Abstract

Multispectral optoacoustic tomography (MSOT) offers the potential to image in high-resolution cells tagged with optical labels. In contrast to single wavelength imaging, multispectral excitation and spectral unmixing can differentiate labeled moieties over tissue absorption in the absence of background measurements. This feature can enable longitudinal cellular biology studies well beyond the depths reached by optical microscopy. However, the relation between spectrally resolved fluorescently labeled cells and optoacoustic detection has not been systematically investigated. Herein, we measured titrations of fluorescently labeled cells and establish the optoacoustic signal generated by these cells as a function of cell number and across different cell types. We then assess the MSOT sensitivity to resolve cells implanted in animals.

© 2014 Optical Society of America

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  1. J. Condeelis and J. E. Segall, Nat. Rev. Cancer 3, 921 (2003).
    [CrossRef]
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    [CrossRef]
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    [CrossRef]
  4. J. A. Thomas, C. Pope, D. Wojtacha, A. J. Robson, T. T. Gordon-Walker, S. Hartland, P. Ramachandran, M. Van Deemter, D. A. Hume, J. P. Iredale, and S. J. Forbes, Hepatology 53, 2003 (2011).
    [CrossRef]
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    [CrossRef]
  6. E. M. Strohm, E. S. Berndl, and M. C. Kolios, J. Photoacoustics 1, 49 (2013).
    [CrossRef]
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    [CrossRef]
  8. A. Taruttis, M. Wildgruber, K. Kosanke, N. Beziere, K. Licha, R. Haag, M. Aichler, A. Walch, E. Rummeny, and V. Ntziachristos, J. Photoacoustics 1, 3 (2013).
    [CrossRef]
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    [CrossRef]
  16. D. Razansky, J. Baeten, and V. Ntziachristos, Med. Phys. 36, 939 (2009).
    [CrossRef]

2014 (1)

S. Tzoumas, N. Deliolanis, S. Morscher, and V. Ntziachristos, IEEE Trans. Med. Imaging, 33, 48 (2014).
[CrossRef]

2013 (5)

P. P. Joshi, S. J. Yoon, Y.-S. Chen, S. Emelianov, and K. V. Sokolov, Biomed. Opt. Express 4, 2609 (2013).
[CrossRef]

S. L. Jacques, Phys. Med. Biol. 58, 37 (2013).
[CrossRef]

H. Liu, X. Wu, S. Wang, W. Deng, L. Zan, and S. Yu, Oncol.Res. 20, 275 (2013).
[CrossRef]

E. M. Strohm, E. S. Berndl, and M. C. Kolios, J. Photoacoustics 1, 49 (2013).
[CrossRef]

A. Taruttis, M. Wildgruber, K. Kosanke, N. Beziere, K. Licha, R. Haag, M. Aichler, A. Walch, E. Rummeny, and V. Ntziachristos, J. Photoacoustics 1, 3 (2013).
[CrossRef]

2012 (2)

S. Y. Nam, L. M. Ricles, L. J. Suggs, and S. Y. Emelianov, PLoS One 7, e37267 (2012).
[CrossRef]

N. P. Restifo, M. E. Dudley, and S. A. Rosenberg, Nat. Rev. Immunol. 12, 269 (2012).
[CrossRef]

2011 (2)

J. A. Thomas, C. Pope, D. Wojtacha, A. J. Robson, T. T. Gordon-Walker, S. Hartland, P. Ramachandran, M. Van Deemter, D. A. Hume, J. P. Iredale, and S. J. Forbes, Hepatology 53, 2003 (2011).
[CrossRef]

A. Sarantopoulos, G. Themelis, and V. Ntziachristos, Molecular Imaging Biol. 13, 874 (2011).
[CrossRef]

2010 (3)

A. Rosenthal, D. Razansky, and V. Ntziachristos, IEEE Trans. Med. Imaging 29, 1275 (2010).
[CrossRef]

A. Buehler, E. Herzog, D. Razansky, and V. Ntziachristos, Opt. Lett. 35, 2475 (2010).
[CrossRef]

D. Ferenbach and D. Kluth, Semin. nephrol. 30, 345 (2010).
[CrossRef]

2009 (2)

D. Razansky, M. Distel, C. Vinegoni, R. Ma, N. Perrimon, R. W. Koster, and V. Ntziachristos, Nat. Photonics 3, 412 (2009).
[CrossRef]

D. Razansky, J. Baeten, and V. Ntziachristos, Med. Phys. 36, 939 (2009).
[CrossRef]

2003 (1)

J. Condeelis and J. E. Segall, Nat. Rev. Cancer 3, 921 (2003).
[CrossRef]

Aichler, M.

