Abstract

Most pathological conditions elicit changes in the tissue optical response that may be interrogated by one or more optical imaging modalities. Any single modality typically only furnishes an incomplete picture of the tissue optical response, hence an approach that integrates complementary optical imaging modalities is needed for a more comprehensive non-destructive and minimally-invasive tissue characterization. We have developed a dual-modality system, incorporating optical coherence tomography (OCT) and fluorescence lifetime imaging microscopy (FLIM), that is capable of simultaneously characterizing the 3-D tissue morphology and its biochemical composition. The Fourier domain OCT subsystem, at an 830 nm center wavelength, provided high-resolution morphological volumetric tissue images with an axial and lateral resolution of 7.3 and 13.4 µm, respectively. The multispectral FLIM subsystem, based on a direct pulse-recording approach (upon 355 nm laser excitation), provided two-dimensional superficial maps of the tissue autofluorescence intensity and lifetime at three customizable emission bands with 100 µm lateral resolution. Both subsystems share the same excitation/illumination optical path and are simultaneously raster scanned on the sample to generate coregistered OCT volumes and FLIM images. The developed OCT/FLIM system was capable of a maximum A-line rate of 59 KHz for OCT and a pixel rate of up to 30 KHz for FLIM. The dual-modality system was validated with standard fluorophore solutions and subsequently applied to the characterization of two biological tissue types: postmortem human coronary atherosclerotic plaques, and in vivo normal and cancerous hamster cheek pouch epithelial tissue.

© 2010 OSA

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    [CrossRef]
  3. J. K. Barton, F. Guzman, and A. Tumlinson, “Dual modality instrument for simultaneous optical coherence tomography imaging and fluorescence spectroscopy,” J. Biomed. Opt. 9(3), 618–623 (2004).
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  4. K. König, M. Speicher, R. Bückle, J. Reckfort, G. McKenzie, J. Welzel, M. J. Koehler, P. Elsner, and M. Kaatz, “Clinical optical coherence tomography combined with multiphoton tomography of patients with skin diseases,” J Biophotonics 2(6-7), 389–397 (2009).
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    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
  23. L. Marcu, J. A. Jo, Q. Fang, T. Papaioannou, T. Reil, J. H. Qiao, J. D. Baker, J. A. Freischlag, and M. C. Fishbein, “Detection of rupture-prone atherosclerotic plaques by time-resolved laser-induced fluorescence spectroscopy,” Atherosclerosis 204(1), 156–164 (2009).
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  24. N. G. Ghoshal and H. S. Bal, “Histomorphology of the hamster cheek pouch,” Lab. Anim. 24(3), 228–233 (1990).
    [CrossRef] [PubMed]
  25. D. G. Farwell, J. D. Meier, J. Park, Y. Sun, H. Coffman, B. Poirier, J. Phipps, S. Tinling, D. J. Enepekides, and L. Marcu, “Time-resolved fluorescence spectroscopy as a diagnostic technique of oral carcinoma: Validation in the hamster buccal pouch model,” Arch. Otolaryngol. Head Neck Surg. 136(2), 126–133 (2010).
    [PubMed]

2010 (2)

P. Thomas, P. Pande, F. Clubb, J. Adame, and J. A. Jo, “Biochemical imaging of human atherosclerotic plaques with fluorescence lifetime angioscopy,” Photochem. Photobiol. 86(3), 727–731 (2010).
[CrossRef] [PubMed]

D. G. Farwell, J. D. Meier, J. Park, Y. Sun, H. Coffman, B. Poirier, J. Phipps, S. Tinling, D. J. Enepekides, and L. Marcu, “Time-resolved fluorescence spectroscopy as a diagnostic technique of oral carcinoma: Validation in the hamster buccal pouch model,” Arch. Otolaryngol. Head Neck Surg. 136(2), 126–133 (2010).
[PubMed]

2009 (5)

J. L. Brandon, C. J. Conti, L. S. Goldstein, J. DiGiovanni, and I. B. Gimenez-Conti, “Carcinogenic effects of MGP-7 and B[a]P on the hamster cheek pouch,” Toxicol. Pathol. 37(6), 733–740 (2009).
[CrossRef] [PubMed]

L. Marcu, J. A. Jo, Q. Fang, T. Papaioannou, T. Reil, J. H. Qiao, J. D. Baker, J. A. Freischlag, and M. C. Fishbein, “Detection of rupture-prone atherosclerotic plaques by time-resolved laser-induced fluorescence spectroscopy,” Atherosclerosis 204(1), 156–164 (2009).
[CrossRef] [PubMed]

C. Balas, “Review of biomedical optical imaging-a powerful, non-invasive, non-ionizing technology for improving in vivo diagnosis,” Meas. Sci. Technol. 20(10), 104020 (2009).
[CrossRef]

K. König, M. Speicher, R. Bückle, J. Reckfort, G. McKenzie, J. Welzel, M. J. Koehler, P. Elsner, and M. Kaatz, “Clinical optical coherence tomography combined with multiphoton tomography of patients with skin diseases,” J Biophotonics 2(6-7), 389–397 (2009).
[CrossRef] [PubMed]

D. N. Stephens, J. Park, Y. Sun, T. Papaioannou, and L. Marcu, “Intraluminal fluorescence spectroscopy catheter with ultrasound guidance,” J. Biomed. Opt. 14(3), 030505 (2009).
[CrossRef] [PubMed]

2008 (2)

2006 (2)

L. P. Hariri, A. R. Tumlinson, D. G. Besselsen, U. Utzinger, E. W. Gerner, and J. K. Barton, “Endoscopic optical coherence tomography and laser-induced fluorescence spectroscopy in a murine colon cancer model,” Lasers Surg. Med. 38(4), 305–313 (2006).
[CrossRef] [PubMed]

C. Vinegoni, T. Ralston, W. Tan, W. Luo, D. L. Marks, and S. A. Boppart, “Integrated structural and functional optical imaging combining spectral-domain optical coherence and multiphoton microscopy,” Appl. Phys. Lett. 88(5), 053901 (2006).
[CrossRef]

2005 (2)

Z. G. Wang, D. B. Durand, M. Schoenberg, and Y. T. Pan, “Fluorescence guided optical coherence tomography for the diagnosis of early bladder cancer in a rat model,” J. Urol. 174(6), 2376–2381 (2005).
[CrossRef] [PubMed]

D. K. Bird, L. Yan, K. M. Vrotsos, K. W. Eliceiri, E. M. Vaughan, P. J. Keely, J. G. White, and N. Ramanujam, “Metabolic mapping of MCF10A human breast cells via multiphoton fluorescence lifetime imaging of the coenzyme NADH,” Cancer Res. 65(19), 8766–8773 (2005).
[CrossRef] [PubMed]

2004 (4)

J. A. Jo, Q. Y. Fang, T. Papaioannou, and L. Marcu, “Fast model-free deconvolution of fluorescence decay for analysis of biological systems,” J. Biomed. Opt. 9(4), 743–752 (2004).
[CrossRef] [PubMed]

