Abstract

Photothermal optical coherence tomography (PT-OCT) is a potentially powerful tool for molecular imaging. Here, we characterize PT-OCT imaging of gold nanorod (GNR) contrast agents in phantoms, and we apply these techniques for in vivo GNR imaging. The PT-OCT signal was compared to the bio-heat equation in phantoms, and in vivo PT-OCT images were acquired from subcutaneous 400 pM GNR Matrigel injections into mice. Experiments revealed that PT-OCT signals varied as predicted by the bio-heat equation, with significant PT-OCT signal increases at 7.5 pM GNR compared to a scattering control (p < 0.01) while imaging in common path configuration. In vivo PT-OCT images demonstrated an appreciable increase in signal in the presence of GNRs compared to controls. Additionally, in vivo PT-OCT GNR signals were spatially distinct from blood vessels imaged with Doppler OCT. We anticipate that the demonstrated in vivo PT-OCT sensitivity to GNR contrast agents is sufficient to image molecular expression in vivo. Therefore, this work demonstrates the translation of PT-OCT to in vivo imaging and represents the next step towards its use as an in vivo molecular imaging tool.

© 2012 OSA

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2012 (5)

2011 (5)

2010 (7)

R. John, R. Rezaeipoor, S. G. Adie, E. J. Chaney, A. L. Oldenburg, M. Marjanovic, J. P. Haldar, B. P. Sutton, and S. A. Boppart, “In vivo magnetomotive optical molecular imaging using targeted magnetic nanoprobes,” Proc. Natl. Acad. Sci. U.S.A.107(18), 8085–8090 (2010).
[CrossRef] [PubMed]

S. Barbosa, A. Agrawal, L. Rodríguez-Lorenzo, I. Pastoriza-Santos, R. A. Alvarez-Puebla, A. Kornowski, H. Weller, and L. M. Liz-Marzán, “Tuning size and sensing properties in colloidal gold nanostars,” Langmuir26(18), 14943–14950 (2010).
[CrossRef] [PubMed]

R. K. Wang and A. L. Nuttall, “Phase-sensitive optical coherence tomography imaging of the tissue motion within the organ of Corti at a subnanometer scale: a preliminary study,” J. Biomed. Opt.15(5), 056005 (2010).
[CrossRef] [PubMed]

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, “Photothermal optical coherence tomography in ex vivo human breast tissues using gold nanoshells,” Opt. Lett.35(5), 700–702 (2010).
[CrossRef] [PubMed]

D. Jacob, R. L. Shelton, and B. E. Applegate, “Fourier domain pump-probe optical coherence tomography imaging of melanin,” Opt. Express18(12), 12399–12410 (2010).
[CrossRef] [PubMed]

A. S. Paranjape, R. Kuranov, S. Baranov, L. L. Ma, J. W. Villard, T. Wang, K. V. Sokolov, M. D. Feldman, K. P. Johnston, and T. E. Milner, “Depth resolved photothermal OCT detection of macrophages in tissue using nanorose,” Biomed. Opt. Express1(1), 2–16 (2010).
[CrossRef] [PubMed]

S. Moon, S. W. Lee, and Z. P. Chen, “Reference spectrum extraction and fixed-pattern noise removal in optical coherence tomography,” Opt. Express18(24), 24395–24404 (2010).
[CrossRef] [PubMed]

2009 (7)

L. Tong, Q. Wei, A. Wei, and J. X. Cheng, “Gold nanorods as contrast agents for biological imaging: optical properties, surface conjugation and photothermal effects,” Photochem. Photobiol.85(1), 21–32 (2009).
[CrossRef] [PubMed]

X. H. Huang, S. Neretina, and M. A. El-Sayed, “Gold Nanorods: From Synthesis and Properties to Biological and Biomedical Applications,” Adv. Mater. (Deerfield Beach Fla.)21(48), 4880–4910 (2009).
[CrossRef]

G. von Maltzahn, J. H. Park, A. Agrawal, N. K. Bandaru, S. K. Das, M. J. Sailor, and S. N. Bhatia, “Computationally guided photothermal tumor therapy using long-circulating gold nanorod antennas,” Cancer Res.69(9), 3892–3900 (2009).
[CrossRef] [PubMed]

J. R. Cole, N. A. Mirin, M. W. Knight, G. P. Goodrich, and N. J. Halas, “Photothermal efficiencies of nanoshells and nanorods for clinical therapeutic applications,” J. Phys. Chem. C113(28), 12090–12094 (2009).
[CrossRef]

R. N. Graf, F. E. Robles, X. X. Chen, and A. Wax, “Detecting precancerous lesions in the hamster cheek pouch using spectroscopic white-light optical coherence tomography to assess nuclear morphology via spectral oscillations,” J. Biomed. Opt.14(6), 064030 (2009).
[CrossRef] [PubMed]

