Abstract

This study investigates the use of two spectroscopic techniques, auto-fluorescence lifetime measurement (AFLM) and light reflectance spectroscopy (LRS), for detecting invasive ductal carcinoma (IDC) in human ex vivo breast specimens. AFLM used excitation at 447 nm with multiple emission wavelengths (532, 562, 632, and 644 nm), at which auto-fluorescence lifetimes and their weight factors were analyzed using a double exponent model. LRS measured reflectance spectra in the range of 500-840 nm and analyzed the spectral slopes empirically at several distinct spectral regions. Our preliminary results based on 93 measured locations (i.e., 34 IDC, 31 benign fibrous, 28 adipose) from 6 specimens show significant differences in 5 AFLM-derived parameters and 9 LRS-based spectral slopes between benign and malignant breast samples. Multinomial logistic regression with a 10-fold cross validation approach was implemented with selected features to classify IDC from benign fibrous and adipose tissues for the two techniques independently as well as for the combined dual-modality approach. The accuracy for classifying IDC was found to be 96.4 ± 0.8%, 92.3 ± 0.8% and 96 ± 1.3% for LRS, AFLM, and dual-modality, respectively.

© 2012 OSA

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G. A. Rahman, “Breast conserving therapy: a surgical technique where little can mean more,” J Surg Tech Case Rep3(1), 1–4 (2011).
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R. Nachabé, D. J. Evers, B. H. Hendriks, G. W. Lucassen, M. van der Voort, E. J. Rutgers, M. J. Peeters, J. A. Van der Hage, H. S. Oldenburg, J. Wesseling, and T. J. Ruers, “Diagnosis of breast cancer using diffuse optical spectroscopy from 500 to 1600 nm: comparison of classification methods,” J. Biomed. Opt.16(8), 087010 (2011).
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[CrossRef] [PubMed]

V. Sharma, N. Patel, J. Chen, L. Tang, G. Alexandrakis, and H. A. N. L. I. Liu, “A dual-modality optical biopsy approach for in vivo detection of prostate cancer in rat model,” J. Innovat. Opt. Health Sci. (JIOHS)04(03), 269–277 (2011).
[CrossRef]

2010

J. McGinty, N. P. Galletly, C. Dunsby, I. Munro, D. S. Elson, J. Requejo-Isidro, P. Cohen, R. Ahmad, A. Forsyth, A. V. Thillainayagam, M. A. Neil, P. M. French, and G. W. Stamp, “Wide-field fluorescence lifetime imaging of cancer,” Biomed. Opt. Express1(2), 627–640 (2010).
[CrossRef] [PubMed]

M. Y. Berezin and S. Achilefu, “Fluorescence lifetime measurements and biological imaging,” Chem. Rev.110(5), 2641–2684 (2010).
[CrossRef] [PubMed]

A. Mukerjee, T. J. Sørensen, A. P. Ranjan, S. Raut, I. Gryczynski, J. K. Vishwanatha, and Z. Gryczynski, “Spectroscopic properties of curcumin: orientation of transition moments,” J. Phys. Chem. B114(39), 12679–12684 (2010).
[CrossRef] [PubMed]

J. Q. Brown, T. M. Bydlon, L. M. Richards, B. Yu, S. A. Kennedy, J. Geradts, L. G. Wilke, M. Junker, J. Gallagher, W. T. Barry, and N. Ramanujam, “Optical assessment of tumor resection margins in the breast,” IEEE J. Sel. Top. Quantum Electron.16(3), 530–544 (2010).
[CrossRef] [PubMed]

M. D. Keller, S. K. Majumder, M. C. Kelley, I. M. Meszoely, F. I. Boulos, G. M. Olivares, and A. Mahadevan-Jansen, “Autofluorescence and diffuse reflectance spectroscopy and spectral imaging for breast surgical margin analysis,” Lasers Surg. Med.42(1), 15–23 (2010).
[CrossRef] [PubMed]

S. Kennedy, J. Geradts, T. Bydlon, J. Q. Brown, J. Gallagher, M. Junker, W. Barry, N. Ramanujam, and L. Wilke, “Optical breast cancer margin assessment: an observational study of the effects of tissue heterogeneity on optical contrast,” Breast Cancer Res.12(6), R91 (2010).
[CrossRef] [PubMed]

2009

R. G. Pleijhuis, M. Graafland, J. de Vries, J. Bart, J. S. de Jong, and G. M. van Dam, “Obtaining adequate surgical margins in breast-conserving therapy for patients with early-stage breast cancer: current modalities and future directions,” Ann. Surg. Oncol.16(10), 2717–2730 (2009).
[CrossRef] [PubMed]

R. Luchowski, Z. Gryczynski, P. Sarkar, J. Borejdo, M. Szabelski, P. Kapusta, and I. Gryczynski, “Instrument response standard in time-resolved fluorescence,” Rev. Sci. Instrum.80(3), 033109 (2009).
[CrossRef] [PubMed]

2008

Z. Volynskaya, A. S. Haka, K. L. Bechtel, M. Fitzmaurice, R. Shenk, N. Wang, J. Nazemi, R. R. Dasari, and M. S. Feld, “Diagnosing breast cancer using diffuse reflectance spectroscopy and intrinsic fluorescence spectroscopy,” J. Biomed. Opt.13(2), 024012 (2008).
[CrossRef] [PubMed]

2007

C. W. Chang, D. Sud, and M. A. Mycek, “Fluorescence lifetime imaging microscopy,” Methods Cell Biol.81, 495–524 (2007).
[CrossRef] [PubMed]

M. C. Skala, K. M. Riching, D. K. Bird, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, P. J. Keely, and N. Ramanujam, “In vivo multiphoton fluorescence lifetime imaging of protein-bound and free nicotinamide adenine dinucleotide in normal and precancerous epithelia,” J. Biomed. Opt.12(2), 024014 (2007).
[CrossRef] [PubMed]

2006

S. G. Demos, A. J. Vogel, and A. H. Gandjbakhche, “Advances in optical spectroscopy and imaging of breast lesions,” J. Mammary Gland Biol. Neoplasia11(2), 165–181 (2006).
[CrossRef] [PubMed]

N. J. Perkins and E. F. Schisterman, “The inconsistency of “optimal” cutpoints obtained using two criteria based on the receiver operating characteristic curve,” Am. J. Epidemiol.163(7), 670–675 (2006).
[CrossRef] [PubMed]

2005

H. M. Chen, C. P. Chiang, C. You, T. C. Hsiao, and C. Y. Wang, “Time-resolved autofluorescence spectroscopy for classifying normal and premalignant oral tissues,” Lasers Surg. Med.37(1), 37–45 (2005).
[CrossRef] [PubMed]

L. L. Burgoyne, D. W. Jay, G. B. Bikhazi, and A. J. De Armendi, “Isosulfan blue causes factitious methemoglobinemia in an infant,” Paediatr. Anaesth.15(12), 1116–1119 (2005).
[CrossRef] [PubMed]

2004

H. Liu, Y. Gu, J. G. Kim, and R. P. Mason, “Near-infrared spectroscopy and imaging of tumor vascular oxygenation,” Methods Enzymol.386, 349–378 (2004).
[CrossRef] [PubMed]

D. Elson, J. Requejo-Isidro, I. Munro, F. Reavell, J. Siegel, K. Suhling, P. Tadrous, R. Benninger, P. Lanigan, J. McGinty, C. Talbot, B. Treanor, S. Webb, A. Sandison, A. Wallace, D. Davis, J. Lever, M. Neil, D. Phillips, G. Stamp, and P. French, “Time-domain fluorescence lifetime imaging applied to biological tissue,” Photochem. Photobiol. Sci.3(8), 795–801 (2004).
[CrossRef] [PubMed]

2003

G. M. Palmer, C. F. Zhu, T. M. Breslin, F. S. 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(11), 1233–1242 (2003).
[CrossRef] [PubMed]

J. Siegel, D. S. Elson, S. E. D. Webb, K. C. B. Lee, A. Vlandas, G. L. Gambaruto, S. Lévêque-Fort, M. J. Lever, P. J. Tadrous, G. W. H. Stamp, A. L. Wallace, A. Sandison, T. F. Watson, F. Alvarez, and P. M. W. French, “Studying biological tissue with fluorescence lifetime imaging: microscopy, endoscopy, and complex decay profiles,” Appl. Opt.42(16), 2995–3004 (2003).
[CrossRef] [PubMed]

P. J. Tadrous, J. Siegel, P. M. French, S. Shousha, N. Lalani, and G. W. Stamp, “Fluorescence lifetime imaging of unstained tissues: early results in human breast cancer,” J. Pathol.199(3), 309–317 (2003).
[CrossRef] [PubMed]

2002

S. E. Singletary, “Surgical margins in patients with early-stage breast cancer treated with breast conservation therapy,” Am. J. Surg.184(5), 383–393 (2002).
[CrossRef] [PubMed]

2000

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(2), 221–228 (2000).
[CrossRef] [PubMed]

N. Ramanujam, “Fluorescence spectroscopy of neoplastic and non-neoplastic tissues,” Neoplasia2(1/2), 89–117 (2000).
[CrossRef] [PubMed]

1998

G. A. Wagnières, W. M. Star, and B. C. Wilson, “In vivo fluorescence spectroscopy and imaging for oncological applications,” Photochem. Photobiol.68(5), 603–632 (1998).
[PubMed]

Achilefu, S.