Q. Y. 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]

J. K. Barton, F. Guzman, and A. Tumlinson, “Dual modality instrument for simultaneous optical coherence tomography imaging and fluorescence spectroscopy,” J. Biomed. Opt. 9(3), 618–623 (2004).
[CrossRef] [PubMed]

A. R. Tumlinson, L. P. Hariri, U. Utzinger, and J. K. Barton, “Miniature endoscope for simultaneous optical coherence tomography and laser-induced fluorescence measurement,” Appl. Opt. 43(1), 113–121 (2004).
[CrossRef] [PubMed]

2003 (1)

P. J. Caspers, G. W. Lucassen, and G. J. Puppels, “Combined in vivo confocal Raman spectroscopy and confocal microscopy of human skin,” Biophys. J. 85(1), 572–580 (2003).
[CrossRef] [PubMed]

2002 (1)

K. Arakawa, K. Isoda, T. Ito, K. Nakajima, T. Shibuya, and F. Ohsuzu, “Fluorescence analysis of biochemical constituents identifies atherosclerotic plaque with a thin fibrous cap,” Arterioscler. Thromb. Vasc. Biol. 22(6), 1002–1007 (2002).
[CrossRef] [PubMed]

1992 (2)

S. T. Flock, S. L. Jacques, B. C. Wilson, W. M. Star, and M. J. C. van Gemert, “Optical properties of Intralipid: a phantom medium for light propagation studies,” Lasers Surg. Med. 12(5), 510–519 (1992).
[CrossRef] [PubMed]

J. R. Lakowicz, H. Szmacinski, K. Nowaczyk, and M. L. Johnson, “Fluorescence lifetime imaging of free and protein-bound NADH,” Proc. Natl. Acad. Sci. U.S.A. 89(4), 1271–1275 (1992).
[CrossRef] [PubMed]

1990 (1)

N. G. Ghoshal and H. S. Bal, “Histomorphology of the hamster cheek pouch,” Lab. Anim. 24(3), 228–233 (1990).
[CrossRef] [PubMed]

Adame, J.

P. Thomas, P. Pande, F. Clubb, J. Adame, and J. A. Jo, “Biochemical imaging of human atherosclerotic plaques with fluorescence lifetime angioscopy,” Photochem. Photobiol. 86(3), 727–731 (2010).
[CrossRef] [PubMed]

Applegate, B. E.

S. Shrestha, B. E. Applegate, J. Park, X. Xiao, P. Pande, and J. A. Jo, “A Novel High-Speed Multispectral Fluorescence Lifetime Imaging Implementation for in vivo Applications,” Opt. Lett. in press.

Arakawa, K.

K. Arakawa, K. Isoda, T. Ito, K. Nakajima, T. Shibuya, and F. Ohsuzu, “Fluorescence analysis of biochemical constituents identifies atherosclerotic plaque with a thin fibrous cap,” Arterioscler. Thromb. Vasc. Biol. 22(6), 1002–1007 (2002).
[CrossRef] [PubMed]

Baker, J. D.

L. Marcu, J. A. Jo, Q. Fang, T. Papaioannou, T. Reil, J. H. Qiao, J. D. Baker, J. A. Freischlag, and M. C. Fishbein, “Detection of rupture-prone atherosclerotic plaques by time-resolved laser-induced fluorescence spectroscopy,” Atherosclerosis 204(1), 156–164 (2009).
[CrossRef] [PubMed]

Bal, H. S.

N. G. Ghoshal and H. S. Bal, “Histomorphology of the hamster cheek pouch,” Lab. Anim. 24(3), 228–233 (1990).
[CrossRef] [PubMed]

Balas, C.

C. Balas, “Review of biomedical optical imaging-a powerful, non-invasive, non-ionizing technology for improving in vivo diagnosis,” Meas. Sci. Technol. 20(10), 104020 (2009).
[CrossRef]

Barton, J. K.

L. P. Hariri, A. R. Tumlinson, D. G. Besselsen, U. Utzinger, E. W. Gerner, and J. K. Barton, “Endoscopic optical coherence tomography and laser-induced fluorescence spectroscopy in a murine colon cancer model,” Lasers Surg. Med. 38(4), 305–313 (2006).
[CrossRef] [PubMed]

A. R. Tumlinson, L. P. Hariri, U. Utzinger, and J. K. Barton, “Miniature endoscope for simultaneous optical coherence tomography and laser-induced fluorescence measurement,” Appl. Opt. 43(1), 113–121 (2004).
[CrossRef] [PubMed]

J. K. Barton, F. Guzman, and A. Tumlinson, “Dual modality instrument for simultaneous optical coherence tomography imaging and fluorescence spectroscopy,” J. Biomed. Opt. 9(3), 618–623 (2004).
[CrossRef] [PubMed]

Besselsen, D. G.

L. P. Hariri, A. R. Tumlinson, D. G. Besselsen, U. Utzinger, E. W. Gerner, and J. K. Barton, “Endoscopic optical coherence tomography and laser-induced fluorescence spectroscopy in a murine colon cancer model,” Lasers Surg. Med. 38(4), 305–313 (2006).
[CrossRef] [PubMed]

Bird, D. K.

D. K. Bird, L. Yan, K. M. Vrotsos, K. W. Eliceiri, E. M. Vaughan, P. J. Keely, J. G. White, and N. Ramanujam, “Metabolic mapping of MCF10A human breast cells via multiphoton fluorescence lifetime imaging of the coenzyme NADH,” Cancer Res. 65(19), 8766–8773 (2005).
[CrossRef] [PubMed]

Boppart, S. A.

C. Vinegoni, T. Ralston, W. Tan, W. Luo, D. L. Marks, and S. A. Boppart, “Integrated structural and functional optical imaging combining spectral-domain optical coherence and multiphoton microscopy,” Appl. Phys. Lett. 88(5), 053901 (2006).
[CrossRef]

Bosschaart, N.

Brandon, J. L.

J. L. Brandon, C. J. Conti, L. S. Goldstein, J. DiGiovanni, and I. B. Gimenez-Conti, “Carcinogenic effects of MGP-7 and B[a]P on the hamster cheek pouch,” Toxicol. Pathol. 37(6), 733–740 (2009).
[CrossRef] [PubMed]

Bückle, R.

K. König, M. Speicher, R. Bückle, J. Reckfort, G. McKenzie, J. Welzel, M. J. Koehler, P. Elsner, and M. Kaatz, “Clinical optical coherence tomography combined with multiphoton tomography of patients with skin diseases,” J Biophotonics 2(6-7), 389–397 (2009).
[CrossRef] [PubMed]

Caspers, P. J.

P. J. Caspers, G. W. Lucassen, and G. J. Puppels, “Combined in vivo confocal Raman spectroscopy and confocal microscopy of human skin,” Biophys. J. 85(1), 572–580 (2003).
[CrossRef] [PubMed]

Clubb, F.

P. Thomas, P. Pande, F. Clubb, J. Adame, and J. A. Jo, “Biochemical imaging of human atherosclerotic plaques with fluorescence lifetime angioscopy,” Photochem. Photobiol. 86(3), 727–731 (2010).
[CrossRef] [PubMed]

Coffman, H.

