Abstract

We propose a method for differentiating classes of light scatterers based upon their temporal and polarization properties computed from time series of polarization-sensitive optical coherence tomography (PS-OCT) images. The amplitude (motility) and time scale (autocorrelation decay time) of the speckle fluctuations are combined with the cross-polarization pixel-wise to render Motility-, autocorrelation-, and polarization-sensitive (MAPS) OCT contrast images. This combination of metrics provides high specificity for discriminating diffusive gold nanorods and mammary epithelial cell spheroids within 3D tissue culture, based on their unique MAPS signature. This has implications toward highly specific contrast in molecular (nanoparticle-based) and functional (cellular activity) imaging using standard PS-OCT hardware.

© 2013 Optical Society of America

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2013

J. Lee, H. Radhakrishnan, W. Wu, A. Daneshmand, M. Climov, C. Ayata, and D. A. Boas, J. Cereb. Blood Flow Metab. 33, 819 (2013).
[CrossRef]

S. Prabhulkar, J. Matthews, S. Rawal, and R. M. Awdeh, Investig. Ophthalmol. Vis. Sci. 54, 1192 (2013).
[CrossRef]

2012

2011

F. E. Robles, C. Wilson, G. Grant, and A. Wax, Nat. Photonics 5, 744 (2011).
[CrossRef]

G. Farhat, A. Mariampillai, V. X. D. Yang, G. J. Czarnota, and M. C. Kolios, J. Biomed. Opt. 16, 070505 (2011).
[CrossRef]

R. K. Chhetri, K. A. Kozek, A. C. Johnston-Peck, J. B. Tracy, and A. L. Oldenburg, Phys. Rev. E 83, 040903 (2011).
[CrossRef]

A. L. Oldenburg and R. K. Chhetri, Proc. SPIE 7889, 78891V (2011).

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

2010

J. Kalkman, R. Sprik, and T. G. van Leeuwen, Phys. Rev. Lett. 105, 198302 (2010).
[CrossRef]

D. Jacob, R. L. Shelton, and B. E. Applegate, Opt. Express 18, 12399 (2010).
[CrossRef]

2009

A. L. Oldenburg, M. N. Hansen, T. S. Ralston, A. Wei, and S. A. Boppart, J. Mater. Chem. 19, 6407 (2009).
[CrossRef]

2008

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

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

2006

N. Khlebtsov, A. Mel’nikov, V. Bogatyrev, A. Alekseeva, and B. Khlebtsov, Opt. Spectrosc. 100, 448 (2006).
[CrossRef]

2003

B. Nikoobakht and M. A. El-Sayed, Chem. Mater. 15, 1957 (2003).
[CrossRef]

2001

M. J. Bissell and D. Radisky, Nat. Rev. Cancer 1, 46 (2001).
[CrossRef]

1997

Adler, D. C.

Alekseeva, A.

N. Khlebtsov, A. Mel’nikov, V. Bogatyrev, A. Alekseeva, and B. Khlebtsov, Opt. Spectrosc. 100, 448 (2006).
[CrossRef]

Alkilany, A. M.

A. M. Alkilany, L. B. Thompson, S. P. Boulos, P. N. Sisco, and C. J. Murphy, Adv. Drug Deliv. Rev. 64, 190 (2012).
[CrossRef]

An, R.

Applegate, B. E.

Awdeh, R. M.

S. Prabhulkar, J. Matthews, S. Rawal, and R. M. Awdeh, Investig. Ophthalmol. Vis. Sci. 54, 1192 (2013).
[CrossRef]

Ayata, C.

J. Lee, H. Radhakrishnan, W. Wu, A. Daneshmand, M. Climov, C. Ayata, and D. A. Boas, J. Cereb. Blood Flow Metab. 33, 819 (2013).
[CrossRef]

Barry, S.

Bissell, M. J.

M. J. Bissell and D. Radisky, Nat. Rev. Cancer 1, 46 (2001).
[CrossRef]

Boas, D. A.

J. Lee, H. Radhakrishnan, W. Wu, A. Daneshmand, M. Climov, C. Ayata, and D. A. Boas, J. Cereb. Blood Flow Metab. 33, 819 (2013).
[CrossRef]

J. Lee, W. Wu, J. Y. Jiang, B. Zhu, and D. A. Boas, Opt. Express 20, 22262 (2012).
[CrossRef]

Bogatyrev, V.

N. Khlebtsov, A. Mel’nikov, V. Bogatyrev, A. Alekseeva, and B. Khlebtsov, Opt. Spectrosc. 100, 448 (2006).
[CrossRef]

Bohren, C. F.

