Abstract

We report the development of a two-color Fourier domain Pump-Probe Optical Coherence Tomography (PPOCT) system. Tissue phantom experiments to characterize the system performance demonstrated imaging depths in excess of 725 μm, nearly comparable to the base Optical Coherence Tomography system. PPOCT A-line rates were also demonstrated in excess of 1 kHz. The physical origin of the PPOCT signal was investigated with a series of experiments which revealed that the signal is a mixture of short and long lifetime component signals. The short lifetime component was attributed to transient absorption while the long lifetime component may be due to a mixture of transient absorption and thermal effects. Ex vivo images of porcine iris demonstrated the potential for imaging melanin in the eye, where cancer of the melanocytes is the most common form of eye cancer in adults.

©2010 Optical Society of America

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  1. D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical Coherence Tomography,” Science 254(5035), 1178–1181 (1991).
    [Crossref] [PubMed]
  2. K. D. Rao, M. A. Choma, S. Yazdanfar, A. M. Rollins, and J. A. Izatt, “Molecular contrast in optical coherence tomography by use of a pump-probe technique,” Opt. Lett. 28(5), 340–342 (2003).
    [Crossref] [PubMed]
  3. B. E. Applegate and J. A. Izatt, “Molecular imaging of endogenous and exogenous chromophores using ground state recovery pump-probe optical coherence tomography,” Opt. Express 14(20), 9142–9155 (2006).
    [Crossref] [PubMed]
  4. C. Yang, L. E. L. McGuckin, J. D. Simon, M. A. Choma, B. E. Applegate, and J. A. Izatt, “Spectral triangulation molecular contrast optical coherence tomography with indocyanine green as the contrast agent,” Opt. Lett. 29(17), 2016–2018 (2004).
    [Crossref] [PubMed]
  5. D. J. Faber, E. G. Mik, M. C. G. Aalders, and T. G. van Leeuwen, “Toward assessment of blood oxygen saturation by spectroscopic optical coherence tomography,” Opt. Lett. 30(9), 1015–1017 (2005).
    [Crossref] [PubMed]
  6. D. J. Faber, E. G. Mik, M. C. G. Aalders, and T. G. van Leeuwen, “Light absorption of (oxy-)hemoglobin assessed by spectroscopic optical coherence tomography,” Opt. Lett. 28(16), 1436–1438 (2003).
    [Crossref] [PubMed]
  7. D. C. Adler, S. W. Huang, R. Huber, and J. G. Fujimoto, “Photothermal detection of gold nanoparticles using phase-sensitive optical coherence tomography,” Opt. Express 16(7), 4376–4393 (2008).
    [Crossref] [PubMed]
  8. M. C. Skala, M. J. Crow, A. Wax, and J. A. Izatt, “Photothermal optical coherence tomography of Epidermal Growth Factor Receptor in Live Cells Using Immunotargeted Gold Nanospheres,” Nano Lett. 8(10), 3461–3467 (2008).
    [Crossref] [PubMed]
  9. M. V. Sarunic, B. E. Applegate, and J. A. Izatt, “Spectral domain second-harmonic optical coherence tomography,” Opt. Lett. 30(18), 2391–2393 (2005).
    [Crossref] [PubMed]
  10. B. E. Applegate, C. Yang, A. M. Rollins, and J. A. Izatt, “Polarization-resolved second-harmonic-generation optical coherence tomography in collagen,” Opt. Lett. 29(19), 2252–2254 (2004).
    [Crossref] [PubMed]
  11. Y. Jiang, I. Tomov, Y. Wang, and Z. Chen, “Second-harmonic optical coherence tomography,” Opt. Lett. 29(10), 1090–1092 (2004).
    [Crossref] [PubMed]
  12. J. S. Bredfeldt, C. Vinegoni, D. L. Marks, and S. A. Boppart, “Molecularly sensitive optical coherence tomography,” Opt. Lett. 30(5), 495–497 (2005).
    [Crossref] [PubMed]
  13. D. L. Marks and S. A. Boppart, “Nonlinear InterferometricVibrational Imaging,” Phys. Rev. Lett. 92(12), 1239051–1239054 (2004).
  14. A. L. Oldenburg, B. E. Applegate, J. A. Izatt, and S. A. Boppart, “Molecular OCT Contrast Enhancement and Imaging,” ˝in Optical Coherence Tomography: Technology and Applications, W. Drexler, and J. G. Fujimoto, eds. (Springer, New York, 2009), pp. 713–752.
  15. B. E. Applegate, C. Yang, and J. A. Izatt, “Theoretical comparison of the sensitivity of molecular contrast optical coherence tomography techniques,” Opt. Express 13(20), 8146–8163 (2005).
    [Crossref] [PubMed]
  16. D. W. Kufe, J. F. Holland, E. Frei, and American Cancer Society., Cancer medicine 6 (BC Decker, Hamilton, Ont.; Lewiston, NY, 2003).
  17. J. Georges and J. M. Mermet, “Thermal Lensing Spectroscopy - Principle and Applications,” Analusis 16, 203–215 (1988).
  18. D. Schweitzer, S. Schenke, M. Hammer, F. Schweitzer, S. Jentsch, E. Birckner, W. Becker, and A. Bergmann, “Towards metabolic mapping of the human retina,” Microsc. Res. Tech. 70(5), 410–419 (2007).
    [Crossref] [PubMed]