A. L. Oldenburg, M. N. Hansen, T. S. Ralston, A. Wei, and S. A. Boppart, “Imaging gold nanorods in excised human breast carcinoma by spectroscopic optical coherence tomography,” J. Mater. Chem.19(35), 6407–6411 (2009).
[CrossRef] [PubMed]

R. K. Wang and L. An, “Doppler optical micro-angiography for volumetric imaging of vascular perfusion in vivo,” Opt. Express17(11), 8926–8940 (2009).
[CrossRef] [PubMed]

2008 (3)

2006 (5)

A. Agrawal, S. Huang, A. Wei Haw Lin, M. H. Lee, J. K. Barton, R. A. Drezek, and T. J. Pfefer, “Quantitative evaluation of optical coherence tomography signal enhancement with gold nanoshells,” J. Biomed. Opt.11(4), 041121 (2006).
[CrossRef] [PubMed]

P. K. Jain, K. S. Lee, I. H. El-Sayed, and M. A. El-Sayed, “Calculated absorption and scattering properties of gold nanoparticles of different size, shape, and composition: applications in biological imaging and biomedicine,” J. Phys. Chem. B110(14), 7238–7248 (2006).
[CrossRef] [PubMed]

C. J. Orendorff and C. J. Murphy, “Quantitation of metal content in the silver-assisted growth of gold nanorods,” J. Phys. Chem. B110(9), 3990–3994 (2006).
[CrossRef] [PubMed]

J. Kim, J. Oh, and T. E. Milner, “Measurement of optical path length change following pulsed laser irradiation using differential phase optical coherence tomography,” J. Biomed. Opt.11(4), 041122 (2006).
[CrossRef] [PubMed]

S. Makita, Y. Hong, M. Yamanari, T. Yatagai, and Y. Yasuno, “Optical coherence angiography,” Opt. Express14(17), 7821–7840 (2006).
[CrossRef] [PubMed]

2005 (7)

C. J. Murphy, T. K. Sau, A. M. Gole, C. J. Orendorff, J. X. Gao, L. Gou, S. E. Hunyadi, and T. Li, “Anisotropic metal nanoparticles: synthesis, assembly, and optical applications,” J. Phys. Chem. B109(29), 13857–13870 (2005).
[CrossRef] [PubMed]

H. W. Liao and J. H. Hafner, “Gold nanorod bioconjugates,” Chem. Mater.17(18), 4636–4641 (2005).
[CrossRef]

J. Chen, F. Saeki, B. J. Wiley, H. Cang, M. J. Cobb, Z. Y. Li, L. Au, H. Zhang, M. B. Kimmey, X. Li, and Y. Xia, “Gold nanocages: bioconjugation and their potential use as optical imaging contrast agents,” Nano Lett.5(3), 473–477 (2005).
[CrossRef] [PubMed]

C. Loo, A. Lowery, N. Halas, J. West, and R. Drezek, “Immunotargeted nanoshells for integrated cancer imaging and therapy,” Nano Lett.5(4), 709–711 (2005).
[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]

M. A. Choma, A. K. Ellerbee, C. H. Yang, T. L. Creazzo, and J. A. Izatt, “Spectral-domain phase microscopy,” Opt. Lett.30(10), 1162–1164 (2005).
[CrossRef] [PubMed]

B. J. Vakoc, S. H. Yun, J. F. de Boer, G. J. Tearney, and B. E. Bouma, “Phase-resolved optical frequency domain imaging,” Opt. Express13(14), 5483–5493 (2005).
[CrossRef] [PubMed]

2004 (1)

2003 (1)

2002 (2)

V. X. D. Yang, M. L. Gordon, A. Mok, Y. H. Zhao, Z. P. Chen, R. S. C. Cobbold, B. C. Wilson, and I. A. Vitkin, “Improved phase-resolved optical Doppler tomography using the Kasai velocity estimator and histogram segmentation,” Opt. Commun.208(4-6), 209–214 (2002).
[CrossRef]

D. Boyer, P. Tamarat, A. Maali, B. Lounis, and M. Orrit, “Photothermal imaging of nanometer-sized metal particles among scatterers,” Science297(5584), 1160–1163 (2002).
[CrossRef] [PubMed]

2001 (1)

D. L. G. Hill, P. G. Batchelor, M. Holden, and D. J. Hawkes, “Medical image registration,” Phys. Med. Biol.46(3), R1–R45 (2001).
[CrossRef] [PubMed]

1996 (1)

M. J. C. van Gemert, G. W. Lucassen, and A. J. Welch, “Time constants in thermal laser medicine: II. Distributions of time constants and thermal relaxation of tissue,” Phys. Med. Biol.41(8), 1381–1399 (1996).
[CrossRef] [PubMed]

1969 (1)

L. R. Rabiner, R. W. Schafer, and C. M. Rader, “Chirp Z-transform algorithm,” IEEE Trans. Acoust. SpeechAu17, 86–92 (1969).