M. Y. Berezin and S. Achilefu, “Fluorescence lifetime measurements and biological imaging,” Chem. Rev.110(5), 2641–2684 (2010).
[CrossRef] [PubMed]

Ahmad, R.

Alexandrakis, G.

V. Sharma, N. Patel, J. Chen, L. Tang, G. Alexandrakis, and H. A. N. L. I. Liu, “A dual-modality optical biopsy approach for in vivo detection of prostate cancer in rat model,” J. Innovat. Opt. Health Sci. (JIOHS)04(03), 269–277 (2011).
[CrossRef]

Alvarez, F.

Barry, W.

S. Kennedy, J. Geradts, T. Bydlon, J. Q. Brown, J. Gallagher, M. Junker, W. Barry, N. Ramanujam, and L. Wilke, “Optical breast cancer margin assessment: an observational study of the effects of tissue heterogeneity on optical contrast,” Breast Cancer Res.12(6), R91 (2010).
[CrossRef] [PubMed]

Barry, W. T.

J. Q. Brown, T. M. Bydlon, L. M. Richards, B. Yu, S. A. Kennedy, J. Geradts, L. G. Wilke, M. Junker, J. Gallagher, W. T. Barry, and N. Ramanujam, “Optical assessment of tumor resection margins in the breast,” IEEE J. Sel. Top. Quantum Electron.16(3), 530–544 (2010).
[CrossRef] [PubMed]

Bart, J.

R. G. Pleijhuis, M. Graafland, J. de Vries, J. Bart, J. S. de Jong, and G. M. van Dam, “Obtaining adequate surgical margins in breast-conserving therapy for patients with early-stage breast cancer: current modalities and future directions,” Ann. Surg. Oncol.16(10), 2717–2730 (2009).
[CrossRef] [PubMed]

Bechtel, K. L.

Z. Volynskaya, A. S. Haka, K. L. Bechtel, M. Fitzmaurice, R. Shenk, N. Wang, J. Nazemi, R. R. Dasari, and M. S. Feld, “Diagnosing breast cancer using diffuse reflectance spectroscopy and intrinsic fluorescence spectroscopy,” J. Biomed. Opt.13(2), 024012 (2008).
[CrossRef] [PubMed]

Benninger, R.

D. Elson, J. Requejo-Isidro, I. Munro, F. Reavell, J. Siegel, K. Suhling, P. Tadrous, R. Benninger, P. Lanigan, J. McGinty, C. Talbot, B. Treanor, S. Webb, A. Sandison, A. Wallace, D. Davis, J. Lever, M. Neil, D. Phillips, G. Stamp, and P. French, “Time-domain fluorescence lifetime imaging applied to biological tissue,” Photochem. Photobiol. Sci.3(8), 795–801 (2004).
[CrossRef] [PubMed]

Berezin, M. Y.

M. Y. Berezin and S. Achilefu, “Fluorescence lifetime measurements and biological imaging,” Chem. Rev.110(5), 2641–2684 (2010).
[CrossRef] [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(2), 221–228 (2000).
[CrossRef] [PubMed]

Bikhazi, G. B.

L. L. Burgoyne, D. W. Jay, G. B. Bikhazi, and A. J. De Armendi, “Isosulfan blue causes factitious methemoglobinemia in an infant,” Paediatr. Anaesth.15(12), 1116–1119 (2005).
[CrossRef] [PubMed]

Bird, D. K.

M. C. Skala, K. M. Riching, D. K. Bird, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, P. J. Keely, and N. Ramanujam, “In vivo multiphoton fluorescence lifetime imaging of protein-bound and free nicotinamide adenine dinucleotide in normal and precancerous epithelia,” J. Biomed. Opt.12(2), 024014 (2007).
[CrossRef] [PubMed]

Borejdo, J.

R. Luchowski, Z. Gryczynski, P. Sarkar, J. Borejdo, M. Szabelski, P. Kapusta, and I. Gryczynski, “Instrument response standard in time-resolved fluorescence,” Rev. Sci. Instrum.80(3), 033109 (2009).
[CrossRef] [PubMed]

Boulos, F. I.

M. D. Keller, S. K. Majumder, M. C. Kelley, I. M. Meszoely, F. I. Boulos, G. M. Olivares, and A. Mahadevan-Jansen, “Autofluorescence and diffuse reflectance spectroscopy and spectral imaging for breast surgical margin analysis,” Lasers Surg. Med.42(1), 15–23 (2010).
[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(2), 221–228 (2000).
[CrossRef] [PubMed]

Breslin, T. M.

G. M. Palmer, C. F. Zhu, T. M. Breslin, F. S. 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(11), 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(2), 221–228 (2000).
[CrossRef] [PubMed]

Brown, J. Q.

S. Kennedy, J. Geradts, T. Bydlon, J. Q. Brown, J. Gallagher, M. Junker, W. Barry, N. Ramanujam, and L. Wilke, “Optical breast cancer margin assessment: an observational study of the effects of tissue heterogeneity on optical contrast,” Breast Cancer Res.12(6), R91 (2010).
[CrossRef] [PubMed]

J. Q. Brown, T. M. Bydlon, L. M. Richards, B. Yu, S. A. Kennedy, J. Geradts, L. G. Wilke, M. Junker, J. Gallagher, W. T. Barry, and N. Ramanujam, “Optical assessment of tumor resection margins in the breast,” IEEE J. Sel. Top. Quantum Electron.16(3), 530–544 (2010).
[CrossRef] [PubMed]

Burgoyne, L. L.

L. L. Burgoyne, D. W. Jay, G. B. Bikhazi, and A. J. De Armendi, “Isosulfan blue causes factitious methemoglobinemia in an infant,” Paediatr. Anaesth.15(12), 1116–1119 (2005).
[CrossRef] [PubMed]

Bydlon, T.

S. Kennedy, J. Geradts, T. Bydlon, J. Q. Brown, J. Gallagher, M. Junker, W. Barry, N. Ramanujam, and L. Wilke, “Optical breast cancer margin assessment: an observational study of the effects of tissue heterogeneity on optical contrast,” Breast Cancer Res.12(6), R91 (2010).
[CrossRef] [PubMed]

Bydlon, T. M.

J. Q. Brown, T. M. Bydlon, L. M. Richards, B. Yu, S. A. Kennedy, J. Geradts, L. G. Wilke, M. Junker, J. Gallagher, W. T. Barry, and N. Ramanujam, “Optical assessment of tumor resection margins in the breast,” IEEE J. Sel. Top. Quantum Electron.16(3), 530–544 (2010).
[CrossRef] [PubMed]

Chang, C. W.

C. W. Chang, D. Sud, and M. A. Mycek, “Fluorescence lifetime imaging microscopy,” Methods Cell Biol.81, 495–524 (2007).
[CrossRef] [PubMed]

Chen, H. M.

H. M. Chen, C. P. Chiang, C. You, T. C. Hsiao, and C. Y. Wang, “Time-resolved autofluorescence spectroscopy for classifying normal and premalignant oral tissues,” Lasers Surg. Med.37(1), 37–45 (2005).
[CrossRef] [PubMed]

Chen, J.

V. Sharma, N. Patel, J. Chen, L. Tang, G. Alexandrakis, and H. A. N. L. I. Liu, “A dual-modality optical biopsy approach for in vivo detection of prostate cancer in rat model,” J. Innovat. Opt. Health Sci. (JIOHS)04(03), 269–277 (2011).
[CrossRef]

Chiang, C. P.

H. M. Chen, C. P. Chiang, C. You, T. C. Hsiao, and C. Y. Wang, “Time-resolved autofluorescence spectroscopy for classifying normal and premalignant oral tissues,” Lasers Surg. Med.37(1), 37–45 (2005).
[CrossRef] [PubMed]

Cohen, P.

Dasari, R. R.

Z. Volynskaya, A. S. Haka, K. L. Bechtel, M. Fitzmaurice, R. Shenk, N. Wang, J. Nazemi, R. R. Dasari, and M. S. Feld, “Diagnosing breast cancer using diffuse reflectance spectroscopy and intrinsic fluorescence spectroscopy,” J. Biomed. Opt.13(2), 024012 (2008).
[CrossRef] [PubMed]

Davis, D.

D. Elson, J. Requejo-Isidro, I. Munro, F. Reavell, J. Siegel, K. Suhling, P. Tadrous, R. Benninger, P. Lanigan, J. McGinty, C. Talbot, B. Treanor, S. Webb, A. Sandison, A. Wallace, D. Davis, J. Lever, M. Neil, D. Phillips, G. Stamp, and P. French, “Time-domain fluorescence lifetime imaging applied to biological tissue,” Photochem. Photobiol. Sci.3(8), 795–801 (2004).
[CrossRef] [PubMed]

De Armendi, A. J.

