Abstract

We report a novel technique for continuous acquisition, processing and display of fluorescence lifetimes enabling real-time tissue diagnosis through a single hand held or biopsy fiber-optic probe. A scanning multispectral time-resolved fluorescence spectroscopy (ms-TRFS) with self-adjustable photon detection range was developed to account for the dynamic changes of fluorescence intensity typically encountered in clinical application. A fast algorithm was implemented in the ms-TRFS software platform, providing up to 15 Hz continuous display of fluorescence lifetime values. Potential applications of this technique, including biopsy guidance, and surgical margins delineation were demonstrated in proof-of-concept experiments. Current results showed accurate display of fluorescence lifetimes values and discrimination of distinct fluorescence markers and tissue types in real-time (< 100 ms per data point).

© 2015 Optical Society of America

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References

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    [Crossref] [PubMed]
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    [Crossref] [PubMed]
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    [Crossref] [PubMed]
  4. L. Marcu, “Fluorescence Lifetime Techniques in Medical Applications,” Ann. Biomed. Eng. 40(2), 304–331 (2012).
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2014 (4)

D. Savastru, E. W. Chang, S. Miclos, M. B. Pitman, A. Patel, and N. Iftimia, “Detection of breast surgical margins with optical coherence tomography imaging: a concept evaluation study,” J. Biomed. Opt. 19(5), 056001 (2014).
[Crossref] [PubMed]

A. C. Croce, A. Ferrigno, G. Santin, V. M. Piccolini, G. Bottiroli, and M. Vairetti, “Autofluorescence of Liver Tissue and Bile: Organ Functionality Monitoring During Ischemia and Reoxygenation,” Lasers Surg. Med. 46(5), 412–421 (2014).
[Crossref] [PubMed]

D. R. Yankelevich, D. Ma, J. Liu, Y. Sun, Y. Sun, J. Bec, D. S. Elson, and L. Marcu, “Design and evaluation of a device for fast multispectral time-resolved fluorescence spectroscopy and imaging,” Rev. Sci. Instrum. 85(3), 034303 (2014).
[Crossref] [PubMed]

O. Assayag, M. Antoine, B. Sigal-Zafrani, M. Riben, F. Harms, A. Burcheri, K. Grieve, E. Dalimier, B. Le Conte de Poly, and C. Boccara, “Large Field, High Resolution Full-Field Optical Coherence Tomography: A Pre-clinical Study of Human Breast Tissue and Cancer Assessment,” Technol. Cancer Res. Treat. 13(5), 455–468 (2014).
[PubMed]

2013 (3)

J. Bec, D. M. Ma, D. R. Yankelevich, J. Liu, W. T. Ferrier, J. Southard, and L. Marcu, “Multispectral fluorescence lifetime imaging system for intravascular diagnostics with ultrasound guidance: in vivo validation in swine arteries,” J. Biophotonics 7, 281–285 (2013).

H. Fatakdawala, S. Poti, F. Zhou, Y. Sun, J. Bec, J. Liu, D. R. Yankelevich, S. P. Tinling, R. F. Gandour-Edwards, D. G. Farwell, and L. Marcu, “Multimodal in vivo imaging of oral cancer using fluorescence lifetime, photoacoustic and ultrasound techniques,” Biomed. Opt. Express 4(9), 1724–1741 (2013).
[Crossref] [PubMed]

C. Kallaway, L. M. Almond, H. Barr, J. Wood, J. Hutchings, C. Kendall, and N. Stone, “Advances in the clinical application of Raman spectroscopy for cancer diagnostics,” Photodiagn. Photodyn. Ther. 10(3), 207–219 (2013).
[Crossref] [PubMed]

2012 (3)

L. Marcu, “Fluorescence Lifetime Techniques in Medical Applications,” Ann. Biomed. Eng. 40(2), 304–331 (2012).
[Crossref] [PubMed]