1967 (1)

P. D. Welch, “Use of fast Fourier transform for estimation of power spectra—a method based on time averaging over short modified periodograms,” IEEE Trans. Acoust. SpeechAu15, 70–73 (1967).

Aalders, M. C. G.

Adie, S. G.

R. John, R. Rezaeipoor, S. G. Adie, E. J. Chaney, A. L. Oldenburg, M. Marjanovic, J. P. Haldar, B. P. Sutton, and S. A. Boppart, “In vivo magnetomotive optical molecular imaging using targeted magnetic nanoprobes,” Proc. Natl. Acad. Sci. U.S.A.107(18), 8085–8090 (2010).
[CrossRef] [PubMed]

Adler, D. C.

Agrawal, A.

S. Barbosa, A. Agrawal, L. Rodríguez-Lorenzo, I. Pastoriza-Santos, R. A. Alvarez-Puebla, A. Kornowski, H. Weller, and L. M. Liz-Marzán, “Tuning size and sensing properties in colloidal gold nanostars,” Langmuir26(18), 14943–14950 (2010).
[CrossRef] [PubMed]

G. von Maltzahn, J. H. Park, A. Agrawal, N. K. Bandaru, S. K. Das, M. J. Sailor, and S. N. Bhatia, “Computationally guided photothermal tumor therapy using long-circulating gold nanorod antennas,” Cancer Res.69(9), 3892–3900 (2009).
[CrossRef] [PubMed]

A. Agrawal, S. Huang, A. Wei Haw Lin, M. H. Lee, J. K. Barton, R. A. Drezek, and T. J. Pfefer, “Quantitative evaluation of optical coherence tomography signal enhancement with gold nanoshells,” J. Biomed. Opt.11(4), 041121 (2006).
[CrossRef] [PubMed]

Almendro, V.

A. Marusyk, V. Almendro, and K. Polyak, “Intra-tumour heterogeneity: a looking glass for cancer?” Nat. Rev. Cancer12(5), 323–334 (2012).
[CrossRef] [PubMed]

Alvarez-Puebla, R. A.

S. Barbosa, A. Agrawal, L. Rodríguez-Lorenzo, I. Pastoriza-Santos, R. A. Alvarez-Puebla, A. Kornowski, H. Weller, and L. M. Liz-Marzán, “Tuning size and sensing properties in colloidal gold nanostars,” Langmuir26(18), 14943–14950 (2010).
[CrossRef] [PubMed]

An, L.

Applegate, B. E.

Au, L.

J. Chen, F. Saeki, B. J. Wiley, H. Cang, M. J. Cobb, Z. Y. Li, L. Au, H. Zhang, M. B. Kimmey, X. Li, and Y. Xia, “Gold nanocages: bioconjugation and their potential use as optical imaging contrast agents,” Nano Lett.5(3), 473–477 (2005).
[CrossRef] [PubMed]

Bandaru, N. K.

G. von Maltzahn, J. H. Park, A. Agrawal, N. K. Bandaru, S. K. Das, M. J. Sailor, and S. N. Bhatia, “Computationally guided photothermal tumor therapy using long-circulating gold nanorod antennas,” Cancer Res.69(9), 3892–3900 (2009).
[CrossRef] [PubMed]

Baranov, S.

Barbosa, S.

S. Barbosa, A. Agrawal, L. Rodríguez-Lorenzo, I. Pastoriza-Santos, R. A. Alvarez-Puebla, A. Kornowski, H. Weller, and L. M. Liz-Marzán, “Tuning size and sensing properties in colloidal gold nanostars,” Langmuir26(18), 14943–14950 (2010).
[CrossRef] [PubMed]

Barton, J. K.

A. Agrawal, S. Huang, A. Wei Haw Lin, M. H. Lee, J. K. Barton, R. A. Drezek, and T. J. Pfefer, “Quantitative evaluation of optical coherence tomography signal enhancement with gold nanoshells,” J. Biomed. Opt.11(4), 041121 (2006).
[CrossRef] [PubMed]

Batchelor, P. G.

D. L. G. Hill, P. G. Batchelor, M. Holden, and D. J. Hawkes, “Medical image registration,” Phys. Med. Biol.46(3), R1–R45 (2001).
[CrossRef] [PubMed]

Berclaz, C.

Bhatia, S. N.

G. von Maltzahn, J. H. Park, A. Agrawal, N. K. Bandaru, S. K. Das, M. J. Sailor, and S. N. Bhatia, “Computationally guided photothermal tumor therapy using long-circulating gold nanorod antennas,” Cancer Res.69(9), 3892–3900 (2009).
[CrossRef] [PubMed]

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Boppart, S. A.

