Abstract

We explored the use of both empirical (Partial Least Squares, PLS) and Monte Carlo model based approaches for the analysis of fluorescence and diffuse reflectance spectra measured ex vivo from freshly excised breast tissues and for the diagnosis of breast cancer. Features extracted using both approaches, i.e. principal components (PCs) obtained from empirical analysis or tissue properties obtained from model based analysis, displayed statistically significant difference between malignant and non-malignant tissues, and can be used to discriminate breast malignancy with comparable sensitivity and specificity of up to 90%. The PC scores of a subset of PCs also displayed significant correlation with the tissue properties extracted from the model based analysis, suggesting both approaches likely probe the same sources of contrast in the tissue spectra that discriminate between malignant and non-malignant breast tissues but in different ways.

© 2008 Optical Society of America

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    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
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2008 (1)

C. Zhu, G. M. Palmer, T. M. Breslin, J. Harter, and N. Ramanujam, "Diagnosis of Breast Cancer using Fluorescence and Diffuse Reflectance Spectroscopy: a Monte Carlo Model Based Approach," J. Biomed. Opt. 13, 034015 (2008).
[CrossRef] [PubMed]

2006 (3)

2005 (1)

C. Zhu, G. M. Palmer, T. M. Breslin, F. Xu, and N. Ramanujam, "The Use of a Multi-separation Fiber Optic Probe for the Optical Diagnosis of Breast Cancer," J. Biomed. Opt. 10, 024032 (2005).
[CrossRef] [PubMed]

2003 (2)

G. M. Palmer, C. Zhu, T. M. Breslin, F. Xu, K. W. Gilchrist, and N. Ramanujam, "Comparison of multiexcitation fluorescence and diffuse reflectance spectroscopy for the diagnosis of breast cancer (March 2003)," IEEE Trans. Biomed. Eng. 50, 1233-1242 (2003).
[CrossRef] [PubMed]

G. M. Palmer, and N. Ramanujam, "Diagnosis of Breast Cancer Using Optical Spectroscopy," Medical Laser Application 18, 233-248 (2003).
[CrossRef]

2001 (2)

Y. Yang, E. J. Celmer, J. A. Koutcher, and R. R. Alfano, "UV reflectance spectroscopy probes DNA and protein changes in human breast tissues," J. Clin. Laser Med. Surg. 19, 35-39 (2001).
[CrossRef] [PubMed]

N. Ghosh, S. K. Mohanty, S. K. Majumder, and P. K. Gupta, "Measurement of optical transport properties of normal and malignant human breast tissue," Appl. Opt. 40, 176-184 (2001).
[CrossRef]

2000 (1)

I. J. Bigio, S. G. Bown, G. Briggs, C. Kelley, S. Lakhani, D. Pickard, P. M. Ripley, I. G. Rose, and C. Saunders, "Diagnosis of breast cancer using elastic-scattering spectroscopy: preliminary clinical results," J. Biomed. Opt. 5, 221-228 (2000).
[CrossRef] [PubMed]

1999 (2)

S. K. Majumder, P. K. Gupta, B. Jain, and A. Uppal, "UV excited autofluorescence spectroscopy of human breast tissues for discriminating cancerous tissue from benign tumor and normal tissue," Lasers in the Life Sciences 8, 249-264 (1999).

S. V. Pushkarev, S. A. Naumov, S. M. Vovk, V. A. Volovodenko, and V. V. Udut, "Application of laser fluorescence spectroscopy and diffuse reflection spectroscopy in diagnosing the states of mammary gland tissue," Optoelectronics-Instrumentation and Data Processing 2, 71-76 (1999).

1998 (1)

C. Burges, "A Tutorial on Support Vector Machines for Pattern Recognition," Data Min. Knowledge Discov. 2, 121-167 (1998).
[CrossRef]

1997 (4)

I. J. Bigio, and J. R. Mourant, "Ultraviolet and visible spectroscopies for tissue diagnostics: fluorescence spectroscopy and elastic-scattering spectroscopy," Phys. Med. Biol. 42, 803-814 (1997).
[CrossRef] [PubMed]

P. K. Gupta, S. K. Majumder, and A. Uppal, "Breast cancer diagnosis using N2 laser excited autofluorescence spectroscopy," Lasers Surg. Med. 21, 417-422 (1997).
[CrossRef] [PubMed]

Y. Yang, E. J. Celmer, M. Zurawska Szczepaniak, and R. R. Alfano, "Excitation spectrum of malignant and benign breast tissues: a potential optical biopsy approach," Lasers in the Life Sciences 7, 249-265 (1997).

Y. Yang, A. Katz, E. J. Celmer, M. Zurawska-Szczepaniak, and R. R. Alfano, "Fundamental differences of excitation spectrum between malignant and benign breast tissues," Photochem. Photobiol. 66, 518-522 (1997).
[CrossRef] [PubMed]

1996 (1)

Y. Yang, A. Katz, E. J. Celmer, M. Zurawska Szczepaniak, and R. R. Alfano, "Optical spectroscopy of benign and malignant breast tissues," Lasers in the Life Sciences 7, 115-127 (1996).

1992 (1)

C.-H. Liu, B. B. Das, W. L. Sha Glassman, G. C. Tang, K. M. Yoo, H. R. Zhu, D. L. Akins, S. S. Lubicz, J. Cleary, R. Prudente, E. J. Celmer, A. Caron, and R. R. Alfano, "Raman, fluorescence, and time-resolved light scattering as optical diagnostic techniques to separate diseased and normal biomedical media," J Photochem. Photobiol., B: Biol. 16, 187-209 (1992).
[CrossRef]

1991 (1)

R. R. Alfano, B. B. Das, J. Cleary, R. Prudente, and E. J. Celmer, "Light sheds light on cancer--distinguishing malignant tumors from benign tissues and tumors," Bull N. Y. Acad. Med. 67, 143-150 (1991).
[PubMed]

1990 (1)

V. G. Peters, D. R. Wyman, M. S. Patterson, and G. L. Frank, "Optical properties of normal and diseased human breast tissues in the visible and near infrared," Phys. Med. Biol. 35, 1317-1334 (1990).
[CrossRef] [PubMed]

Akins, D. L.