2008 (2)

D. C. Adler, S. W. Huang, R. Huber, and J. G. Fujimoto, “Photothermal detection of gold nanoparticles using phase-sensitive optical coherence tomography,” Opt. Express 16(7), 4376–4393 (2008).
[Crossref] [PubMed]

M. C. Skala, M. J. Crow, A. Wax, and J. A. Izatt, “Photothermal optical coherence tomography of Epidermal Growth Factor Receptor in Live Cells Using Immunotargeted Gold Nanospheres,” Nano Lett. 8(10), 3461–3467 (2008).
[Crossref] [PubMed]

2007 (1)

D. Schweitzer, S. Schenke, M. Hammer, F. Schweitzer, S. Jentsch, E. Birckner, W. Becker, and A. Bergmann, “Towards metabolic mapping of the human retina,” Microsc. Res. Tech. 70(5), 410–419 (2007).
[Crossref] [PubMed]

2006 (1)

2005 (4)

2004 (4)

2003 (2)

1991 (1)

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical Coherence Tomography,” Science 254(5035), 1178–1181 (1991).
[Crossref] [PubMed]

1988 (1)

J. Georges and J. M. Mermet, “Thermal Lensing Spectroscopy - Principle and Applications,” Analusis 16, 203–215 (1988).

Aalders, M. C. G.

Adler, D. C.

Applegate, B. E.

Becker, W.

D. Schweitzer, S. Schenke, M. Hammer, F. Schweitzer, S. Jentsch, E. Birckner, W. Becker, and A. Bergmann, “Towards metabolic mapping of the human retina,” Microsc. Res. Tech. 70(5), 410–419 (2007).
[Crossref] [PubMed]

Bergmann, A.

D. Schweitzer, S. Schenke, M. Hammer, F. Schweitzer, S. Jentsch, E. Birckner, W. Becker, and A. Bergmann, “Towards metabolic mapping of the human retina,” Microsc. Res. Tech. 70(5), 410–419 (2007).
[Crossref] [PubMed]

Birckner, E.

D. Schweitzer, S. Schenke, M. Hammer, F. Schweitzer, S. Jentsch, E. Birckner, W. Becker, and A. Bergmann, “Towards metabolic mapping of the human retina,” Microsc. Res. Tech. 70(5), 410–419 (2007).
[Crossref] [PubMed]

Boppart, S. A.

J. S. Bredfeldt, C. Vinegoni, D. L. Marks, and S. A. Boppart, “Molecularly sensitive optical coherence tomography,” Opt. Lett. 30(5), 495–497 (2005).
[Crossref] [PubMed]

D. L. Marks and S. A. Boppart, “Nonlinear InterferometricVibrational Imaging,” Phys. Rev. Lett. 92(12), 1239051–1239054 (2004).

Bredfeldt, J. S.

Chang, W.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical Coherence Tomography,” Science 254(5035), 1178–1181 (1991).
[Crossref] [PubMed]

Chen, Z.

Choma, M. A.

Crow, M. J.

M. C. Skala, M. J. Crow, A. Wax, and J. A. Izatt, “Photothermal optical coherence tomography of Epidermal Growth Factor Receptor in Live Cells Using Immunotargeted Gold Nanospheres,” Nano Lett. 8(10), 3461–3467 (2008).
[Crossref] [PubMed]

Faber, D. J.

Flotte, T.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical Coherence Tomography,” Science 254(5035), 1178–1181 (1991).
[Crossref] [PubMed]

Fujimoto, J. G.

