Abstract

A fiber-optic system was developed to rapidly acquire tissue fluorescence wavelength-time matrices (WTMs) with high signal-to-noise ratio (SNR). The essential system components (473 nm microchip laser operating at 3 kHz repetition frequency, fiber-probe assemblies, emission monochromator, photomultiplier tube, and digitizer) were assembled into a compact and clinically-compatible unit. Data were acquired from fluorescence standards and tissue-simulating phantoms to test system performance. Fluorescence decay waveforms with SNR > 100 at the decay curve peak were obtained in less than 30 ms. With optimized data transfer and monochromator stepping functions, it should be feasible to acquire a full WTM at 5 nm emission wavelength intervals over a 200 nm range in under 2 seconds.

© 2010 OSA

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2010 (3)

M. Chandra, J. Scheiman, D. Simeone, B. McKenna, J. Purdy, and M.-A. Mycek, “Spectral areas and ratios classifier algorithm for pancreatic tissue classification using optical spectroscopy,” J. Biomed. Opt. 15(1), 010514 (2010).
[CrossRef] [PubMed]

L. Marcu, “Fluorescence lifetime in cardiovascular diagnostics,” J. Biomed. Opt. 15(1), 011106 (2010).
[CrossRef] [PubMed]

R. Mekhala, D. S. Nadder, H. W. Robert, M. Mary-Ann, P. Nancy, H. K. David, and D. M. Michael, “Quantitative polarized Raman spectroscopy in highly turbid bone tissue,” J. Biomed. Opt. 15, 037001 (2010).

2009 (2)

P. Uehlinger, T. Gabrecht, T. Glanzmann, J.-P. Ballini, A. Radu, S. Andrejevic, P. Monnier, and G. Wagnières, “In vivo time-resolved spectroscopy of the human bronchial early cancer autofluorescence,” J. Biomed. Opt. 14(2), 024011 (2009).
[CrossRef] [PubMed]

R. H. Wilson, M. Chandra, J. Scheiman, D. Simeone, B. McKenna, J. Purdy, and M. A. Mycek, “Optical spectroscopy detects histological hallmarks of pancreatic cancer,” Opt. Express 17(20), 17502–17516 (2009).
[CrossRef] [PubMed]

2008 (3)

J. Blackwell, K. M. Katika, L. Pilon, K. M. Dipple, S. R. Levin, and A. Nouvong, “In vivo time-resolved autofluorescence measurements to test for glycation of human skin,” J. Biomed. Opt. 13(1), 014004 (2008).
[CrossRef] [PubMed]

Y. S. Fawzy and H. Zeng, “Intrinsic fluorescence spectroscopy for endoscopic detection and localization of the endobronchial cancerous lesions,” J. Biomed. Opt. 13(6), 064022 (2008).
[CrossRef] [PubMed]

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 (1)

M. Chandra, J. Scheiman, D. Heidt, D. Simeone, B. McKenna, and M.-A. Mycek, “Probing pancreatic disease using tissue optical spectroscopy,” J. Biomed. Opt. 12(6), 060501 (2007).
[CrossRef] [PubMed]

2006 (4)

S. K. Chang, N. Marin, M. Follen, and R. Richards-Kortum, “Model-based analysis of clinical fluorescence spectroscopy for in vivo detection of cervical intraepithelial dysplasia,” J. Biomed. Opt. 11(2), 024008 (2006).
[CrossRef] [PubMed]

W. H. Yong, P. V. Butte, B. K. Pikul, J. A. Jo, Q. Y. Fang, T. Papaioannou, K. Black, and L. Marcu, “Distinction of brain tissue, low grade and high grade glioma with time-resolved fluorescence spectroscopy,” Front. Biosci. 11(1), 1255–1263 (2006).
[CrossRef] [PubMed]

M. Chandra, K. Vishwanath, G. D. Fichter, E. Liao, S. J. Hollister, and M.-A. Mycek, “Quantitative molecular sensing in biological tissues: an approach to non-invasive optical characterization,” Opt. Express 14(13), 6157–6171 (2006).
[CrossRef] [PubMed]

K. Vishwanath, W. Zhong, M. Close, and M.-A. Mycek, “Fluorescence quenching by polystyrene microspheres in UV-visible and NIR tissue-simulating phantoms,” Opt. Express 14(17), 7776–7788 (2006).
[CrossRef] [PubMed]

2005 (1)

2004 (4)

K. Vishwanath and M.-A. Mycek, “Do fluorescence decays remitted from tissues accurately reflect intrinsic fluorophore lifetimes?” Opt. Lett. 29(13), 1512–1514 (2004).
[CrossRef] [PubMed]

L. Marcu, J. A. Jo, P. V. Butte, W. H. Yong, B. K. Pikul, K. L. Black, and R. C. Thompson, “Fluorescence lifetime spectroscopy of glioblastoma multiforme,” Photochem. Photobiol. 80(1), 98–103 (2004).
[CrossRef] [PubMed]

I. Georgakoudi and M. S. Feld, “The combined use of fluorescence, reflectance, and light-scattering spectroscopy for evaluating dysplasia in Barrett’s esophagus,” Gastrointest. Endosc. Clin. N. Am. 14(3), 519–537, ix (2004).
[CrossRef] [PubMed]

Q. Fang, T. Papaioannou, J. A. Jo, R. Vaitha, K. Shastry, and L. Marcu, “Time-domain laser-induced fluorescence spectroscopy apparatus for clinical diagnostics,” Rev. Sci. Instrum. 75(1), 151–162 (2004).
[CrossRef]

2003 (1)

T. J. Pfefer, D. Y. Paithankar, J. M. Poneros, K. T. Schomacker, and N. S. Nishioka, “Temporally and spectrally resolved fluorescence spectroscopy for the detection of high grade dysplasia in Barrett’s esophagus,” Lasers Surg. Med. 32(1), 10–16 (2003).
[CrossRef] [PubMed]

2002 (2)

A. J. Bystol, T. Thorstenson, and A. D. Campiglia, “Laser-induced multidimensional fluorescence spectroscopy in Shpol’skii matrixes for the analysis of polycyclic aromatic hydrocarbons in HPLC fractions and complex environmental extracts,” Environ. Sci. Technol. 36(20), 4424–4429 (2002).
[CrossRef] [PubMed]