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Y. Jung, R. Reif, Y. Zeng, and R. K. Wang, “Three-dimensional high-resolution imaging of gold nanorods uptake in sentinel lymph nodes,” Nano Lett.11(7), 2938–2943 (2011).
[CrossRef] [PubMed]

G. Y. Guan, R. Reif, Z. H. Huang, and R. K. K. Wang, “Depth profiling of photothermal compound concentrations using phase sensitive optical coherence tomography,” J. Biomed. Opt.16(12), 126003 (2011).
[CrossRef] [PubMed]

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R. John, R. Rezaeipoor, S. G. Adie, E. J. Chaney, A. L. Oldenburg, M. Marjanovic, J. P. Haldar, B. P. Sutton, and S. A. Boppart, “In vivo magnetomotive optical molecular imaging using targeted magnetic nanoprobes,” Proc. Natl. Acad. Sci. U.S.A.107(18), 8085–8090 (2010).
[CrossRef] [PubMed]

Rinne, S. A.

Robles, F. E.

R. N. Graf, F. E. Robles, X. X. Chen, and A. Wax, “Detecting precancerous lesions in the hamster cheek pouch using spectroscopic white-light optical coherence tomography to assess nuclear morphology via spectral oscillations,” J. Biomed. Opt.14(6), 064030 (2009).
[CrossRef] [PubMed]

Rodríguez-Lorenzo, L.

S. Barbosa, A. Agrawal, L. Rodríguez-Lorenzo, I. Pastoriza-Santos, R. A. Alvarez-Puebla, A. Kornowski, H. Weller, and L. M. Liz-Marzán, “Tuning size and sensing properties in colloidal gold nanostars,” Langmuir26(18), 14943–14950 (2010).
[CrossRef] [PubMed]

Rollins, A. M.

Rosenthal, A.

Saeki, F.

J. Chen, F. Saeki, B. J. Wiley, H. Cang, M. J. Cobb, Z. Y. Li, L. Au, H. Zhang, M. B. Kimmey, X. Li, and Y. Xia, “Gold nanocages: bioconjugation and their potential use as optical imaging contrast agents,” Nano Lett.5(3), 473–477 (2005).
[CrossRef] [PubMed]

Sailor, M. J.

G. von Maltzahn, J. H. Park, A. Agrawal, N. K. Bandaru, S. K. Das, M. J. Sailor, and S. N. Bhatia, “Computationally guided photothermal tumor therapy using long-circulating gold nanorod antennas,” Cancer Res.69(9), 3892–3900 (2009).
[CrossRef] [PubMed]

Salvaggio, A.

Santschi, C.

Sau, T. K.

C. J. Murphy, T. K. Sau, A. M. Gole, C. J. Orendorff, J. X. Gao, L. Gou, S. E. Hunyadi, and T. Li, “Anisotropic metal nanoparticles: synthesis, assembly, and optical applications,” J. Phys. Chem. B109(29), 13857–13870 (2005).
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L. R. Rabiner, R. W. Schafer, and C. M. Rader, “Chirp Z-transform algorithm,” IEEE Trans. Acoust. SpeechAu17, 86–92 (1969).

Shelton, R. L.

Skala, M. C.

J. M. Tucker-Schwartz, T. Hong, D. C. Colvin, Y. Xu, and M. C. Skala, “Dual-modality photothermal optical coherence tomography and magnetic-resonance imaging of carbon nanotubes,” Opt. Lett.37(5), 872–874 (2012).
[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]

Smith, J. W.

Sokolov, K. V.

Srinivasan, V. J.

Subhash, H. M.

Sutton, B. P.

R. John, R. Rezaeipoor, S. G. Adie, E. J. Chaney, A. L. Oldenburg, M. Marjanovic, J. P. Haldar, B. P. Sutton, and S. A. Boppart, “In vivo magnetomotive optical molecular imaging using targeted magnetic nanoprobes,” Proc. Natl. Acad. Sci. U.S.A.107(18), 8085–8090 (2010).
[CrossRef] [PubMed]

Tamarat, P.

D. Boyer, P. Tamarat, A. Maali, B. Lounis, and M. Orrit, “Photothermal imaging of nanometer-sized metal particles among scatterers,” Science297(5584), 1160–1163 (2002).
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Tearney, G. J.

Tong, L.

L. Tong, Q. Wei, A. Wei, and J. X. Cheng, “Gold nanorods as contrast agents for biological imaging: optical properties, surface conjugation and photothermal effects,” Photochem. Photobiol.85(1), 21–32 (2009).
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Tucker-Schwartz, J. M.

Vakoc, B. J.