H. T. Xie, J. Bec, J. Liu, Y. Sun, M. Lam, D. R. Yankelevich, and L. Marcu, “Multispectral scanning time-resolved fluorescence spectroscopy (TRFS) technique for intravascular diagnosis,” Biomed. Opt. Express 3(7), 1521–1533 (2012).
[Crossref] [PubMed]

J. Liu, Y. Sun, J. Y. Qi, and L. Marcu, “A novel method for fast and robust estimation of fluorescence decay dynamics using constrained least-squares deconvolution with Laguerre expansion,” Phys. Med. Biol. 57(4), 843–865 (2012).
[Crossref] [PubMed]

2011 (1)

2008 (1)

2000 (1)

F. del Monte, J. D. Mackenzie, and D. Levy, “Rhodamine fluorescent dimers adsorbed on the porous surface of silica gels,” Langmuir 16(19), 7377–7382 (2000).
[Crossref]

Almond, L. M.

C. Kallaway, L. M. Almond, H. Barr, J. Wood, J. Hutchings, C. Kendall, and N. Stone, “Advances in the clinical application of Raman spectroscopy for cancer diagnostics,” Photodiagn. Photodyn. Ther. 10(3), 207–219 (2013).
[Crossref] [PubMed]

Antoine, M.

O. Assayag, M. Antoine, B. Sigal-Zafrani, M. Riben, F. Harms, A. Burcheri, K. Grieve, E. Dalimier, B. Le Conte de Poly, and C. Boccara, “Large Field, High Resolution Full-Field Optical Coherence Tomography: A Pre-clinical Study of Human Breast Tissue and Cancer Assessment,” Technol. Cancer Res. Treat. 13(5), 455–468 (2014).
[PubMed]

Assayag, O.

O. Assayag, M. Antoine, B. Sigal-Zafrani, M. Riben, F. Harms, A. Burcheri, K. Grieve, E. Dalimier, B. Le Conte de Poly, and C. Boccara, “Large Field, High Resolution Full-Field Optical Coherence Tomography: A Pre-clinical Study of Human Breast Tissue and Cancer Assessment,” Technol. Cancer Res. Treat. 13(5), 455–468 (2014).
[PubMed]

Barr, H.

C. Kallaway, L. M. Almond, H. Barr, J. Wood, J. Hutchings, C. Kendall, and N. Stone, “Advances in the clinical application of Raman spectroscopy for cancer diagnostics,” Photodiagn. Photodyn. Ther. 10(3), 207–219 (2013).
[Crossref] [PubMed]

Bec, J.

D. R. Yankelevich, D. Ma, J. Liu, Y. Sun, Y. Sun, J. Bec, D. S. Elson, and L. Marcu, “Design and evaluation of a device for fast multispectral time-resolved fluorescence spectroscopy and imaging,” Rev. Sci. Instrum. 85(3), 034303 (2014).
[Crossref] [PubMed]

H. Fatakdawala, S. Poti, F. Zhou, Y. Sun, J. Bec, J. Liu, D. R. Yankelevich, S. P. Tinling, R. F. Gandour-Edwards, D. G. Farwell, and L. Marcu, “Multimodal in vivo imaging of oral cancer using fluorescence lifetime, photoacoustic and ultrasound techniques,” Biomed. Opt. Express 4(9), 1724–1741 (2013).
[Crossref] [PubMed]

J. Bec, D. M. Ma, D. R. Yankelevich, J. Liu, W. T. Ferrier, J. Southard, and L. Marcu, “Multispectral fluorescence lifetime imaging system for intravascular diagnostics with ultrasound guidance: in vivo validation in swine arteries,” J. Biophotonics 7, 281–285 (2013).

H. T. Xie, J. Bec, J. Liu, Y. Sun, M. Lam, D. R. Yankelevich, and L. Marcu, “Multispectral scanning time-resolved fluorescence spectroscopy (TRFS) technique for intravascular diagnosis,” Biomed. Opt. Express 3(7), 1521–1533 (2012).
[Crossref] [PubMed]

Boccara, C.