C.-H. Liu, B. B. Das, W. L. Sha Glassman, G. C. Tang, K. M. Yoo, H. R. Zhu, D. L. Akins, S. S. Lubicz, J. Cleary, R. Prudente, E. J. Celmer, A. Caron, and R. R. Alfano, "Raman, fluorescence, and time-resolved light scattering as optical diagnostic techniques to separate diseased and normal biomedical media," J Photochem. Photobiol., B: Biol. 16, 187-209 (1992).
[CrossRef]

Alfano, R. R.

Y. Yang, E. J. Celmer, J. A. Koutcher, and R. R. Alfano, "UV reflectance spectroscopy probes DNA and protein changes in human breast tissues," J. Clin. Laser Med. Surg. 19, 35-39 (2001).
[CrossRef] [PubMed]

Y. Yang, A. Katz, E. J. Celmer, M. Zurawska-Szczepaniak, and R. R. Alfano, "Fundamental differences of excitation spectrum between malignant and benign breast tissues," Photochem. Photobiol. 66, 518-522 (1997).
[CrossRef] [PubMed]

Y. Yang, E. J. Celmer, M. Zurawska Szczepaniak, and R. R. Alfano, "Excitation spectrum of malignant and benign breast tissues: a potential optical biopsy approach," Lasers in the Life Sciences 7, 249-265 (1997).

Y. Yang, A. Katz, E. J. Celmer, M. Zurawska Szczepaniak, and R. R. Alfano, "Optical spectroscopy of benign and malignant breast tissues," Lasers in the Life Sciences 7, 115-127 (1996).

C.-H. Liu, B. B. Das, W. L. Sha Glassman, G. C. Tang, K. M. Yoo, H. R. Zhu, D. L. Akins, S. S. Lubicz, J. Cleary, R. Prudente, E. J. Celmer, A. Caron, and R. R. Alfano, "Raman, fluorescence, and time-resolved light scattering as optical diagnostic techniques to separate diseased and normal biomedical media," J Photochem. Photobiol., B: Biol. 16, 187-209 (1992).
[CrossRef]

R. R. Alfano, B. B. Das, J. Cleary, R. Prudente, and E. J. Celmer, "Light sheds light on cancer--distinguishing malignant tumors from benign tissues and tumors," Bull N. Y. Acad. Med. 67, 143-150 (1991).
[PubMed]

Bigio, I. J.

I. J. Bigio, S. G. Bown, G. Briggs, C. Kelley, S. Lakhani, D. Pickard, P. M. Ripley, I. G. Rose, and C. Saunders, "Diagnosis of breast cancer using elastic-scattering spectroscopy: preliminary clinical results," J. Biomed. Opt. 5, 221-228 (2000).
[CrossRef] [PubMed]

I. J. Bigio, and J. R. Mourant, "Ultraviolet and visible spectroscopies for tissue diagnostics: fluorescence spectroscopy and elastic-scattering spectroscopy," Phys. Med. Biol. 42, 803-814 (1997).
[CrossRef] [PubMed]

Bown, S. G.

I. J. Bigio, S. G. Bown, G. Briggs, C. Kelley, S. Lakhani, D. Pickard, P. M. Ripley, I. G. Rose, and C. Saunders, "Diagnosis of breast cancer using elastic-scattering spectroscopy: preliminary clinical results," J. Biomed. Opt. 5, 221-228 (2000).
[CrossRef] [PubMed]

Breslin, T. M.

C. Zhu, G. M. Palmer, T. M. Breslin, J. Harter, and N. Ramanujam, "Diagnosis of Breast Cancer using Fluorescence and Diffuse Reflectance Spectroscopy: a Monte Carlo Model Based Approach," J. Biomed. Opt. 13, 034015 (2008).
[CrossRef] [PubMed]

C. Zhu, G. M. Palmer, T. M. Breslin, J. Harter, and N. Ramanujam, "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, 714-724 (2006).
[CrossRef] [PubMed]

G. M. Palmer, C. Zhu, T. M. Breslin, F. Xu, K. W. Gilchrist, and N. Ramanujam, "Monte Carlo-based inverse model for calculating tissue optical properties. Part II: Application to breast cancer diagnosis," Appl. Opt. 45, 1072-1078 (2006).
[CrossRef] [PubMed]

C. Zhu, G. M. Palmer, T. M. Breslin, F. Xu, and N. Ramanujam, "The Use of a Multi-separation Fiber Optic Probe for the Optical Diagnosis of Breast Cancer," J. Biomed. Opt. 10, 024032 (2005).
[CrossRef] [PubMed]

G. M. Palmer, C. Zhu, T. M. Breslin, F. Xu, K. W. Gilchrist, and N. Ramanujam, "Comparison of multiexcitation fluorescence and diffuse reflectance spectroscopy for the diagnosis of breast cancer (March 2003)," IEEE Trans. Biomed. Eng. 50, 1233-1242 (2003).
[CrossRef] [PubMed]

Briggs, G.

I. J. Bigio, S. G. Bown, G. Briggs, C. Kelley, S. Lakhani, D. Pickard, P. M. Ripley, I. G. Rose, and C. Saunders, "Diagnosis of breast cancer using elastic-scattering spectroscopy: preliminary clinical results," J. Biomed. Opt. 5, 221-228 (2000).
[CrossRef] [PubMed]

Burges, C.

C. Burges, "A Tutorial on Support Vector Machines for Pattern Recognition," Data Min. Knowledge Discov. 2, 121-167 (1998).
[CrossRef]

Caron, A.

C.-H. Liu, B. B. Das, W. L. Sha Glassman, G. C. Tang, K. M. Yoo, H. R. Zhu, D. L. Akins, S. S. Lubicz, J. Cleary, R. Prudente, E. J. Celmer, A. Caron, and R. R. Alfano, "Raman, fluorescence, and time-resolved light scattering as optical diagnostic techniques to separate diseased and normal biomedical media," J Photochem. Photobiol., B: Biol. 16, 187-209 (1992).
[CrossRef]

Celmer, E. J.