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M. J. C. van Gemert, G. W. Lucassen, and A. J. Welch, “Time constants in thermal laser medicine: II. Distributions of time constants and thermal relaxation of tissue,” Phys. Med. Biol.41(8), 1381–1399 (1996).
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G. von Maltzahn, J. H. Park, A. Agrawal, N. K. Bandaru, S. K. Das, M. J. Sailor, and S. N. Bhatia, “Computationally guided photothermal tumor therapy using long-circulating gold nanorod antennas,” Cancer Res.69(9), 3892–3900 (2009).
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Y. Jung, R. Reif, Y. Zeng, and R. K. Wang, “Three-dimensional high-resolution imaging of gold nanorods uptake in sentinel lymph nodes,” Nano Lett.11(7), 2938–2943 (2011).
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R. K. Wang and A. L. Nuttall, “Phase-sensitive optical coherence tomography imaging of the tissue motion within the organ of Corti at a subnanometer scale: a preliminary study,” J. Biomed. Opt.15(5), 056005 (2010).
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R. K. Wang and L. An, “Doppler optical micro-angiography for volumetric imaging of vascular perfusion in vivo,” Opt. Express17(11), 8926–8940 (2009).
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Wang, R. K. K.

G. Y. Guan, R. Reif, Z. H. Huang, and R. K. K. Wang, “Depth profiling of photothermal compound concentrations using phase sensitive optical coherence tomography,” J. Biomed. Opt.16(12), 126003 (2011).
[CrossRef] [PubMed]

Wang, T.

Wang, Y.

Wax, A.

R. N. Graf, F. E. Robles, X. X. Chen, and A. Wax, “Detecting precancerous lesions in the hamster cheek pouch using spectroscopic white-light optical coherence tomography to assess nuclear morphology via spectral oscillations,” J. Biomed. Opt.14(6), 064030 (2009).
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Wei, A.

L. Tong, Q. Wei, A. Wei, and J. X. Cheng, “Gold nanorods as contrast agents for biological imaging: optical properties, surface conjugation and photothermal effects,” Photochem. Photobiol.85(1), 21–32 (2009).
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A. L. Oldenburg, M. N. Hansen, T. S. Ralston, A. Wei, and S. A. Boppart, “Imaging gold nanorods in excised human breast carcinoma by spectroscopic optical coherence tomography,” J. Mater. Chem.19(35), 6407–6411 (2009).
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M. J. C. van Gemert, G. W. Lucassen, and A. J. Welch, “Time constants in thermal laser medicine: II. Distributions of time constants and thermal relaxation of tissue,” Phys. Med. Biol.41(8), 1381–1399 (1996).
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S. Barbosa, A. Agrawal, L. Rodríguez-Lorenzo, I. Pastoriza-Santos, R. A. Alvarez-Puebla, A. Kornowski, H. Weller, and L. M. Liz-Marzán, “Tuning size and sensing properties in colloidal gold nanostars,” Langmuir26(18), 14943–14950 (2010).
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Xia, Y.

J. Chen, F. Saeki, B. J. Wiley, H. Cang, M. J. Cobb, Z. Y. Li, L. Au, H. Zhang, M. B. Kimmey, X. Li, and Y. Xia, “Gold nanocages: bioconjugation and their potential use as optical imaging contrast agents,” Nano Lett.5(3), 473–477 (2005).
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V. X. D. Yang, M. L. Gordon, A. Mok, Y. H. Zhao, Z. P. Chen, R. S. C. Cobbold, B. C. Wilson, and I. A. Vitkin, “Improved phase-resolved optical Doppler tomography using the Kasai velocity estimator and histogram segmentation,” Opt. Commun.208(4-6), 209–214 (2002).
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Yatagai, T.

Yazdanfar, S.

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Zeng, Y.

Y. Jung, R. Reif, Y. Zeng, and R. K. Wang, “Three-dimensional high-resolution imaging of gold nanorods uptake in sentinel lymph nodes,” Nano Lett.11(7), 2938–2943 (2011).
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Zhang, H.

J. Chen, F. Saeki, B. J. Wiley, H. Cang, M. J. Cobb, Z. Y. Li, L. Au, H. Zhang, M. B. Kimmey, X. Li, and Y. Xia, “Gold nanocages: bioconjugation and their potential use as optical imaging contrast agents,” Nano Lett.5(3), 473–477 (2005).
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Zhao, Y. H.

V. X. D. Yang, M. L. Gordon, A. Mok, Y. H. Zhao, Z. P. Chen, R. S. C. Cobbold, B. C. Wilson, and I. A. Vitkin, “Improved phase-resolved optical Doppler tomography using the Kasai velocity estimator and histogram segmentation,” Opt. Commun.208(4-6), 209–214 (2002).
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Adv. Mater. (Deerfield Beach Fla.) (1)

X. H. Huang, S. Neretina, and M. A. El-Sayed, “Gold Nanorods: From Synthesis and Properties to Biological and Biomedical Applications,” Adv. Mater. (Deerfield Beach Fla.)21(48), 4880–4910 (2009).
[CrossRef]

Biomed. Opt. Express (2)