K. Vishwanath, B. W. Pogue, and M.-A. Mycek, “Quantitative fluorescence lifetime spectroscopy in turbid media: comparison of theoretical, experimental and computational methods,” Phys. Med. Biol. 47(18), 3387–3405 (2002).
[CrossRef] [PubMed]

2001 (2)

A. J. Bystol, A. D. Campiglia, and G. D. Gillispie, “Laser-induced multidimensional fluorescence spectroscopy in Shpol’skii matrixes with a fiber-optic probe at liquid helium temperature,” Anal. Chem. 73(23), 5762–5770 (2001).
[CrossRef] [PubMed]

J. D. Pitts and M.-A. Mycek, “Design and development of a rapid acquisition laser-based fluorometer with simultaneous spectral and temporal resolution,” Rev. Sci. Instrum. 72(7), 3061–3072 (2001).
[CrossRef]

2000 (1)

1999 (1)

D. Magde, G. E. Rojas, and P. G. Seybold, “Solvent dependence of the fluorescence lifetimes of xanthene dyes,” Photochem. Photobiol. 70(5), 737–744 (1999).
[CrossRef]

1998 (2)

D. Hai, F. Ru-Chun Amy, L. Junzhong, L. A. Corkan, and S. L. Jonathan, “PhotochemCAD: A Computer-Aided Design and Research Tool in Photochemistry,” Photochem. Photobiol. 68, 141–142 (1998).

M.-A. Mycek, K. T. Schomacker, and N. S. Nishioka, “Colonic polyp differentiation using time-resolved autofluorescence spectroscopy,” Gastrointest. Endosc. 48(4), 390–394 (1998).
[CrossRef] [PubMed]

1993 (1)

Andrejevic, S.

P. Uehlinger, T. Gabrecht, T. Glanzmann, J.-P. Ballini, A. Radu, S. Andrejevic, P. Monnier, and G. Wagnières, “In vivo time-resolved spectroscopy of the human bronchial early cancer autofluorescence,” J. Biomed. Opt. 14(2), 024011 (2009).
[CrossRef] [PubMed]

Ballini, J.-P.

P. Uehlinger, T. Gabrecht, T. Glanzmann, J.-P. Ballini, A. Radu, S. Andrejevic, P. Monnier, and G. Wagnières, “In vivo time-resolved spectroscopy of the human bronchial early cancer autofluorescence,” J. Biomed. Opt. 14(2), 024011 (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]

Black, K.

W. H. Yong, P. V. Butte, B. K. Pikul, J. A. Jo, Q. Y. Fang, T. Papaioannou, K. Black, and L. Marcu, “Distinction of brain tissue, low grade and high grade glioma with time-resolved fluorescence spectroscopy,” Front. Biosci. 11(1), 1255–1263 (2006).
[CrossRef] [PubMed]

Black, K. L.

L. Marcu, J. A. Jo, P. V. Butte, W. H. Yong, B. K. Pikul, K. L. Black, and R. C. Thompson, “Fluorescence lifetime spectroscopy of glioblastoma multiforme,” Photochem. Photobiol. 80(1), 98–103 (2004).
[CrossRef] [PubMed]

Blackwell, J.

J. Blackwell, K. M. Katika, L. Pilon, K. M. Dipple, S. R. Levin, and A. Nouvong, “In vivo time-resolved autofluorescence measurements to test for glycation of human skin,” J. Biomed. Opt. 13(1), 014004 (2008).
[CrossRef] [PubMed]

Butte, P. V.

W. H. Yong, P. V. Butte, B. K. Pikul, J. A. Jo, Q. Y. Fang, T. Papaioannou, K. Black, and L. Marcu, “Distinction of brain tissue, low grade and high grade glioma with time-resolved fluorescence spectroscopy,” Front. Biosci. 11(1), 1255–1263 (2006).
[CrossRef] [PubMed]

L. Marcu, J. A. Jo, P. V. Butte, W. H. Yong, B. K. Pikul, K. L. Black, and R. C. Thompson, “Fluorescence lifetime spectroscopy of glioblastoma multiforme,” Photochem. Photobiol. 80(1), 98–103 (2004).
[CrossRef] [PubMed]

Bystol, A. J.

A. J. Bystol, T. Thorstenson, and A. D. Campiglia, “Laser-induced multidimensional fluorescence spectroscopy in Shpol’skii matrixes for the analysis of polycyclic aromatic hydrocarbons in HPLC fractions and complex environmental extracts,” Environ. Sci. Technol. 36(20), 4424–4429 (2002).
[CrossRef] [PubMed]

A. J. Bystol, A. D. Campiglia, and G. D. Gillispie, “Laser-induced multidimensional fluorescence spectroscopy in Shpol’skii matrixes with a fiber-optic probe at liquid helium temperature,” Anal. Chem. 73(23), 5762–5770 (2001).
[CrossRef] [PubMed]

A. J. Bystol, A. D. Campiglia, and G. D. Gillispie, “Time-resolved laser-excited Shpol'skii spectrometry with a fiber-optic probe and ICCD camera,” Appl. Spectrosc. 54(6), 910–917 (2000).
[CrossRef]

Campiglia, A. D.

A. J. Bystol, T. Thorstenson, and A. D. Campiglia, “Laser-induced multidimensional fluorescence spectroscopy in Shpol’skii matrixes for the analysis of polycyclic aromatic hydrocarbons in HPLC fractions and complex environmental extracts,” Environ. Sci. Technol. 36(20), 4424–4429 (2002).
[CrossRef] [PubMed]

A. J. Bystol, A. D. Campiglia, and G. D. Gillispie, “Laser-induced multidimensional fluorescence spectroscopy in Shpol’skii matrixes with a fiber-optic probe at liquid helium temperature,” Anal. Chem. 73(23), 5762–5770 (2001).
[CrossRef] [PubMed]

A. J. Bystol, A. D. Campiglia, and G. D. Gillispie, “Time-resolved laser-excited Shpol'skii spectrometry with a fiber-optic probe and ICCD camera,” Appl. Spectrosc. 54(6), 910–917 (2000).
[CrossRef]

Chandra, M.

