4):879–888
Breiman L, Friedman J, Olshen R, Stone C (1984) Classification and regression trees. Statistics/probability series. Wadsworth Publishing Company, Belmont, CA
Kruskal W, Wallis W (1952) Use of ranks in one-criterion variance analysis. J Am Stat Assoc 47(260):583–621
Zhu C, Breslin T, Harter J, Ramanujam N (2008) Model based and empirical spectral analysis for the diagnosis of breast cancer. Biomed Opt Express 16(19):14961–14978
Majumder S, Keller M, Boulos F, Kelley M, Mahadevan-Jansen A (2008) Comparison of autofluorescence, diffuse reflectance, and Raman spectroscopy for breast tissue discrimination. J Biomed Opt 13(5):054009
Laughney A, Krishnaswamy V, Garcia-Allende P, Conde O, Wells W, Paulsen K, Pogue B (2010) Automated classification of breast pathology using local measures of broadband reflectance. J Biomed Opt 15(6):066019
Taroni P, Bassi A, Comelli D, Farina A, Cubeddu R, Pifferi A (2009) Diffuse optical spectroscopy of breast tissue extended to 1100 nm. J Biomed Opt 14(5):054030
Taroni P, Comelli D, Pifferi A, Torricelli A, Cubeddu R (2007) Absorption of collagen: effects on the estimate of breast composition and related diagnostic implications. J Biomed Opt 12(1):014021
Taroni P, Pifferi A, Quarto G, Spinelli L, Torricelli A, Abbate F, Villa A, Balestreri N, Menna S, Cassano E, Cubeddu R (2010) Noninvasive assessment of breast cancer risk using time-resolved diffuse optical spectroscopy. J Biomed Opt 15(6):060501
Acknowledgments
We would like to thank all colleagues of the NKI pathology department and Philips Research project members for their contribution in the optical data collection and assessment. In particular we would like to thank W. Bierhoff for the probe development and J. Horikx for the console development. This study was supported by Philips Research, Eindhoven, The Netherlands.
Conflicts of interest
None of the authors who are affiliated with clinical institutions (DE, MVP, JH, HO, ER, JW and TR) have financial interests in the subject matter, materials, or equipment or with any competing materials. These authors received no payment for any kind for their participation in this research project, nor did their institutions receive payment for anything beyond the direct costs of performing this research project at The Netherlands Cancer Institute, NKI-AVL Amsterdam. Their interests are purely at a scientific level. All of the authors who are affiliated with Philips Research and Philips Healthcare (RN, GL and BH) have financial interests in the subject matter, materials, and equipment, in the sense that they are employees of Philips. The prototype system described in this article is currently only a research prototype and is not for commercial use. It is the intention of Philips to develop the prototype system into a commercial system that would be sold by Philips.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Evers, D.J., Nachabe, R., Vranken Peeters, MJ. et al. Diffuse reflectance spectroscopy: towards clinical application in breast cancer. Breast Cancer Res Treat 137, 155–165 (2013). https://doi.org/10.1007/s10549-012-2350-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10549-012-2350-8