O. Assayag, M. Antoine, B. Sigal-Zafrani, M. Riben, F. Harms, A. Burcheri, K. Grieve, E. Dalimier, B. Le Conte de Poly, and C. Boccara, “Large Field, High Resolution Full-Field Optical Coherence Tomography: A Pre-clinical Study of Human Breast Tissue and Cancer Assessment,” Technol. Cancer Res. Treat. 13(5), 455–468 (2014).
[PubMed]

Bottiroli, G.

A. C. Croce, A. Ferrigno, G. Santin, V. M. Piccolini, G. Bottiroli, and M. Vairetti, “Autofluorescence of Liver Tissue and Bile: Organ Functionality Monitoring During Ischemia and Reoxygenation,” Lasers Surg. Med. 46(5), 412–421 (2014).
[Crossref] [PubMed]

Burcheri, A.

O. Assayag, M. Antoine, B. Sigal-Zafrani, M. Riben, F. Harms, A. Burcheri, K. Grieve, E. Dalimier, B. Le Conte de Poly, and C. Boccara, “Large Field, High Resolution Full-Field Optical Coherence Tomography: A Pre-clinical Study of Human Breast Tissue and Cancer Assessment,” Technol. Cancer Res. Treat. 13(5), 455–468 (2014).
[PubMed]

Chang, E. W.

D. Savastru, E. W. Chang, S. Miclos, M. B. Pitman, A. Patel, and N. Iftimia, “Detection of breast surgical margins with optical coherence tomography imaging: a concept evaluation study,” J. Biomed. Opt. 19(5), 056001 (2014).
[Crossref] [PubMed]

Croce, A. C.

A. C. Croce, A. Ferrigno, G. Santin, V. M. Piccolini, G. Bottiroli, and M. Vairetti, “Autofluorescence of Liver Tissue and Bile: Organ Functionality Monitoring During Ischemia and Reoxygenation,” Lasers Surg. Med. 46(5), 412–421 (2014).
[Crossref] [PubMed]

Dalimier, E.

O. Assayag, M. Antoine, B. Sigal-Zafrani, M. Riben, F. Harms, A. Burcheri, K. Grieve, E. Dalimier, B. Le Conte de Poly, and C. Boccara, “Large Field, High Resolution Full-Field Optical Coherence Tomography: A Pre-clinical Study of Human Breast Tissue and Cancer Assessment,” Technol. Cancer Res. Treat. 13(5), 455–468 (2014).
[PubMed]

del Monte, F.

F. del Monte, J. D. Mackenzie, and D. Levy, “Rhodamine fluorescent dimers adsorbed on the porous surface of silica gels,” Langmuir 16(19), 7377–7382 (2000).
[Crossref]

Elson, D. S.

Farwell, D. G.

Fatakdawala, H.

Ferrier, W. T.

J. Bec, D. M. Ma, D. R. Yankelevich, J. Liu, W. T. Ferrier, J. Southard, and L. Marcu, “Multispectral fluorescence lifetime imaging system for intravascular diagnostics with ultrasound guidance: in vivo validation in swine arteries,” J. Biophotonics 7, 281–285 (2013).

Ferrigno, A.

A. C. Croce, A. Ferrigno, G. Santin, V. M. Piccolini, G. Bottiroli, and M. Vairetti, “Autofluorescence of Liver Tissue and Bile: Organ Functionality Monitoring During Ischemia and Reoxygenation,” Lasers Surg. Med. 46(5), 412–421 (2014).
[Crossref] [PubMed]

Gandour-Edwards, R. F.

Grieve, K.

O. Assayag, M. Antoine, B. Sigal-Zafrani, M. Riben, F. Harms, A. Burcheri, K. Grieve, E. Dalimier, B. Le Conte de Poly, and C. Boccara, “Large Field, High Resolution Full-Field Optical Coherence Tomography: A Pre-clinical Study of Human Breast Tissue and Cancer Assessment,” Technol. Cancer Res. Treat. 13(5), 455–468 (2014).
[PubMed]

Harms, F.