Cancer Res. (1)

G. von Maltzahn, J. H. Park, A. Agrawal, N. K. Bandaru, S. K. Das, M. J. Sailor, and S. N. Bhatia, “Computationally guided photothermal tumor therapy using long-circulating gold nanorod antennas,” Cancer Res.69(9), 3892–3900 (2009).
[CrossRef] [PubMed]

Chem. Mater. (1)

H. W. Liao and J. H. Hafner, “Gold nanorod bioconjugates,” Chem. Mater.17(18), 4636–4641 (2005).
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IEEE Trans. Acoust. Speech (2)

L. R. Rabiner, R. W. Schafer, and C. M. Rader, “Chirp Z-transform algorithm,” IEEE Trans. Acoust. SpeechAu17, 86–92 (1969).

P. D. Welch, “Use of fast Fourier transform for estimation of power spectra—a method based on time averaging over short modified periodograms,” IEEE Trans. Acoust. SpeechAu15, 70–73 (1967).

J. Biomed. Opt. (6)

R. K. Wang and A. L. Nuttall, “Phase-sensitive optical coherence tomography imaging of the tissue motion within the organ of Corti at a subnanometer scale: a preliminary study,” J. Biomed. Opt.15(5), 056005 (2010).
[CrossRef] [PubMed]

G. Y. Guan, R. Reif, Z. H. Huang, and R. K. K. Wang, “Depth profiling of photothermal compound concentrations using phase sensitive optical coherence tomography,” J. Biomed. Opt.16(12), 126003 (2011).
[CrossRef] [PubMed]

A. Agrawal, S. Huang, A. Wei Haw Lin, M. H. Lee, J. K. Barton, R. A. Drezek, and T. J. Pfefer, “Quantitative evaluation of optical coherence tomography signal enhancement with gold nanoshells,” J. Biomed. Opt.11(4), 041121 (2006).
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N. Krstajić, C. T. A. Brown, K. Dholakia, and M. E. Giardini, “Tissue surface as the reference arm in Fourier domain optical coherence tomography,” J. Biomed. Opt.17(7), 071305 (2012).
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J. Kim, J. Oh, and T. E. Milner, “Measurement of optical path length change following pulsed laser irradiation using differential phase optical coherence tomography,” J. Biomed. Opt.11(4), 041122 (2006).
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R. N. Graf, F. E. Robles, X. X. Chen, and A. Wax, “Detecting precancerous lesions in the hamster cheek pouch using spectroscopic white-light optical coherence tomography to assess nuclear morphology via spectral oscillations,” J. Biomed. Opt.14(6), 064030 (2009).
[CrossRef] [PubMed]

J. Mater. Chem. (1)

A. L. Oldenburg, M. N. Hansen, T. S. Ralston, A. Wei, and S. A. Boppart, “Imaging gold nanorods in excised human breast carcinoma by spectroscopic optical coherence tomography,” J. Mater. Chem.19(35), 6407–6411 (2009).
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J. Phys. Chem. B (3)

C. J. Orendorff and C. J. Murphy, “Quantitation of metal content in the silver-assisted growth of gold nanorods,” J. Phys. Chem. B110(9), 3990–3994 (2006).
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C. J. Murphy, T. K. Sau, A. M. Gole, C. J. Orendorff, J. X. Gao, L. Gou, S. E. Hunyadi, and T. Li, “Anisotropic metal nanoparticles: synthesis, assembly, and optical applications,” J. Phys. Chem. B109(29), 13857–13870 (2005).
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Langmuir (1)

S. Barbosa, A. Agrawal, L. Rodríguez-Lorenzo, I. Pastoriza-Santos, R. A. Alvarez-Puebla, A. Kornowski, H. Weller, and L. M. Liz-Marzán, “Tuning size and sensing properties in colloidal gold nanostars,” Langmuir26(18), 14943–14950 (2010).
[CrossRef] [PubMed]

Nano Lett. (4)

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).
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Y. Jung, R. Reif, Y. Zeng, and R. K. Wang, “Three-dimensional high-resolution imaging of gold nanorods uptake in sentinel lymph nodes,” Nano Lett.11(7), 2938–2943 (2011).
[CrossRef] [PubMed]

J. Chen, F. Saeki, B. J. Wiley, H. Cang, M. J. Cobb, Z. Y. Li, L. Au, H. Zhang, M. B. Kimmey, X. Li, and Y. Xia, “Gold nanocages: bioconjugation and their potential use as optical imaging contrast agents,” Nano Lett.5(3), 473–477 (2005).
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C. Loo, A. Lowery, N. Halas, J. West, and R. Drezek, “Immunotargeted nanoshells for integrated cancer imaging and therapy,” Nano Lett.5(4), 709–711 (2005).
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Opt. Commun. (1)