M. Chandra, J. Scheiman, D. Simeone, B. McKenna, J. Purdy, and M.-A. Mycek, “Spectral areas and ratios classifier algorithm for pancreatic tissue classification using optical spectroscopy,” J. Biomed. Opt. 15(1), 010514 (2010).
[CrossRef] [PubMed]

R. H. Wilson, M. Chandra, J. Scheiman, D. Simeone, B. McKenna, J. Purdy, and M. A. Mycek, “Optical spectroscopy detects histological hallmarks of pancreatic cancer,” Opt. Express 17(20), 17502–17516 (2009).
[CrossRef] [PubMed]

M. Chandra, J. Scheiman, D. Heidt, D. Simeone, B. McKenna, and M.-A. Mycek, “Probing pancreatic disease using tissue optical spectroscopy,” J. Biomed. Opt. 12(6), 060501 (2007).
[CrossRef] [PubMed]

M. Chandra, K. Vishwanath, G. D. Fichter, E. Liao, S. J. Hollister, and M.-A. Mycek, “Quantitative molecular sensing in biological tissues: an approach to non-invasive optical characterization,” Opt. Express 14(13), 6157–6171 (2006).
[CrossRef] [PubMed]

Chang, S. K.

S. K. Chang, N. Marin, M. Follen, and R. Richards-Kortum, “Model-based analysis of clinical fluorescence spectroscopy for in vivo detection of cervical intraepithelial dysplasia,” J. Biomed. Opt. 11(2), 024008 (2006).
[CrossRef] [PubMed]

Close, M.

Corkan, L. A.

D. Hai, F. Ru-Chun Amy, L. Junzhong, L. A. Corkan, and S. L. Jonathan, “PhotochemCAD: A Computer-Aided Design and Research Tool in Photochemistry,” Photochem. Photobiol. 68, 141–142 (1998).

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]

David, H. K.

R. Mekhala, D. S. Nadder, H. W. Robert, M. Mary-Ann, P. Nancy, H. K. David, and D. M. Michael, “Quantitative polarized Raman spectroscopy in highly turbid bone tissue,” J. Biomed. Opt. 15, 037001 (2010).

Dipple, K. M.

J. Blackwell, K. M. Katika, L. Pilon, K. M. Dipple, S. R. Levin, and A. Nouvong, “In vivo time-resolved autofluorescence measurements to test for glycation of human skin,” J. Biomed. Opt. 13(1), 014004 (2008).
[CrossRef] [PubMed]

Fang, Q.

Q. Fang, T. Papaioannou, J. A. Jo, R. Vaitha, K. Shastry, and L. Marcu, “Time-domain laser-induced fluorescence spectroscopy apparatus for clinical diagnostics,” Rev. Sci. Instrum. 75(1), 151–162 (2004).
[CrossRef]

Fang, Q. Y.

W. H. Yong, P. V. Butte, B. K. Pikul, J. A. Jo, Q. Y. Fang, T. Papaioannou, K. Black, and L. Marcu, “Distinction of brain tissue, low grade and high grade glioma with time-resolved fluorescence spectroscopy,” Front. Biosci. 11(1), 1255–1263 (2006).
[CrossRef] [PubMed]

Fawzy, Y. S.

Y. S. Fawzy and H. Zeng, “Intrinsic fluorescence spectroscopy for endoscopic detection and localization of the endobronchial cancerous lesions,” J. Biomed. Opt. 13(6), 064022 (2008).
[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]

I. Georgakoudi and M. S. Feld, “The combined use of fluorescence, reflectance, and light-scattering spectroscopy for evaluating dysplasia in Barrett’s esophagus,” Gastrointest. Endosc. Clin. N. Am. 14(3), 519–537, ix (2004).
[CrossRef] [PubMed]

Fichter, G. D.

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]

Follen, M.

S. K. Chang, N. Marin, M. Follen, and R. Richards-Kortum, “Model-based analysis of clinical fluorescence spectroscopy for in vivo detection of cervical intraepithelial dysplasia,” J. Biomed. Opt. 11(2), 024008 (2006).
[CrossRef] [PubMed]

Gabrecht, T.

P. Uehlinger, T. Gabrecht, T. Glanzmann, J.-P. Ballini, A. Radu, S. Andrejevic, P. Monnier, and G. Wagnières, “In vivo time-resolved spectroscopy of the human bronchial early cancer autofluorescence,” J. Biomed. Opt. 14(2), 024011 (2009).
[CrossRef] [PubMed]

Georgakoudi, I.

I. Georgakoudi and M. S. Feld, “The combined use of fluorescence, reflectance, and light-scattering spectroscopy for evaluating dysplasia in Barrett’s esophagus,” Gastrointest. Endosc. Clin. N. Am. 14(3), 519–537, ix (2004).
[CrossRef] [PubMed]

Gillispie, G. D.

A. J. Bystol, A. D. Campiglia, and G. D. Gillispie, “Laser-induced multidimensional fluorescence spectroscopy in Shpol’skii matrixes with a fiber-optic probe at liquid helium temperature,” Anal. Chem. 73(23), 5762–5770 (2001).
[CrossRef] [PubMed]

A. J. Bystol, A. D. Campiglia, and G. D. Gillispie, “Time-resolved laser-excited Shpol'skii spectrometry with a fiber-optic probe and ICCD camera,” Appl. Spectrosc. 54(6), 910–917 (2000).
[CrossRef]

Glanzmann, T.

P. Uehlinger, T. Gabrecht, T. Glanzmann, J.-P. Ballini, A. Radu, S. Andrejevic, P. Monnier, and G. Wagnières, “In vivo time-resolved spectroscopy of the human bronchial early cancer autofluorescence,” J. Biomed. Opt. 14(2), 024011 (2009).
[CrossRef] [PubMed]

Hai, D.

D. Hai, F. Ru-Chun Amy, L. Junzhong, L. A. Corkan, and S. L. Jonathan, “PhotochemCAD: A Computer-Aided Design and Research Tool in Photochemistry,” Photochem. Photobiol. 68, 141–142 (1998).

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]

Heidt, D.

M. Chandra, J. Scheiman, D. Heidt, D. Simeone, B. McKenna, and M.-A. Mycek, “Probing pancreatic disease using tissue optical spectroscopy,” J. Biomed. Opt. 12(6), 060501 (2007).
[CrossRef] [PubMed]

Hollister, S. J.

Jo, J. A.