O. Assayag, M. Antoine, B. Sigal-Zafrani, M. Riben, F. Harms, A. Burcheri, K. Grieve, E. Dalimier, B. Le Conte de Poly, and C. Boccara, “Large Field, High Resolution Full-Field Optical Coherence Tomography: A Pre-clinical Study of Human Breast Tissue and Cancer Assessment,” Technol. Cancer Res. Treat. 13(5), 455–468 (2014).
[PubMed]

Hollars, C. W.

Hutchings, J.

C. Kallaway, L. M. Almond, H. Barr, J. Wood, J. Hutchings, C. Kendall, and N. Stone, “Advances in the clinical application of Raman spectroscopy for cancer diagnostics,” Photodiagn. Photodyn. Ther. 10(3), 207–219 (2013).
[Crossref] [PubMed]

Iftimia, N.

D. Savastru, E. W. Chang, S. Miclos, M. B. Pitman, A. Patel, and N. Iftimia, “Detection of breast surgical margins with optical coherence tomography imaging: a concept evaluation study,” J. Biomed. Opt. 19(5), 056001 (2014).
[Crossref] [PubMed]

Jo, J. A.

Kallaway, C.

C. Kallaway, L. M. Almond, H. Barr, J. Wood, J. Hutchings, C. Kendall, and N. Stone, “Advances in the clinical application of Raman spectroscopy for cancer diagnostics,” Photodiagn. Photodyn. Ther. 10(3), 207–219 (2013).
[Crossref] [PubMed]

Kendall, C.

C. Kallaway, L. M. Almond, H. Barr, J. Wood, J. Hutchings, C. Kendall, and N. Stone, “Advances in the clinical application of Raman spectroscopy for cancer diagnostics,” Photodiagn. Photodyn. Ther. 10(3), 207–219 (2013).
[Crossref] [PubMed]

Lam, M.

Le Conte de Poly, B.

O. Assayag, M. Antoine, B. Sigal-Zafrani, M. Riben, F. Harms, A. Burcheri, K. Grieve, E. Dalimier, B. Le Conte de Poly, and C. Boccara, “Large Field, High Resolution Full-Field Optical Coherence Tomography: A Pre-clinical Study of Human Breast Tissue and Cancer Assessment,” Technol. Cancer Res. Treat. 13(5), 455–468 (2014).
[PubMed]

Levy, D.

F. del Monte, J. D. Mackenzie, and D. Levy, “Rhodamine fluorescent dimers adsorbed on the porous surface of silica gels,” Langmuir 16(19), 7377–7382 (2000).
[Crossref]

Liu, J.

D. R. Yankelevich, D. Ma, J. Liu, Y. Sun, Y. Sun, J. Bec, D. S. Elson, and L. Marcu, “Design and evaluation of a device for fast multispectral time-resolved fluorescence spectroscopy and imaging,” Rev. Sci. Instrum. 85(3), 034303 (2014).
[Crossref] [PubMed]

H. Fatakdawala, S. Poti, F. Zhou, Y. Sun, J. Bec, J. Liu, D. R. Yankelevich, S. P. Tinling, R. F. Gandour-Edwards, D. G. Farwell, and L. Marcu, “Multimodal in vivo imaging of oral cancer using fluorescence lifetime, photoacoustic and ultrasound techniques,” Biomed. Opt. Express 4(9), 1724–1741 (2013).
[Crossref] [PubMed]

J. Bec, D. M. Ma, D. R. Yankelevich, J. Liu, W. T. Ferrier, J. Southard, and L. Marcu, “Multispectral fluorescence lifetime imaging system for intravascular diagnostics with ultrasound guidance: in vivo validation in swine arteries,” J. Biophotonics 7, 281–285 (2013).