V. X. D. Yang, M. L. Gordon, A. Mok, Y. H. Zhao, Z. P. Chen, R. S. C. Cobbold, B. C. Wilson, and I. A. Vitkin, “Improved phase-resolved optical Doppler tomography using the Kasai velocity estimator and histogram segmentation,” Opt. Commun.208(4-6), 209–214 (2002).
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Opt. Express (10)

M. Wojtkowski, V. J. Srinivasan, T. H. Ko, J. G. Fujimoto, A. Kowalczyk, and J. S. Duker, “Ultrahigh-resolution, high-speed, Fourier domain optical coherence tomography and methods for dispersion compensation,” Opt. Express12(11), 2404–2422 (2004).
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B. J. Vakoc, S. H. Yun, J. F. de Boer, G. J. Tearney, and B. E. Bouma, “Phase-resolved optical frequency domain imaging,” Opt. Express13(14), 5483–5493 (2005).
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S. Makita, Y. Hong, M. Yamanari, T. Yatagai, and Y. Yasuno, “Optical coherence angiography,” Opt. Express14(17), 7821–7840 (2006).
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D. C. Adler, S. W. Huang, R. Huber, and J. G. Fujimoto, “Photothermal detection of gold nanoparticles using phase-sensitive optical coherence tomography,” Opt. Express16(7), 4376–4393 (2008).
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A. L. Oldenburg, V. Crecea, S. A. Rinne, and S. A. Boppart, “Phase-resolved magnetomotive OCT for imaging nanomolar concentrations of magnetic nanoparticles in tissues,” Opt. Express16(15), 11525–11539 (2008).
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R. K. Wang and L. An, “Doppler optical micro-angiography for volumetric imaging of vascular perfusion in vivo,” Opt. Express17(11), 8926–8940 (2009).
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R. V. Kuranov, S. Kazmi, A. B. McElroy, J. W. Kiel, A. K. Dunn, T. E. Milner, and T. Q. Duong, “In vivo depth-resolved oxygen saturation by dual-wavelength photothermal (DWP) OCT,” Opt. Express19(24), 23831–23844 (2011).
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S. Moon, S. W. Lee, and Z. P. Chen, “Reference spectrum extraction and fixed-pattern noise removal in optical coherence tomography,” Opt. Express18(24), 24395–24404 (2010).
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D. Jacob, R. L. Shelton, and B. E. Applegate, “Fourier domain pump-probe optical coherence tomography imaging of melanin,” Opt. Express18(12), 12399–12410 (2010).
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C. Pache, N. L. Bocchio, A. Bouwens, M. Villiger, C. Berclaz, J. Goulley, M. I. Gibson, C. Santschi, and T. Lasser, “Fast three-dimensional imaging of gold nanoparticles in living cells with photothermal optical lock-in optical coherence microscopy,” Opt. Express20(19), 21385–21399 (2012).
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Opt. Lett. (7)

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).
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J. M. Tucker-Schwartz, T. Hong, D. C. Colvin, Y. Xu, and M. C. Skala, “Dual-modality photothermal optical coherence tomography and magnetic-resonance imaging of carbon nanotubes,” Opt. Lett.37(5), 872–874 (2012).
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H. M. Subhash, H. Xie, J. W. Smith, and O. J. McCarty, “Optical detection of indocyanine green encapsulated biocompatible poly (lactic-co-glycolic) acid nanoparticles with photothermal optical coherence tomography,” Opt. Lett.37(5), 981–983 (2012).
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Photochem. Photobiol. (1)

L. Tong, Q. Wei, A. Wei, and J. X. Cheng, “Gold nanorods as contrast agents for biological imaging: optical properties, surface conjugation and photothermal effects,” Photochem. Photobiol.85(1), 21–32 (2009).
[CrossRef] [PubMed]

Phys. Med. Biol. (2)

M. J. C. van Gemert, G. W. Lucassen, and A. J. Welch, “Time constants in thermal laser medicine: II. Distributions of time constants and thermal relaxation of tissue,” Phys. Med. Biol.41(8), 1381–1399 (1996).
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Science (1)

D. Boyer, P. Tamarat, A. Maali, B. Lounis, and M. Orrit, “Photothermal imaging of nanometer-sized metal particles among scatterers,” Science297(5584), 1160–1163 (2002).
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Figures (7)

Fig. 1
Fig. 1

GNR characterization and imaging instrumentation. (a) Spectrophotometry curves of GNRs before (dashed) and after (solid) PEG coating, showing peak extinction at 725 nm. (b-c) TEM images of GNR sample at two scales. GNR size was 45.2 ± 5.7 nm long by 13.2 ± 1.8 nm (n = 20). (d) DLS curve before (dashed) and after (solid) addition of PEG coating, showing rightwards shift and increase in overall size. (e) PT-OCT imaging instrumentation. SLD: super luminescent diode; CCD: charge coupled device; 50/50: 50/50 fiber splitter.