L. L. Burgoyne, D. W. Jay, G. B. Bikhazi, and A. J. De Armendi, “Isosulfan blue causes factitious methemoglobinemia in an infant,” Paediatr. Anaesth.15(12), 1116–1119 (2005).
[CrossRef] [PubMed]

de Jong, J. S.

R. G. Pleijhuis, M. Graafland, J. de Vries, J. Bart, J. S. de Jong, and G. M. van Dam, “Obtaining adequate surgical margins in breast-conserving therapy for patients with early-stage breast cancer: current modalities and future directions,” Ann. Surg. Oncol.16(10), 2717–2730 (2009).
[CrossRef] [PubMed]

de Vries, J.

R. G. Pleijhuis, M. Graafland, J. de Vries, J. Bart, J. S. de Jong, and G. M. van Dam, “Obtaining adequate surgical margins in breast-conserving therapy for patients with early-stage breast cancer: current modalities and future directions,” Ann. Surg. Oncol.16(10), 2717–2730 (2009).
[CrossRef] [PubMed]

Demos, S. G.

S. G. Demos, A. J. Vogel, and A. H. Gandjbakhche, “Advances in optical spectroscopy and imaging of breast lesions,” J. Mammary Gland Biol. Neoplasia11(2), 165–181 (2006).
[CrossRef] [PubMed]

Dunsby, C.

Eickhoff, J.

M. C. Skala, K. M. Riching, D. K. Bird, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, P. J. Keely, and N. Ramanujam, “In vivo multiphoton fluorescence lifetime imaging of protein-bound and free nicotinamide adenine dinucleotide in normal and precancerous epithelia,” J. Biomed. Opt.12(2), 024014 (2007).
[CrossRef] [PubMed]

Eliceiri, K. W.

M. C. Skala, K. M. Riching, D. K. Bird, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, P. J. Keely, and N. Ramanujam, “In vivo multiphoton fluorescence lifetime imaging of protein-bound and free nicotinamide adenine dinucleotide in normal and precancerous epithelia,” J. Biomed. Opt.12(2), 024014 (2007).
[CrossRef] [PubMed]

Elson, D.

D. Elson, J. Requejo-Isidro, I. Munro, F. Reavell, J. Siegel, K. Suhling, P. Tadrous, R. Benninger, P. Lanigan, J. McGinty, C. Talbot, B. Treanor, S. Webb, A. Sandison, A. Wallace, D. Davis, J. Lever, M. Neil, D. Phillips, G. Stamp, and P. French, “Time-domain fluorescence lifetime imaging applied to biological tissue,” Photochem. Photobiol. Sci.3(8), 795–801 (2004).
[CrossRef] [PubMed]

Elson, D. S.

Evers, D. J.

R. Nachabé, D. J. Evers, B. H. Hendriks, G. W. Lucassen, M. van der Voort, E. J. Rutgers, M. J. Peeters, J. A. Van der Hage, H. S. Oldenburg, J. Wesseling, and T. J. Ruers, “Diagnosis of breast cancer using diffuse optical spectroscopy from 500 to 1600 nm: comparison of classification methods,” J. Biomed. Opt.16(8), 087010 (2011).
[CrossRef] [PubMed]

Feld, M. S.

Z. Volynskaya, A. S. Haka, K. L. Bechtel, M. Fitzmaurice, R. Shenk, N. Wang, J. Nazemi, R. R. Dasari, and M. S. Feld, “Diagnosing breast cancer using diffuse reflectance spectroscopy and intrinsic fluorescence spectroscopy,” J. Biomed. Opt.13(2), 024012 (2008).
[CrossRef] [PubMed]

Fitzmaurice, M.

Z. Volynskaya, A. S. Haka, K. L. Bechtel, M. Fitzmaurice, R. Shenk, N. Wang, J. Nazemi, R. R. Dasari, and M. S. Feld, “Diagnosing breast cancer using diffuse reflectance spectroscopy and intrinsic fluorescence spectroscopy,” J. Biomed. Opt.13(2), 024012 (2008).
[CrossRef] [PubMed]

Forsyth, A.

French, P.

D. Elson, J. Requejo-Isidro, I. Munro, F. Reavell, J. Siegel, K. Suhling, P. Tadrous, R. Benninger, P. Lanigan, J. McGinty, C. Talbot, B. Treanor, S. Webb, A. Sandison, A. Wallace, D. Davis, J. Lever, M. Neil, D. Phillips, G. Stamp, and P. French, “Time-domain fluorescence lifetime imaging applied to biological tissue,” Photochem. Photobiol. Sci.3(8), 795–801 (2004).
[CrossRef] [PubMed]

French, P. M.

J. McGinty, N. P. Galletly, C. Dunsby, I. Munro, D. S. Elson, J. Requejo-Isidro, P. Cohen, R. Ahmad, A. Forsyth, A. V. Thillainayagam, M. A. Neil, P. M. French, and G. W. Stamp, “Wide-field fluorescence lifetime imaging of cancer,” Biomed. Opt. Express1(2), 627–640 (2010).
[CrossRef] [PubMed]

P. J. Tadrous, J. Siegel, P. M. French, S. Shousha, N. Lalani, and G. W. Stamp, “Fluorescence lifetime imaging of unstained tissues: early results in human breast cancer,” J. Pathol.199(3), 309–317 (2003).
[CrossRef] [PubMed]

French, P. M. W.

Gallagher, J.

S. Kennedy, J. Geradts, T. Bydlon, J. Q. Brown, J. Gallagher, M. Junker, W. Barry, N. Ramanujam, and L. Wilke, “Optical breast cancer margin assessment: an observational study of the effects of tissue heterogeneity on optical contrast,” Breast Cancer Res.12(6), R91 (2010).
[CrossRef] [PubMed]

J. Q. Brown, T. M. Bydlon, L. M. Richards, B. Yu, S. A. Kennedy, J. Geradts, L. G. Wilke, M. Junker, J. Gallagher, W. T. Barry, and N. Ramanujam, “Optical assessment of tumor resection margins in the breast,” IEEE J. Sel. Top. Quantum Electron.16(3), 530–544 (2010).
[CrossRef] [PubMed]

Galletly, N. P.

Gambaruto, G. L.

Gandjbakhche, A. H.

S. G. Demos, A. J. Vogel, and A. H. Gandjbakhche, “Advances in optical spectroscopy and imaging of breast lesions,” J. Mammary Gland Biol. Neoplasia11(2), 165–181 (2006).
[CrossRef] [PubMed]

Gendron-Fitzpatrick, A.

M. C. Skala, K. M. Riching, D. K. Bird, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, P. J. Keely, and N. Ramanujam, “In vivo multiphoton fluorescence lifetime imaging of protein-bound and free nicotinamide adenine dinucleotide in normal and precancerous epithelia,” J. Biomed. Opt.12(2), 024014 (2007).
[CrossRef] [PubMed]

Geradts, J.

S. Kennedy, J. Geradts, T. Bydlon, J. Q. Brown, J. Gallagher, M. Junker, W. Barry, N. Ramanujam, and L. Wilke, “Optical breast cancer margin assessment: an observational study of the effects of tissue heterogeneity on optical contrast,” Breast Cancer Res.12(6), R91 (2010).
[CrossRef] [PubMed]

J. Q. Brown, T. M. Bydlon, L. M. Richards, B. Yu, S. A. Kennedy, J. Geradts, L. G. Wilke, M. Junker, J. Gallagher, W. T. Barry, and N. Ramanujam, “Optical assessment of tumor resection margins in the breast,” IEEE J. Sel. Top. Quantum Electron.16(3), 530–544 (2010).
[CrossRef] [PubMed]

Gilchrist, K. W.

G. M. Palmer, C. F. Zhu, T. M. Breslin, F. S. 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(11), 1233–1242 (2003).
[CrossRef] [PubMed]

Graafland, M.

R. G. Pleijhuis, M. Graafland, J. de Vries, J. Bart, J. S. de Jong, and G. M. van Dam, “Obtaining adequate surgical margins in breast-conserving therapy for patients with early-stage breast cancer: current modalities and future directions,” Ann. Surg. Oncol.16(10), 2717–2730 (2009).
[CrossRef] [PubMed]

Gryczynski, I.

A. Mukerjee, T. J. Sørensen, A. P. Ranjan, S. Raut, I. Gryczynski, J. K. Vishwanatha, and Z. Gryczynski, “Spectroscopic properties of curcumin: orientation of transition moments,” J. Phys. Chem. B114(39), 12679–12684 (2010).
[CrossRef] [PubMed]

R. Luchowski, Z. Gryczynski, P. Sarkar, J. Borejdo, M. Szabelski, P. Kapusta, and I. Gryczynski, “Instrument response standard in time-resolved fluorescence,” Rev. Sci. Instrum.80(3), 033109 (2009).
[CrossRef] [PubMed]

Gryczynski, Z.