H. T. Xie, J. Bec, J. Liu, Y. Sun, M. Lam, D. R. Yankelevich, and L. Marcu, “Multispectral scanning time-resolved fluorescence spectroscopy (TRFS) technique for intravascular diagnosis,” Biomed. Opt. Express 3(7), 1521–1533 (2012).
[Crossref] [PubMed]

J. Liu, Y. Sun, J. Y. Qi, and L. Marcu, “A novel method for fast and robust estimation of fluorescence decay dynamics using constrained least-squares deconvolution with Laguerre expansion,” Phys. Med. Biol. 57(4), 843–865 (2012).
[Crossref] [PubMed]

Liu, R.

Ma, D.

D. R. Yankelevich, D. Ma, J. Liu, Y. Sun, Y. Sun, J. Bec, D. S. Elson, and L. Marcu, “Design and evaluation of a device for fast multispectral time-resolved fluorescence spectroscopy and imaging,” Rev. Sci. Instrum. 85(3), 034303 (2014).
[Crossref] [PubMed]

Ma, D. M.

J. Bec, D. M. Ma, D. R. Yankelevich, J. Liu, W. T. Ferrier, J. Southard, and L. Marcu, “Multispectral fluorescence lifetime imaging system for intravascular diagnostics with ultrasound guidance: in vivo validation in swine arteries,” J. Biophotonics 7, 281–285 (2013).

Mackenzie, J. D.

F. del Monte, J. D. Mackenzie, and D. Levy, “Rhodamine fluorescent dimers adsorbed on the porous surface of silica gels,” Langmuir 16(19), 7377–7382 (2000).
[Crossref]

Marcu, L.

D. R. Yankelevich, D. Ma, J. Liu, Y. Sun, Y. Sun, J. Bec, D. S. Elson, and L. Marcu, “Design and evaluation of a device for fast multispectral time-resolved fluorescence spectroscopy and imaging,” Rev. Sci. Instrum. 85(3), 034303 (2014).
[Crossref] [PubMed]

H. Fatakdawala, S. Poti, F. Zhou, Y. Sun, J. Bec, J. Liu, D. R. Yankelevich, S. P. Tinling, R. F. Gandour-Edwards, D. G. Farwell, and L. Marcu, “Multimodal in vivo imaging of oral cancer using fluorescence lifetime, photoacoustic and ultrasound techniques,” Biomed. Opt. Express 4(9), 1724–1741 (2013).
[Crossref] [PubMed]

J. Bec, D. M. Ma, D. R. Yankelevich, J. Liu, W. T. Ferrier, J. Southard, and L. Marcu, “Multispectral fluorescence lifetime imaging system for intravascular diagnostics with ultrasound guidance: in vivo validation in swine arteries,” J. Biophotonics 7, 281–285 (2013).

H. T. Xie, J. Bec, J. Liu, Y. Sun, M. Lam, D. R. Yankelevich, and L. Marcu, “Multispectral scanning time-resolved fluorescence spectroscopy (TRFS) technique for intravascular diagnosis,” Biomed. Opt. Express 3(7), 1521–1533 (2012).
[Crossref] [PubMed]

J. Liu, Y. Sun, J. Y. Qi, and L. Marcu, “A novel method for fast and robust estimation of fluorescence decay dynamics using constrained least-squares deconvolution with Laguerre expansion,” Phys. Med. Biol. 57(4), 843–865 (2012).
[Crossref] [PubMed]

L. Marcu, “Fluorescence Lifetime Techniques in Medical Applications,” Ann. Biomed. Eng. 40(2), 304–331 (2012).
[Crossref] [PubMed]

Y. H. Sun, Y. Sun, D. Stephens, H. T. Xie, J. Phipps, R. Saroufeem, J. Southard, D. S. Elson, and L. Marcu, “Dynamic tissue analysis using time- and wavelength-resolved fluorescence spectroscopy for atherosclerosis diagnosis,” Opt. Express 19(5), 3890–3901 (2011).
[Crossref] [PubMed]

Y. Sun, R. Liu, D. S. Elson, C. W. Hollars, J. A. Jo, J. Park, Y. Sun, and L. Marcu, “Simultaneous time- and wavelength-resolved fluorescence spectroscopy for near real-time tissue diagnosis,” Opt. Lett. 33(6), 630–632 (2008).
[Crossref] [PubMed]

Miclos, S.