D. G. Farwell, J. D. Meier, J. Park, Y. Sun, H. Coffman, B. Poirier, J. Phipps, S. Tinling, D. J. Enepekides, and L. Marcu, “Time-resolved fluorescence spectroscopy as a diagnostic technique of oral carcinoma: Validation in the hamster buccal pouch model,” Arch. Otolaryngol. Head Neck Surg. 136(2), 126–133 (2010).
[PubMed]

Conti, C. J.

J. L. Brandon, C. J. Conti, L. S. Goldstein, J. DiGiovanni, and I. B. Gimenez-Conti, “Carcinogenic effects of MGP-7 and B[a]P on the hamster cheek pouch,” Toxicol. Pathol. 37(6), 733–740 (2009).
[CrossRef] [PubMed]

DiGiovanni, J.

J. L. Brandon, C. J. Conti, L. S. Goldstein, J. DiGiovanni, and I. B. Gimenez-Conti, “Carcinogenic effects of MGP-7 and B[a]P on the hamster cheek pouch,” Toxicol. Pathol. 37(6), 733–740 (2009).
[CrossRef] [PubMed]

Durand, D. B.

Z. G. Wang, D. B. Durand, M. Schoenberg, and Y. T. Pan, “Fluorescence guided optical coherence tomography for the diagnosis of early bladder cancer in a rat model,” J. Urol. 174(6), 2376–2381 (2005).
[CrossRef] [PubMed]

Eliceiri, K. W.

D. K. Bird, L. Yan, K. M. Vrotsos, K. W. Eliceiri, E. M. Vaughan, P. J. Keely, J. G. White, and N. Ramanujam, “Metabolic mapping of MCF10A human breast cells via multiphoton fluorescence lifetime imaging of the coenzyme NADH,” Cancer Res. 65(19), 8766–8773 (2005).
[CrossRef] [PubMed]

Elsner, P.

K. König, M. Speicher, R. Bückle, J. Reckfort, G. McKenzie, J. Welzel, M. J. Koehler, P. Elsner, and M. Kaatz, “Clinical optical coherence tomography combined with multiphoton tomography of patients with skin diseases,” J Biophotonics 2(6-7), 389–397 (2009).
[CrossRef] [PubMed]

Elson, D. S.

Enepekides, D. J.

D. G. Farwell, J. D. Meier, J. Park, Y. Sun, H. Coffman, B. Poirier, J. Phipps, S. Tinling, D. J. Enepekides, and L. Marcu, “Time-resolved fluorescence spectroscopy as a diagnostic technique of oral carcinoma: Validation in the hamster buccal pouch model,” Arch. Otolaryngol. Head Neck Surg. 136(2), 126–133 (2010).
[PubMed]

Fang, Q.

L. Marcu, J. A. Jo, Q. Fang, T. Papaioannou, T. Reil, J. H. Qiao, J. D. Baker, J. A. Freischlag, and M. C. Fishbein, “Detection of rupture-prone atherosclerotic plaques by time-resolved laser-induced fluorescence spectroscopy,” Atherosclerosis 204(1), 156–164 (2009).
[CrossRef] [PubMed]

Fang, Q. Y.

J. A. Jo, Q. Y. Fang, T. Papaioannou, and L. Marcu, “Fast model-free deconvolution of fluorescence decay for analysis of biological systems,” J. Biomed. Opt. 9(4), 743–752 (2004).
[CrossRef] [PubMed]

Q. Y. 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]

Farwell, D. G.

D. G. Farwell, J. D. Meier, J. Park, Y. Sun, H. Coffman, B. Poirier, J. Phipps, S. Tinling, D. J. Enepekides, and L. Marcu, “Time-resolved fluorescence spectroscopy as a diagnostic technique of oral carcinoma: Validation in the hamster buccal pouch model,” Arch. Otolaryngol. Head Neck Surg. 136(2), 126–133 (2010).
[PubMed]

Fishbein, M. C.

L. Marcu, J. A. Jo, Q. Fang, T. Papaioannou, T. Reil, J. H. Qiao, J. D. Baker, J. A. Freischlag, and M. C. Fishbein, “Detection of rupture-prone atherosclerotic plaques by time-resolved laser-induced fluorescence spectroscopy,” Atherosclerosis 204(1), 156–164 (2009).
[CrossRef] [PubMed]

Flock, S. T.

S. T. Flock, S. L. Jacques, B. C. Wilson, W. M. Star, and M. J. C. van Gemert, “Optical properties of Intralipid: a phantom medium for light propagation studies,” Lasers Surg. Med. 12(5), 510–519 (1992).
[CrossRef] [PubMed]

Freischlag, J. A.

L. Marcu, J. A. Jo, Q. Fang, T. Papaioannou, T. Reil, J. H. Qiao, J. D. Baker, J. A. Freischlag, and M. C. Fishbein, “Detection of rupture-prone atherosclerotic plaques by time-resolved laser-induced fluorescence spectroscopy,” Atherosclerosis 204(1), 156–164 (2009).
[CrossRef] [PubMed]

Gerner, E. W.

L. P. Hariri, A. R. Tumlinson, D. G. Besselsen, U. Utzinger, E. W. Gerner, and J. K. Barton, “Endoscopic optical coherence tomography and laser-induced fluorescence spectroscopy in a murine colon cancer model,” Lasers Surg. Med. 38(4), 305–313 (2006).
[CrossRef] [PubMed]

Ghoshal, N. G.

N. G. Ghoshal and H. S. Bal, “Histomorphology of the hamster cheek pouch,” Lab. Anim. 24(3), 228–233 (1990).
[CrossRef] [PubMed]

Gimenez-Conti, I. B.

J. L. Brandon, C. J. Conti, L. S. Goldstein, J. DiGiovanni, and I. B. Gimenez-Conti, “Carcinogenic effects of MGP-7 and B[a]P on the hamster cheek pouch,” Toxicol. Pathol. 37(6), 733–740 (2009).
[CrossRef] [PubMed]

Goldstein, L. S.

J. L. Brandon, C. J. Conti, L. S. Goldstein, J. DiGiovanni, and I. B. Gimenez-Conti, “Carcinogenic effects of MGP-7 and B[a]P on the hamster cheek pouch,” Toxicol. Pathol. 37(6), 733–740 (2009).
[CrossRef] [PubMed]

Guzman, F.

J. K. Barton, F. Guzman, and A. Tumlinson, “Dual modality instrument for simultaneous optical coherence tomography imaging and fluorescence spectroscopy,” J. Biomed. Opt. 9(3), 618–623 (2004).
[CrossRef] [PubMed]

Hariri, L. P.

L. P. Hariri, A. R. Tumlinson, D. G. Besselsen, U. Utzinger, E. W. Gerner, and J. K. Barton, “Endoscopic optical coherence tomography and laser-induced fluorescence spectroscopy in a murine colon cancer model,” Lasers Surg. Med. 38(4), 305–313 (2006).
[CrossRef] [PubMed]

A. R. Tumlinson, L. P. Hariri, U. Utzinger, and J. K. Barton, “Miniature endoscope for simultaneous optical coherence tomography and laser-induced fluorescence measurement,” Appl. Opt. 43(1), 113–121 (2004).
[CrossRef] [PubMed]

Hollars, C. W.