A. Mukerjee, T. J. Sørensen, A. P. Ranjan, S. Raut, I. Gryczynski, J. K. Vishwanatha, and Z. Gryczynski, “Spectroscopic properties of curcumin: orientation of transition moments,” J. Phys. Chem. B114(39), 12679–12684 (2010).
[CrossRef] [PubMed]

R. Luchowski, Z. Gryczynski, P. Sarkar, J. Borejdo, M. Szabelski, P. Kapusta, and I. Gryczynski, “Instrument response standard in time-resolved fluorescence,” Rev. Sci. Instrum.80(3), 033109 (2009).
[CrossRef] [PubMed]

Gu, Y.

H. Liu, Y. Gu, J. G. Kim, and R. P. Mason, “Near-infrared spectroscopy and imaging of tumor vascular oxygenation,” Methods Enzymol.386, 349–378 (2004).
[CrossRef] [PubMed]

Haka, A. S.

Z. Volynskaya, A. S. Haka, K. L. Bechtel, M. Fitzmaurice, R. Shenk, N. Wang, J. Nazemi, R. R. Dasari, and M. S. Feld, “Diagnosing breast cancer using diffuse reflectance spectroscopy and intrinsic fluorescence spectroscopy,” J. Biomed. Opt.13(2), 024012 (2008).
[CrossRef] [PubMed]

He, J. W.

V. Sharma, J. W. He, S. Narvenkar, Y. B. Peng, and H. Liu, “Quantification of light reflectance spectroscopy and its application: determination of hemodynamics on the rat spinal cord and brain induced by electrical stimulation,” Neuroimage56(3), 1316–1328 (2011).
[CrossRef] [PubMed]

Hendriks, B. H.

R. Nachabé, D. J. Evers, B. H. Hendriks, G. W. Lucassen, M. van der Voort, E. J. Rutgers, M. J. Peeters, J. A. Van der Hage, H. S. Oldenburg, J. Wesseling, and T. J. Ruers, “Diagnosis of breast cancer using diffuse optical spectroscopy from 500 to 1600 nm: comparison of classification methods,” J. Biomed. Opt.16(8), 087010 (2011).
[CrossRef] [PubMed]

Hsiao, T. C.

H. M. Chen, C. P. Chiang, C. You, T. C. Hsiao, and C. Y. Wang, “Time-resolved autofluorescence spectroscopy for classifying normal and premalignant oral tissues,” Lasers Surg. Med.37(1), 37–45 (2005).
[CrossRef] [PubMed]

Jay, D. W.

L. L. Burgoyne, D. W. Jay, G. B. Bikhazi, and A. J. De Armendi, “Isosulfan blue causes factitious methemoglobinemia in an infant,” Paediatr. Anaesth.15(12), 1116–1119 (2005).
[CrossRef] [PubMed]

Junker, M.

J. Q. Brown, T. M. Bydlon, L. M. Richards, B. Yu, S. A. Kennedy, J. Geradts, L. G. Wilke, M. Junker, J. Gallagher, W. T. Barry, and N. Ramanujam, “Optical assessment of tumor resection margins in the breast,” IEEE J. Sel. Top. Quantum Electron.16(3), 530–544 (2010).
[CrossRef] [PubMed]

S. Kennedy, J. Geradts, T. Bydlon, J. Q. Brown, J. Gallagher, M. Junker, W. Barry, N. Ramanujam, and L. Wilke, “Optical breast cancer margin assessment: an observational study of the effects of tissue heterogeneity on optical contrast,” Breast Cancer Res.12(6), R91 (2010).
[CrossRef] [PubMed]

Kapusta, P.

R. Luchowski, Z. Gryczynski, P. Sarkar, J. Borejdo, M. Szabelski, P. Kapusta, and I. Gryczynski, “Instrument response standard in time-resolved fluorescence,” Rev. Sci. Instrum.80(3), 033109 (2009).
[CrossRef] [PubMed]

Keely, P. J.

M. C. Skala, K. M. Riching, D. K. Bird, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, P. J. Keely, and N. Ramanujam, “In vivo multiphoton fluorescence lifetime imaging of protein-bound and free nicotinamide adenine dinucleotide in normal and precancerous epithelia,” J. Biomed. Opt.12(2), 024014 (2007).
[CrossRef] [PubMed]

Keller, M. D.

M. D. Keller, S. K. Majumder, M. C. Kelley, I. M. Meszoely, F. I. Boulos, G. M. Olivares, and A. Mahadevan-Jansen, “Autofluorescence and diffuse reflectance spectroscopy and spectral imaging for breast surgical margin analysis,” Lasers Surg. Med.42(1), 15–23 (2010).
[CrossRef] [PubMed]

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(2), 221–228 (2000).
[CrossRef] [PubMed]

Kelley, M. C.

M. D. Keller, S. K. Majumder, M. C. Kelley, I. M. Meszoely, F. I. Boulos, G. M. Olivares, and A. Mahadevan-Jansen, “Autofluorescence and diffuse reflectance spectroscopy and spectral imaging for breast surgical margin analysis,” Lasers Surg. Med.42(1), 15–23 (2010).
[CrossRef] [PubMed]

Kennedy, S.

S. Kennedy, J. Geradts, T. Bydlon, J. Q. Brown, J. Gallagher, M. Junker, W. Barry, N. Ramanujam, and L. Wilke, “Optical breast cancer margin assessment: an observational study of the effects of tissue heterogeneity on optical contrast,” Breast Cancer Res.12(6), R91 (2010).
[CrossRef] [PubMed]

Kennedy, S. A.

J. Q. Brown, T. M. Bydlon, L. M. Richards, B. Yu, S. A. Kennedy, J. Geradts, L. G. Wilke, M. Junker, J. Gallagher, W. T. Barry, and N. Ramanujam, “Optical assessment of tumor resection margins in the breast,” IEEE J. Sel. Top. Quantum Electron.16(3), 530–544 (2010).
[CrossRef] [PubMed]

Kim, J. G.

H. Liu, Y. Gu, J. G. Kim, and R. P. Mason, “Near-infrared spectroscopy and imaging of tumor vascular oxygenation,” Methods Enzymol.386, 349–378 (2004).
[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(2), 221–228 (2000).
[CrossRef] [PubMed]

Lalani, N.

P. J. Tadrous, J. Siegel, P. M. French, S. Shousha, N. Lalani, and G. W. Stamp, “Fluorescence lifetime imaging of unstained tissues: early results in human breast cancer,” J. Pathol.199(3), 309–317 (2003).
[CrossRef] [PubMed]

Lanigan, P.

D. Elson, J. Requejo-Isidro, I. Munro, F. Reavell, J. Siegel, K. Suhling, P. Tadrous, R. Benninger, P. Lanigan, J. McGinty, C. Talbot, B. Treanor, S. Webb, A. Sandison, A. Wallace, D. Davis, J. Lever, M. Neil, D. Phillips, G. Stamp, and P. French, “Time-domain fluorescence lifetime imaging applied to biological tissue,” Photochem. Photobiol. Sci.3(8), 795–801 (2004).
[CrossRef] [PubMed]

Lee, K. C. B.

Lévêque-Fort, S.

Lever, J.

D. Elson, J. Requejo-Isidro, I. Munro, F. Reavell, J. Siegel, K. Suhling, P. Tadrous, R. Benninger, P. Lanigan, J. McGinty, C. Talbot, B. Treanor, S. Webb, A. Sandison, A. Wallace, D. Davis, J. Lever, M. Neil, D. Phillips, G. Stamp, and P. French, “Time-domain fluorescence lifetime imaging applied to biological tissue,” Photochem. Photobiol. Sci.3(8), 795–801 (2004).
[CrossRef] [PubMed]

Lever, M. J.

Liu, H.

V. Sharma, J. W. He, S. Narvenkar, Y. B. Peng, and H. Liu, “Quantification of light reflectance spectroscopy and its application: determination of hemodynamics on the rat spinal cord and brain induced by electrical stimulation,” Neuroimage56(3), 1316–1328 (2011).
[CrossRef] [PubMed]

H. Liu, Y. Gu, J. G. Kim, and R. P. Mason, “Near-infrared spectroscopy and imaging of tumor vascular oxygenation,” Methods Enzymol.386, 349–378 (2004).
[CrossRef] [PubMed]

Liu, H. A. N. L. I.

V. Sharma, N. Patel, J. Chen, L. Tang, G. Alexandrakis, and H. A. N. L. I. Liu, “A dual-modality optical biopsy approach for in vivo detection of prostate cancer in rat model,” J. Innovat. Opt. Health Sci. (JIOHS)04(03), 269–277 (2011).
[CrossRef]

Lucassen, G. W.

