Abstract

We describe a functional imaging paradigm that uses photothermal optical coherence tomography (PT-OCT) to detect indocyanine green (ICG)-encapsulated biocompatible poly(lactic-co-glycolic) acid (PLGA) nanoparticles embedded in highly scattering tissue phantoms with high resolution and sensitivity. The ICG-loaded PLGA nanoparticles were fabricated using a modified emulsification solvent diffusion method. With a 20 kHz axial scan rate, PT-OCT based on spectral-domain interferometric configuration at 1310 nm was used to detect phase changes induced by a 808 nm photothermal excitation of ICG-encapsulated PLGA nanoparticles. An algorithm based on Fourier transform analysis of differential phase of the spectral interferogram was developed for detecting the depth resolved localized photothermal signal. Excellent contrast difference was observed with PT-OCT between phantoms containing different concentrations of ICG-encapsulated PLGA nanoparticles. This technique has the potential to provide simultaneous structural and molecular-targeted imaging with excellent signal-to-noise for various clinical applications.

© 2012 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, Science 254, 1178 (1991).
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  3. C. Yang, M. A. Choma, L. E. Lamb, J. D. Simon, and J. A. Izatt, Opt. Lett. 29, 1396 (2004).
    [CrossRef]
  4. C. Xu, J. Ye, D. L. Marks, and S. A. Boppart, Opt. Lett. 29, 1647 (2004).
    [CrossRef]
  5. M. C. Skala, M. J. Crow, A. Wax, and J. A. Izatt, Nano. Lett. 8, 3461 (2008).
    [CrossRef]
  6. D. C. Adler, S. W. Huang, R. Huber, and J. G. Fujimoto, Opt. Express 16, 4376 (2008).
    [CrossRef]
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    [CrossRef]
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    [CrossRef]
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    [CrossRef]
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    [CrossRef]
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    [CrossRef]
  13. Y. Pan, S. Neuss, A. Leifert, M. Fischler, F. Wen, and U. Simon, Small 3, 1941 (2007).
    [CrossRef]
  14. V. Saxena, M. Sadoqi, and J. Shao, Int. J. Pharm. 278, 293 (2004).
  15. N. Shah, K. Chaudhari, P. Dantuluri, R. S. Murthy, and S. Das, J. Drug Target. 17, 533 (2009).
    [CrossRef]
  16. R. C. Benson and H. A. Kues, Phys. Med. Biol. 23 (1), 159 (1978).
    [CrossRef]

2011

Y. Jung, R. Reif, Y. Zeng, and R. K. Wang, Nano. Lett. 11, 2938 (2011).
[CrossRef]

2010

2009

N. Shah, K. Chaudhari, P. Dantuluri, R. S. Murthy, and S. Das, J. Drug Target. 17, 533 (2009).
[CrossRef]

2008

N. Lewinski, V. Colvin, and R. Drezek, Small 4, 26 (2008).
[CrossRef]

D. C. Adler, S. W. Huang, R. Huber, and J. G. Fujimoto, Opt. Express 16, 4376 (2008).
[CrossRef]

M. C. Skala, M. J. Crow, A. Wax, and J. A. Izatt, Nano. Lett. 8, 3461 (2008).
[CrossRef]

2007

S. K. Murthy, Int. J. Nanomed. 2, 129 (2007).

Y. Pan, S. Neuss, A. Leifert, M. Fischler, F. Wen, and U. Simon, Small 3, 1941 (2007).
[CrossRef]

2006

V. Wagner, A. Dullaart, A. K. Bock, and A. Zweck, Nat. Biotechnol. 24, 1211 (2006).
[CrossRef]

2005

2004

C. Yang, M. A. Choma, L. E. Lamb, J. D. Simon, and J. A. Izatt, Opt. Lett. 29, 1396 (2004).
[CrossRef]

C. Xu, J. Ye, D. L. Marks, and S. A. Boppart, Opt. Lett. 29, 1647 (2004).
[CrossRef]

C. M. Goodman, C. D. McCusker, T. Yilmaz, and V. M. Rotello, Bioconjugate Chemistry 15, 897 (2004).
[CrossRef]

V. Saxena, M. Sadoqi, and J. Shao, Int. J. Pharm. 278, 293 (2004).

1991

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, Science 254, 1178 (1991).
[CrossRef]

1978

R. C. Benson and H. A. Kues, Phys. Med. Biol. 23 (1), 159 (1978).
[CrossRef]

Adler, D. C.

Benson, R. C.

R. C. Benson and H. A. Kues, Phys. Med. Biol. 23 (1), 159 (1978).
[CrossRef]

Bock, A. K.

V. Wagner, A. Dullaart, A. K. Bock, and A. Zweck, Nat. Biotechnol. 24, 1211 (2006).
[CrossRef]

Boppart, S. A.

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, Science 254, 1178 (1991).
[CrossRef]

Chaudhari, K.

N. Shah, K. Chaudhari, P. Dantuluri, R. S. Murthy, and S. Das, J. Drug Target. 17, 533 (2009).
[CrossRef]

Choma, M. A.

Cohen, D. W.

Colvin, V.