Isoda, K.

K. Arakawa, K. Isoda, T. Ito, K. Nakajima, T. Shibuya, and F. Ohsuzu, “Fluorescence analysis of biochemical constituents identifies atherosclerotic plaque with a thin fibrous cap,” Arterioscler. Thromb. Vasc. Biol. 22(6), 1002–1007 (2002).
[CrossRef] [PubMed]

Ito, T.

K. Arakawa, K. Isoda, T. Ito, K. Nakajima, T. Shibuya, and F. Ohsuzu, “Fluorescence analysis of biochemical constituents identifies atherosclerotic plaque with a thin fibrous cap,” Arterioscler. Thromb. Vasc. Biol. 22(6), 1002–1007 (2002).
[CrossRef] [PubMed]

Jacques, S. L.

S. T. Flock, S. L. Jacques, B. C. Wilson, W. M. Star, and M. J. C. van Gemert, “Optical properties of Intralipid: a phantom medium for light propagation studies,” Lasers Surg. Med. 12(5), 510–519 (1992).
[CrossRef] [PubMed]

Jo, J. A.

P. Thomas, P. Pande, F. Clubb, J. Adame, and J. A. Jo, “Biochemical imaging of human atherosclerotic plaques with fluorescence lifetime angioscopy,” Photochem. Photobiol. 86(3), 727–731 (2010).
[CrossRef] [PubMed]

L. Marcu, J. A. Jo, Q. Fang, T. Papaioannou, T. Reil, J. H. Qiao, J. D. Baker, J. A. Freischlag, and M. C. Fishbein, “Detection of rupture-prone atherosclerotic plaques by time-resolved laser-induced fluorescence spectroscopy,” Atherosclerosis 204(1), 156–164 (2009).
[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]

J. A. Jo, Q. Y. Fang, T. Papaioannou, and L. Marcu, “Fast model-free deconvolution of fluorescence decay for analysis of biological systems,” J. Biomed. Opt. 9(4), 743–752 (2004).
[CrossRef] [PubMed]

Q. Y. 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]

S. Shrestha, B. E. Applegate, J. Park, X. Xiao, P. Pande, and J. A. Jo, “A Novel High-Speed Multispectral Fluorescence Lifetime Imaging Implementation for in vivo Applications,” Opt. Lett. in press.

Johnson, M. L.

J. R. Lakowicz, H. Szmacinski, K. Nowaczyk, and M. L. Johnson, “Fluorescence lifetime imaging of free and protein-bound NADH,” Proc. Natl. Acad. Sci. U.S.A. 89(4), 1271–1275 (1992).
[CrossRef] [PubMed]

Kaatz, M.

K. König, M. Speicher, R. Bückle, J. Reckfort, G. McKenzie, J. Welzel, M. J. Koehler, P. Elsner, and M. Kaatz, “Clinical optical coherence tomography combined with multiphoton tomography of patients with skin diseases,” J Biophotonics 2(6-7), 389–397 (2009).
[CrossRef] [PubMed]

Keely, P. J.

D. K. Bird, L. Yan, K. M. Vrotsos, K. W. Eliceiri, E. M. Vaughan, P. J. Keely, J. G. White, and N. Ramanujam, “Metabolic mapping of MCF10A human breast cells via multiphoton fluorescence lifetime imaging of the coenzyme NADH,” Cancer Res. 65(19), 8766–8773 (2005).
[CrossRef] [PubMed]

Keller, M. D.

Koehler, M. J.

K. König, M. Speicher, R. Bückle, J. Reckfort, G. McKenzie, J. Welzel, M. J. Koehler, P. Elsner, and M. Kaatz, “Clinical optical coherence tomography combined with multiphoton tomography of patients with skin diseases,” J Biophotonics 2(6-7), 389–397 (2009).
[CrossRef] [PubMed]

König, K.

K. König, M. Speicher, R. Bückle, J. Reckfort, G. McKenzie, J. Welzel, M. J. Koehler, P. Elsner, and M. Kaatz, “Clinical optical coherence tomography combined with multiphoton tomography of patients with skin diseases,” J Biophotonics 2(6-7), 389–397 (2009).
[CrossRef] [PubMed]

Lakowicz, J. R.

J. R. Lakowicz, H. Szmacinski, K. Nowaczyk, and M. L. Johnson, “Fluorescence lifetime imaging of free and protein-bound NADH,” Proc. Natl. Acad. Sci. U.S.A. 89(4), 1271–1275 (1992).
[CrossRef] [PubMed]

Liu, R.

Lucassen, G. W.

P. J. Caspers, G. W. Lucassen, and G. J. Puppels, “Combined in vivo confocal Raman spectroscopy and confocal microscopy of human skin,” Biophys. J. 85(1), 572–580 (2003).
[CrossRef] [PubMed]

Luo, W.

C. Vinegoni, T. Ralston, W. Tan, W. Luo, D. L. Marks, and S. A. Boppart, “Integrated structural and functional optical imaging combining spectral-domain optical coherence and multiphoton microscopy,” Appl. Phys. Lett. 88(5), 053901 (2006).
[CrossRef]

Mahadevan-Jansen, A.

Marcu, L.

D. G. Farwell, J. D. Meier, J. Park, Y. Sun, H. Coffman, B. Poirier, J. Phipps, S. Tinling, D. J. Enepekides, and L. Marcu, “Time-resolved fluorescence spectroscopy as a diagnostic technique of oral carcinoma: Validation in the hamster buccal pouch model,” Arch. Otolaryngol. Head Neck Surg. 136(2), 126–133 (2010).
[PubMed]

L. Marcu, J. A. Jo, Q. Fang, T. Papaioannou, T. Reil, J. H. Qiao, J. D. Baker, J. A. Freischlag, and M. C. Fishbein, “Detection of rupture-prone atherosclerotic plaques by time-resolved laser-induced fluorescence spectroscopy,” Atherosclerosis 204(1), 156–164 (2009).
[CrossRef] [PubMed]

D. N. Stephens, J. Park, Y. Sun, T. Papaioannou, and L. Marcu, “Intraluminal fluorescence spectroscopy catheter with ultrasound guidance,” J. Biomed. Opt. 14(3), 030505 (2009).
[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]

Q. Y. 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]

J. A. Jo, Q. Y. Fang, T. Papaioannou, and L. Marcu, “Fast model-free deconvolution of fluorescence decay for analysis of biological systems,” J. Biomed. Opt. 9(4), 743–752 (2004).
[CrossRef] [PubMed]

Marks, D. L.

C. Vinegoni, T. Ralston, W. Tan, W. Luo, D. L. Marks, and S. A. Boppart, “Integrated structural and functional optical imaging combining spectral-domain optical coherence and multiphoton microscopy,” Appl. Phys. Lett. 88(5), 053901 (2006).
[CrossRef]

McKenzie, G.