R. Nachabé, D. J. Evers, B. H. Hendriks, G. W. Lucassen, M. van der Voort, E. J. Rutgers, M. J. Peeters, J. A. Van der Hage, H. S. Oldenburg, J. Wesseling, and T. J. Ruers, “Diagnosis of breast cancer using diffuse optical spectroscopy from 500 to 1600 nm: comparison of classification methods,” J. Biomed. Opt.16(8), 087010 (2011).
[CrossRef] [PubMed]

Luchowski, R.

R. Luchowski, Z. Gryczynski, P. Sarkar, J. Borejdo, M. Szabelski, P. Kapusta, and I. Gryczynski, “Instrument response standard in time-resolved fluorescence,” Rev. Sci. Instrum.80(3), 033109 (2009).
[CrossRef] [PubMed]

Mahadevan-Jansen, A.

M. D. Keller, S. K. Majumder, M. C. Kelley, I. M. Meszoely, F. I. Boulos, G. M. Olivares, and A. Mahadevan-Jansen, “Autofluorescence and diffuse reflectance spectroscopy and spectral imaging for breast surgical margin analysis,” Lasers Surg. Med.42(1), 15–23 (2010).
[CrossRef] [PubMed]

Majumder, S. K.

M. D. Keller, S. K. Majumder, M. C. Kelley, I. M. Meszoely, F. I. Boulos, G. M. Olivares, and A. Mahadevan-Jansen, “Autofluorescence and diffuse reflectance spectroscopy and spectral imaging for breast surgical margin analysis,” Lasers Surg. Med.42(1), 15–23 (2010).
[CrossRef] [PubMed]

Mason, R. P.

H. Liu, Y. Gu, J. G. Kim, and R. P. Mason, “Near-infrared spectroscopy and imaging of tumor vascular oxygenation,” Methods Enzymol.386, 349–378 (2004).
[CrossRef] [PubMed]

McGinty, J.

J. McGinty, N. P. Galletly, C. Dunsby, I. Munro, D. S. Elson, J. Requejo-Isidro, P. Cohen, R. Ahmad, A. Forsyth, A. V. Thillainayagam, M. A. Neil, P. M. French, and G. W. Stamp, “Wide-field fluorescence lifetime imaging of cancer,” Biomed. Opt. Express1(2), 627–640 (2010).
[CrossRef] [PubMed]

D. Elson, J. Requejo-Isidro, I. Munro, F. Reavell, J. Siegel, K. Suhling, P. Tadrous, R. Benninger, P. Lanigan, J. McGinty, C. Talbot, B. Treanor, S. Webb, A. Sandison, A. Wallace, D. Davis, J. Lever, M. Neil, D. Phillips, G. Stamp, and P. French, “Time-domain fluorescence lifetime imaging applied to biological tissue,” Photochem. Photobiol. Sci.3(8), 795–801 (2004).
[CrossRef] [PubMed]

Meszoely, I. M.

M. D. Keller, S. K. Majumder, M. C. Kelley, I. M. Meszoely, F. I. Boulos, G. M. Olivares, and A. Mahadevan-Jansen, “Autofluorescence and diffuse reflectance spectroscopy and spectral imaging for breast surgical margin analysis,” Lasers Surg. Med.42(1), 15–23 (2010).
[CrossRef] [PubMed]

Mukerjee, A.

A. Mukerjee, T. J. Sørensen, A. P. Ranjan, S. Raut, I. Gryczynski, J. K. Vishwanatha, and Z. Gryczynski, “Spectroscopic properties of curcumin: orientation of transition moments,” J. Phys. Chem. B114(39), 12679–12684 (2010).
[CrossRef] [PubMed]

Munro, I.

J. McGinty, N. P. Galletly, C. Dunsby, I. Munro, D. S. Elson, J. Requejo-Isidro, P. Cohen, R. Ahmad, A. Forsyth, A. V. Thillainayagam, M. A. Neil, P. M. French, and G. W. Stamp, “Wide-field fluorescence lifetime imaging of cancer,” Biomed. Opt. Express1(2), 627–640 (2010).
[CrossRef] [PubMed]

D. Elson, J. Requejo-Isidro, I. Munro, F. Reavell, J. Siegel, K. Suhling, P. Tadrous, R. Benninger, P. Lanigan, J. McGinty, C. Talbot, B. Treanor, S. Webb, A. Sandison, A. Wallace, D. Davis, J. Lever, M. Neil, D. Phillips, G. Stamp, and P. French, “Time-domain fluorescence lifetime imaging applied to biological tissue,” Photochem. Photobiol. Sci.3(8), 795–801 (2004).
[CrossRef] [PubMed]

Mycek, M. A.

C. W. Chang, D. Sud, and M. A. Mycek, “Fluorescence lifetime imaging microscopy,” Methods Cell Biol.81, 495–524 (2007).
[CrossRef] [PubMed]

Nachabé, R.

R. Nachabé, D. J. Evers, B. H. Hendriks, G. W. Lucassen, M. van der Voort, E. J. Rutgers, M. J. Peeters, J. A. Van der Hage, H. S. Oldenburg, J. Wesseling, and T. J. Ruers, “Diagnosis of breast cancer using diffuse optical spectroscopy from 500 to 1600 nm: comparison of classification methods,” J. Biomed. Opt.16(8), 087010 (2011).
[CrossRef] [PubMed]

Narvenkar, S.

V. Sharma, J. W. He, S. Narvenkar, Y. B. Peng, and H. Liu, “Quantification of light reflectance spectroscopy and its application: determination of hemodynamics on the rat spinal cord and brain induced by electrical stimulation,” Neuroimage56(3), 1316–1328 (2011).
[CrossRef] [PubMed]

Nazemi, J.

Z. Volynskaya, A. S. Haka, K. L. Bechtel, M. Fitzmaurice, R. Shenk, N. Wang, J. Nazemi, R. R. Dasari, and M. S. Feld, “Diagnosing breast cancer using diffuse reflectance spectroscopy and intrinsic fluorescence spectroscopy,” J. Biomed. Opt.13(2), 024012 (2008).
[CrossRef] [PubMed]

Neil, M.

D. Elson, J. Requejo-Isidro, I. Munro, F. Reavell, J. Siegel, K. Suhling, P. Tadrous, R. Benninger, P. Lanigan, J. McGinty, C. Talbot, B. Treanor, S. Webb, A. Sandison, A. Wallace, D. Davis, J. Lever, M. Neil, D. Phillips, G. Stamp, and P. French, “Time-domain fluorescence lifetime imaging applied to biological tissue,” Photochem. Photobiol. Sci.3(8), 795–801 (2004).
[CrossRef] [PubMed]

Neil, M. A.

Oldenburg, H. S.

R. Nachabé, D. J. Evers, B. H. Hendriks, G. W. Lucassen, M. van der Voort, E. J. Rutgers, M. J. Peeters, J. A. Van der Hage, H. S. Oldenburg, J. Wesseling, and T. J. Ruers, “Diagnosis of breast cancer using diffuse optical spectroscopy from 500 to 1600 nm: comparison of classification methods,” J. Biomed. Opt.16(8), 087010 (2011).
[CrossRef] [PubMed]

Olivares, G. M.

M. D. Keller, S. K. Majumder, M. C. Kelley, I. M. Meszoely, F. I. Boulos, G. M. Olivares, and A. Mahadevan-Jansen, “Autofluorescence and diffuse reflectance spectroscopy and spectral imaging for breast surgical margin analysis,” Lasers Surg. Med.42(1), 15–23 (2010).
[CrossRef] [PubMed]

Palmer, G. M.

G. M. Palmer, C. F. Zhu, T. M. Breslin, F. S. 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(11), 1233–1242 (2003).
[CrossRef] [PubMed]

Patel, N.

V. Sharma, N. Patel, J. Chen, L. Tang, G. Alexandrakis, and H. A. N. L. I. Liu, “A dual-modality optical biopsy approach for in vivo detection of prostate cancer in rat model,” J. Innovat. Opt. Health Sci. (JIOHS)04(03), 269–277 (2011).
[CrossRef]

Peeters, M. J.

R. Nachabé, D. J. Evers, B. H. Hendriks, G. W. Lucassen, M. van der Voort, E. J. Rutgers, M. J. Peeters, J. A. Van der Hage, H. S. Oldenburg, J. Wesseling, and T. J. Ruers, “Diagnosis of breast cancer using diffuse optical spectroscopy from 500 to 1600 nm: comparison of classification methods,” J. Biomed. Opt.16(8), 087010 (2011).
[CrossRef] [PubMed]

Peng, Y. B.

V. Sharma, J. W. He, S. Narvenkar, Y. B. Peng, and H. Liu, “Quantification of light reflectance spectroscopy and its application: determination of hemodynamics on the rat spinal cord and brain induced by electrical stimulation,” Neuroimage56(3), 1316–1328 (2011).
[CrossRef] [PubMed]

Perkins, N. J.

N. J. Perkins and E. F. Schisterman, “The inconsistency of “optimal” cutpoints obtained using two criteria based on the receiver operating characteristic curve,” Am. J. Epidemiol.163(7), 670–675 (2006).
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Phillips, D.