Y. Yang, E. J. Celmer, J. A. Koutcher, and R. R. Alfano, "UV reflectance spectroscopy probes DNA and protein changes in human breast tissues," J. Clin. Laser Med. Surg. 19, 35-39 (2001).
[CrossRef] [PubMed]

Y. Yang, E. J. Celmer, M. Zurawska Szczepaniak, and R. R. Alfano, "Excitation spectrum of malignant and benign breast tissues: a potential optical biopsy approach," Lasers in the Life Sciences 7, 249-265 (1997).

Y. Yang, A. Katz, E. J. Celmer, M. Zurawska-Szczepaniak, and R. R. Alfano, "Fundamental differences of excitation spectrum between malignant and benign breast tissues," Photochem. Photobiol. 66, 518-522 (1997).
[CrossRef] [PubMed]

Y. Yang, A. Katz, E. J. Celmer, M. Zurawska Szczepaniak, and R. R. Alfano, "Optical spectroscopy of benign and malignant breast tissues," Lasers in the Life Sciences 7, 115-127 (1996).

C.-H. Liu, B. B. Das, W. L. Sha Glassman, G. C. Tang, K. M. Yoo, H. R. Zhu, D. L. Akins, S. S. Lubicz, J. Cleary, R. Prudente, E. J. Celmer, A. Caron, and R. R. Alfano, "Raman, fluorescence, and time-resolved light scattering as optical diagnostic techniques to separate diseased and normal biomedical media," J Photochem. Photobiol., B: Biol. 16, 187-209 (1992).
[CrossRef]

R. R. Alfano, B. B. Das, J. Cleary, R. Prudente, and E. J. Celmer, "Light sheds light on cancer--distinguishing malignant tumors from benign tissues and tumors," Bull N. Y. Acad. Med. 67, 143-150 (1991).
[PubMed]

Cleary, J.

C.-H. Liu, B. B. Das, W. L. Sha Glassman, G. C. Tang, K. M. Yoo, H. R. Zhu, D. L. Akins, S. S. Lubicz, J. Cleary, R. Prudente, E. J. Celmer, A. Caron, and R. R. Alfano, "Raman, fluorescence, and time-resolved light scattering as optical diagnostic techniques to separate diseased and normal biomedical media," J Photochem. Photobiol., B: Biol. 16, 187-209 (1992).
[CrossRef]

R. R. Alfano, B. B. Das, J. Cleary, R. Prudente, and E. J. Celmer, "Light sheds light on cancer--distinguishing malignant tumors from benign tissues and tumors," Bull N. Y. Acad. Med. 67, 143-150 (1991).
[PubMed]

Das, B. B.

C.-H. Liu, B. B. Das, W. L. Sha Glassman, G. C. Tang, K. M. Yoo, H. R. Zhu, D. L. Akins, S. S. Lubicz, J. Cleary, R. Prudente, E. J. Celmer, A. Caron, and R. R. Alfano, "Raman, fluorescence, and time-resolved light scattering as optical diagnostic techniques to separate diseased and normal biomedical media," J Photochem. Photobiol., B: Biol. 16, 187-209 (1992).
[CrossRef]

R. R. Alfano, B. B. Das, J. Cleary, R. Prudente, and E. J. Celmer, "Light sheds light on cancer--distinguishing malignant tumors from benign tissues and tumors," Bull N. Y. Acad. Med. 67, 143-150 (1991).
[PubMed]

Frank, G. L.

V. G. Peters, D. R. Wyman, M. S. Patterson, and G. L. Frank, "Optical properties of normal and diseased human breast tissues in the visible and near infrared," Phys. Med. Biol. 35, 1317-1334 (1990).
[CrossRef] [PubMed]

Ghosh, N.

N. Ghosh, S. K. Mohanty, S. K. Majumder, and P. K. Gupta, "Measurement of optical transport properties of normal and malignant human breast tissue," Appl. Opt. 40, 176-184 (2001).
[CrossRef]

Gilchrist, K. W.

G. M. Palmer, C. Zhu, T. M. Breslin, F. Xu, K. W. Gilchrist, and N. Ramanujam, "Monte Carlo-based inverse model for calculating tissue optical properties. Part II: Application to breast cancer diagnosis," Appl. Opt. 45, 1072-1078 (2006).
[CrossRef] [PubMed]

G. M. Palmer, C. Zhu, T. M. Breslin, F. Xu, K. W. Gilchrist, and N. Ramanujam, "Comparison of multiexcitation fluorescence and diffuse reflectance spectroscopy for the diagnosis of breast cancer (March 2003)," IEEE Trans. Biomed. Eng. 50, 1233-1242 (2003).
[CrossRef] [PubMed]

Gupta, P. K.

N. Ghosh, S. K. Mohanty, S. K. Majumder, and P. K. Gupta, "Measurement of optical transport properties of normal and malignant human breast tissue," Appl. Opt. 40, 176-184 (2001).
[CrossRef]

S. K. Majumder, P. K. Gupta, B. Jain, and A. Uppal, "UV excited autofluorescence spectroscopy of human breast tissues for discriminating cancerous tissue from benign tumor and normal tissue," Lasers in the Life Sciences 8, 249-264 (1999).

P. K. Gupta, S. K. Majumder, and A. Uppal, "Breast cancer diagnosis using N2 laser excited autofluorescence spectroscopy," Lasers Surg. Med. 21, 417-422 (1997).
[CrossRef] [PubMed]

Harter, J.

C. Zhu, G. M. Palmer, T. M. Breslin, J. Harter, and N. Ramanujam, "Diagnosis of Breast Cancer using Fluorescence and Diffuse Reflectance Spectroscopy: a Monte Carlo Model Based Approach," J. Biomed. Opt. 13, 034015 (2008).
[CrossRef] [PubMed]

C. Zhu, G. M. Palmer, T. M. Breslin, J. Harter, and N. Ramanujam, "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, 714-724 (2006).
[CrossRef] [PubMed]

Jain, B.

S. K. Majumder, P. K. Gupta, B. Jain, and A. Uppal, "UV excited autofluorescence spectroscopy of human breast tissues for discriminating cancerous tissue from benign tumor and normal tissue," Lasers in the Life Sciences 8, 249-264 (1999).