K. König, M. Speicher, R. Bückle, J. Reckfort, G. McKenzie, J. Welzel, M. J. Koehler, P. Elsner, and M. Kaatz, “Clinical optical coherence tomography combined with multiphoton tomography of patients with skin diseases,” J Biophotonics 2(6-7), 389–397 (2009).
[CrossRef] [PubMed]

Meier, J. D.

D. G. Farwell, J. D. Meier, J. Park, Y. Sun, H. Coffman, B. Poirier, J. Phipps, S. Tinling, D. J. Enepekides, and L. Marcu, “Time-resolved fluorescence spectroscopy as a diagnostic technique of oral carcinoma: Validation in the hamster buccal pouch model,” Arch. Otolaryngol. Head Neck Surg. 136(2), 126–133 (2010).
[PubMed]

Nakajima, K.

K. Arakawa, K. Isoda, T. Ito, K. Nakajima, T. Shibuya, and F. Ohsuzu, “Fluorescence analysis of biochemical constituents identifies atherosclerotic plaque with a thin fibrous cap,” Arterioscler. Thromb. Vasc. Biol. 22(6), 1002–1007 (2002).
[CrossRef] [PubMed]

Nowaczyk, K.

J. R. Lakowicz, H. Szmacinski, K. Nowaczyk, and M. L. Johnson, “Fluorescence lifetime imaging of free and protein-bound NADH,” Proc. Natl. Acad. Sci. U.S.A. 89(4), 1271–1275 (1992).
[CrossRef] [PubMed]

Ohsuzu, F.

K. Arakawa, K. Isoda, T. Ito, K. Nakajima, T. Shibuya, and F. Ohsuzu, “Fluorescence analysis of biochemical constituents identifies atherosclerotic plaque with a thin fibrous cap,” Arterioscler. Thromb. Vasc. Biol. 22(6), 1002–1007 (2002).
[CrossRef] [PubMed]

Pan, Y. T.

Z. G. Wang, D. B. Durand, M. Schoenberg, and Y. T. Pan, “Fluorescence guided optical coherence tomography for the diagnosis of early bladder cancer in a rat model,” J. Urol. 174(6), 2376–2381 (2005).
[CrossRef] [PubMed]

Pande, P.

P. Thomas, P. Pande, F. Clubb, J. Adame, and J. A. Jo, “Biochemical imaging of human atherosclerotic plaques with fluorescence lifetime angioscopy,” Photochem. Photobiol. 86(3), 727–731 (2010).
[CrossRef] [PubMed]

S. Shrestha, B. E. Applegate, J. Park, X. Xiao, P. Pande, and J. A. Jo, “A Novel High-Speed Multispectral Fluorescence Lifetime Imaging Implementation for in vivo Applications,” Opt. Lett. in press.

Papaioannou, T.

L. Marcu, J. A. Jo, Q. Fang, T. Papaioannou, T. Reil, J. H. Qiao, J. D. Baker, J. A. Freischlag, and M. C. Fishbein, “Detection of rupture-prone atherosclerotic plaques by time-resolved laser-induced fluorescence spectroscopy,” Atherosclerosis 204(1), 156–164 (2009).
[CrossRef] [PubMed]

D. N. Stephens, J. Park, Y. Sun, T. Papaioannou, and L. Marcu, “Intraluminal fluorescence spectroscopy catheter with ultrasound guidance,” J. Biomed. Opt. 14(3), 030505 (2009).
[CrossRef] [PubMed]

Q. Y. 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]

J. A. Jo, Q. Y. Fang, T. Papaioannou, and L. Marcu, “Fast model-free deconvolution of fluorescence decay for analysis of biological systems,” J. Biomed. Opt. 9(4), 743–752 (2004).
[CrossRef] [PubMed]

Park, J.

D. G. Farwell, J. D. Meier, J. Park, Y. Sun, H. Coffman, B. Poirier, J. Phipps, S. Tinling, D. J. Enepekides, and L. Marcu, “Time-resolved fluorescence spectroscopy as a diagnostic technique of oral carcinoma: Validation in the hamster buccal pouch model,” Arch. Otolaryngol. Head Neck Surg. 136(2), 126–133 (2010).
[PubMed]

D. N. Stephens, J. Park, Y. Sun, T. Papaioannou, and L. Marcu, “Intraluminal fluorescence spectroscopy catheter with ultrasound guidance,” J. Biomed. Opt. 14(3), 030505 (2009).
[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]

S. Shrestha, B. E. Applegate, J. Park, X. Xiao, P. Pande, and J. A. Jo, “A Novel High-Speed Multispectral Fluorescence Lifetime Imaging Implementation for in vivo Applications,” Opt. Lett. in press.

Patil, C. A.

Phipps, J.

D. G. Farwell, J. D. Meier, J. Park, Y. Sun, H. Coffman, B. Poirier, J. Phipps, S. Tinling, D. J. Enepekides, and L. Marcu, “Time-resolved fluorescence spectroscopy as a diagnostic technique of oral carcinoma: Validation in the hamster buccal pouch model,” Arch. Otolaryngol. Head Neck Surg. 136(2), 126–133 (2010).
[PubMed]

Poirier, B.

D. G. Farwell, J. D. Meier, J. Park, Y. Sun, H. Coffman, B. Poirier, J. Phipps, S. Tinling, D. J. Enepekides, and L. Marcu, “Time-resolved fluorescence spectroscopy as a diagnostic technique of oral carcinoma: Validation in the hamster buccal pouch model,” Arch. Otolaryngol. Head Neck Surg. 136(2), 126–133 (2010).
[PubMed]

Puppels, G. J.

P. J. Caspers, G. W. Lucassen, and G. J. Puppels, “Combined in vivo confocal Raman spectroscopy and confocal microscopy of human skin,” Biophys. J. 85(1), 572–580 (2003).
[CrossRef] [PubMed]

Qiao, J. H.

L. Marcu, J. A. Jo, Q. Fang, T. Papaioannou, T. Reil, J. H. Qiao, J. D. Baker, J. A. Freischlag, and M. C. Fishbein, “Detection of rupture-prone atherosclerotic plaques by time-resolved laser-induced fluorescence spectroscopy,” Atherosclerosis 204(1), 156–164 (2009).
[CrossRef] [PubMed]

Ralston, T.

C. Vinegoni, T. Ralston, W. Tan, W. Luo, D. L. Marks, and S. A. Boppart, “Integrated structural and functional optical imaging combining spectral-domain optical coherence and multiphoton microscopy,” Appl. Phys. Lett. 88(5), 053901 (2006).
[CrossRef]

Ramanujam, N.

D. K. Bird, L. Yan, K. M. Vrotsos, K. W. Eliceiri, E. M. Vaughan, P. J. Keely, J. G. White, and N. Ramanujam, “Metabolic mapping of MCF10A human breast cells via multiphoton fluorescence lifetime imaging of the coenzyme NADH,” Cancer Res. 65(19), 8766–8773 (2005).
[CrossRef] [PubMed]

Reckfort, J.