W. H. Yong, P. V. Butte, B. K. Pikul, J. A. Jo, Q. Y. Fang, T. Papaioannou, K. Black, and L. Marcu, “Distinction of brain tissue, low grade and high grade glioma with time-resolved fluorescence spectroscopy,” Front. Biosci. 11(1), 1255–1263 (2006).
[CrossRef] [PubMed]

Q. Fang, T. Papaioannou, J. A. Jo, R. Vaitha, K. Shastry, and L. Marcu, “Time-domain laser-induced fluorescence spectroscopy apparatus for clinical diagnostics,” Rev. Sci. Instrum. 75(1), 151–162 (2004).
[CrossRef]

L. Marcu, J. A. Jo, P. V. Butte, W. H. Yong, B. K. Pikul, K. L. Black, and R. C. Thompson, “Fluorescence lifetime spectroscopy of glioblastoma multiforme,” Photochem. Photobiol. 80(1), 98–103 (2004).
[CrossRef] [PubMed]

Jonathan, S. L.

D. Hai, F. Ru-Chun Amy, L. Junzhong, L. A. Corkan, and S. L. Jonathan, “PhotochemCAD: A Computer-Aided Design and Research Tool in Photochemistry,” Photochem. Photobiol. 68, 141–142 (1998).

Junzhong, L.

D. Hai, F. Ru-Chun Amy, L. Junzhong, L. A. Corkan, and S. L. Jonathan, “PhotochemCAD: A Computer-Aided Design and Research Tool in Photochemistry,” Photochem. Photobiol. 68, 141–142 (1998).

Katika, K. M.

J. Blackwell, K. M. Katika, L. Pilon, K. M. Dipple, S. R. Levin, and A. Nouvong, “In vivo time-resolved autofluorescence measurements to test for glycation of human skin,” J. Biomed. Opt. 13(1), 014004 (2008).
[CrossRef] [PubMed]

Levin, S. R.

J. Blackwell, K. M. Katika, L. Pilon, K. M. Dipple, S. R. Levin, and A. Nouvong, “In vivo time-resolved autofluorescence measurements to test for glycation of human skin,” J. Biomed. Opt. 13(1), 014004 (2008).
[CrossRef] [PubMed]

Liao, E.

Magde, D.

D. Magde, G. E. Rojas, and P. G. Seybold, “Solvent dependence of the fluorescence lifetimes of xanthene dyes,” Photochem. Photobiol. 70(5), 737–744 (1999).
[CrossRef]

Marcu, L.

L. Marcu, “Fluorescence lifetime in cardiovascular diagnostics,” J. Biomed. Opt. 15(1), 011106 (2010).
[CrossRef] [PubMed]

W. H. Yong, P. V. Butte, B. K. Pikul, J. A. Jo, Q. Y. Fang, T. Papaioannou, K. Black, and L. Marcu, “Distinction of brain tissue, low grade and high grade glioma with time-resolved fluorescence spectroscopy,” Front. Biosci. 11(1), 1255–1263 (2006).
[CrossRef] [PubMed]

Q. Fang, T. Papaioannou, J. A. Jo, R. Vaitha, K. Shastry, and L. Marcu, “Time-domain laser-induced fluorescence spectroscopy apparatus for clinical diagnostics,” Rev. Sci. Instrum. 75(1), 151–162 (2004).
[CrossRef]

L. Marcu, J. A. Jo, P. V. Butte, W. H. Yong, B. K. Pikul, K. L. Black, and R. C. Thompson, “Fluorescence lifetime spectroscopy of glioblastoma multiforme,” Photochem. Photobiol. 80(1), 98–103 (2004).
[CrossRef] [PubMed]

Marin, N.

S. K. Chang, N. Marin, M. Follen, and R. Richards-Kortum, “Model-based analysis of clinical fluorescence spectroscopy for in vivo detection of cervical intraepithelial dysplasia,” J. Biomed. Opt. 11(2), 024008 (2006).
[CrossRef] [PubMed]

Mary-Ann, M.

R. Mekhala, D. S. Nadder, H. W. Robert, M. Mary-Ann, P. Nancy, H. K. David, and D. M. Michael, “Quantitative polarized Raman spectroscopy in highly turbid bone tissue,” J. Biomed. Opt. 15, 037001 (2010).

McKenna, B.

M. Chandra, J. Scheiman, D. Simeone, B. McKenna, J. Purdy, and M.-A. Mycek, “Spectral areas and ratios classifier algorithm for pancreatic tissue classification using optical spectroscopy,” J. Biomed. Opt. 15(1), 010514 (2010).
[CrossRef] [PubMed]

R. H. Wilson, M. Chandra, J. Scheiman, D. Simeone, B. McKenna, J. Purdy, and M. A. Mycek, “Optical spectroscopy detects histological hallmarks of pancreatic cancer,” Opt. Express 17(20), 17502–17516 (2009).
[CrossRef] [PubMed]

M. Chandra, J. Scheiman, D. Heidt, D. Simeone, B. McKenna, and M.-A. Mycek, “Probing pancreatic disease using tissue optical spectroscopy,” J. Biomed. Opt. 12(6), 060501 (2007).
[CrossRef] [PubMed]

Mekhala, R.

R. Mekhala, D. S. Nadder, H. W. Robert, M. Mary-Ann, P. Nancy, H. K. David, and D. M. Michael, “Quantitative polarized Raman spectroscopy in highly turbid bone tissue,” J. Biomed. Opt. 15, 037001 (2010).

Michael, D. M.

R. Mekhala, D. S. Nadder, H. W. Robert, M. Mary-Ann, P. Nancy, H. K. David, and D. M. Michael, “Quantitative polarized Raman spectroscopy in highly turbid bone tissue,” J. Biomed. Opt. 15, 037001 (2010).

Monnier, P.

P. Uehlinger, T. Gabrecht, T. Glanzmann, J.-P. Ballini, A. Radu, S. Andrejevic, P. Monnier, and G. Wagnières, “In vivo time-resolved spectroscopy of the human bronchial early cancer autofluorescence,” J. Biomed. Opt. 14(2), 024011 (2009).
[CrossRef] [PubMed]

Mycek, M. A.

Mycek, M.-A.