N. Lewinski, V. Colvin, and R. Drezek, Small 4, 26 (2008).
[CrossRef]

Connolly, J. L.

Crow, M. J.

M. C. Skala, M. J. Crow, A. Wax, and J. A. Izatt, Nano. Lett. 8, 3461 (2008).
[CrossRef]

Dantuluri, P.

N. Shah, K. Chaudhari, P. Dantuluri, R. S. Murthy, and S. Das, J. Drug Target. 17, 533 (2009).
[CrossRef]

Das, S.

N. Shah, K. Chaudhari, P. Dantuluri, R. S. Murthy, and S. Das, J. Drug Target. 17, 533 (2009).
[CrossRef]

Drezek, R.

N. Lewinski, V. Colvin, and R. Drezek, Small 4, 26 (2008).
[CrossRef]

Dullaart, A.

V. Wagner, A. Dullaart, A. K. Bock, and A. Zweck, Nat. Biotechnol. 24, 1211 (2006).
[CrossRef]

Fischler, M.

Y. Pan, S. Neuss, A. Leifert, M. Fischler, F. Wen, and U. Simon, Small 3, 1941 (2007).
[CrossRef]

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, Science 254, 1178 (1991).
[CrossRef]

Fujimoto, J. G.

C. Zhou, T. H. Tsai, D. C. Adler, H. C. Lee, D. W. Cohen, A. Mondelblatt, Y. Wang, J. L. Connolly, and J. G. Fujimoto, Opt. Lett. 35, 700 (2010).
[CrossRef]

D. C. Adler, S. W. Huang, R. Huber, and J. G. Fujimoto, Opt. Express 16, 4376 (2008).
[CrossRef]

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, Science 254, 1178 (1991).
[CrossRef]

Goodman, C. M.

C. M. Goodman, C. D. McCusker, T. Yilmaz, and V. M. Rotello, Bioconjugate Chemistry 15, 897 (2004).
[CrossRef]

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, Science 254, 1178 (1991).
[CrossRef]

Gunther, J. R.

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, Science 254, 1178 (1991).
[CrossRef]

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, Science 254, 1178 (1991).
[CrossRef]

Huang, S. W.

Huber, R.

Izatt, J. A.

M. C. Skala, M. J. Crow, A. Wax, and J. A. Izatt, Nano. Lett. 8, 3461 (2008).
[CrossRef]

C. Yang, M. A. Choma, L. E. Lamb, J. D. Simon, and J. A. Izatt, Opt. Lett. 29, 1396 (2004).
[CrossRef]

Jung, Y.

Y. Jung, R. Reif, Y. Zeng, and R. K. Wang, Nano. Lett. 11, 2938 (2011).
[CrossRef]

Kues, H. A.

R. C. Benson and H. A. Kues, Phys. Med. Biol. 23 (1), 159 (1978).
[CrossRef]

Lamb, L. E.

Lee, H. C.

Leifert, A.

Y. Pan, S. Neuss, A. Leifert, M. Fischler, F. Wen, and U. Simon, Small 3, 1941 (2007).
[CrossRef]

Lewinski, N.

N. Lewinski, V. Colvin, and R. Drezek, Small 4, 26 (2008).
[CrossRef]

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, Science 254, 1178 (1991).
[CrossRef]

Marks, D. L.

McCusker, C. D.

C. M. Goodman, C. D. McCusker, T. Yilmaz, and V. M. Rotello, Bioconjugate Chemistry 15, 897 (2004).
[CrossRef]

Mondelblatt, A.

Murthy, R. S.

N. Shah, K. Chaudhari, P. Dantuluri, R. S. Murthy, and S. Das, J. Drug Target. 17, 533 (2009).
[CrossRef]

Murthy, S. K.

S. K. Murthy, Int. J. Nanomed. 2, 129 (2007).

Neuss, S.

Y. Pan, S. Neuss, A. Leifert, M. Fischler, F. Wen, and U. Simon, Small 3, 1941 (2007).
[CrossRef]

Oldenburg, A. L.

Pan, Y.

Y. Pan, S. Neuss, A. Leifert, M. Fischler, F. Wen, and U. Simon, Small 3, 1941 (2007).
[CrossRef]

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, Science 254, 1178 (1991).
[CrossRef]

Reif, R.

Y. Jung, R. Reif, Y. Zeng, and R. K. Wang, Nano. Lett. 11, 2938 (2011).
[CrossRef]

Rotello, V. M.

C. M. Goodman, C. D. McCusker, T. Yilmaz, and V. M. Rotello, Bioconjugate Chemistry 15, 897 (2004).
[CrossRef]

Sadoqi, M.

V. Saxena, M. Sadoqi, and J. Shao, Int. J. Pharm. 278, 293 (2004).

Saxena, V.

V. Saxena, M. Sadoqi, and J. Shao, Int. J. Pharm. 278, 293 (2004).

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, Science 254, 1178 (1991).
[CrossRef]

Shah, N.

N. Shah, K. Chaudhari, P. Dantuluri, R. S. Murthy, and S. Das, J. Drug Target. 17, 533 (2009).
[CrossRef]

Shao, J.