D. C. Adler, S. W. Huang, R. Huber, and J. G. Fujimoto, “Photothermal detection of gold nanoparticles using phase-sensitive optical coherence tomography,” Opt. Express 16(7), 4376–4393 (2008).
[Crossref] [PubMed]

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical Coherence Tomography,” Science 254(5035), 1178–1181 (1991).
[Crossref] [PubMed]

Georges, J.

J. Georges and J. M. Mermet, “Thermal Lensing Spectroscopy - Principle and Applications,” Analusis 16, 203–215 (1988).

Gregory, K.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical Coherence Tomography,” Science 254(5035), 1178–1181 (1991).
[Crossref] [PubMed]

Hammer, M.

D. Schweitzer, S. Schenke, M. Hammer, F. Schweitzer, S. Jentsch, E. Birckner, W. Becker, and A. Bergmann, “Towards metabolic mapping of the human retina,” Microsc. Res. Tech. 70(5), 410–419 (2007).
[Crossref] [PubMed]

Hee, M. R.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical Coherence Tomography,” Science 254(5035), 1178–1181 (1991).
[Crossref] [PubMed]

Huang, D.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical Coherence Tomography,” Science 254(5035), 1178–1181 (1991).
[Crossref] [PubMed]

Huang, S. W.

Huber, R.

Izatt, J. A.

M. C. Skala, M. J. Crow, A. Wax, and J. A. Izatt, “Photothermal optical coherence tomography of Epidermal Growth Factor Receptor in Live Cells Using Immunotargeted Gold Nanospheres,” Nano Lett. 8(10), 3461–3467 (2008).
[Crossref] [PubMed]

B. E. Applegate and J. A. Izatt, “Molecular imaging of endogenous and exogenous chromophores using ground state recovery pump-probe optical coherence tomography,” Opt. Express 14(20), 9142–9155 (2006).
[Crossref] [PubMed]

M. V. Sarunic, B. E. Applegate, and J. A. Izatt, “Spectral domain second-harmonic optical coherence tomography,” Opt. Lett. 30(18), 2391–2393 (2005).
[Crossref] [PubMed]

B. E. Applegate, C. Yang, and J. A. Izatt, “Theoretical comparison of the sensitivity of molecular contrast optical coherence tomography techniques,” Opt. Express 13(20), 8146–8163 (2005).
[Crossref] [PubMed]

B. E. Applegate, C. Yang, A. M. Rollins, and J. A. Izatt, “Polarization-resolved second-harmonic-generation optical coherence tomography in collagen,” Opt. Lett. 29(19), 2252–2254 (2004).
[Crossref] [PubMed]

C. Yang, L. E. L. McGuckin, J. D. Simon, M. A. Choma, B. E. Applegate, and J. A. Izatt, “Spectral triangulation molecular contrast optical coherence tomography with indocyanine green as the contrast agent,” Opt. Lett. 29(17), 2016–2018 (2004).
[Crossref] [PubMed]

K. D. Rao, M. A. Choma, S. Yazdanfar, A. M. Rollins, and J. A. Izatt, “Molecular contrast in optical coherence tomography by use of a pump-probe technique,” Opt. Lett. 28(5), 340–342 (2003).
[Crossref] [PubMed]

Jentsch, S.

D. Schweitzer, S. Schenke, M. Hammer, F. Schweitzer, S. Jentsch, E. Birckner, W. Becker, and A. Bergmann, “Towards metabolic mapping of the human retina,” Microsc. Res. Tech. 70(5), 410–419 (2007).
[Crossref] [PubMed]

Jiang, Y.

Lin, C. P.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical Coherence Tomography,” Science 254(5035), 1178–1181 (1991).
[Crossref] [PubMed]

Marks, D. L.

J. S. Bredfeldt, C. Vinegoni, D. L. Marks, and S. A. Boppart, “Molecularly sensitive optical coherence tomography,” Opt. Lett. 30(5), 495–497 (2005).
[Crossref] [PubMed]

D. L. Marks and S. A. Boppart, “Nonlinear InterferometricVibrational Imaging,” Phys. Rev. Lett. 92(12), 1239051–1239054 (2004).

McGuckin, L. E. L.

Mermet, J. M.

J. Georges and J. M. Mermet, “Thermal Lensing Spectroscopy - Principle and Applications,” Analusis 16, 203–215 (1988).

Mik, E. G.

Puliafito, C. A.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical Coherence Tomography,” Science 254(5035), 1178–1181 (1991).
[Crossref] [PubMed]

Rao, K. D.