K. König, M. Speicher, R. Bückle, J. Reckfort, G. McKenzie, J. Welzel, M. J. Koehler, P. Elsner, and M. Kaatz, “Clinical optical coherence tomography combined with multiphoton tomography of patients with skin diseases,” J Biophotonics 2(6-7), 389–397 (2009).
[CrossRef] [PubMed]

Reil, T.

L. Marcu, J. A. Jo, Q. Fang, T. Papaioannou, T. Reil, J. H. Qiao, J. D. Baker, J. A. Freischlag, and M. C. Fishbein, “Detection of rupture-prone atherosclerotic plaques by time-resolved laser-induced fluorescence spectroscopy,” Atherosclerosis 204(1), 156–164 (2009).
[CrossRef] [PubMed]

Schoenberg, M.

Z. G. Wang, D. B. Durand, M. Schoenberg, and Y. T. Pan, “Fluorescence guided optical coherence tomography for the diagnosis of early bladder cancer in a rat model,” J. Urol. 174(6), 2376–2381 (2005).
[CrossRef] [PubMed]

Shastry, K.

Q. Y. 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]

Shibuya, T.

K. Arakawa, K. Isoda, T. Ito, K. Nakajima, T. Shibuya, and F. Ohsuzu, “Fluorescence analysis of biochemical constituents identifies atherosclerotic plaque with a thin fibrous cap,” Arterioscler. Thromb. Vasc. Biol. 22(6), 1002–1007 (2002).
[CrossRef] [PubMed]

Shrestha, S.

S. Shrestha, B. E. Applegate, J. Park, X. Xiao, P. Pande, and J. A. Jo, “A Novel High-Speed Multispectral Fluorescence Lifetime Imaging Implementation for in vivo Applications,” Opt. Lett. in press.

Speicher, M.

K. König, M. Speicher, R. Bückle, J. Reckfort, G. McKenzie, J. Welzel, M. J. Koehler, P. Elsner, and M. Kaatz, “Clinical optical coherence tomography combined with multiphoton tomography of patients with skin diseases,” J Biophotonics 2(6-7), 389–397 (2009).
[CrossRef] [PubMed]

Star, W. M.

S. T. Flock, S. L. Jacques, B. C. Wilson, W. M. Star, and M. J. C. van Gemert, “Optical properties of Intralipid: a phantom medium for light propagation studies,” Lasers Surg. Med. 12(5), 510–519 (1992).
[CrossRef] [PubMed]

Stephens, D. N.

D. N. Stephens, J. Park, Y. Sun, T. Papaioannou, and L. Marcu, “Intraluminal fluorescence spectroscopy catheter with ultrasound guidance,” J. Biomed. Opt. 14(3), 030505 (2009).
[CrossRef] [PubMed]

Sun, Y.

D. G. Farwell, J. D. Meier, J. Park, Y. Sun, H. Coffman, B. Poirier, J. Phipps, S. Tinling, D. J. Enepekides, and L. Marcu, “Time-resolved fluorescence spectroscopy as a diagnostic technique of oral carcinoma: Validation in the hamster buccal pouch model,” Arch. Otolaryngol. Head Neck Surg. 136(2), 126–133 (2010).
[PubMed]

D. N. Stephens, J. Park, Y. Sun, T. Papaioannou, and L. Marcu, “Intraluminal fluorescence spectroscopy catheter with ultrasound guidance,” J. Biomed. Opt. 14(3), 030505 (2009).
[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]

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]

Szmacinski, H.

J. R. Lakowicz, H. Szmacinski, K. Nowaczyk, and M. L. Johnson, “Fluorescence lifetime imaging of free and protein-bound NADH,” Proc. Natl. Acad. Sci. U.S.A. 89(4), 1271–1275 (1992).
[CrossRef] [PubMed]

Tan, W.

C. Vinegoni, T. Ralston, W. Tan, W. Luo, D. L. Marks, and S. A. Boppart, “Integrated structural and functional optical imaging combining spectral-domain optical coherence and multiphoton microscopy,” Appl. Phys. Lett. 88(5), 053901 (2006).
[CrossRef]

Thomas, P.

P. Thomas, P. Pande, F. Clubb, J. Adame, and J. A. Jo, “Biochemical imaging of human atherosclerotic plaques with fluorescence lifetime angioscopy,” Photochem. Photobiol. 86(3), 727–731 (2010).
[CrossRef] [PubMed]

Tinling, S.

D. G. Farwell, J. D. Meier, J. Park, Y. Sun, H. Coffman, B. Poirier, J. Phipps, S. Tinling, D. J. Enepekides, and L. Marcu, “Time-resolved fluorescence spectroscopy as a diagnostic technique of oral carcinoma: Validation in the hamster buccal pouch model,” Arch. Otolaryngol. Head Neck Surg. 136(2), 126–133 (2010).
[PubMed]

Tumlinson, A.

J. K. Barton, F. Guzman, and A. Tumlinson, “Dual modality instrument for simultaneous optical coherence tomography imaging and fluorescence spectroscopy,” J. Biomed. Opt. 9(3), 618–623 (2004).
[CrossRef] [PubMed]

Tumlinson, A. R.

L. P. Hariri, A. R. Tumlinson, D. G. Besselsen, U. Utzinger, E. W. Gerner, and J. K. Barton, “Endoscopic optical coherence tomography and laser-induced fluorescence spectroscopy in a murine colon cancer model,” Lasers Surg. Med. 38(4), 305–313 (2006).
[CrossRef] [PubMed]

A. R. Tumlinson, L. P. Hariri, U. Utzinger, and J. K. Barton, “Miniature endoscope for simultaneous optical coherence tomography and laser-induced fluorescence measurement,” Appl. Opt. 43(1), 113–121 (2004).
[CrossRef] [PubMed]

Utzinger, U.

L. P. Hariri, A. R. Tumlinson, D. G. Besselsen, U. Utzinger, E. W. Gerner, and J. K. Barton, “Endoscopic optical coherence tomography and laser-induced fluorescence spectroscopy in a murine colon cancer model,” Lasers Surg. Med. 38(4), 305–313 (2006).
[CrossRef] [PubMed]

A. R. Tumlinson, L. P. Hariri, U. Utzinger, and J. K. Barton, “Miniature endoscope for simultaneous optical coherence tomography and laser-induced fluorescence measurement,” Appl. Opt. 43(1), 113–121 (2004).
[CrossRef] [PubMed]

Vaitha, R.

Q. Y. 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.

S. T. Flock, S. L. Jacques, B. C. Wilson, W. M. Star, and M. J. C. van Gemert, “Optical properties of Intralipid: a phantom medium for light propagation studies,” Lasers Surg. Med. 12(5), 510–519 (1992).
[CrossRef] [PubMed]

van Leeuwen, T. G.

Vaughan, E. M.

D. K. Bird, L. Yan, K. M. Vrotsos, K. W. Eliceiri, E. M. Vaughan, P. J. Keely, J. G. White, and N. Ramanujam, “Metabolic mapping of MCF10A human breast cells via multiphoton fluorescence lifetime imaging of the coenzyme NADH,” Cancer Res. 65(19), 8766–8773 (2005).
[CrossRef] [PubMed]

Vinegoni, C.