Katz, A.

Y. Yang, A. Katz, E. J. Celmer, M. Zurawska-Szczepaniak, and R. R. Alfano, "Fundamental differences of excitation spectrum between malignant and benign breast tissues," Photochem. Photobiol. 66, 518-522 (1997).
[CrossRef] [PubMed]

Y. Yang, A. Katz, E. J. Celmer, M. Zurawska Szczepaniak, and R. R. Alfano, "Optical spectroscopy of benign and malignant breast tissues," Lasers in the Life Sciences 7, 115-127 (1996).

Kelley, C.

I. J. Bigio, S. G. Bown, G. Briggs, C. Kelley, S. Lakhani, D. Pickard, P. M. Ripley, I. G. Rose, and C. Saunders, "Diagnosis of breast cancer using elastic-scattering spectroscopy: preliminary clinical results," J. Biomed. Opt. 5, 221-228 (2000).
[CrossRef] [PubMed]

Koutcher, J. A.

Y. Yang, E. J. Celmer, J. A. Koutcher, and R. R. Alfano, "UV reflectance spectroscopy probes DNA and protein changes in human breast tissues," J. Clin. Laser Med. Surg. 19, 35-39 (2001).
[CrossRef] [PubMed]

Lakhani, S.

I. J. Bigio, S. G. Bown, G. Briggs, C. Kelley, S. Lakhani, D. Pickard, P. M. Ripley, I. G. Rose, and C. Saunders, "Diagnosis of breast cancer using elastic-scattering spectroscopy: preliminary clinical results," J. Biomed. Opt. 5, 221-228 (2000).
[CrossRef] [PubMed]

Liu, C.-H.

C.-H. Liu, B. B. Das, W. L. Sha Glassman, G. C. Tang, K. M. Yoo, H. R. Zhu, D. L. Akins, S. S. Lubicz, J. Cleary, R. Prudente, E. J. Celmer, A. Caron, and R. R. Alfano, "Raman, fluorescence, and time-resolved light scattering as optical diagnostic techniques to separate diseased and normal biomedical media," J Photochem. Photobiol., B: Biol. 16, 187-209 (1992).
[CrossRef]

Lubicz, S. S.

C.-H. Liu, B. B. Das, W. L. Sha Glassman, G. C. Tang, K. M. Yoo, H. R. Zhu, D. L. Akins, S. S. Lubicz, J. Cleary, R. Prudente, E. J. Celmer, A. Caron, and R. R. Alfano, "Raman, fluorescence, and time-resolved light scattering as optical diagnostic techniques to separate diseased and normal biomedical media," J Photochem. Photobiol., B: Biol. 16, 187-209 (1992).
[CrossRef]

Majumder, S. K.

N. Ghosh, S. K. Mohanty, S. K. Majumder, and P. K. Gupta, "Measurement of optical transport properties of normal and malignant human breast tissue," Appl. Opt. 40, 176-184 (2001).
[CrossRef]

S. K. Majumder, P. K. Gupta, B. Jain, and A. Uppal, "UV excited autofluorescence spectroscopy of human breast tissues for discriminating cancerous tissue from benign tumor and normal tissue," Lasers in the Life Sciences 8, 249-264 (1999).

P. K. Gupta, S. K. Majumder, and A. Uppal, "Breast cancer diagnosis using N2 laser excited autofluorescence spectroscopy," Lasers Surg. Med. 21, 417-422 (1997).
[CrossRef] [PubMed]

Mohanty, S. K.

N. Ghosh, S. K. Mohanty, S. K. Majumder, and P. K. Gupta, "Measurement of optical transport properties of normal and malignant human breast tissue," Appl. Opt. 40, 176-184 (2001).
[CrossRef]

Mourant, J. R.

I. J. Bigio, and J. R. Mourant, "Ultraviolet and visible spectroscopies for tissue diagnostics: fluorescence spectroscopy and elastic-scattering spectroscopy," Phys. Med. Biol. 42, 803-814 (1997).
[CrossRef] [PubMed]

Naumov, S. A.

S. V. Pushkarev, S. A. Naumov, S. M. Vovk, V. A. Volovodenko, and V. V. Udut, "Application of laser fluorescence spectroscopy and diffuse reflection spectroscopy in diagnosing the states of mammary gland tissue," Optoelectronics-Instrumentation and Data Processing 2, 71-76 (1999).

Palmer, G. M.

C. Zhu, G. M. Palmer, T. M. Breslin, J. Harter, and N. Ramanujam, "Diagnosis of Breast Cancer using Fluorescence and Diffuse Reflectance Spectroscopy: a Monte Carlo Model Based Approach," J. Biomed. Opt. 13, 034015 (2008).
[CrossRef] [PubMed]

C. Zhu, G. M. Palmer, T. M. Breslin, J. Harter, and N. Ramanujam, "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, 714-724 (2006).
[CrossRef] [PubMed]

G. M. Palmer, and N. Ramanujam, "Monte Carlo-based inverse model for calculating tissue optical properties. Part I: Theory and validation on synthetic phantoms," Appl. Opt. 45, 1062-1071 (2006).
[CrossRef] [PubMed]

G. M. Palmer, C. Zhu, T. M. Breslin, F. Xu, K. W. Gilchrist, and N. Ramanujam, "Monte Carlo-based inverse model for calculating tissue optical properties. Part II: Application to breast cancer diagnosis," Appl. Opt. 45, 1072-1078 (2006).
[CrossRef] [PubMed]

C. Zhu, G. M. Palmer, T. M. Breslin, F. Xu, and N. Ramanujam, "The Use of a Multi-separation Fiber Optic Probe for the Optical Diagnosis of Breast Cancer," J. Biomed. Opt. 10, 024032 (2005).
[CrossRef] [PubMed]

G. M. Palmer, C. Zhu, T. M. Breslin, F. Xu, K. W. Gilchrist, and N. Ramanujam, "Comparison of multiexcitation fluorescence and diffuse reflectance spectroscopy for the diagnosis of breast cancer (March 2003)," IEEE Trans. Biomed. Eng. 50, 1233-1242 (2003).
[CrossRef] [PubMed]

G. M. Palmer, and N. Ramanujam, "Diagnosis of Breast Cancer Using Optical Spectroscopy," Medical Laser Application 18, 233-248 (2003).
[CrossRef]

Patterson, M. S.