M. Chandra, J. Scheiman, D. Simeone, B. McKenna, J. Purdy, and M.-A. Mycek, “Spectral areas and ratios classifier algorithm for pancreatic tissue classification using optical spectroscopy,” J. Biomed. Opt. 15(1), 010514 (2010).
[CrossRef] [PubMed]

M. Chandra, J. Scheiman, D. Heidt, D. Simeone, B. McKenna, and M.-A. Mycek, “Probing pancreatic disease using tissue optical spectroscopy,” J. Biomed. Opt. 12(6), 060501 (2007).
[CrossRef] [PubMed]

K. Vishwanath, W. Zhong, M. Close, and M.-A. Mycek, “Fluorescence quenching by polystyrene microspheres in UV-visible and NIR tissue-simulating phantoms,” Opt. Express 14(17), 7776–7788 (2006).
[CrossRef] [PubMed]

M. Chandra, K. Vishwanath, G. D. Fichter, E. Liao, S. J. Hollister, and M.-A. Mycek, “Quantitative molecular sensing in biological tissues: an approach to non-invasive optical characterization,” Opt. Express 14(13), 6157–6171 (2006).
[CrossRef] [PubMed]

K. Vishwanath and M.-A. Mycek, “Time-resolved photon migration in bi-layered tissue models,” Opt. Express 13(19), 7466–7482 (2005).
[CrossRef] [PubMed]

K. Vishwanath and M.-A. Mycek, “Do fluorescence decays remitted from tissues accurately reflect intrinsic fluorophore lifetimes?” Opt. Lett. 29(13), 1512–1514 (2004).
[CrossRef] [PubMed]

K. Vishwanath, B. W. Pogue, and M.-A. Mycek, “Quantitative fluorescence lifetime spectroscopy in turbid media: comparison of theoretical, experimental and computational methods,” Phys. Med. Biol. 47(18), 3387–3405 (2002).
[CrossRef] [PubMed]

J. D. Pitts and M.-A. Mycek, “Design and development of a rapid acquisition laser-based fluorometer with simultaneous spectral and temporal resolution,” Rev. Sci. Instrum. 72(7), 3061–3072 (2001).
[CrossRef]

M.-A. Mycek, K. T. Schomacker, and N. S. Nishioka, “Colonic polyp differentiation using time-resolved autofluorescence spectroscopy,” Gastrointest. Endosc. 48(4), 390–394 (1998).
[CrossRef] [PubMed]

Nadder, D. S.

R. Mekhala, D. S. Nadder, H. W. Robert, M. Mary-Ann, P. Nancy, H. K. David, and D. M. Michael, “Quantitative polarized Raman spectroscopy in highly turbid bone tissue,” J. Biomed. Opt. 15, 037001 (2010).

Nancy, P.

R. Mekhala, D. S. Nadder, H. W. Robert, M. Mary-Ann, P. Nancy, H. K. David, and D. M. Michael, “Quantitative polarized Raman spectroscopy in highly turbid bone tissue,” J. Biomed. Opt. 15, 037001 (2010).

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]

Nishioka, N. S.

T. J. Pfefer, D. Y. Paithankar, J. M. Poneros, K. T. Schomacker, and N. S. Nishioka, “Temporally and spectrally resolved fluorescence spectroscopy for the detection of high grade dysplasia in Barrett’s esophagus,” Lasers Surg. Med. 32(1), 10–16 (2003).
[CrossRef] [PubMed]

M.-A. Mycek, K. T. Schomacker, and N. S. Nishioka, “Colonic polyp differentiation using time-resolved autofluorescence spectroscopy,” Gastrointest. Endosc. 48(4), 390–394 (1998).
[CrossRef] [PubMed]

Nouvong, A.

J. Blackwell, K. M. Katika, L. Pilon, K. M. Dipple, S. R. Levin, and A. Nouvong, “In vivo time-resolved autofluorescence measurements to test for glycation of human skin,” J. Biomed. Opt. 13(1), 014004 (2008).
[CrossRef] [PubMed]

Paithankar, D. Y.

T. J. Pfefer, D. Y. Paithankar, J. M. Poneros, K. T. Schomacker, and N. S. Nishioka, “Temporally and spectrally resolved fluorescence spectroscopy for the detection of high grade dysplasia in Barrett’s esophagus,” Lasers Surg. Med. 32(1), 10–16 (2003).
[CrossRef] [PubMed]

Papaioannou, T.

W. H. Yong, P. V. Butte, B. K. Pikul, J. A. Jo, Q. Y. Fang, T. Papaioannou, K. Black, and L. Marcu, “Distinction of brain tissue, low grade and high grade glioma with time-resolved fluorescence spectroscopy,” Front. Biosci. 11(1), 1255–1263 (2006).
[CrossRef] [PubMed]

Q. Fang, T. Papaioannou, J. A. Jo, R. Vaitha, K. Shastry, and L. Marcu, “Time-domain laser-induced fluorescence spectroscopy apparatus for clinical diagnostics,” Rev. Sci. Instrum. 75(1), 151–162 (2004).
[CrossRef]

Pfefer, T. J.

T. J. Pfefer, D. Y. Paithankar, J. M. Poneros, K. T. Schomacker, and N. S. Nishioka, “Temporally and spectrally resolved fluorescence spectroscopy for the detection of high grade dysplasia in Barrett’s esophagus,” Lasers Surg. Med. 32(1), 10–16 (2003).
[CrossRef] [PubMed]

Pikul, B. K.

W. H. Yong, P. V. Butte, B. K. Pikul, J. A. Jo, Q. Y. Fang, T. Papaioannou, K. Black, and L. Marcu, “Distinction of brain tissue, low grade and high grade glioma with time-resolved fluorescence spectroscopy,” Front. Biosci. 11(1), 1255–1263 (2006).
[CrossRef] [PubMed]

L. Marcu, J. A. Jo, P. V. Butte, W. H. Yong, B. K. Pikul, K. L. Black, and R. C. Thompson, “Fluorescence lifetime spectroscopy of glioblastoma multiforme,” Photochem. Photobiol. 80(1), 98–103 (2004).
[CrossRef] [PubMed]

Pilon, L.

J. Blackwell, K. M. Katika, L. Pilon, K. M. Dipple, S. R. Levin, and A. Nouvong, “In vivo time-resolved autofluorescence measurements to test for glycation of human skin,” J. Biomed. Opt. 13(1), 014004 (2008).
[CrossRef] [PubMed]

Pitts, J. D.

J. D. Pitts and M.-A. Mycek, “Design and development of a rapid acquisition laser-based fluorometer with simultaneous spectral and temporal resolution,” Rev. Sci. Instrum. 72(7), 3061–3072 (2001).
[CrossRef]

Pogue, B. W.

K. Vishwanath, B. W. Pogue, and M.-A. Mycek, “Quantitative fluorescence lifetime spectroscopy in turbid media: comparison of theoretical, experimental and computational methods,” Phys. Med. Biol. 47(18), 3387–3405 (2002).
[CrossRef] [PubMed]

Poneros, J. M.