D. Elson, J. Requejo-Isidro, I. Munro, F. Reavell, J. Siegel, K. Suhling, P. Tadrous, R. Benninger, P. Lanigan, J. McGinty, C. Talbot, B. Treanor, S. Webb, A. Sandison, A. Wallace, D. Davis, J. Lever, M. Neil, D. Phillips, G. Stamp, and P. French, “Time-domain fluorescence lifetime imaging applied to biological tissue,” Photochem. Photobiol. Sci.3(8), 795–801 (2004).
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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(2), 221–228 (2000).
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R. G. Pleijhuis, M. Graafland, J. de Vries, J. Bart, J. S. de Jong, and G. M. van Dam, “Obtaining adequate surgical margins in breast-conserving therapy for patients with early-stage breast cancer: current modalities and future directions,” Ann. Surg. Oncol.16(10), 2717–2730 (2009).
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G. A. Rahman, “Breast conserving therapy: a surgical technique where little can mean more,” J Surg Tech Case Rep3(1), 1–4 (2011).
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S. Kennedy, J. Geradts, T. Bydlon, J. Q. Brown, J. Gallagher, M. Junker, W. Barry, N. Ramanujam, and L. Wilke, “Optical breast cancer margin assessment: an observational study of the effects of tissue heterogeneity on optical contrast,” Breast Cancer Res.12(6), R91 (2010).
[CrossRef] [PubMed]

J. Q. Brown, T. M. Bydlon, L. M. Richards, B. Yu, S. A. Kennedy, J. Geradts, L. G. Wilke, M. Junker, J. Gallagher, W. T. Barry, and N. Ramanujam, “Optical assessment of tumor resection margins in the breast,” IEEE J. Sel. Top. Quantum Electron.16(3), 530–544 (2010).
[CrossRef] [PubMed]

M. C. Skala, K. M. Riching, D. K. Bird, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, P. J. Keely, and N. Ramanujam, “In vivo multiphoton fluorescence lifetime imaging of protein-bound and free nicotinamide adenine dinucleotide in normal and precancerous epithelia,” J. Biomed. Opt.12(2), 024014 (2007).
[CrossRef] [PubMed]

G. M. Palmer, C. F. Zhu, T. M. Breslin, F. S. 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(11), 1233–1242 (2003).
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N. Ramanujam, “Fluorescence spectroscopy of neoplastic and non-neoplastic tissues,” Neoplasia2(1/2), 89–117 (2000).
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A. Mukerjee, T. J. Sørensen, A. P. Ranjan, S. Raut, I. Gryczynski, J. K. Vishwanatha, and Z. Gryczynski, “Spectroscopic properties of curcumin: orientation of transition moments,” J. Phys. Chem. B114(39), 12679–12684 (2010).
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Raut, S.

A. Mukerjee, T. J. Sørensen, A. P. Ranjan, S. Raut, I. Gryczynski, J. K. Vishwanatha, and Z. Gryczynski, “Spectroscopic properties of curcumin: orientation of transition moments,” J. Phys. Chem. B114(39), 12679–12684 (2010).
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D. Elson, J. Requejo-Isidro, I. Munro, F. Reavell, J. Siegel, K. Suhling, P. Tadrous, R. Benninger, P. Lanigan, J. McGinty, C. Talbot, B. Treanor, S. Webb, A. Sandison, A. Wallace, D. Davis, J. Lever, M. Neil, D. Phillips, G. Stamp, and P. French, “Time-domain fluorescence lifetime imaging applied to biological tissue,” Photochem. Photobiol. Sci.3(8), 795–801 (2004).
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J. McGinty, N. P. Galletly, C. Dunsby, I. Munro, D. S. Elson, J. Requejo-Isidro, P. Cohen, R. Ahmad, A. Forsyth, A. V. Thillainayagam, M. A. Neil, P. M. French, and G. W. Stamp, “Wide-field fluorescence lifetime imaging of cancer,” Biomed. Opt. Express1(2), 627–640 (2010).
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D. Elson, J. Requejo-Isidro, I. Munro, F. Reavell, J. Siegel, K. Suhling, P. Tadrous, R. Benninger, P. Lanigan, J. McGinty, C. Talbot, B. Treanor, S. Webb, A. Sandison, A. Wallace, D. Davis, J. Lever, M. Neil, D. Phillips, G. Stamp, and P. French, “Time-domain fluorescence lifetime imaging applied to biological tissue,” Photochem. Photobiol. Sci.3(8), 795–801 (2004).
[CrossRef] [PubMed]

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J. Q. Brown, T. M. Bydlon, L. M. Richards, B. Yu, S. A. Kennedy, J. Geradts, L. G. Wilke, M. Junker, J. Gallagher, W. T. Barry, and N. Ramanujam, “Optical assessment of tumor resection margins in the breast,” IEEE J. Sel. Top. Quantum Electron.16(3), 530–544 (2010).
[CrossRef] [PubMed]

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M. C. Skala, K. M. Riching, D. K. Bird, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, P. J. Keely, and N. Ramanujam, “In vivo multiphoton fluorescence lifetime imaging of protein-bound and free nicotinamide adenine dinucleotide in normal and precancerous epithelia,” J. Biomed. Opt.12(2), 024014 (2007).
[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(2), 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(2), 221–228 (2000).
[CrossRef] [PubMed]

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R. Nachabé, D. J. Evers, B. H. Hendriks, G. W. Lucassen, M. van der Voort, E. J. Rutgers, M. J. Peeters, J. A. Van der Hage, H. S. Oldenburg, J. Wesseling, and T. J. Ruers, “Diagnosis of breast cancer using diffuse optical spectroscopy from 500 to 1600 nm: comparison of classification methods,” J. Biomed. Opt.16(8), 087010 (2011).
[CrossRef] [PubMed]

Rutgers, E. J.

R. Nachabé, D. J. Evers, B. H. Hendriks, G. W. Lucassen, M. van der Voort, E. J. Rutgers, M. J. Peeters, J. A. Van der Hage, H. S. Oldenburg, J. Wesseling, and T. J. Ruers, “Diagnosis of breast cancer using diffuse optical spectroscopy from 500 to 1600 nm: comparison of classification methods,” J. Biomed. Opt.16(8), 087010 (2011).
[CrossRef] [PubMed]

Sandison, A.

D. Elson, J. Requejo-Isidro, I. Munro, F. Reavell, J. Siegel, K. Suhling, P. Tadrous, R. Benninger, P. Lanigan, J. McGinty, C. Talbot, B. Treanor, S. Webb, A. Sandison, A. Wallace, D. Davis, J. Lever, M. Neil, D. Phillips, G. Stamp, and P. French, “Time-domain fluorescence lifetime imaging applied to biological tissue,” Photochem. Photobiol. Sci.3(8), 795–801 (2004).
[CrossRef] [PubMed]

J. Siegel, D. S. Elson, S. E. D. Webb, K. C. B. Lee, A. Vlandas, G. L. Gambaruto, S. Lévêque-Fort, M. J. Lever, P. J. Tadrous, G. W. H. Stamp, A. L. Wallace, A. Sandison, T. F. Watson, F. Alvarez, and P. M. W. French, “Studying biological tissue with fluorescence lifetime imaging: microscopy, endoscopy, and complex decay profiles,” Appl. Opt.42(16), 2995–3004 (2003).
[CrossRef] [PubMed]

Sarkar, P.

R. Luchowski, Z. Gryczynski, P. Sarkar, J. Borejdo, M. Szabelski, P. Kapusta, and I. Gryczynski, “Instrument response standard in time-resolved fluorescence,” Rev. Sci. Instrum.80(3), 033109 (2009).
[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(2), 221–228 (2000).
[CrossRef] [PubMed]

Schisterman, E. F.

N. J. Perkins and E. F. Schisterman, “The inconsistency of “optimal” cutpoints obtained using two criteria based on the receiver operating characteristic curve,” Am. J. Epidemiol.163(7), 670–675 (2006).
[CrossRef] [PubMed]

Sharma, V.

V. Sharma, N. Patel, J. Chen, L. Tang, G. Alexandrakis, and H. A. N. L. I. Liu, “A dual-modality optical biopsy approach for in vivo detection of prostate cancer in rat model,” J. Innovat. Opt. Health Sci. (JIOHS)04(03), 269–277 (2011).
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V. Sharma, J. W. He, S. Narvenkar, Y. B. Peng, and H. Liu, “Quantification of light reflectance spectroscopy and its application: determination of hemodynamics on the rat spinal cord and brain induced by electrical stimulation,” Neuroimage56(3), 1316–1328 (2011).
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Shenk, R.

Z. Volynskaya, A. S. Haka, K. L. Bechtel, M. Fitzmaurice, R. Shenk, N. Wang, J. Nazemi, R. R. Dasari, and M. S. Feld, “Diagnosing breast cancer using diffuse reflectance spectroscopy and intrinsic fluorescence spectroscopy,” J. Biomed. Opt.13(2), 024012 (2008).
[CrossRef] [PubMed]

Shousha, S.