A. Taruttis, M. Wildgruber, K. Kosanke, N. Beziere, K. Licha, R. Haag, M. Aichler, A. Walch, E. Rummeny, and V. Ntziachristos, J. Photoacoustics 1, 3 (2013).
[CrossRef]

Baeten, J.

D. Razansky, J. Baeten, and V. Ntziachristos, Med. Phys. 36, 939 (2009).
[CrossRef]

Berndl, E. S.

E. M. Strohm, E. S. Berndl, and M. C. Kolios, J. Photoacoustics 1, 49 (2013).
[CrossRef]

Beziere, N.

A. Taruttis, M. Wildgruber, K. Kosanke, N. Beziere, K. Licha, R. Haag, M. Aichler, A. Walch, E. Rummeny, and V. Ntziachristos, J. Photoacoustics 1, 3 (2013).
[CrossRef]

Buehler, A.

Chen, Y.-S.

Condeelis, J.

J. Condeelis and J. E. Segall, Nat. Rev. Cancer 3, 921 (2003).
[CrossRef]

Deliolanis, N.

S. Tzoumas, N. Deliolanis, S. Morscher, and V. Ntziachristos, IEEE Trans. Med. Imaging, 33, 48 (2014).
[CrossRef]

Deng, W.

H. Liu, X. Wu, S. Wang, W. Deng, L. Zan, and S. Yu, Oncol.Res. 20, 275 (2013).
[CrossRef]

Distel, M.

D. Razansky, M. Distel, C. Vinegoni, R. Ma, N. Perrimon, R. W. Koster, and V. Ntziachristos, Nat. Photonics 3, 412 (2009).
[CrossRef]

Dudley, M. E.

N. P. Restifo, M. E. Dudley, and S. A. Rosenberg, Nat. Rev. Immunol. 12, 269 (2012).
[CrossRef]

Emelianov, S.

Emelianov, S. Y.

S. Y. Nam, L. M. Ricles, L. J. Suggs, and S. Y. Emelianov, PLoS One 7, e37267 (2012).
[CrossRef]

Ferenbach, D.

D. Ferenbach and D. Kluth, Semin. nephrol. 30, 345 (2010).
[CrossRef]

Forbes, S. J.

J. A. Thomas, C. Pope, D. Wojtacha, A. J. Robson, T. T. Gordon-Walker, S. Hartland, P. Ramachandran, M. Van Deemter, D. A. Hume, J. P. Iredale, and S. J. Forbes, Hepatology 53, 2003 (2011).
[CrossRef]

Gordon-Walker, T. T.

J. A. Thomas, C. Pope, D. Wojtacha, A. J. Robson, T. T. Gordon-Walker, S. Hartland, P. Ramachandran, M. Van Deemter, D. A. Hume, J. P. Iredale, and S. J. Forbes, Hepatology 53, 2003 (2011).
[CrossRef]

Haag, R.

A. Taruttis, M. Wildgruber, K. Kosanke, N. Beziere, K. Licha, R. Haag, M. Aichler, A. Walch, E. Rummeny, and V. Ntziachristos, J. Photoacoustics 1, 3 (2013).
[CrossRef]

Hartland, S.

J. A. Thomas, C. Pope, D. Wojtacha, A. J. Robson, T. T. Gordon-Walker, S. Hartland, P. Ramachandran, M. Van Deemter, D. A. Hume, J. P. Iredale, and S. J. Forbes, Hepatology 53, 2003 (2011).
[CrossRef]

Herzog, E.

Hume, D. A.

J. A. Thomas, C. Pope, D. Wojtacha, A. J. Robson, T. T. Gordon-Walker, S. Hartland, P. Ramachandran, M. Van Deemter, D. A. Hume, J. P. Iredale, and S. J. Forbes, Hepatology 53, 2003 (2011).
[CrossRef]

Iredale, J. P.