C. F. Bohren and D. R. Huffman, Absorption and Scattering of Light by Small Particles (Wiley, 1983).

Boppart, S. A.

A. L. Oldenburg, M. N. Hansen, T. S. Ralston, A. Wei, and S. A. Boppart, J. Mater. Chem. 19, 6407 (2009).
[CrossRef]

Boulos, S. P.

A. M. Alkilany, L. B. Thompson, S. P. Boulos, P. N. Sisco, and C. J. Murphy, Adv. Drug Deliv. Rev. 64, 190 (2012).
[CrossRef]

Brauer, H. A.

P. Casbas-Hernandez, M. D’Arcy, E. Roman-Perez, H. A. Brauer, K. McNaughton, R. K. Chhetri, A. L. Oldenburg, and M. A. Troester, Breast Cancer Res. (2013) (to be published).

Button, B.

Cable, A. E.

Casbas-Hernandez, P.

P. Casbas-Hernandez, M. D’Arcy, E. Roman-Perez, H. A. Brauer, K. McNaughton, R. K. Chhetri, A. L. Oldenburg, and M. A. Troester, Breast Cancer Res. (2013) (to be published).

Chhetri, R. K.

R. K. Chhetri, Z. F. Phillips, M. A. Troester, and A. L. Oldenburg, PLoS One 7, e49148 (2012).
[CrossRef]

A. L. Oldenburg, R. K. Chhetri, D. B. Hill, and B. Button, Biomed. Opt. Express 3, 1978 (2012).
[CrossRef]

R. K. Chhetri, K. A. Kozek, A. C. Johnston-Peck, J. B. Tracy, and A. L. Oldenburg, Phys. Rev. E 83, 040903 (2011).
[CrossRef]

A. L. Oldenburg and R. K. Chhetri, Proc. SPIE 7889, 78891V (2011).

P. Casbas-Hernandez, M. D’Arcy, E. Roman-Perez, H. A. Brauer, K. McNaughton, R. K. Chhetri, A. L. Oldenburg, and M. A. Troester, Breast Cancer Res. (2013) (to be published).

Climov, M.

J. Lee, H. Radhakrishnan, W. Wu, A. Daneshmand, M. Climov, C. Ayata, and D. A. Boas, J. Cereb. Blood Flow Metab. 33, 819 (2013).
[CrossRef]

Crow, M. J.

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

Czarnota, G. J.

G. Farhat, A. Mariampillai, V. X. D. Yang, G. J. Czarnota, and M. C. Kolios, J. Biomed. Opt. 16, 070505 (2011).
[CrossRef]

D’Arcy, M.

P. Casbas-Hernandez, M. D’Arcy, E. Roman-Perez, H. A. Brauer, K. McNaughton, R. K. Chhetri, A. L. Oldenburg, and M. A. Troester, Breast Cancer Res. (2013) (to be published).

Daneshmand, A.

J. Lee, H. Radhakrishnan, W. Wu, A. Daneshmand, M. Climov, C. Ayata, and D. A. Boas, J. Cereb. Blood Flow Metab. 33, 819 (2013).
[CrossRef]

de Boer, J. F.

Duvall, C. L.

El-Sayed, M. A.

B. Nikoobakht and M. A. El-Sayed, Chem. Mater. 15, 1957 (2003).
[CrossRef]

Farhat, G.

G. Farhat, A. Mariampillai, V. X. D. Yang, G. J. Czarnota, and M. C. Kolios, J. Biomed. Opt. 16, 070505 (2011).
[CrossRef]

Fischer, T. H.

A. L. Oldenburg, G. Wu, D. Spivak, F. Tsui, A. S. Wolberg, and T. H. Fischer, IEEE J. Sel. Top. Quantum Electron. 18, 1100 (2012).
[CrossRef]

Fujimoto, J. G.

Grant, G.

F. E. Robles, C. Wilson, G. Grant, and A. Wax, Nat. Photonics 5, 744 (2011).
[CrossRef]

Hansen, M. N.

A. L. Oldenburg, M. N. Hansen, T. S. Ralston, A. Wei, and S. A. Boppart, J. Mater. Chem. 19, 6407 (2009).
[CrossRef]

Hill, D. B.

Huang, S.-W.

Huber, R.

Huffman, D. R.

C. F. Bohren and D. R. Huffman, Absorption and Scattering of Light by Small Particles (Wiley, 1983).

Izatt, J. A.

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

Jacob, D.

Jeong, K.

Jiang, J. Y.

Johnston-Peck, A. C.

R. K. Chhetri, K. A. Kozek, A. C. Johnston-Peck, J. B. Tracy, and A. L. Oldenburg, Phys. Rev. E 83, 040903 (2011).
[CrossRef]

Jung, Y.