D. Savastru, E. W. Chang, S. Miclos, M. B. Pitman, A. Patel, and N. Iftimia, “Detection of breast surgical margins with optical coherence tomography imaging: a concept evaluation study,” J. Biomed. Opt. 19(5), 056001 (2014).
[Crossref] [PubMed]

Park, J.

Patel, A.

D. Savastru, E. W. Chang, S. Miclos, M. B. Pitman, A. Patel, and N. Iftimia, “Detection of breast surgical margins with optical coherence tomography imaging: a concept evaluation study,” J. Biomed. Opt. 19(5), 056001 (2014).
[Crossref] [PubMed]

Phipps, J.

Piccolini, V. M.

A. C. Croce, A. Ferrigno, G. Santin, V. M. Piccolini, G. Bottiroli, and M. Vairetti, “Autofluorescence of Liver Tissue and Bile: Organ Functionality Monitoring During Ischemia and Reoxygenation,” Lasers Surg. Med. 46(5), 412–421 (2014).
[Crossref] [PubMed]

Pitman, M. B.

D. Savastru, E. W. Chang, S. Miclos, M. B. Pitman, A. Patel, and N. Iftimia, “Detection of breast surgical margins with optical coherence tomography imaging: a concept evaluation study,” J. Biomed. Opt. 19(5), 056001 (2014).
[Crossref] [PubMed]

Poti, S.

Qi, J. Y.

J. Liu, Y. Sun, J. Y. Qi, and L. Marcu, “A novel method for fast and robust estimation of fluorescence decay dynamics using constrained least-squares deconvolution with Laguerre expansion,” Phys. Med. Biol. 57(4), 843–865 (2012).
[Crossref] [PubMed]

Riben, M.

O. Assayag, M. Antoine, B. Sigal-Zafrani, M. Riben, F. Harms, A. Burcheri, K. Grieve, E. Dalimier, B. Le Conte de Poly, and C. Boccara, “Large Field, High Resolution Full-Field Optical Coherence Tomography: A Pre-clinical Study of Human Breast Tissue and Cancer Assessment,” Technol. Cancer Res. Treat. 13(5), 455–468 (2014).
[PubMed]

Santin, G.

A. C. Croce, A. Ferrigno, G. Santin, V. M. Piccolini, G. Bottiroli, and M. Vairetti, “Autofluorescence of Liver Tissue and Bile: Organ Functionality Monitoring During Ischemia and Reoxygenation,” Lasers Surg. Med. 46(5), 412–421 (2014).
[Crossref] [PubMed]

Saroufeem, R.

Savastru, D.

D. Savastru, E. W. Chang, S. Miclos, M. B. Pitman, A. Patel, and N. Iftimia, “Detection of breast surgical margins with optical coherence tomography imaging: a concept evaluation study,” J. Biomed. Opt. 19(5), 056001 (2014).
[Crossref] [PubMed]

Sigal-Zafrani, B.

O. Assayag, M. Antoine, B. Sigal-Zafrani, M. Riben, F. Harms, A. Burcheri, K. Grieve, E. Dalimier, B. Le Conte de Poly, and C. Boccara, “Large Field, High Resolution Full-Field Optical Coherence Tomography: A Pre-clinical Study of Human Breast Tissue and Cancer Assessment,” Technol. Cancer Res. Treat. 13(5), 455–468 (2014).
[PubMed]

Southard, J.

J. Bec, D. M. Ma, D. R. Yankelevich, J. Liu, W. T. Ferrier, J. Southard, and L. Marcu, “Multispectral fluorescence lifetime imaging system for intravascular diagnostics with ultrasound guidance: in vivo validation in swine arteries,” J. Biophotonics 7, 281–285 (2013).