Fig. 2
Fig. 2

PT-OCT signal processing basics. (a) M-mode OCT magnitude scan (a.u.) as a function of time and depth. (b) Accompanying M-mode OCT phase (in radians) scan as a function of depth and time. (c) Representative temporal phase information at one point in depth (red arrow in 1b), showing amplitude modulated fluctuations of phase due to photothermal heating. (d) Fourier transform of temporal phase data, showing distinct peak at the photothermal modulation frequency (200 Hz) in units of nm displacement in OPL. Data taken in common path configuration.

Fig. 3
Fig. 3

Comparison of experimental PT-OCT and theoretical photothermal heating signals. (a) Temporal plot of one photothermal heating cycle at f0 = 200 Hz. The model (dashed, change in degrees K) predicts temperature dynamics similar to the experimentally measured (solid, change in radians) phase changes of an 800 pM GNR sample imaged with PT-OCT. (b) The photothermal pump laser power and the PT-OCT signal are linearly related in both the model and experiments. (c) An increase in the chopping frequency of the photothermal pump laser causes a logarithmic decrease in the PT-OCT signal in both the model and experiments. All experimental data collected in common-path mode. Experimental data in (b), (c) plotted as signal ± s.d.

Fig. 4
Fig. 4

The effect of OCT magnitude signal on the photothermal signal. (a) Decreases in the OCT magnitude signal cause no change in the mean PT-OCT signal, as demonstrated by the low correlation coefficient and horizontal linear fit. (b) Decreasing the OCT magnitude signal increases the noise in the PT-OCT signal, due to decreased phase stability of low SNR image points as previously predicted [41,43]. All experimental data collected with a reference arm. Values are plotted as signal ± s.d.

Fig. 5
Fig. 5

PT-OCT signal is linearly related to the concentration of GNR. A GNR sample with a concentration as low as 7.5 pM has a significantly higher (p < 0.01, figure inset) PT-OCT signal than a scattering control (1% Intralipid, red). Values are plotted as signal ± s.d. Data collected in common path configuration.

Fig. 6
Fig. 6

PT-OCT images of capillary tube phantoms. (a) Example OCT magnitude images of GNR + (left) and GNR- (right) solid agarose capillary tube phantoms (a.u.). (b) Mean ± standard deviation OCT signal (a.u.) from a series of n = 5 capillary tube images. (c) Example PT-OCT images of capillary tubes from Fig. 5(a), displaying the ability of PT-OCT to distinguish GNR + from GNR- sample (units of nm optical path length displacement). (d) Mean ± standard deviation of PT-OCT signal (units of nm optical path length displacement) from a series of n = 5 capillary tube images. Data collected with the reference arm intact.

Fig. 7
Fig. 7

In vivo PT-OCT of GNRs. (a) PT-OCT signal in the control mouse ear injected with only Matrigel. (b) The OCT image (grayscale channel) of the control ear, with Doppler (red and blue channels) and PT-OCT (green channel) overlaid. (c) PT-OCT signal in the experimental mouse ear injected with 400 pM GNR in Matrigel. (d) OCT image (grayscale channel) of experimental ear with Doppler (red and blue channels) and PT-OCT (green channel) overlaid. Data collected with the reference arm intact.

Equations (11)

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I(k, t 0 )=2| E R E S |cos(2kz+φ)
I(z, t 0 )= CZT[I(k, t 0 )] | k =| M(z, t 0 ) |exp[iΦ(z, t 0 )]
Φ( z 0 ,t)= 4π λ A( z 0 )sin(2π f 0 t)+φ
ΔΦ( z 0 ,t)= 8 π 2 λ A( z 0 ) f 0 cos(2π f 0 t)Δt+ξ(t)= tan 1 { Im[I( z 0 ,t)I*( z 0 ,t1)] Re[I( z 0 ,t)I*( z 0 ,t1)] }
FT[ΔΦ( z 0 ,t)] | t =| p( z 0 ,f) |exp[iθ( z 0 ,f)]= 8 π 2 λ A( z 0 ) f 0 Δt{ 1 2 [δ(f f 0 )+δ(f+ f 0 )]}
OPL(z)=A(z)= | p(z, f 0 ) |λ 4 π 2 f 0 Δt
T t = ϕ μ a ρc +α 2 T
ΔT(t,r=0)= P μ a 4απρc ln( 1+ tα ω 2 /8 ),ω 1 μ a ,t< t L
ΔT(t t L ,r=0)= P μ a 4απρc ln( 1+ t L α ω 2 /8+α(t t L ) ),ω 1 μ a ,t t L
ΔT(t= t L ,r=0)=Δ T max = P μ a 4απρc ln( 1+ t L α ω 2 /8 )
Δ T max = P μ a 4απρc ln( 1+ α/(2 f 0 ) ω 2 /8 )

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