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

Kalkman, J.

J. Kalkman, R. Sprik, and T. G. van Leeuwen, Phys. Rev. Lett. 105, 198302 (2010).
[CrossRef]

Khlebtsov, B.

N. Khlebtsov, A. Mel’nikov, V. Bogatyrev, A. Alekseeva, and B. Khlebtsov, Opt. Spectrosc. 100, 448 (2006).
[CrossRef]

Khlebtsov, N.

N. Khlebtsov, A. Mel’nikov, V. Bogatyrev, A. Alekseeva, and B. Khlebtsov, Opt. Spectrosc. 100, 448 (2006).
[CrossRef]

Kolios, M. C.

G. Farhat, A. Mariampillai, V. X. D. Yang, G. J. Czarnota, and M. C. Kolios, J. Biomed. Opt. 16, 070505 (2011).
[CrossRef]

Kozek, K. A.

R. K. Chhetri, K. A. Kozek, A. C. Johnston-Peck, J. B. Tracy, and A. L. Oldenburg, Phys. Rev. E 83, 040903 (2011).
[CrossRef]

Lee, J.

J. Lee, H. Radhakrishnan, W. Wu, A. Daneshmand, M. Climov, C. Ayata, and D. A. Boas, J. Cereb. Blood Flow Metab. 33, 819 (2013).
[CrossRef]

J. Lee, W. Wu, J. Y. Jiang, B. Zhu, and D. A. Boas, Opt. Express 20, 22262 (2012).
[CrossRef]

Lo, E. H.

Mandeville, E. T.

Mariampillai, A.

G. Farhat, A. Mariampillai, V. X. D. Yang, G. J. Czarnota, and M. C. Kolios, J. Biomed. Opt. 16, 070505 (2011).
[CrossRef]

Matthews, J.

S. Prabhulkar, J. Matthews, S. Rawal, and R. M. Awdeh, Investig. Ophthalmol. Vis. Sci. 54, 1192 (2013).
[CrossRef]

McNaughton, K.

P. Casbas-Hernandez, M. D’Arcy, E. Roman-Perez, H. A. Brauer, K. McNaughton, R. K. Chhetri, A. L. Oldenburg, and M. A. Troester, Breast Cancer Res. (2013) (to be published).

Mel’nikov, A.

N. Khlebtsov, A. Mel’nikov, V. Bogatyrev, A. Alekseeva, and B. Khlebtsov, Opt. Spectrosc. 100, 448 (2006).
[CrossRef]

Meyer, T. A.

Milner, T. E.

Murphy, C. J.

A. M. Alkilany, L. B. Thompson, S. P. Boulos, P. N. Sisco, and C. J. Murphy, Adv. Drug Deliv. Rev. 64, 190 (2012).
[CrossRef]

Nelson, J. S.

Nikoobakht, B.

B. Nikoobakht and M. A. El-Sayed, Chem. Mater. 15, 1957 (2003).
[CrossRef]

Nolte, D. D.

Oldenburg, A. L.

A. L. Oldenburg, G. Wu, D. Spivak, F. Tsui, A. S. Wolberg, and T. H. Fischer, IEEE J. Sel. Top. Quantum Electron. 18, 1100 (2012).
[CrossRef]

R. K. Chhetri, Z. F. Phillips, M. A. Troester, and A. L. Oldenburg, PLoS One 7, e49148 (2012).
[CrossRef]

A. L. Oldenburg, R. K. Chhetri, D. B. Hill, and B. Button, Biomed. Opt. Express 3, 1978 (2012).
[CrossRef]

R. K. Chhetri, K. A. Kozek, A. C. Johnston-Peck, J. B. Tracy, and A. L. Oldenburg, Phys. Rev. E 83, 040903 (2011).
[CrossRef]

A. L. Oldenburg and R. K. Chhetri, Proc. SPIE 7889, 78891V (2011).

A. L. Oldenburg, M. N. Hansen, T. S. Ralston, A. Wei, and S. A. Boppart, J. Mater. Chem. 19, 6407 (2009).
[CrossRef]

P. Casbas-Hernandez, M. D’Arcy, E. Roman-Perez, H. A. Brauer, K. McNaughton, R. K. Chhetri, A. L. Oldenburg, and M. A. Troester, Breast Cancer Res. (2013) (to be published).

Patil, C. A.

Phillips, Z. F.

R. K. Chhetri, Z. F. Phillips, M. A. Troester, and A. L. Oldenburg, PLoS One 7, e49148 (2012).
[CrossRef]

Prabhulkar, S.