C. Vinegoni, T. Ralston, W. Tan, W. Luo, D. L. Marks, and S. A. Boppart, “Integrated structural and functional optical imaging combining spectral-domain optical coherence and multiphoton microscopy,” Appl. Phys. Lett. 88(5), 053901 (2006).
[CrossRef]

Vrotsos, K. M.

D. K. Bird, L. Yan, K. M. Vrotsos, K. W. Eliceiri, E. M. Vaughan, P. J. Keely, J. G. White, and N. Ramanujam, “Metabolic mapping of MCF10A human breast cells via multiphoton fluorescence lifetime imaging of the coenzyme NADH,” Cancer Res. 65(19), 8766–8773 (2005).
[CrossRef] [PubMed]

Wang, Z. G.

Z. G. Wang, D. B. Durand, M. Schoenberg, and Y. T. Pan, “Fluorescence guided optical coherence tomography for the diagnosis of early bladder cancer in a rat model,” J. Urol. 174(6), 2376–2381 (2005).
[CrossRef] [PubMed]

Welzel, J.

K. König, M. Speicher, R. Bückle, J. Reckfort, G. McKenzie, J. Welzel, M. J. Koehler, P. Elsner, and M. Kaatz, “Clinical optical coherence tomography combined with multiphoton tomography of patients with skin diseases,” J Biophotonics 2(6-7), 389–397 (2009).
[CrossRef] [PubMed]

White, J. G.

D. K. Bird, L. Yan, K. M. Vrotsos, K. W. Eliceiri, E. M. Vaughan, P. J. Keely, J. G. White, and N. Ramanujam, “Metabolic mapping of MCF10A human breast cells via multiphoton fluorescence lifetime imaging of the coenzyme NADH,” Cancer Res. 65(19), 8766–8773 (2005).
[CrossRef] [PubMed]

Wilson, B. C.

S. T. Flock, S. L. Jacques, B. C. Wilson, W. M. Star, and M. J. C. van Gemert, “Optical properties of Intralipid: a phantom medium for light propagation studies,” Lasers Surg. Med. 12(5), 510–519 (1992).
[CrossRef] [PubMed]

Xiao, X.

S. Shrestha, B. E. Applegate, J. Park, X. Xiao, P. Pande, and J. A. Jo, “A Novel High-Speed Multispectral Fluorescence Lifetime Imaging Implementation for in vivo Applications,” Opt. Lett. in press.

Yan, L.

D. K. Bird, L. Yan, K. M. Vrotsos, K. W. Eliceiri, E. M. Vaughan, P. J. Keely, J. G. White, and N. Ramanujam, “Metabolic mapping of MCF10A human breast cells via multiphoton fluorescence lifetime imaging of the coenzyme NADH,” Cancer Res. 65(19), 8766–8773 (2005).
[CrossRef] [PubMed]

Appl. Opt. (1)

Appl. Phys. Lett. (1)

C. Vinegoni, T. Ralston, W. Tan, W. Luo, D. L. Marks, and S. A. Boppart, “Integrated structural and functional optical imaging combining spectral-domain optical coherence and multiphoton microscopy,” Appl. Phys. Lett. 88(5), 053901 (2006).
[CrossRef]

Arch. Otolaryngol. Head Neck Surg. (1)

D. G. Farwell, J. D. Meier, J. Park, Y. Sun, H. Coffman, B. Poirier, J. Phipps, S. Tinling, D. J. Enepekides, and L. Marcu, “Time-resolved fluorescence spectroscopy as a diagnostic technique of oral carcinoma: Validation in the hamster buccal pouch model,” Arch. Otolaryngol. Head Neck Surg. 136(2), 126–133 (2010).
[PubMed]

Arterioscler. Thromb. Vasc. Biol. (1)

K. Arakawa, K. Isoda, T. Ito, K. Nakajima, T. Shibuya, and F. Ohsuzu, “Fluorescence analysis of biochemical constituents identifies atherosclerotic plaque with a thin fibrous cap,” Arterioscler. Thromb. Vasc. Biol. 22(6), 1002–1007 (2002).
[CrossRef] [PubMed]

Atherosclerosis (1)

L. Marcu, J. A. Jo, Q. Fang, T. Papaioannou, T. Reil, J. H. Qiao, J. D. Baker, J. A. Freischlag, and M. C. Fishbein, “Detection of rupture-prone atherosclerotic plaques by time-resolved laser-induced fluorescence spectroscopy,” Atherosclerosis 204(1), 156–164 (2009).
[CrossRef] [PubMed]

Biophys. J. (1)

P. J. Caspers, G. W. Lucassen, and G. J. Puppels, “Combined in vivo confocal Raman spectroscopy and confocal microscopy of human skin,” Biophys. J. 85(1), 572–580 (2003).
[CrossRef] [PubMed]

Cancer Res. (1)

D. K. Bird, L. Yan, K. M. Vrotsos, K. W. Eliceiri, E. M. Vaughan, P. J. Keely, J. G. White, and N. Ramanujam, “Metabolic mapping of MCF10A human breast cells via multiphoton fluorescence lifetime imaging of the coenzyme NADH,” Cancer Res. 65(19), 8766–8773 (2005).
[CrossRef] [PubMed]

J Biophotonics (1)

K. König, M. Speicher, R. Bückle, J. Reckfort, G. McKenzie, J. Welzel, M. J. Koehler, P. Elsner, and M. Kaatz, “Clinical optical coherence tomography combined with multiphoton tomography of patients with skin diseases,” J Biophotonics 2(6-7), 389–397 (2009).
[CrossRef] [PubMed]

J. Biomed. Opt. (3)

J. K. Barton, F. Guzman, and A. Tumlinson, “Dual modality instrument for simultaneous optical coherence tomography imaging and fluorescence spectroscopy,” J. Biomed. Opt. 9(3), 618–623 (2004).
[CrossRef] [PubMed]

J. A. Jo, Q. Y. Fang, T. Papaioannou, and L. Marcu, “Fast model-free deconvolution of fluorescence decay for analysis of biological systems,” J. Biomed. Opt. 9(4), 743–752 (2004).
[CrossRef] [PubMed]

D. N. Stephens, J. Park, Y. Sun, T. Papaioannou, and L. Marcu, “Intraluminal fluorescence spectroscopy catheter with ultrasound guidance,” J. Biomed. Opt. 14(3), 030505 (2009).
[CrossRef] [PubMed]

J. Urol. (1)

Z. G. Wang, D. B. Durand, M. Schoenberg, and Y. T. Pan, “Fluorescence guided optical coherence tomography for the diagnosis of early bladder cancer in a rat model,” J. Urol. 174(6), 2376–2381 (2005).
[CrossRef] [PubMed]

Lab. Anim. (1)

N. G. Ghoshal and H. S. Bal, “Histomorphology of the hamster cheek pouch,” Lab. Anim. 24(3), 228–233 (1990).
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Lasers Surg. Med. (2)