P. J. Tadrous, J. Siegel, P. M. French, S. Shousha, N. Lalani, and G. W. Stamp, “Fluorescence lifetime imaging of unstained tissues: early results in human breast cancer,” J. Pathol.199(3), 309–317 (2003).
[CrossRef] [PubMed]

Siegel, J.

D. Elson, J. Requejo-Isidro, I. Munro, F. Reavell, J. Siegel, K. Suhling, P. Tadrous, R. Benninger, P. Lanigan, J. McGinty, C. Talbot, B. Treanor, S. Webb, A. Sandison, A. Wallace, D. Davis, J. Lever, M. Neil, D. Phillips, G. Stamp, and P. French, “Time-domain fluorescence lifetime imaging applied to biological tissue,” Photochem. Photobiol. Sci.3(8), 795–801 (2004).
[CrossRef] [PubMed]

J. Siegel, D. S. Elson, S. E. D. Webb, K. C. B. Lee, A. Vlandas, G. L. Gambaruto, S. Lévêque-Fort, M. J. Lever, P. J. Tadrous, G. W. H. Stamp, A. L. Wallace, A. Sandison, T. F. Watson, F. Alvarez, and P. M. W. French, “Studying biological tissue with fluorescence lifetime imaging: microscopy, endoscopy, and complex decay profiles,” Appl. Opt.42(16), 2995–3004 (2003).
[CrossRef] [PubMed]

P. J. Tadrous, J. Siegel, P. M. French, S. Shousha, N. Lalani, and G. W. Stamp, “Fluorescence lifetime imaging of unstained tissues: early results in human breast cancer,” J. Pathol.199(3), 309–317 (2003).
[CrossRef] [PubMed]

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S. E. Singletary, “Surgical margins in patients with early-stage breast cancer treated with breast conservation therapy,” Am. J. Surg.184(5), 383–393 (2002).
[CrossRef] [PubMed]

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M. C. Skala, K. M. Riching, D. K. Bird, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, P. J. Keely, and N. Ramanujam, “In vivo multiphoton fluorescence lifetime imaging of protein-bound and free nicotinamide adenine dinucleotide in normal and precancerous epithelia,” J. Biomed. Opt.12(2), 024014 (2007).
[CrossRef] [PubMed]

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A. Mukerjee, T. J. Sørensen, A. P. Ranjan, S. Raut, I. Gryczynski, J. K. Vishwanatha, and Z. Gryczynski, “Spectroscopic properties of curcumin: orientation of transition moments,” J. Phys. Chem. B114(39), 12679–12684 (2010).
[CrossRef] [PubMed]

Stamp, G.

D. Elson, J. Requejo-Isidro, I. Munro, F. Reavell, J. Siegel, K. Suhling, P. Tadrous, R. Benninger, P. Lanigan, J. McGinty, C. Talbot, B. Treanor, S. Webb, A. Sandison, A. Wallace, D. Davis, J. Lever, M. Neil, D. Phillips, G. Stamp, and P. French, “Time-domain fluorescence lifetime imaging applied to biological tissue,” Photochem. Photobiol. Sci.3(8), 795–801 (2004).
[CrossRef] [PubMed]

Stamp, G. W.

J. McGinty, N. P. Galletly, C. Dunsby, I. Munro, D. S. Elson, J. Requejo-Isidro, P. Cohen, R. Ahmad, A. Forsyth, A. V. Thillainayagam, M. A. Neil, P. M. French, and G. W. Stamp, “Wide-field fluorescence lifetime imaging of cancer,” Biomed. Opt. Express1(2), 627–640 (2010).
[CrossRef] [PubMed]

P. J. Tadrous, J. Siegel, P. M. French, S. Shousha, N. Lalani, and G. W. Stamp, “Fluorescence lifetime imaging of unstained tissues: early results in human breast cancer,” J. Pathol.199(3), 309–317 (2003).
[CrossRef] [PubMed]

Stamp, G. W. H.

Star, W. M.

G. A. Wagnières, W. M. Star, and B. C. Wilson, “In vivo fluorescence spectroscopy and imaging for oncological applications,” Photochem. Photobiol.68(5), 603–632 (1998).
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D. Elson, J. Requejo-Isidro, I. Munro, F. Reavell, J. Siegel, K. Suhling, P. Tadrous, R. Benninger, P. Lanigan, J. McGinty, C. Talbot, B. Treanor, S. Webb, A. Sandison, A. Wallace, D. Davis, J. Lever, M. Neil, D. Phillips, G. Stamp, and P. French, “Time-domain fluorescence lifetime imaging applied to biological tissue,” Photochem. Photobiol. Sci.3(8), 795–801 (2004).
[CrossRef] [PubMed]

Szabelski, M.

R. Luchowski, Z. Gryczynski, P. Sarkar, J. Borejdo, M. Szabelski, P. Kapusta, and I. Gryczynski, “Instrument response standard in time-resolved fluorescence,” Rev. Sci. Instrum.80(3), 033109 (2009).
[CrossRef] [PubMed]

Tadrous, P.

D. Elson, J. Requejo-Isidro, I. Munro, F. Reavell, J. Siegel, K. Suhling, P. Tadrous, R. Benninger, P. Lanigan, J. McGinty, C. Talbot, B. Treanor, S. Webb, A. Sandison, A. Wallace, D. Davis, J. Lever, M. Neil, D. Phillips, G. Stamp, and P. French, “Time-domain fluorescence lifetime imaging applied to biological tissue,” Photochem. Photobiol. Sci.3(8), 795–801 (2004).
[CrossRef] [PubMed]

Tadrous, P. J.

Talbot, C.

D. Elson, J. Requejo-Isidro, I. Munro, F. Reavell, J. Siegel, K. Suhling, P. Tadrous, R. Benninger, P. Lanigan, J. McGinty, C. Talbot, B. Treanor, S. Webb, A. Sandison, A. Wallace, D. Davis, J. Lever, M. Neil, D. Phillips, G. Stamp, and P. French, “Time-domain fluorescence lifetime imaging applied to biological tissue,” Photochem. Photobiol. Sci.3(8), 795–801 (2004).
[CrossRef] [PubMed]

Tang, L.

V. Sharma, N. Patel, J. Chen, L. Tang, G. Alexandrakis, and H. A. N. L. I. Liu, “A dual-modality optical biopsy approach for in vivo detection of prostate cancer in rat model,” J. Innovat. Opt. Health Sci. (JIOHS)04(03), 269–277 (2011).
[CrossRef]

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Treanor, B.

D. Elson, J. Requejo-Isidro, I. Munro, F. Reavell, J. Siegel, K. Suhling, P. Tadrous, R. Benninger, P. Lanigan, J. McGinty, C. Talbot, B. Treanor, S. Webb, A. Sandison, A. Wallace, D. Davis, J. Lever, M. Neil, D. Phillips, G. Stamp, and P. French, “Time-domain fluorescence lifetime imaging applied to biological tissue,” Photochem. Photobiol. Sci.3(8), 795–801 (2004).
[CrossRef] [PubMed]

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R. G. Pleijhuis, M. Graafland, J. de Vries, J. Bart, J. S. de Jong, and G. M. van Dam, “Obtaining adequate surgical margins in breast-conserving therapy for patients with early-stage breast cancer: current modalities and future directions,” Ann. Surg. Oncol.16(10), 2717–2730 (2009).
[CrossRef] [PubMed]

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R. Nachabé, D. J. Evers, B. H. Hendriks, G. W. Lucassen, M. van der Voort, E. J. Rutgers, M. J. Peeters, J. A. Van der Hage, H. S. Oldenburg, J. Wesseling, and T. J. Ruers, “Diagnosis of breast cancer using diffuse optical spectroscopy from 500 to 1600 nm: comparison of classification methods,” J. Biomed. Opt.16(8), 087010 (2011).
[CrossRef] [PubMed]

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R. Nachabé, D. J. Evers, B. H. Hendriks, G. W. Lucassen, M. van der Voort, E. J. Rutgers, M. J. Peeters, J. A. Van der Hage, H. S. Oldenburg, J. Wesseling, and T. J. Ruers, “Diagnosis of breast cancer using diffuse optical spectroscopy from 500 to 1600 nm: comparison of classification methods,” J. Biomed. Opt.16(8), 087010 (2011).
[CrossRef] [PubMed]

Vishwanatha, J. K.

A. Mukerjee, T. J. Sørensen, A. P. Ranjan, S. Raut, I. Gryczynski, J. K. Vishwanatha, and Z. Gryczynski, “Spectroscopic properties of curcumin: orientation of transition moments,” J. Phys. Chem. B114(39), 12679–12684 (2010).
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Vogel, A. J.

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[CrossRef] [PubMed]

Wagnières, G. A.