T. J. Pfefer, D. Y. Paithankar, J. M. Poneros, K. T. Schomacker, and N. S. Nishioka, “Temporally and spectrally resolved fluorescence spectroscopy for the detection of high grade dysplasia in Barrett’s esophagus,” Lasers Surg. Med. 32(1), 10–16 (2003).
[CrossRef] [PubMed]

Prahl, S. A.

Purdy, J.

M. Chandra, J. Scheiman, D. Simeone, B. McKenna, J. Purdy, and M.-A. Mycek, “Spectral areas and ratios classifier algorithm for pancreatic tissue classification using optical spectroscopy,” J. Biomed. Opt. 15(1), 010514 (2010).
[CrossRef] [PubMed]

R. H. Wilson, M. Chandra, J. Scheiman, D. Simeone, B. McKenna, J. Purdy, and M. A. Mycek, “Optical spectroscopy detects histological hallmarks of pancreatic cancer,” Opt. Express 17(20), 17502–17516 (2009).
[CrossRef] [PubMed]

Radu, A.

P. Uehlinger, T. Gabrecht, T. Glanzmann, J.-P. Ballini, A. Radu, S. Andrejevic, P. Monnier, and G. Wagnières, “In vivo time-resolved spectroscopy of the human bronchial early cancer autofluorescence,” J. Biomed. Opt. 14(2), 024011 (2009).
[CrossRef] [PubMed]

Richards-Kortum, R.

S. K. Chang, N. Marin, M. Follen, and R. Richards-Kortum, “Model-based analysis of clinical fluorescence spectroscopy for in vivo detection of cervical intraepithelial dysplasia,” J. Biomed. Opt. 11(2), 024008 (2006).
[CrossRef] [PubMed]

Robert, H. W.

R. Mekhala, D. S. Nadder, H. W. Robert, M. Mary-Ann, P. Nancy, H. K. David, and D. M. Michael, “Quantitative polarized Raman spectroscopy in highly turbid bone tissue,” J. Biomed. Opt. 15, 037001 (2010).

Rojas, G. E.

D. Magde, G. E. Rojas, and P. G. Seybold, “Solvent dependence of the fluorescence lifetimes of xanthene dyes,” Photochem. Photobiol. 70(5), 737–744 (1999).
[CrossRef]

Ru-Chun Amy, F.

D. Hai, F. Ru-Chun Amy, L. Junzhong, L. A. Corkan, and S. L. Jonathan, “PhotochemCAD: A Computer-Aided Design and Research Tool in Photochemistry,” Photochem. Photobiol. 68, 141–142 (1998).

Scheiman, J.

M. Chandra, J. Scheiman, D. Simeone, B. McKenna, J. Purdy, and M.-A. Mycek, “Spectral areas and ratios classifier algorithm for pancreatic tissue classification using optical spectroscopy,” J. Biomed. Opt. 15(1), 010514 (2010).
[CrossRef] [PubMed]

R. H. Wilson, M. Chandra, J. Scheiman, D. Simeone, B. McKenna, J. Purdy, and M. A. Mycek, “Optical spectroscopy detects histological hallmarks of pancreatic cancer,” Opt. Express 17(20), 17502–17516 (2009).
[CrossRef] [PubMed]

M. Chandra, J. Scheiman, D. Heidt, D. Simeone, B. McKenna, and M.-A. Mycek, “Probing pancreatic disease using tissue optical spectroscopy,” J. Biomed. Opt. 12(6), 060501 (2007).
[CrossRef] [PubMed]

Schomacker, K. T.

T. J. Pfefer, D. Y. Paithankar, J. M. Poneros, K. T. Schomacker, and N. S. Nishioka, “Temporally and spectrally resolved fluorescence spectroscopy for the detection of high grade dysplasia in Barrett’s esophagus,” Lasers Surg. Med. 32(1), 10–16 (2003).
[CrossRef] [PubMed]

M.-A. Mycek, K. T. Schomacker, and N. S. Nishioka, “Colonic polyp differentiation using time-resolved autofluorescence spectroscopy,” Gastrointest. Endosc. 48(4), 390–394 (1998).
[CrossRef] [PubMed]

Seybold, P. G.

D. Magde, G. E. Rojas, and P. G. Seybold, “Solvent dependence of the fluorescence lifetimes of xanthene dyes,” Photochem. Photobiol. 70(5), 737–744 (1999).
[CrossRef]

Shastry, K.

Q. Fang, T. Papaioannou, J. A. Jo, R. Vaitha, K. Shastry, and L. Marcu, “Time-domain laser-induced fluorescence spectroscopy apparatus for clinical diagnostics,” Rev. Sci. Instrum. 75(1), 151–162 (2004).
[CrossRef]

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]

Simeone, D.

M. Chandra, J. Scheiman, D. Simeone, B. McKenna, J. Purdy, and M.-A. Mycek, “Spectral areas and ratios classifier algorithm for pancreatic tissue classification using optical spectroscopy,” J. Biomed. Opt. 15(1), 010514 (2010).
[CrossRef] [PubMed]

R. H. Wilson, M. Chandra, J. Scheiman, D. Simeone, B. McKenna, J. Purdy, and M. A. Mycek, “Optical spectroscopy detects histological hallmarks of pancreatic cancer,” Opt. Express 17(20), 17502–17516 (2009).
[CrossRef] [PubMed]

M. Chandra, J. Scheiman, D. Heidt, D. Simeone, B. McKenna, and M.-A. Mycek, “Probing pancreatic disease using tissue optical spectroscopy,” J. Biomed. Opt. 12(6), 060501 (2007).
[CrossRef] [PubMed]

Thompson, R. C.

L. Marcu, J. A. Jo, P. V. Butte, W. H. Yong, B. K. Pikul, K. L. Black, and R. C. Thompson, “Fluorescence lifetime spectroscopy of glioblastoma multiforme,” Photochem. Photobiol. 80(1), 98–103 (2004).
[CrossRef] [PubMed]

Thorstenson, T.

A. J. Bystol, T. Thorstenson, and A. D. Campiglia, “Laser-induced multidimensional fluorescence spectroscopy in Shpol’skii matrixes for the analysis of polycyclic aromatic hydrocarbons in HPLC fractions and complex environmental extracts,” Environ. Sci. Technol. 36(20), 4424–4429 (2002).
[CrossRef] [PubMed]

Uehlinger, P.