Y. H. Sun, Y. Sun, D. Stephens, H. T. Xie, J. Phipps, R. Saroufeem, J. Southard, D. S. Elson, and L. Marcu, “Dynamic tissue analysis using time- and wavelength-resolved fluorescence spectroscopy for atherosclerosis diagnosis,” Opt. Express 19(5), 3890–3901 (2011).
[Crossref] [PubMed]

Stephens, D.

Stone, N.

C. Kallaway, L. M. Almond, H. Barr, J. Wood, J. Hutchings, C. Kendall, and N. Stone, “Advances in the clinical application of Raman spectroscopy for cancer diagnostics,” Photodiagn. Photodyn. Ther. 10(3), 207–219 (2013).
[Crossref] [PubMed]

Sun, Y.

D. R. Yankelevich, D. Ma, J. Liu, Y. Sun, Y. Sun, J. Bec, D. S. Elson, and L. Marcu, “Design and evaluation of a device for fast multispectral time-resolved fluorescence spectroscopy and imaging,” Rev. Sci. Instrum. 85(3), 034303 (2014).
[Crossref] [PubMed]

D. R. Yankelevich, D. Ma, J. Liu, Y. Sun, Y. Sun, J. Bec, D. S. Elson, and L. Marcu, “Design and evaluation of a device for fast multispectral time-resolved fluorescence spectroscopy and imaging,” Rev. Sci. Instrum. 85(3), 034303 (2014).
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H. T. Xie, J. Bec, J. Liu, Y. Sun, M. Lam, D. R. Yankelevich, and L. Marcu, “Multispectral scanning time-resolved fluorescence spectroscopy (TRFS) technique for intravascular diagnosis,” Biomed. Opt. Express 3(7), 1521–1533 (2012).
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J. Liu, Y. Sun, J. Y. Qi, and L. Marcu, “A novel method for fast and robust estimation of fluorescence decay dynamics using constrained least-squares deconvolution with Laguerre expansion,” Phys. Med. Biol. 57(4), 843–865 (2012).
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Y. H. Sun, Y. Sun, D. Stephens, H. T. Xie, J. Phipps, R. Saroufeem, J. Southard, D. S. Elson, and L. Marcu, “Dynamic tissue analysis using time- and wavelength-resolved fluorescence spectroscopy for atherosclerosis diagnosis,” Opt. Express 19(5), 3890–3901 (2011).
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[Crossref] [PubMed]

H. Fatakdawala, S. Poti, F. Zhou, Y. Sun, J. Bec, J. Liu, D. R. Yankelevich, S. P. Tinling, R. F. Gandour-Edwards, D. G. Farwell, and L. Marcu, “Multimodal in vivo imaging of oral cancer using fluorescence lifetime, photoacoustic and ultrasound techniques,” Biomed. Opt. Express 4(9), 1724–1741 (2013).
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J. Bec, D. M. Ma, D. R. Yankelevich, J. Liu, W. T. Ferrier, J. Southard, and L. Marcu, “Multispectral fluorescence lifetime imaging system for intravascular diagnostics with ultrasound guidance: in vivo validation in swine arteries,” J. Biophotonics 7, 281–285 (2013).

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Supplementary Material (2)

» Media 1: AVI (167911 KB)     
» Media 2: AVI (117321 KB)     

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Figures (8)