S. Prabhulkar, J. Matthews, S. Rawal, and R. M. Awdeh, Investig. Ophthalmol. Vis. Sci. 54, 1192 (2013).
[CrossRef]

Radhakrishnan, H.

J. Lee, H. Radhakrishnan, W. Wu, A. Daneshmand, M. Climov, C. Ayata, and D. A. Boas, J. Cereb. Blood Flow Metab. 33, 819 (2013).
[CrossRef]

V. J. Srinivasan, H. Radhakrishnan, E. H. Lo, E. T. Mandeville, J. Y. Jiang, S. Barry, and A. E. Cable, Biomed. Opt. Express 3, 612 (2012).
[CrossRef]

Radisky, D.

M. J. Bissell and D. Radisky, Nat. Rev. Cancer 1, 46 (2001).
[CrossRef]

Ralston, T. S.

A. L. Oldenburg, M. N. Hansen, T. S. Ralston, A. Wei, and S. A. Boppart, J. Mater. Chem. 19, 6407 (2009).
[CrossRef]

Rawal, S.

S. Prabhulkar, J. Matthews, S. Rawal, and R. M. Awdeh, Investig. Ophthalmol. Vis. Sci. 54, 1192 (2013).
[CrossRef]

Reif, R.

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

Robles, F. E.

F. E. Robles, C. Wilson, G. Grant, and A. Wax, Nat. Photonics 5, 744 (2011).
[CrossRef]

Roman-Perez, E.

P. Casbas-Hernandez, M. D’Arcy, E. Roman-Perez, H. A. Brauer, K. McNaughton, R. K. Chhetri, A. L. Oldenburg, and M. A. Troester, Breast Cancer Res. (2013) (to be published).

Shelton, R. L.

Sisco, P. N.

A. M. Alkilany, L. B. Thompson, S. P. Boulos, P. N. Sisco, and C. J. Murphy, Adv. Drug Deliv. Rev. 64, 190 (2012).
[CrossRef]

Skala, M. C.

Spivak, D.

A. L. Oldenburg, G. Wu, D. Spivak, F. Tsui, A. S. Wolberg, and T. H. Fischer, IEEE J. Sel. Top. Quantum Electron. 18, 1100 (2012).
[CrossRef]

Sprik, R.

J. Kalkman, R. Sprik, and T. G. van Leeuwen, Phys. Rev. Lett. 105, 198302 (2010).
[CrossRef]

Srinivasan, V. J.

Thompson, L. B.

A. M. Alkilany, L. B. Thompson, S. P. Boulos, P. N. Sisco, and C. J. Murphy, Adv. Drug Deliv. Rev. 64, 190 (2012).
[CrossRef]

Tracy, J. B.

R. K. Chhetri, K. A. Kozek, A. C. Johnston-Peck, J. B. Tracy, and A. L. Oldenburg, Phys. Rev. E 83, 040903 (2011).
[CrossRef]

Troester, M. A.

R. K. Chhetri, Z. F. Phillips, M. A. Troester, and A. L. Oldenburg, PLoS One 7, e49148 (2012).
[CrossRef]

P. Casbas-Hernandez, M. D’Arcy, E. Roman-Perez, H. A. Brauer, K. McNaughton, R. K. Chhetri, A. L. Oldenburg, and M. A. Troester, Breast Cancer Res. (2013) (to be published).

Tsui, F.

A. L. Oldenburg, G. Wu, D. Spivak, F. Tsui, A. S. Wolberg, and T. H. Fischer, IEEE J. Sel. Top. Quantum Electron. 18, 1100 (2012).
[CrossRef]

Tucker-Schwartz, J. M.

Turek, J.

van Gemert, M. J.

van Leeuwen, T. G.

J. Kalkman, R. Sprik, and T. G. van Leeuwen, Phys. Rev. Lett. 105, 198302 (2010).
[CrossRef]

Wang, R. K.

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

Wax, A.

F. E. Robles, C. Wilson, G. Grant, and A. Wax, Nat. Photonics 5, 744 (2011).
[CrossRef]

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

Wei, A.

A. L. Oldenburg, M. N. Hansen, T. S. Ralston, A. Wei, and S. A. Boppart, J. Mater. Chem. 19, 6407 (2009).
[CrossRef]

Wilson, C.

F. E. Robles, C. Wilson, G. Grant, and A. Wax, Nat. Photonics 5, 744 (2011).
[CrossRef]

Wolberg, A. S.

A. L. Oldenburg, G. Wu, D. Spivak, F. Tsui, A. S. Wolberg, and T. H. Fischer, IEEE J. Sel. Top. Quantum Electron. 18, 1100 (2012).
[CrossRef]

Wu, G.