Rollins, A. M.

Sarunic, M. V.

Schenke, S.

D. Schweitzer, S. Schenke, M. Hammer, F. Schweitzer, S. Jentsch, E. Birckner, W. Becker, and A. Bergmann, “Towards metabolic mapping of the human retina,” Microsc. Res. Tech. 70(5), 410–419 (2007).
[Crossref] [PubMed]

Schuman, J. S.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical Coherence Tomography,” Science 254(5035), 1178–1181 (1991).
[Crossref] [PubMed]

Schweitzer, D.

D. Schweitzer, S. Schenke, M. Hammer, F. Schweitzer, S. Jentsch, E. Birckner, W. Becker, and A. Bergmann, “Towards metabolic mapping of the human retina,” Microsc. Res. Tech. 70(5), 410–419 (2007).
[Crossref] [PubMed]

Schweitzer, F.

D. Schweitzer, S. Schenke, M. Hammer, F. Schweitzer, S. Jentsch, E. Birckner, W. Becker, and A. Bergmann, “Towards metabolic mapping of the human retina,” Microsc. Res. Tech. 70(5), 410–419 (2007).
[Crossref] [PubMed]

Simon, J. D.

Skala, M. C.

M. C. Skala, M. J. Crow, A. Wax, and J. A. Izatt, “Photothermal optical coherence tomography of Epidermal Growth Factor Receptor in Live Cells Using Immunotargeted Gold Nanospheres,” Nano Lett. 8(10), 3461–3467 (2008).
[Crossref] [PubMed]

Stinson, W. G.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical Coherence Tomography,” Science 254(5035), 1178–1181 (1991).
[Crossref] [PubMed]

Swanson, E. A.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical Coherence Tomography,” Science 254(5035), 1178–1181 (1991).
[Crossref] [PubMed]

Tomov, I.

van Leeuwen, T. G.

Vinegoni, C.

Wang, Y.

Wax, A.

M. C. Skala, M. J. Crow, A. Wax, and J. A. Izatt, “Photothermal optical coherence tomography of Epidermal Growth Factor Receptor in Live Cells Using Immunotargeted Gold Nanospheres,” Nano Lett. 8(10), 3461–3467 (2008).
[Crossref] [PubMed]

Yang, C.

Yazdanfar, S.

Analusis (1)

J. Georges and J. M. Mermet, “Thermal Lensing Spectroscopy - Principle and Applications,” Analusis 16, 203–215 (1988).

Microsc. Res. Tech. (1)

D. Schweitzer, S. Schenke, M. Hammer, F. Schweitzer, S. Jentsch, E. Birckner, W. Becker, and A. Bergmann, “Towards metabolic mapping of the human retina,” Microsc. Res. Tech. 70(5), 410–419 (2007).
[Crossref] [PubMed]

Nano Lett. (1)

M. C. Skala, M. J. Crow, A. Wax, and J. A. Izatt, “Photothermal optical coherence tomography of Epidermal Growth Factor Receptor in Live Cells Using Immunotargeted Gold Nanospheres,” Nano Lett. 8(10), 3461–3467 (2008).
[Crossref] [PubMed]

Opt. Express (3)

Opt. Lett. (8)

K. D. Rao, M. A. Choma, S. Yazdanfar, A. M. Rollins, and J. A. Izatt, “Molecular contrast in optical coherence tomography by use of a pump-probe technique,” Opt. Lett. 28(5), 340–342 (2003).
[Crossref] [PubMed]

C. Yang, L. E. L. McGuckin, J. D. Simon, M. A. Choma, B. E. Applegate, and J. A. Izatt, “Spectral triangulation molecular contrast optical coherence tomography with indocyanine green as the contrast agent,” Opt. Lett. 29(17), 2016–2018 (2004).
[Crossref] [PubMed]

D. J. Faber, E. G. Mik, M. C. G. Aalders, and T. G. van Leeuwen, “Toward assessment of blood oxygen saturation by spectroscopic optical coherence tomography,” Opt. Lett. 30(9), 1015–1017 (2005).
[Crossref] [PubMed]

D. J. Faber, E. G. Mik, M. C. G. Aalders, and T. G. van Leeuwen, “Light absorption of (oxy-)hemoglobin assessed by spectroscopic optical coherence tomography,” Opt. Lett. 28(16), 1436–1438 (2003).
[Crossref] [PubMed]