V. G. Peters, D. R. Wyman, M. S. Patterson, and G. L. Frank, "Optical properties of normal and diseased human breast tissues in the visible and near infrared," Phys. Med. Biol. 35, 1317-1334 (1990).
[CrossRef] [PubMed]

Peters, V. G.

V. G. Peters, D. R. Wyman, M. S. Patterson, and G. L. Frank, "Optical properties of normal and diseased human breast tissues in the visible and near infrared," Phys. Med. Biol. 35, 1317-1334 (1990).
[CrossRef] [PubMed]

Pickard, D.

I. J. Bigio, S. G. Bown, G. Briggs, C. Kelley, S. Lakhani, D. Pickard, P. M. Ripley, I. G. Rose, and C. Saunders, "Diagnosis of breast cancer using elastic-scattering spectroscopy: preliminary clinical results," J. Biomed. Opt. 5, 221-228 (2000).
[CrossRef] [PubMed]

Prudente, R.

C.-H. Liu, B. B. Das, W. L. Sha Glassman, G. C. Tang, K. M. Yoo, H. R. Zhu, D. L. Akins, S. S. Lubicz, J. Cleary, R. Prudente, E. J. Celmer, A. Caron, and R. R. Alfano, "Raman, fluorescence, and time-resolved light scattering as optical diagnostic techniques to separate diseased and normal biomedical media," J Photochem. Photobiol., B: Biol. 16, 187-209 (1992).
[CrossRef]

R. R. Alfano, B. B. Das, J. Cleary, R. Prudente, and E. J. Celmer, "Light sheds light on cancer--distinguishing malignant tumors from benign tissues and tumors," Bull N. Y. Acad. Med. 67, 143-150 (1991).
[PubMed]

Pushkarev, S. V.

S. V. Pushkarev, S. A. Naumov, S. M. Vovk, V. A. Volovodenko, and V. V. Udut, "Application of laser fluorescence spectroscopy and diffuse reflection spectroscopy in diagnosing the states of mammary gland tissue," Optoelectronics-Instrumentation and Data Processing 2, 71-76 (1999).

Ramanujam, N.

C. Zhu, G. M. Palmer, T. M. Breslin, J. Harter, and N. Ramanujam, "Diagnosis of Breast Cancer using Fluorescence and Diffuse Reflectance Spectroscopy: a Monte Carlo Model Based Approach," J. Biomed. Opt. 13, 034015 (2008).
[CrossRef] [PubMed]

C. Zhu, G. M. Palmer, T. M. Breslin, J. Harter, and N. Ramanujam, "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, 714-724 (2006).
[CrossRef] [PubMed]

G. M. Palmer, and N. Ramanujam, "Monte Carlo-based inverse model for calculating tissue optical properties. Part I: Theory and validation on synthetic phantoms," Appl. Opt. 45, 1062-1071 (2006).
[CrossRef] [PubMed]

G. M. Palmer, C. Zhu, T. M. Breslin, F. Xu, K. W. Gilchrist, and N. Ramanujam, "Monte Carlo-based inverse model for calculating tissue optical properties. Part II: Application to breast cancer diagnosis," Appl. Opt. 45, 1072-1078 (2006).
[CrossRef] [PubMed]

C. Zhu, G. M. Palmer, T. M. Breslin, F. Xu, and N. Ramanujam, "The Use of a Multi-separation Fiber Optic Probe for the Optical Diagnosis of Breast Cancer," J. Biomed. Opt. 10, 024032 (2005).
[CrossRef] [PubMed]

G. M. Palmer, and N. Ramanujam, "Diagnosis of Breast Cancer Using Optical Spectroscopy," Medical Laser Application 18, 233-248 (2003).
[CrossRef]

G. M. Palmer, C. Zhu, T. M. Breslin, F. Xu, K. W. Gilchrist, and N. Ramanujam, "Comparison of multiexcitation fluorescence and diffuse reflectance spectroscopy for the diagnosis of breast cancer (March 2003)," IEEE Trans. Biomed. Eng. 50, 1233-1242 (2003).
[CrossRef] [PubMed]

Ripley, P. M.

I. J. Bigio, S. G. Bown, G. Briggs, C. Kelley, S. Lakhani, D. Pickard, P. M. Ripley, I. G. Rose, and C. Saunders, "Diagnosis of breast cancer using elastic-scattering spectroscopy: preliminary clinical results," J. Biomed. Opt. 5, 221-228 (2000).
[CrossRef] [PubMed]

Rose, I. G.

I. J. Bigio, S. G. Bown, G. Briggs, C. Kelley, S. Lakhani, D. Pickard, P. M. Ripley, I. G. Rose, and C. Saunders, "Diagnosis of breast cancer using elastic-scattering spectroscopy: preliminary clinical results," J. Biomed. Opt. 5, 221-228 (2000).
[CrossRef] [PubMed]

Saunders, C.

I. J. Bigio, S. G. Bown, G. Briggs, C. Kelley, S. Lakhani, D. Pickard, P. M. Ripley, I. G. Rose, and C. Saunders, "Diagnosis of breast cancer using elastic-scattering spectroscopy: preliminary clinical results," J. Biomed. Opt. 5, 221-228 (2000).
[CrossRef] [PubMed]

Sha Glassman, W. L.

C.-H. Liu, B. B. Das, W. L. Sha Glassman, G. C. Tang, K. M. Yoo, H. R. Zhu, D. L. Akins, S. S. Lubicz, J. Cleary, R. Prudente, E. J. Celmer, A. Caron, and R. R. Alfano, "Raman, fluorescence, and time-resolved light scattering as optical diagnostic techniques to separate diseased and normal biomedical media," J Photochem. Photobiol., B: Biol. 16, 187-209 (1992).
[CrossRef]

Tang, G. C.