Fig. 1
Fig. 1 (a) Closed-loop control diagram of ms-TRFS signal amplitude. After signal digitization the processor reads out the data and calculates feedback HV value using the control algorithm which consists of two controllers. The internal model controller (IMC) was based on the current gain characteristics of the MCP-PMT and the proportional controller was based on empirical linear coefficients multiplied to the error ε. (b) Transient response of the high voltage (HV) power supply. Left: Step-wise HV change commands sent to the power supply. Right: The ms-TRFS signal amplitude of a fluorescent dye recorded after receiving the commands. 10 – 90% rise time and 90 – 10% fall time of the transients are shown next to the edges.
Fig. 2
Fig. 2 Spatial resolution computed as the FWHM obtained by scanning across a sub-resolution target (80 μm fluorescent wire) at various distances using a 400 µm core 0.22 NA silica fiber integrated into a hand held probe.
Fig. 3
Fig. 3 Experiment for evaluation of close-loop control performance. (a) Close-up of the line-scanning setup. Picture of the 5 blocks (silicone gel mixed with R6G) with variable heights and the tip of the fiber optic probe. (b) Signal amplitude variation during the line scan. For reference the 1 mm/s line scan with fixed HV (closed-loop control disabled) was recorded. (c) Fluorescence lifetimes from each line scan (for channel 3). (d) Boxplot of the all lifetime values (line scans at different speeds). Box edges correspond to the 25 – 75% quartile and the whiskers correspond to the width extending 1.5 of the box width from each side of the box.
Fig. 4
Fig. 4 (a) The single fluorescence decay computation time and (b) lifetime standard deviation (SD) were quantified with various signal amplitude and averaging factors using same number of photons detected (3.8 × 105 photons). (c) The single fluorescence decay computation time and lifetime standard deviation were quantified using different number of photons.
Fig. 5
Fig. 5 Real-time ms-TRFS line scanning measurement of fluorescence phantoms with fluorophore species and concentration changes. (a – b) Close-up of Phantom1 with three distinctive species of fluorophores (C1, C120 and 9CA) and Phantom 2 with three different fluorophore concentrations (200 µM, 20 µM, 2µM). (c – d) The number of fluorescence photons collected during the line scan quantified based on the fluorescence intensity. (e – f) The fluorescence lifetime profile of the line scans.
Fig. 6
Fig. 6 Needle fiber-optic probe biopsy of a brain shaped phantom embedded with two fluorescent agar layers. (a) Top: A picture of the needle fiber-optic probe advancing into the phantom; Bottom: Schematic of the layered phantom and biopsy setup. The needle fiber-optic probe was advanced by a motorized stage to penetrate through different layers of the phantom at 1 mm/s speed. The interfaces between null agar – C120 agar, C120 agar – C1 agar and C1 agar – null agar were located at approximately 14, 20 and 27 mm depth in the phantom. (b) Post-processed fluorescence lifetime profile during the biopsy. Red arrows show the interfaces between layers. (c) Screen shot of ms-TRFS software displaying the results in real-time. (See Media 1 for a video of the experiment.)
Fig. 7
Fig. 7 Identification of fluorescence marker by surface scanning of hand held probe in a brain shaped agar phantom. An excision cavity were created and filled with agar mixed with fluorescent dye (C120). A fluorescent silicone gel block (C1) was embedded in the cavity as a distinct fluorescence marker. (a) A picture of raster scanning using the hand held fiber-optic probe on the surface of the cavity. (b) A fluorescent intensity image of the cavity taken under wide-field UV illumination. The location of the embedded marker is shown by the red arrow. A close-up of the fluorescence marker is shown at top right. (c) The number of fluorescence photons and fluorescence lifetime profile during the hand held scanning. The red arrows show the identification of the marker. (d) A screen shot of the real-time display during the test. (See Media 2 for a complete video of the experiment)
Fig. 8
Fig. 8 Characterization of biological tissue by real-time ms-TRFS. (a) A picture of the stereotactic frame setup mounted on the sacrificed rat. (b) A close-up of the expose brain cortex of the rat with different tissue types denoted along the line scan (red arrow). (1) the muscle tissue covering the skull; (2) exposed bone tissue after craniotomy surgery; (3) exposed brain matter after removal of dura matter; (4) Blood vessel in superior sagittal sinus; (c) A screen shot of real-time display during the line scan. (d) Top panel: number of collected fluorescence photons along the line scan; bottom panel: fluorescence lifetimes along the line scan. The approximate location along the line scan was estimated based on the scanned length and total scanning time. The differentiated tissue types were denoted according to (b).

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