S. T. Flock, S. L. Jacques, B. C. Wilson, W. M. Star, and M. J. C. van Gemert, “Optical properties of Intralipid: a phantom medium for light propagation studies,” Lasers Surg. Med. 12(5), 510–519 (1992).
[CrossRef] [PubMed]

L. P. Hariri, A. R. Tumlinson, D. G. Besselsen, U. Utzinger, E. W. Gerner, and J. K. Barton, “Endoscopic optical coherence tomography and laser-induced fluorescence spectroscopy in a murine colon cancer model,” Lasers Surg. Med. 38(4), 305–313 (2006).
[CrossRef] [PubMed]

Meas. Sci. Technol. (1)

C. Balas, “Review of biomedical optical imaging-a powerful, non-invasive, non-ionizing technology for improving in vivo diagnosis,” Meas. Sci. Technol. 20(10), 104020 (2009).
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Opt. Lett. (3)

Photochem. Photobiol. (1)

P. Thomas, P. Pande, F. Clubb, J. Adame, and J. A. Jo, “Biochemical imaging of human atherosclerotic plaques with fluorescence lifetime angioscopy,” Photochem. Photobiol. 86(3), 727–731 (2010).
[CrossRef] [PubMed]

Proc. Natl. Acad. Sci. U.S.A. (1)

J. R. Lakowicz, H. Szmacinski, K. Nowaczyk, and M. L. Johnson, “Fluorescence lifetime imaging of free and protein-bound NADH,” Proc. Natl. Acad. Sci. U.S.A. 89(4), 1271–1275 (1992).
[CrossRef] [PubMed]

Rev. Sci. Instrum. (1)

Q. Y. 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]

Toxicol. Pathol. (1)

J. L. Brandon, C. J. Conti, L. S. Goldstein, J. DiGiovanni, and I. B. Gimenez-Conti, “Carcinogenic effects of MGP-7 and B[a]P on the hamster cheek pouch,” Toxicol. Pathol. 37(6), 733–740 (2009).
[CrossRef] [PubMed]

Other (2)

R. M. Clegg, Fluorescence lifetime-resolved imaging, FLIM microscopy in biology and medicine (CRC Press, Boca Raton, Fla., 2010).

J. Fujimoto, and W. Drexler, Introduction to Optical Coherence Tomography, Optical Coherence Tomography: Technology and Applications (Springer, Berlin, Germany, 2008).

Supplementary Material (9)

» Media 1: AVI (2538 KB)     
» Media 2: AVI (2810 KB)     
» Media 3: AVI (3385 KB)     
» Media 4: AVI (3844 KB)     
» Media 5: AVI (3364 KB)     
» Media 6: AVI (2739 KB)     
» Media 7: AVI (3638 KB)     
» Media 8: AVI (3905 KB)     
» Media 9: AVI (3090 KB)     

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Figures (6)

Fig. 1
Fig. 1

Schematic diagram of the dual-modality imaging system. La1-La5: free-space collimation and coupling lenses, Lf1-Lf7: fiber-connected collimation and coupling lenses, NDF: neutral density filter, M1-M4: mirrors, DM1-DM4: dichroic mirrors, and F1-F3: filters

Fig. 2
Fig. 2

Dual-modal OCT and FLIM images of three capillary tubes loaded with POPOP (left tube), NADH (center tube) and FAD (right tube) within the 2% intralipid (2500 (x) x 2500 (y) x 600 (z) µm). (a) 3-D OCT volume, (b) 2-D OCT B-scan, (c) Normalized fluorescence intensity maps, (d) Fluorescence lifetime maps, (e) 3-D OCT/FLIM volume with fluorescence intensity at the 550 nm band and (f) 2-D OCT/FLIM B-scan image with fluorescence intensity at the 550 nm band. Horizontal scale bar = 500 µm and vertical scale bar = 100 µm. A movie showing 3D nature of OCT/FLIM volume: (Media 1).

Fig. 3
Fig. 3

Dual-modal OCT and FLIM images of an ex vivo human atherosclerotic artery tissue with thin fibrotic plaque (2000 (x) x 2000 (y) x 350 (z) µm). (a) 3-D OCT volume, (b) 2-D OCT B-scan (FB: Fibrotic plaque in Intima, M: Media and A: Adventitia), (c) H&E histology corresponding to (b), (d) Normalized fluorescence intensity maps, (e) Fluorescence lifetime maps, (f) 3-D OCT/FLIM volume with fluorescence lifetime in 390 nm band, and (g) Ortho- sliced image from (f). Horizontal scale bar = 400 µm and vertical scale bar = 100 µm. Movies showing 3D nature of OCT/FLIM volume: Media 2 and Media 3.

Fig. 4
Fig. 4

Dual-modal OCT and FLIM maps of an ex vivo calcified human atherosclerotic artery tissue (2000 (x) x 2000 (y) x 650 (z) µm). (a) 3-D OCT volume, (b) 2-D OCT B-scan (TFC: thick fibrotic cap, CNC: calcified necrotic core), (c) H&E histology corresponding to (b), (d) Normalized fluorescence intensity maps, (e) Fluorescence lifetime maps, (f) 3-D OCT/FLIM volume with fluorescence lifetime in 390 nm band, and (g) Ortho-sliced image from (f). Horizontal scale bar = 400 µm and vertical scale bar = 100 µm. Movies showing 3D nature of OCT/FLIM volumes: Media 4 and Media 5.

Fig. 5
Fig. 5

Dual-modal OCT images and FLIM maps of in vivo normal hamster cheek pouch (2000 (x) x 2000 (y) x 450 (z) µm). (a) 3-D OCT volume, (b) 2-D OCT B-scan (KE: Keratinized stratified squamous epithelium, SC: subepithelial connective tissue (lamina propria), SM: skeletal muscle layer (tunica muscularis), AC: adventitial connective tissue, and BV: Blood vessel), (c) H&E histology corresponding to (b), (d) Normalized fluorescence intensity maps, (e) Fluorescence lifetime maps, (f) 3-D OCT/FLIM volume with a fluorescence lifetime map in 390 nm band, and (g) Ortho-sliced image from (f). Horizontal scale bar = 400 µm and vertical scale bar = 100 µm. Movies showing 3D nature of OCT/FLIM volume: Media 6 and Media 7.

Fig. 6
Fig. 6

Dual-modal OCT images and FLIM maps of in vivo cancerous hamster cheek pouch (2000 (x) x 2000 (y) x 650 (z) µm). (a) 3-D OCT volume, (b) 2-D OCT B-scan (KE: Keratinized stratified squamous epithelium, and SC: subepithelial connective tissue), (c) H&E histology corresponding to (b), (d) Normalized fluorescence intensity maps, (e) Fluorescence lifetime maps, (f) 3-D OCT/FLIM volume with fluorescence lifetime in 390 nm band, and (g) Ortho-sliced image from (f). Horizontal scale bar = 400 µm and vertical scale bar = 100 µm. Movies showing 3D nature of OCT/FLIM volume: Media 8 and Media 9.

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