C.-H. Liu, B. B. Das, W. L. Sha Glassman, G. C. Tang, K. M. Yoo, H. R. Zhu, D. L. Akins, S. S. Lubicz, J. Cleary, R. Prudente, E. J. Celmer, A. Caron, and R. R. Alfano, "Raman, fluorescence, and time-resolved light scattering as optical diagnostic techniques to separate diseased and normal biomedical media," J Photochem. Photobiol., B: Biol. 16, 187-209 (1992).
[CrossRef]

Udut, V. V.

S. V. Pushkarev, S. A. Naumov, S. M. Vovk, V. A. Volovodenko, and V. V. Udut, "Application of laser fluorescence spectroscopy and diffuse reflection spectroscopy in diagnosing the states of mammary gland tissue," Optoelectronics-Instrumentation and Data Processing 2, 71-76 (1999).

Uppal, A.

S. K. Majumder, P. K. Gupta, B. Jain, and A. Uppal, "UV excited autofluorescence spectroscopy of human breast tissues for discriminating cancerous tissue from benign tumor and normal tissue," Lasers in the Life Sciences 8, 249-264 (1999).

P. K. Gupta, S. K. Majumder, and A. Uppal, "Breast cancer diagnosis using N2 laser excited autofluorescence spectroscopy," Lasers Surg. Med. 21, 417-422 (1997).
[CrossRef] [PubMed]

Volovodenko, V. A.

S. V. Pushkarev, S. A. Naumov, S. M. Vovk, V. A. Volovodenko, and V. V. Udut, "Application of laser fluorescence spectroscopy and diffuse reflection spectroscopy in diagnosing the states of mammary gland tissue," Optoelectronics-Instrumentation and Data Processing 2, 71-76 (1999).

Vovk, S. M.

S. V. Pushkarev, S. A. Naumov, S. M. Vovk, V. A. Volovodenko, and V. V. Udut, "Application of laser fluorescence spectroscopy and diffuse reflection spectroscopy in diagnosing the states of mammary gland tissue," Optoelectronics-Instrumentation and Data Processing 2, 71-76 (1999).

Wyman, D. R.

V. G. Peters, D. R. Wyman, M. S. Patterson, and G. L. Frank, "Optical properties of normal and diseased human breast tissues in the visible and near infrared," Phys. Med. Biol. 35, 1317-1334 (1990).
[CrossRef] [PubMed]

Xu, F.

G. M. Palmer, C. Zhu, T. M. Breslin, F. Xu, K. W. Gilchrist, and N. Ramanujam, "Monte Carlo-based inverse model for calculating tissue optical properties. Part II: Application to breast cancer diagnosis," Appl. Opt. 45, 1072-1078 (2006).
[CrossRef] [PubMed]

C. Zhu, G. M. Palmer, T. M. Breslin, F. Xu, and N. Ramanujam, "The Use of a Multi-separation Fiber Optic Probe for the Optical Diagnosis of Breast Cancer," J. Biomed. Opt. 10, 024032 (2005).
[CrossRef] [PubMed]

G. M. Palmer, C. Zhu, T. M. Breslin, F. Xu, K. W. Gilchrist, and N. Ramanujam, "Comparison of multiexcitation fluorescence and diffuse reflectance spectroscopy for the diagnosis of breast cancer (March 2003)," IEEE Trans. Biomed. Eng. 50, 1233-1242 (2003).
[CrossRef] [PubMed]

Yang, Y.

Y. Yang, E. J. Celmer, J. A. Koutcher, and R. R. Alfano, "UV reflectance spectroscopy probes DNA and protein changes in human breast tissues," J. Clin. Laser Med. Surg. 19, 35-39 (2001).
[CrossRef] [PubMed]

Y. Yang, E. J. Celmer, M. Zurawska Szczepaniak, and R. R. Alfano, "Excitation spectrum of malignant and benign breast tissues: a potential optical biopsy approach," Lasers in the Life Sciences 7, 249-265 (1997).

Y. Yang, A. Katz, E. J. Celmer, M. Zurawska-Szczepaniak, and R. R. Alfano, "Fundamental differences of excitation spectrum between malignant and benign breast tissues," Photochem. Photobiol. 66, 518-522 (1997).
[CrossRef] [PubMed]

Y. Yang, A. Katz, E. J. Celmer, M. Zurawska Szczepaniak, and R. R. Alfano, "Optical spectroscopy of benign and malignant breast tissues," Lasers in the Life Sciences 7, 115-127 (1996).

Yoo, K. M.

C.-H. Liu, B. B. Das, W. L. Sha Glassman, G. C. Tang, K. M. Yoo, H. R. Zhu, D. L. Akins, S. S. Lubicz, J. Cleary, R. Prudente, E. J. Celmer, A. Caron, and R. R. Alfano, "Raman, fluorescence, and time-resolved light scattering as optical diagnostic techniques to separate diseased and normal biomedical media," J Photochem. Photobiol., B: Biol. 16, 187-209 (1992).
[CrossRef]

Zhu, C.

C. Zhu, G. M. Palmer, T. M. Breslin, J. Harter, and N. Ramanujam, "Diagnosis of Breast Cancer using Fluorescence and Diffuse Reflectance Spectroscopy: a Monte Carlo Model Based Approach," J. Biomed. Opt. 13, 034015 (2008).
[CrossRef] [PubMed]

C. Zhu, G. M. Palmer, T. M. Breslin, J. Harter, and N. Ramanujam, "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, 714-724 (2006).
[CrossRef] [PubMed]

G. M. Palmer, C. Zhu, T. M. Breslin, F. Xu, K. W. Gilchrist, and N. Ramanujam, "Monte Carlo-based inverse model for calculating tissue optical properties. Part II: Application to breast cancer diagnosis," Appl. Opt. 45, 1072-1078 (2006).
[CrossRef] [PubMed]

C. Zhu, G. M. Palmer, T. M. Breslin, F. Xu, and N. Ramanujam, "The Use of a Multi-separation Fiber Optic Probe for the Optical Diagnosis of Breast Cancer," J. Biomed. Opt. 10, 024032 (2005).
[CrossRef] [PubMed]

G. M. Palmer, C. Zhu, T. M. Breslin, F. Xu, K. W. Gilchrist, and N. Ramanujam, "Comparison of multiexcitation fluorescence and diffuse reflectance spectroscopy for the diagnosis of breast cancer (March 2003)," IEEE Trans. Biomed. Eng. 50, 1233-1242 (2003).
[CrossRef] [PubMed]

Zhu, H. R.