P. Uehlinger, T. Gabrecht, T. Glanzmann, J.-P. Ballini, A. Radu, S. Andrejevic, P. Monnier, and G. Wagnières, “In vivo time-resolved spectroscopy of the human bronchial early cancer autofluorescence,” J. Biomed. Opt. 14(2), 024011 (2009).
[CrossRef] [PubMed]

Vaitha, R.

Q. Fang, T. Papaioannou, J. A. Jo, R. Vaitha, K. Shastry, and L. Marcu, “Time-domain laser-induced fluorescence spectroscopy apparatus for clinical diagnostics,” Rev. Sci. Instrum. 75(1), 151–162 (2004).
[CrossRef]

van Gemert, M. J. C.

Vishwanath, K.

Volynskaya, Z.

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]

Wagnières, G.

P. Uehlinger, T. Gabrecht, T. Glanzmann, J.-P. Ballini, A. Radu, S. Andrejevic, P. Monnier, and G. Wagnières, “In vivo time-resolved spectroscopy of the human bronchial early cancer autofluorescence,” J. Biomed. Opt. 14(2), 024011 (2009).
[CrossRef] [PubMed]

Wang, N.

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]

Welch, A. J.

Wilson, R. H.

Yong, W. H.

W. H. Yong, P. V. Butte, B. K. Pikul, J. A. Jo, Q. Y. Fang, T. Papaioannou, K. Black, and L. Marcu, “Distinction of brain tissue, low grade and high grade glioma with time-resolved fluorescence spectroscopy,” Front. Biosci. 11(1), 1255–1263 (2006).
[CrossRef] [PubMed]

L. Marcu, J. A. Jo, P. V. Butte, W. H. Yong, B. K. Pikul, K. L. Black, and R. C. Thompson, “Fluorescence lifetime spectroscopy of glioblastoma multiforme,” Photochem. Photobiol. 80(1), 98–103 (2004).
[CrossRef] [PubMed]

Zeng, H.

Y. S. Fawzy and H. Zeng, “Intrinsic fluorescence spectroscopy for endoscopic detection and localization of the endobronchial cancerous lesions,” J. Biomed. Opt. 13(6), 064022 (2008).
[CrossRef] [PubMed]

Zhong, W.

Anal. Chem. (1)

A. J. Bystol, A. D. Campiglia, and G. D. Gillispie, “Laser-induced multidimensional fluorescence spectroscopy in Shpol’skii matrixes with a fiber-optic probe at liquid helium temperature,” Anal. Chem. 73(23), 5762–5770 (2001).
[CrossRef] [PubMed]

Appl. Opt. (1)

Appl. Spectrosc. (1)

Environ. Sci. Technol. (1)

A. J. Bystol, T. Thorstenson, and A. D. Campiglia, “Laser-induced multidimensional fluorescence spectroscopy in Shpol’skii matrixes for the analysis of polycyclic aromatic hydrocarbons in HPLC fractions and complex environmental extracts,” Environ. Sci. Technol. 36(20), 4424–4429 (2002).
[CrossRef] [PubMed]

Front. Biosci. (1)

W. H. Yong, P. V. Butte, B. K. Pikul, J. A. Jo, Q. Y. Fang, T. Papaioannou, K. Black, and L. Marcu, “Distinction of brain tissue, low grade and high grade glioma with time-resolved fluorescence spectroscopy,” Front. Biosci. 11(1), 1255–1263 (2006).
[CrossRef] [PubMed]

Gastrointest. Endosc. (1)

M.-A. Mycek, K. T. Schomacker, and N. S. Nishioka, “Colonic polyp differentiation using time-resolved autofluorescence spectroscopy,” Gastrointest. Endosc. 48(4), 390–394 (1998).
[CrossRef] [PubMed]

Gastrointest. Endosc. Clin. N. Am. (1)

I. Georgakoudi and M. S. Feld, “The combined use of fluorescence, reflectance, and light-scattering spectroscopy for evaluating dysplasia in Barrett’s esophagus,” Gastrointest. Endosc. Clin. N. Am. 14(3), 519–537, ix (2004).
[CrossRef] [PubMed]

J. Biomed. Opt. (9)

Y. S. Fawzy and H. Zeng, “Intrinsic fluorescence spectroscopy for endoscopic detection and localization of the endobronchial cancerous lesions,” J. Biomed. Opt. 13(6), 064022 (2008).
[CrossRef] [PubMed]

M. Chandra, J. Scheiman, D. Heidt, D. Simeone, B. McKenna, and M.-A. Mycek, “Probing pancreatic disease using tissue optical spectroscopy,” J. Biomed. Opt. 12(6), 060501 (2007).
[CrossRef] [PubMed]

M. Chandra, J. Scheiman, D. Simeone, B. McKenna, J. Purdy, and M.-A. Mycek, “Spectral areas and ratios classifier algorithm for pancreatic tissue classification using optical spectroscopy,” J. Biomed. Opt. 15(1), 010514 (2010).
[CrossRef] [PubMed]

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]

S. K. Chang, N. Marin, M. Follen, and R. Richards-Kortum, “Model-based analysis of clinical fluorescence spectroscopy for in vivo detection of cervical intraepithelial dysplasia,” J. Biomed. Opt. 11(2), 024008 (2006).
[CrossRef] [PubMed]

P. Uehlinger, T. Gabrecht, T. Glanzmann, J.-P. Ballini, A. Radu, S. Andrejevic, P. Monnier, and G. Wagnières, “In vivo time-resolved spectroscopy of the human bronchial early cancer autofluorescence,” J. Biomed. Opt. 14(2), 024011 (2009).
[CrossRef] [PubMed]

L. Marcu, “Fluorescence lifetime in cardiovascular diagnostics,” J. Biomed. Opt. 15(1), 011106 (2010).
[CrossRef] [PubMed]

J. Blackwell, K. M. Katika, L. Pilon, K. M. Dipple, S. R. Levin, and A. Nouvong, “In vivo time-resolved autofluorescence measurements to test for glycation of human skin,” J. Biomed. Opt. 13(1), 014004 (2008).
[CrossRef] [PubMed]

R. Mekhala, D. S. Nadder, H. W. Robert, M. Mary-Ann, P. Nancy, H. K. David, and D. M. Michael, “Quantitative polarized Raman spectroscopy in highly turbid bone tissue,” J. Biomed. Opt. 15, 037001 (2010).