V. Saxena, M. Sadoqi, and J. Shao, Int. J. Pharm. 278, 293 (2004).

Simon, J. D.

Simon, U.

Y. Pan, S. Neuss, A. Leifert, M. Fischler, F. Wen, and U. Simon, Small 3, 1941 (2007).
[CrossRef]

Skala, M. C.

M. C. Skala, M. J. Crow, A. Wax, and J. A. Izatt, Nano. Lett. 8, 3461 (2008).
[CrossRef]

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, Science 254, 1178 (1991).
[CrossRef]

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, Science 254, 1178 (1991).
[CrossRef]

Tsai, T. H.

Wagner, V.

V. Wagner, A. Dullaart, A. K. Bock, and A. Zweck, Nat. Biotechnol. 24, 1211 (2006).
[CrossRef]

Wang, R. K.

Y. Jung, R. Reif, Y. Zeng, and R. K. Wang, Nano. Lett. 11, 2938 (2011).
[CrossRef]

Wang, Y.

Wax, A.

M. C. Skala, M. J. Crow, A. Wax, and J. A. Izatt, Nano. Lett. 8, 3461 (2008).
[CrossRef]

Wen, F.

Y. Pan, S. Neuss, A. Leifert, M. Fischler, F. Wen, and U. Simon, Small 3, 1941 (2007).
[CrossRef]

Xu, C.

Yang, C.

Ye, J.

Yilmaz, T.

C. M. Goodman, C. D. McCusker, T. Yilmaz, and V. M. Rotello, Bioconjugate Chemistry 15, 897 (2004).
[CrossRef]

Zeng, Y.

Y. Jung, R. Reif, Y. Zeng, and R. K. Wang, Nano. Lett. 11, 2938 (2011).
[CrossRef]

Zhou, C.

Zweck, A.

V. Wagner, A. Dullaart, A. K. Bock, and A. Zweck, Nat. Biotechnol. 24, 1211 (2006).
[CrossRef]

Bioconjugate Chemistry

C. M. Goodman, C. D. McCusker, T. Yilmaz, and V. M. Rotello, Bioconjugate Chemistry 15, 897 (2004).
[CrossRef]

Int. J. Nanomed.

S. K. Murthy, Int. J. Nanomed. 2, 129 (2007).

Int. J. Pharm.

V. Saxena, M. Sadoqi, and J. Shao, Int. J. Pharm. 278, 293 (2004).

J. Drug Target.

N. Shah, K. Chaudhari, P. Dantuluri, R. S. Murthy, and S. Das, J. Drug Target. 17, 533 (2009).
[CrossRef]

Nano. Lett.

Y. Jung, R. Reif, Y. Zeng, and R. K. Wang, Nano. Lett. 11, 2938 (2011).
[CrossRef]

M. C. Skala, M. J. Crow, A. Wax, and J. A. Izatt, Nano. Lett. 8, 3461 (2008).
[CrossRef]

Nat. Biotechnol.

V. Wagner, A. Dullaart, A. K. Bock, and A. Zweck, Nat. Biotechnol. 24, 1211 (2006).
[CrossRef]

Opt. Express

Opt. Lett.

Phys. Med. Biol.

R. C. Benson and H. A. Kues, Phys. Med. Biol. 23 (1), 159 (1978).
[CrossRef]

Science

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, Science 254, 1178 (1991).
[CrossRef]

Small

N. Lewinski, V. Colvin, and R. Drezek, Small 4, 26 (2008).
[CrossRef]

Y. Pan, S. Neuss, A. Leifert, M. Fischler, F. Wen, and U. Simon, Small 3, 1941 (2007).
[CrossRef]

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Figures (3)

Fig. 1.
Fig. 1.

Schematic of PT-OCT setup based on a spectral—domain interferometric configuration with photothermal modulation system. L1-L6, lenses. PC, polarization controller. FC, fiber coupler. DG, diffraction grating. OC, optical circulator. RM, reference mirror. SLD, superluminescent diode. DCM, diachronic mirror. COMP, computer.

Fig. 2.
Fig. 2.

Fourier transform of phase difference of M-scan spectral interferogram taken with ICG-encapsulated PLGA nanoparticles (7.5mg/ml) at a particular depth inside the embedded tissue phantom with a modulation frequency of 1 KHz. (b) Optical path length change detected with PT-OCT for samples with five increasing concentrations (0mg/ml, 2.5mg/ml, 5mg/ml, 7.5mg/ml, and 10mg/ml).

Fig. 3.
Fig. 3.

(a) Conventional spectral domain structural OCT image of the tissue phantoms with four increasing nanoparticle concentrations of 0mg/ml, 2.5mg/ml, 5mg/ml, and 10mg/ml (from left to right). (b) PT-OCT image of the sample with ICG-encapsulated PLGA nanoparticle concentrations of 0mg/ml, 2.5mg/ml, 5mg/ml, and 10mg/ml (from left to right). The scale bar corresponds to 500 μm.

Equations (1)

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ΔΦ(z,t)=arctan(Im[I(z,tj)I*(z,tj1)]/Re[I(z,tj)I*(z,tj1)]),

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