C.-H. Liu, B. B. Das, W. L. Sha Glassman, G. C. Tang, K. M. Yoo, H. R. Zhu, D. L. Akins, S. S. Lubicz, J. Cleary, R. Prudente, E. J. Celmer, A. Caron, and R. R. Alfano, "Raman, fluorescence, and time-resolved light scattering as optical diagnostic techniques to separate diseased and normal biomedical media," J Photochem. Photobiol., B: Biol. 16, 187-209 (1992).
[CrossRef]

Zurawska Szczepaniak, M.

Y. Yang, E. J. Celmer, M. Zurawska Szczepaniak, and R. R. Alfano, "Excitation spectrum of malignant and benign breast tissues: a potential optical biopsy approach," Lasers in the Life Sciences 7, 249-265 (1997).

Y. Yang, A. Katz, E. J. Celmer, M. Zurawska Szczepaniak, and R. R. Alfano, "Optical spectroscopy of benign and malignant breast tissues," Lasers in the Life Sciences 7, 115-127 (1996).

Zurawska-Szczepaniak, M.

Y. Yang, A. Katz, E. J. Celmer, M. Zurawska-Szczepaniak, and R. R. Alfano, "Fundamental differences of excitation spectrum between malignant and benign breast tissues," Photochem. Photobiol. 66, 518-522 (1997).
[CrossRef] [PubMed]

Appl. Opt. (2)

Applied Optics (1)

N. Ghosh, S. K. Mohanty, S. K. Majumder, and P. K. Gupta, "Measurement of optical transport properties of normal and malignant human breast tissue," Appl. Opt. 40, 176-184 (2001).
[CrossRef]

B: Biol. (1)

C.-H. Liu, B. B. Das, W. L. Sha Glassman, G. C. Tang, K. M. Yoo, H. R. Zhu, D. L. Akins, S. S. Lubicz, J. Cleary, R. Prudente, E. J. Celmer, A. Caron, and R. R. Alfano, "Raman, fluorescence, and time-resolved light scattering as optical diagnostic techniques to separate diseased and normal biomedical media," J Photochem. Photobiol., B: Biol. 16, 187-209 (1992).
[CrossRef]

Bull N. Y. Acad. Med. (1)

R. R. Alfano, B. B. Das, J. Cleary, R. Prudente, and E. J. Celmer, "Light sheds light on cancer--distinguishing malignant tumors from benign tissues and tumors," Bull N. Y. Acad. Med. 67, 143-150 (1991).
[PubMed]

Data Min. Knowl. Discov. (1)

C. Burges, "A Tutorial on Support Vector Machines for Pattern Recognition," Data Min. Knowledge Discov. 2, 121-167 (1998).
[CrossRef]

IEEE Trans. Biomed. Eng. (1)

G. M. Palmer, C. Zhu, T. M. Breslin, F. Xu, K. W. Gilchrist, and N. Ramanujam, "Comparison of multiexcitation fluorescence and diffuse reflectance spectroscopy for the diagnosis of breast cancer (March 2003)," IEEE Trans. Biomed. Eng. 50, 1233-1242 (2003).
[CrossRef] [PubMed]

J. Biomed. Opt. (3)

C. Zhu, G. M. Palmer, T. M. Breslin, F. Xu, and N. Ramanujam, "The Use of a Multi-separation Fiber Optic Probe for the Optical Diagnosis of Breast Cancer," J. Biomed. Opt. 10, 024032 (2005).
[CrossRef] [PubMed]

C. Zhu, G. M. Palmer, T. M. Breslin, J. Harter, and N. Ramanujam, "Diagnosis of Breast Cancer using Fluorescence and Diffuse Reflectance Spectroscopy: a Monte Carlo Model Based Approach," J. Biomed. Opt. 13, 034015 (2008).
[CrossRef] [PubMed]

I. J. Bigio, S. G. Bown, G. Briggs, C. Kelley, S. Lakhani, D. Pickard, P. M. Ripley, I. G. Rose, and C. Saunders, "Diagnosis of breast cancer using elastic-scattering spectroscopy: preliminary clinical results," J. Biomed. Opt. 5, 221-228 (2000).
[CrossRef] [PubMed]

J. Clin. Laser Med. Surg. (1)

Y. Yang, E. J. Celmer, J. A. Koutcher, and R. R. Alfano, "UV reflectance spectroscopy probes DNA and protein changes in human breast tissues," J. Clin. Laser Med. Surg. 19, 35-39 (2001).
[CrossRef] [PubMed]

Lasers in the Life Sciences (3)

S. K. Majumder, P. K. Gupta, B. Jain, and A. Uppal, "UV excited autofluorescence spectroscopy of human breast tissues for discriminating cancerous tissue from benign tumor and normal tissue," Lasers in the Life Sciences 8, 249-264 (1999).

Y. Yang, A. Katz, E. J. Celmer, M. Zurawska Szczepaniak, and R. R. Alfano, "Optical spectroscopy of benign and malignant breast tissues," Lasers in the Life Sciences 7, 115-127 (1996).

Y. Yang, E. J. Celmer, M. Zurawska Szczepaniak, and R. R. Alfano, "Excitation spectrum of malignant and benign breast tissues: a potential optical biopsy approach," Lasers in the Life Sciences 7, 249-265 (1997).

Lasers Surg. Med. (2)

C. Zhu, G. M. Palmer, T. M. Breslin, J. Harter, and N. Ramanujam, "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, 714-724 (2006).
[CrossRef] [PubMed]

P. K. Gupta, S. K. Majumder, and A. Uppal, "Breast cancer diagnosis using N2 laser excited autofluorescence spectroscopy," Lasers Surg. Med. 21, 417-422 (1997).
[CrossRef] [PubMed]

Medical Laser Application (1)

G. M. Palmer, and N. Ramanujam, "Diagnosis of Breast Cancer Using Optical Spectroscopy," Medical Laser Application 18, 233-248 (2003).
[CrossRef]

Optoelectronics-Instrumentation and Data Processing (1)

S. V. Pushkarev, S. A. Naumov, S. M. Vovk, V. A. Volovodenko, and V. V. Udut, "Application of laser fluorescence spectroscopy and diffuse reflection spectroscopy in diagnosing the states of mammary gland tissue," Optoelectronics-Instrumentation and Data Processing 2, 71-76 (1999).