M. V. Sarunic, B. E. Applegate, and J. A. Izatt, “Spectral domain second-harmonic optical coherence tomography,” Opt. Lett. 30(18), 2391–2393 (2005).
[Crossref] [PubMed]

B. E. Applegate, C. Yang, A. M. Rollins, and J. A. Izatt, “Polarization-resolved second-harmonic-generation optical coherence tomography in collagen,” Opt. Lett. 29(19), 2252–2254 (2004).
[Crossref] [PubMed]

Y. Jiang, I. Tomov, Y. Wang, and Z. Chen, “Second-harmonic optical coherence tomography,” Opt. Lett. 29(10), 1090–1092 (2004).
[Crossref] [PubMed]

J. S. Bredfeldt, C. Vinegoni, D. L. Marks, and S. A. Boppart, “Molecularly sensitive optical coherence tomography,” Opt. Lett. 30(5), 495–497 (2005).
[Crossref] [PubMed]

Phys. Rev. Lett. (1)

D. L. Marks and S. A. Boppart, “Nonlinear InterferometricVibrational Imaging,” Phys. Rev. Lett. 92(12), 1239051–1239054 (2004).

Science (1)

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical Coherence Tomography,” Science 254(5035), 1178–1181 (1991).
[Crossref] [PubMed]

Other (2)

D. W. Kufe, J. F. Holland, E. Frei, and American Cancer Society., Cancer medicine 6 (BC Decker, Hamilton, Ont.; Lewiston, NY, 2003).

A. L. Oldenburg, B. E. Applegate, J. A. Izatt, and S. A. Boppart, “Molecular OCT Contrast Enhancement and Imaging,” ˝in Optical Coherence Tomography: Technology and Applications, W. Drexler, and J. G. Fujimoto, eds. (Springer, New York, 2009), pp. 713–752.

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Figures (8)

Fig. 1
Fig. 1

Representative biomolecular energy level diagram illustrating some of the potential physical processes as well as how pump-probe spectroscopy might interrogate them. The solid arrows represent driven transitions either by the pump (blue) or probe (red, green, and cyan). The dashed arrows represent spontaneous transitions.

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Fig. 2
Fig. 2

Schematic diagram of the Fourier domain Pump-Probe Optical Coherence Tomography system.

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Fig. 3
Fig. 3

PPOCT and OCT images of a human hair embedded in chicken breast at various depths in the tissue. The depth corresponds to the center of the hair. The scale bar is 100 μm. For the 315 mm depth both pump on and pump off images are shown while only pump on images are shown for other depths. The color scale bar to the right is the signal to noise ratio in dB for the PPOCT images. All images are on a log intensity scale.

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Fig. 4
Fig. 4

OCT (blue), PPOCT (green) and PPOCT background (red) A-lines on an SNR dB scale. The A-lines were taken from the 319 μm B-scans. The PPOCT background corresponds to the pump off image.

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Fig. 5
Fig. 5

OCT (grayscale) and PPOCT B-scans of a human hair embedded in chicken breast, recorded at different PPOCT line rates. In all cases the OCT line rate was 12.2 kHz, hence 24.4 Hz corresponds to 500 OCT lines/ PPOCT line. The scale bar is 100 μm. All images are on a log intensity scale.

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Fig. 6
Fig. 6

A) Pump power dependence of the PPOCT signal measured with a black (eumelanin) human hair sample. B) Pump amplitude modulation frequency dependence of the PPOCT signal from a similar sample. The estimated error is ± 5%

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Fig. 7
Fig. 7

Modulated pump signal (blue) and peak of the OCT M-scan (red), filtered around the pump modulation frequency.

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Fig. 8
Fig. 8

A) OCT image of the porcine lens and iris. The scale bar is 200 μm. B) PPOCT image mapping the melanin in the iris. The color bar is in dB SNR. C) PPOCT background image recorded without the pump radiation. The color bar is in dB SNR. D) Background subtracted PPOCT image derived from spatially averaged version of B and C. The color bar is in dB SNR. E) Reflectivity independent molecular image on a linear scale where 1 indicates the maximum concentration. All images except E are on a log scale.

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Equations (3)

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W 1 ∝ R P p r ( σ 0 , m q m , n σ 0 , n N 0 0 ) P p u
W 2 ∝ R P p r ( σ 0 , m σ m , l N 0 0 ) P p u
W 3 ∝ R P p r ( σ 0 , m q m , k σ k , i N 0 0 ) P p u

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