G. A. Wagnières, W. M. Star, and B. C. Wilson, “In vivo fluorescence spectroscopy and imaging for oncological applications,” Photochem. Photobiol.68(5), 603–632 (1998).
[PubMed]

Wallace, A.

D. Elson, J. Requejo-Isidro, I. Munro, F. Reavell, J. Siegel, K. Suhling, P. Tadrous, R. Benninger, P. Lanigan, J. McGinty, C. Talbot, B. Treanor, S. Webb, A. Sandison, A. Wallace, D. Davis, J. Lever, M. Neil, D. Phillips, G. Stamp, and P. French, “Time-domain fluorescence lifetime imaging applied to biological tissue,” Photochem. Photobiol. Sci.3(8), 795–801 (2004).
[CrossRef] [PubMed]

Wallace, A. L.

Wang, C. Y.

H. M. Chen, C. P. Chiang, C. You, T. C. Hsiao, and C. Y. Wang, “Time-resolved autofluorescence spectroscopy for classifying normal and premalignant oral tissues,” Lasers Surg. Med.37(1), 37–45 (2005).
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Z. Volynskaya, A. S. Haka, K. L. Bechtel, M. Fitzmaurice, R. Shenk, N. Wang, J. Nazemi, R. R. Dasari, and M. S. Feld, “Diagnosing breast cancer using diffuse reflectance spectroscopy and intrinsic fluorescence spectroscopy,” J. Biomed. Opt.13(2), 024012 (2008).
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Watson, T. F.

Webb, S.

D. Elson, J. Requejo-Isidro, I. Munro, F. Reavell, J. Siegel, K. Suhling, P. Tadrous, R. Benninger, P. Lanigan, J. McGinty, C. Talbot, B. Treanor, S. Webb, A. Sandison, A. Wallace, D. Davis, J. Lever, M. Neil, D. Phillips, G. Stamp, and P. French, “Time-domain fluorescence lifetime imaging applied to biological tissue,” Photochem. Photobiol. Sci.3(8), 795–801 (2004).
[CrossRef] [PubMed]

Webb, S. E. D.

Wesseling, J.

R. Nachabé, D. J. Evers, B. H. Hendriks, G. W. Lucassen, M. van der Voort, E. J. Rutgers, M. J. Peeters, J. A. Van der Hage, H. S. Oldenburg, J. Wesseling, and T. J. Ruers, “Diagnosis of breast cancer using diffuse optical spectroscopy from 500 to 1600 nm: comparison of classification methods,” J. Biomed. Opt.16(8), 087010 (2011).
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Wilke, L.

S. Kennedy, J. Geradts, T. Bydlon, J. Q. Brown, J. Gallagher, M. Junker, W. Barry, N. Ramanujam, and L. Wilke, “Optical breast cancer margin assessment: an observational study of the effects of tissue heterogeneity on optical contrast,” Breast Cancer Res.12(6), R91 (2010).
[CrossRef] [PubMed]

Wilke, L. G.

J. Q. Brown, T. M. Bydlon, L. M. Richards, B. Yu, S. A. Kennedy, J. Geradts, L. G. Wilke, M. Junker, J. Gallagher, W. T. Barry, and N. Ramanujam, “Optical assessment of tumor resection margins in the breast,” IEEE J. Sel. Top. Quantum Electron.16(3), 530–544 (2010).
[CrossRef] [PubMed]

Wilson, B. C.

G. A. Wagnières, W. M. Star, and B. C. Wilson, “In vivo fluorescence spectroscopy and imaging for oncological applications,” Photochem. Photobiol.68(5), 603–632 (1998).
[PubMed]

Xu, F. S.

G. M. Palmer, C. F. Zhu, T. M. Breslin, F. S. 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(11), 1233–1242 (2003).
[CrossRef] [PubMed]

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H. M. Chen, C. P. Chiang, C. You, T. C. Hsiao, and C. Y. Wang, “Time-resolved autofluorescence spectroscopy for classifying normal and premalignant oral tissues,” Lasers Surg. Med.37(1), 37–45 (2005).
[CrossRef] [PubMed]

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J. Q. Brown, T. M. Bydlon, L. M. Richards, B. Yu, S. A. Kennedy, J. Geradts, L. G. Wilke, M. Junker, J. Gallagher, W. T. Barry, and N. Ramanujam, “Optical assessment of tumor resection margins in the breast,” IEEE J. Sel. Top. Quantum Electron.16(3), 530–544 (2010).
[CrossRef] [PubMed]

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G. M. Palmer, C. F. Zhu, T. M. Breslin, F. S. 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(11), 1233–1242 (2003).
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Am. J. Epidemiol.

N. J. Perkins and E. F. Schisterman, “The inconsistency of “optimal” cutpoints obtained using two criteria based on the receiver operating characteristic curve,” Am. J. Epidemiol.163(7), 670–675 (2006).
[CrossRef] [PubMed]

Am. J. Surg.

S. E. Singletary, “Surgical margins in patients with early-stage breast cancer treated with breast conservation therapy,” Am. J. Surg.184(5), 383–393 (2002).
[CrossRef] [PubMed]

Ann. Surg. Oncol.

R. G. Pleijhuis, M. Graafland, J. de Vries, J. Bart, J. S. de Jong, and G. M. van Dam, “Obtaining adequate surgical margins in breast-conserving therapy for patients with early-stage breast cancer: current modalities and future directions,” Ann. Surg. Oncol.16(10), 2717–2730 (2009).
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Biomed. Opt. Express

Breast Cancer Res.

S. Kennedy, J. Geradts, T. Bydlon, J. Q. Brown, J. Gallagher, M. Junker, W. Barry, N. Ramanujam, and L. Wilke, “Optical breast cancer margin assessment: an observational study of the effects of tissue heterogeneity on optical contrast,” Breast Cancer Res.12(6), R91 (2010).
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Chem. Rev.

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IEEE J. Sel. Top. Quantum Electron.

J. Q. Brown, T. M. Bydlon, L. M. Richards, B. Yu, S. A. Kennedy, J. Geradts, L. G. Wilke, M. Junker, J. Gallagher, W. T. Barry, and N. Ramanujam, “Optical assessment of tumor resection margins in the breast,” IEEE J. Sel. Top. Quantum Electron.16(3), 530–544 (2010).
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IEEE Trans. Biomed. Eng.

G. M. Palmer, C. F. Zhu, T. M. Breslin, F. S. 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(11), 1233–1242 (2003).
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Figures (5)

Fig. 1
Fig. 1

(a) A simplified block diagram of the dual-modality data acquisition system; (b) an illustration of the probe tip geometry; (c) A picture showing breast specimen being measured by the optical fiber. The colors on the edges of the specimen are due to ink labeling done by the pathologist as a conventional procedure to mark anatomical/structural sides of the breast sample.

Fig. 2
Fig. 2

Histological findings showing an example of histological difference between (a) invasive ductal carcinoma and (b) benign breast stroma in pink color.

Fig. 3
Fig. 3

(a) Mean AFLM parameters that showed a significant difference between IDC (n = 34) and FT (n = 31), as well as IDC and AT (n = 28). (b) Average of τm plotted for all three tissue types as a function of emission wavelength. The error bars in both (a) and (b) represent standard error of the mean.

Fig. 4
Fig. 4

(a) Average reflectance spectra of IDC (n = 34), FT (n = 31) and AT (n = 28). Vertical black lines indicate the 20-nm spectral windows (S1-S17) selected for spectral slope analysis. The gray bars on the bottom of figure mark the spectral windows whose spectral slopes are significantly different between IDC and two other types of breast tissue. (b) Means of scaled spectral slopes (Slope x 103) along with standard errors, for 5 out of 10 selected spectral regions, which showed a significant difference between IDC and the other two breast tissue types.

Fig. 5
Fig. 5

Box plots showing distribution of data for AFLM (left) and LRS (right) parameters. Five features plotted for AFLM from left to right are τ1, τ2, τm at 532 nm, and τ2, τm at 562 nm. For LRS, 10 slopes plotted from left to right are S1, S3, S4, S7, S12, S13, S14, S15, S16, S17. Y-axis on AFLM has a unit of “Litetime (ns)”, and on LRS has a unit of “Slope * 103 (a.u.).”

Tables (3)

Tables Icon

Table 1 The p-values of significant features of both modalities, derived from mixed model regression analysis for test of significant differences between IDC and other two types. λ represents wavelength.

Tables Icon

Table 2 Classification statistics obtained using three methods: (a) AFLM-only, (b) LRS-only, (c) dual-modality (LRS + AFLM) method

Tables Icon

Table 3 Goodness of fit parameters for lifetime curve fitting with a two exponent model, and the peak counts of lifetime measurements. The peak counts are rounded to the nearest 100.

Equations (3)

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τ m =( a 1 τ 1 2 + a 2 τ 2 2 )/( a 1 τ 1 + a 2 τ 2 )
  g j ( x )=ln( P( Y=j ) P( Y=0 ) )= β j0 + β j1 x 1 ++ β jn x n ,      for j=1,2
g j ( x )=0,      for j=0 

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