Photochem. Photobiol. (1)

Y. Yang, A. Katz, E. J. Celmer, M. Zurawska-Szczepaniak, and R. R. Alfano, "Fundamental differences of excitation spectrum between malignant and benign breast tissues," Photochem. Photobiol. 66, 518-522 (1997).
[CrossRef] [PubMed]

Phys. Med. Biol. (2)

I. J. Bigio, and J. R. Mourant, "Ultraviolet and visible spectroscopies for tissue diagnostics: fluorescence spectroscopy and elastic-scattering spectroscopy," Phys. Med. Biol. 42, 803-814 (1997).
[CrossRef] [PubMed]

V. G. Peters, D. R. Wyman, M. S. Patterson, and G. L. Frank, "Optical properties of normal and diseased human breast tissues in the visible and near infrared," Phys. Med. Biol. 35, 1317-1334 (1990).
[CrossRef] [PubMed]

Other (6)

N. Cristianini, and J. Shawe-Taylor, An Introduction to Support Vector Machines: and other Kernel-based Learning Methods (Cambridge University Press, Cambridge, New York, 2000).

J. S. U. Hjorth, Computer Intensive Statistical Methods: Validation, Model Selection, and Bootstrap (Chapman & Hall, London, New York, 1994).

R. Tauler, "Multivariate Curve Resolution, MCR-ALS Command Line Toolbox," (2006).

R. M. Bethea, B. S. Duran, and T. L. Boullion, Statistical methods for engineers and scientists (M. Dekker, New York, 1995).

G. M. Palmer, and N. Ramanujam, "Monte Carlo based Model to Extract Intrinsic Fluorescence from Turbid Media: Theory and Phantom Validation," (2007).

H. Martens, Multivariate Calibration (John Wiley & Sons, New York, 1989).

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Figures (2)

Fig. 1.
Fig. 1.

(a) average fluorescence spectra of malignant (n = 37) and non-malignant (n = 46) tissue samples at the excitation wavelength of 340 nm, (b) 340nm PC1 and 360nm PC2 obtained from fluorescence spectra, (c) the correlation of 340nm PC1 with the extracted fluorescence contribution of collagen (denoted with *) and retinol (denoted with Δ), and (d) the correlation of 360nm PC2 with the extracted fluorescence contribution of NADH.

Fig. 2.
Fig. 2.

(a) average calibrated diffuse reflectance spectra of malignant (n = 37) and non-malignant (n = 46) tissue samples, (b) PC1 and PC2 obtained from the diffuse reflectance spectra (Refl PC1 and Refl PC2), (c) the correlation of Refl PC1 with extracted mean reduced scattering coefficients µs’, (d) correlation of Refl PC1 with β-carotene concentration, (e) correlation of Refl PC1 with hemoglobin saturation, and (f) the correlation of Refl PC2 with β-carotene concentration.

Tables (10)

Tables Icon

Table 1. (a) Histological breakdown of the breast samples investigated in this study; and (b) distribution of percent malignancy in malignant samples

Tables Icon

Table 2. PCs identified from Wilcoxon rank-sum test as displaying statistically significant difference between malignant and other non-malignant breast tissues (at significance level of p < 0.05). The variance that each PC accounts for was also listed in the table.

Tables Icon

Table 3. Pair wise linear correlation coefficients between the scores of PCs that were listed in Table 2 as displaying statistically significant difference between malignant and non-malignant tissue samples. The pair of PCs whose scores were significantly correlated, i.e. p < 0.01, were marked with asterisk*. The highlighted PCs (340nm PC1 and 360nm PC1) were selected for tissue classification.

Tables Icon

Table 4. Results from the leave-one-out cross validation of a linear SVM classification for discriminating malignant and non-malignant breast tissue samples using (1) two fluorescence PCs that are diagnostically the most significant and uncorrelated (i.e. 340nm PC1 and 360nm PC2); (2) two reflectance PCs that are diagnostically most significant (Refl PC1 and Refl PC2); and (3) the combined PCs of (1) and (2).

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Table 5. Results from Wilcoxon rank-sum test on extracted absorption, scattering and fluorescence properties for the statistical significant difference (at least p < 0.05) between (1) malignant and fibrous/benign; (2) malignant and adipose, and (3) malignant and non-malignant breast tissues (fluorescence properties were marked with *).

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Table 6. Results from the leave-one-out cross validation of a linear SVM classification for discriminating malignant from non-malignant breast tissue samples using (1) fluorescence properties only (relative fluorescence contribution of collagen, NADH and retinol), (2) absorption and scattering properties only (mean µs’, β-carotene concentration and hemoglobin saturation), and (3) combination of fluorescence, absorption and scattering properties in (1) and (2).

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Table 7. Fraction of misclassified samples of each tissue category. The sample number of each misclassified sample is listed in the parentheses. Malignant samples were broken down by percentage of malignancy and non-malignant samples were broken down by tissue type.

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Table 8. (a) Correlation between fluorescence PCs and the extracted fluorophore properties; and (b) Correlation between reflectance PCs and the absorption and scattering properties. Correlation was considered significant if p < 0.01 and the correlation coefficient was shown in the table, otherwise a symbol Ø was shown indicating no significant correlation. The correlation coefficients marked with ** have a p-value of p < 1e-6.

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Table 9. Results from Wilcoxon rank-sum test on the extracted tissue properties for the statistically significant difference between malignant and fibrous/benign breast tissues when breast reduction samples were combined into the sample set.

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Table 10. Diagnostic accuracy of a linear SVM classification for discriminating malignant from fibrous/benign breast tissues, using (1) diagnostically significant fluorescence properties only, (2) diagnostically significant absorption and scattering properties only, and (3) the combined tissue properties.

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