A. L. Oldenburg, G. Wu, D. Spivak, F. Tsui, A. S. Wolberg, and T. H. Fischer, IEEE J. Sel. Top. Quantum Electron. 18, 1100 (2012).
[CrossRef]

Wu, W.

J. Lee, H. Radhakrishnan, W. Wu, A. Daneshmand, M. Climov, C. Ayata, and D. A. Boas, J. Cereb. Blood Flow Metab. 33, 819 (2013).
[CrossRef]

J. Lee, W. Wu, J. Y. Jiang, B. Zhu, and D. A. Boas, Opt. Express 20, 22262 (2012).
[CrossRef]

Yang, V. X. D.

G. Farhat, A. Mariampillai, V. X. D. Yang, G. J. Czarnota, and M. C. Kolios, J. Biomed. Opt. 16, 070505 (2011).
[CrossRef]

Zeng, Y.

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

Zhu, B.

Adv. Drug Deliv. Rev.

A. M. Alkilany, L. B. Thompson, S. P. Boulos, P. N. Sisco, and C. J. Murphy, Adv. Drug Deliv. Rev. 64, 190 (2012).
[CrossRef]

Biomed. Opt. Express

Chem. Mater.

B. Nikoobakht and M. A. El-Sayed, Chem. Mater. 15, 1957 (2003).
[CrossRef]

IEEE J. Sel. Top. Quantum Electron.

A. L. Oldenburg, G. Wu, D. Spivak, F. Tsui, A. S. Wolberg, and T. H. Fischer, IEEE J. Sel. Top. Quantum Electron. 18, 1100 (2012).
[CrossRef]

Investig. Ophthalmol. Vis. Sci.

S. Prabhulkar, J. Matthews, S. Rawal, and R. M. Awdeh, Investig. Ophthalmol. Vis. Sci. 54, 1192 (2013).
[CrossRef]

J. Biomed. Opt.

G. Farhat, A. Mariampillai, V. X. D. Yang, G. J. Czarnota, and M. C. Kolios, J. Biomed. Opt. 16, 070505 (2011).
[CrossRef]

J. Cereb. Blood Flow Metab.

J. Lee, H. Radhakrishnan, W. Wu, A. Daneshmand, M. Climov, C. Ayata, and D. A. Boas, J. Cereb. Blood Flow Metab. 33, 819 (2013).
[CrossRef]

J. Mater. Chem.

A. L. Oldenburg, M. N. Hansen, T. S. Ralston, A. Wei, and S. A. Boppart, J. Mater. Chem. 19, 6407 (2009).
[CrossRef]

Nano Lett.

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

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

Nat. Photonics

F. E. Robles, C. Wilson, G. Grant, and A. Wax, Nat. Photonics 5, 744 (2011).
[CrossRef]

Nat. Rev. Cancer

M. J. Bissell and D. Radisky, Nat. Rev. Cancer 1, 46 (2001).
[CrossRef]

Opt. Express

Opt. Lett.

Opt. Spectrosc.

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Figures (4)

Fig. 1.
Fig. 1.

Transmission electron microscopy (left) and extinction spectrum (right) of the PEGylated GNRs used in these experiments.

Fig. 2.
Fig. 2.

Image stacks of 4 collagen:Matrigel tissue cultures containing both MECs and GNRs (top row), MECs only (second row), GNRs only (third row) and control (bottom row). Each column displays a different way of processing the image stacks, as described in the text. Images represent 1.4mm×0.6mm in x and z.

Fig. 3.
Fig. 3.

MAPS images for tissue culture samples corresponding to the top two rows of Fig. 2. The GNRs MAPS signature (left column) and MECs MAPS signature (middle) are combined to display a multicontrast image of both GNRs and MECs (right).

Fig. 4.
Fig. 4.

Magnified views (0.27mm×0.21mm, x×z) of MEC spheroids in MEC tissue cultures with GNRs (top half) and without GNRs (bottom half), corresponding to the data of Figs. 2 and 3.

Tables (1)

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Table 1. MAPS Signature for Each Object Class, where and Indicate a High or Low Value, Respectively

Equations (3)

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M(x,z)=1Ni=1N(SOCT(x,z,ti)SOCT(x,z))2SOCT(x,z),
C(x,z)=1Ni=1N(SHV(x,z,ti)2SHH(x,z,ti)2+SHV(x,z,ti)2),
SMEC(x,z)=M(x,z)*τ(x,z)*(255C(x,z))SGNR(x,z)=M(x,z)*(255τ(x,z))*C(x,z).

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