Lasers Surg. Med. (1)

T. J. Pfefer, D. Y. Paithankar, J. M. Poneros, K. T. Schomacker, and N. S. Nishioka, “Temporally and spectrally resolved fluorescence spectroscopy for the detection of high grade dysplasia in Barrett’s esophagus,” Lasers Surg. Med. 32(1), 10–16 (2003).
[CrossRef] [PubMed]

Opt. Express (4)

Opt. Lett. (1)

Photochem. Photobiol. (3)

D. Hai, F. Ru-Chun Amy, L. Junzhong, L. A. Corkan, and S. L. Jonathan, “PhotochemCAD: A Computer-Aided Design and Research Tool in Photochemistry,” Photochem. Photobiol. 68, 141–142 (1998).

D. Magde, G. E. Rojas, and P. G. Seybold, “Solvent dependence of the fluorescence lifetimes of xanthene dyes,” Photochem. Photobiol. 70(5), 737–744 (1999).
[CrossRef]

L. Marcu, J. A. Jo, P. V. Butte, W. H. Yong, B. K. Pikul, K. L. Black, and R. C. Thompson, “Fluorescence lifetime spectroscopy of glioblastoma multiforme,” Photochem. Photobiol. 80(1), 98–103 (2004).
[CrossRef] [PubMed]

Phys. Med. Biol. (1)

K. Vishwanath, B. W. Pogue, and M.-A. Mycek, “Quantitative fluorescence lifetime spectroscopy in turbid media: comparison of theoretical, experimental and computational methods,” Phys. Med. Biol. 47(18), 3387–3405 (2002).
[CrossRef] [PubMed]

Rev. Sci. Instrum. (2)

J. D. Pitts and M.-A. Mycek, “Design and development of a rapid acquisition laser-based fluorometer with simultaneous spectral and temporal resolution,” Rev. Sci. Instrum. 72(7), 3061–3072 (2001).
[CrossRef]

Q. Fang, T. Papaioannou, J. A. Jo, R. Vaitha, K. Shastry, and L. Marcu, “Time-domain laser-induced fluorescence spectroscopy apparatus for clinical diagnostics,” Rev. Sci. Instrum. 75(1), 151–162 (2004).
[CrossRef]

Other (4)

J. R. Lakowicz, Principles of Fluorescence Spectroscopy (Kluwer Academic/Plenum, New York, 1999).

N. Lois, and J. V. Forrester, Fundus Autofluorescence (Lippincott Williams & Wilkins, Philadelphia, 2009).

F. G. Holz, and R. F. Spaide, Medical Retina: Focus on Retinal Imaging (Springer-Verlag, Berlin, 2010).

M. A. Mycek, and B. W. Pogue, eds., Handbook of Biomedical Fluorescence (Marcel-Dekker Inc., New York, New York, 2003).

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Figures (7)

Fig. 1
Fig. 1

Fluorescence wavelength-time matrix (WTM) of 1 μM Rhodamine 6G in ethanol acquired with fiber-optic probes for light delivery and detection. The WTM contains both wavelength-resolved and time-resolved fluorescence data.

Fig. 2
Fig. 2

Schematic of the instrumentation developed for rapid acquisition of fluorescence WTMs, using fiber-optic probes for light delivery and detection (set-up 4, Table 1). WTMs were also obtained with three other set-ups (Table 1): (1) right-angle free-space geometry, in place of the fiber-probes, for light delivery and detection; (2) free-space light delivery and a fiber-probe for fluorescence detection; (3) a fiber-probe for light delivery and right-angle free-space geometry for detection.

Fig. 3
Fig. 3

Signal-to-noise characterization of the system, performed on a stock solution of fluorescent beads: (a) standard deviation of measured fluorescence intensity (green curve), compared to prediction of Poisson theory (blue curve), as a function of acquisition time; (b) normalized fluorescence decay curves for 5 laser pulses averaged (red curve, corresponding to red circle in (a)) and 1250 laser pulses averaged (purple curve, corresponding to purple circle in (a)). The arrow in (a) denotes data acquisition with 125 laser pulses averaged; the standard deviation of the relative peak intensity at this point is ~0.25 (a.u.) with a peak signal intensity of ~28 (a.u.), yielding a SNR greater than 100.

Fig. 5
Fig. 5

Time-resolved fluorescence decay curves measured on solutions of rhodamine 6G ((a), (d)), rose bengal ((b), (e)), and fluorescein ((c), (f)). Panel (a) plots 36 averaged rhodamine 6G fluorescence decays, panel (b) plots 36 averaged rose bengal fluorescence decays, and panel (c) plots 24 averaged fluorescein fluorescence decays (four system set-ups per fluorophore, three emission wavelengths for rhodamine 6G and rose bengal, two emission wavelengths for fluorescein). The error bars represent standard deviation. In panels (d), (e), and (f), one representative decay curve for each fluorophore measured with set-up 4 was fit to a single exponential decay.

Fig. 4
Fig. 4

Fluorescence spectra of rhodamine 6G (blue curve), rose bengal (red curve), and fluorescein (green curve), measured with the fiber-based system set-up 4 and normalized to the area under the curve. Each curve is the average of three measurements; the error bars represent the standard deviation.

Fig. 6
Fig. 6

Wavelength-resolved (a) and time-resolved (b) fluorescence from tissue-simulating phantoms with varying scattering coefficients (measured with a source detector separation of 0.66 mm). Three sites on each phantom were measured. The spectra represent the average of the three sites, with error bars representing standard deviation. Panel (a) also includes spectra from pure gelatin and from a solution of rhodamine B in deionized water.

Fig. 7
Fig. 7

Measured time-resolved fluorescence decay curves from two phantoms with biologically-relevant scattering coefficients at a source-detector separation of 4.66 mm (a), compared with the predictions of diffusion theory (b). Each curve in (b) is a convolution of the diffusion theory result with the instrument response function of the corresponding tissue-simulating phantom. For the sake of comparison, the experimental results and the diffusion theory predictions were time-shifted to align the rising shoulders of the curves. In both panels, the time-resolved decay from the medium with the higher scattering coefficient (red dashed curve) was noticeably broader than the decay from the medium with the lower scattering coefficient (blue solid curve).

Tables (2)

Tables Icon

Table 1 Set-ups employed to acquire fluorescence WTMs

Tables Icon

Table 2 Lifetime values obtained from standard fluorophore solutions

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