J. A. Thomas, C. Pope, D. Wojtacha, A. J. Robson, T. T. Gordon-Walker, S. Hartland, P. Ramachandran, M. Van Deemter, D. A. Hume, J. P. Iredale, and S. J. Forbes, Hepatology 53, 2003 (2011).
[CrossRef]

Jacques, S. L.

S. L. Jacques, Phys. Med. Biol. 58, 37 (2013).
[CrossRef]

Joshi, P. P.

Kluth, D.

D. Ferenbach and D. Kluth, Semin. nephrol. 30, 345 (2010).
[CrossRef]

Kolios, M. C.

E. M. Strohm, E. S. Berndl, and M. C. Kolios, J. Photoacoustics 1, 49 (2013).
[CrossRef]

Kosanke, K.

A. Taruttis, M. Wildgruber, K. Kosanke, N. Beziere, K. Licha, R. Haag, M. Aichler, A. Walch, E. Rummeny, and V. Ntziachristos, J. Photoacoustics 1, 3 (2013).
[CrossRef]

Koster, R. W.

D. Razansky, M. Distel, C. Vinegoni, R. Ma, N. Perrimon, R. W. Koster, and V. Ntziachristos, Nat. Photonics 3, 412 (2009).
[CrossRef]

Licha, K.

A. Taruttis, M. Wildgruber, K. Kosanke, N. Beziere, K. Licha, R. Haag, M. Aichler, A. Walch, E. Rummeny, and V. Ntziachristos, J. Photoacoustics 1, 3 (2013).
[CrossRef]

Liu, H.

H. Liu, X. Wu, S. Wang, W. Deng, L. Zan, and S. Yu, Oncol.Res. 20, 275 (2013).
[CrossRef]

Ma, R.

D. Razansky, M. Distel, C. Vinegoni, R. Ma, N. Perrimon, R. W. Koster, and V. Ntziachristos, Nat. Photonics 3, 412 (2009).
[CrossRef]

Morscher, S.

S. Tzoumas, N. Deliolanis, S. Morscher, and V. Ntziachristos, IEEE Trans. Med. Imaging, 33, 48 (2014).
[CrossRef]

Nam, S. Y.

S. Y. Nam, L. M. Ricles, L. J. Suggs, and S. Y. Emelianov, PLoS One 7, e37267 (2012).
[CrossRef]

Ntziachristos, V.

S. Tzoumas, N. Deliolanis, S. Morscher, and V. Ntziachristos, IEEE Trans. Med. Imaging, 33, 48 (2014).
[CrossRef]

A. Taruttis, M. Wildgruber, K. Kosanke, N. Beziere, K. Licha, R. Haag, M. Aichler, A. Walch, E. Rummeny, and V. Ntziachristos, J. Photoacoustics 1, 3 (2013).
[CrossRef]

A. Sarantopoulos, G. Themelis, and V. Ntziachristos, Molecular Imaging Biol. 13, 874 (2011).
[CrossRef]

A. Buehler, E. Herzog, D. Razansky, and V. Ntziachristos, Opt. Lett. 35, 2475 (2010).
[CrossRef]

A. Rosenthal, D. Razansky, and V. Ntziachristos, IEEE Trans. Med. Imaging 29, 1275 (2010).
[CrossRef]

D. Razansky, J. Baeten, and V. Ntziachristos, Med. Phys. 36, 939 (2009).
[CrossRef]

D. Razansky, M. Distel, C. Vinegoni, R. Ma, N. Perrimon, R. W. Koster, and V. Ntziachristos, Nat. Photonics 3, 412 (2009).
[CrossRef]

Perrimon, N.

D. Razansky, M. Distel, C. Vinegoni, R. Ma, N. Perrimon, R. W. Koster, and V. Ntziachristos, Nat. Photonics 3, 412 (2009).
[CrossRef]

Pope, C.

J. A. Thomas, C. Pope, D. Wojtacha, A. J. Robson, T. T. Gordon-Walker, S. Hartland, P. Ramachandran, M. Van Deemter, D. A. Hume, J. P. Iredale, and S. J. Forbes, Hepatology 53, 2003 (2011).
[CrossRef]

Ramachandran, P.

J. A. Thomas, C. Pope, D. Wojtacha, A. J. Robson, T. T. Gordon-Walker, S. Hartland, P. Ramachandran, M. Van Deemter, D. A. Hume, J. P. Iredale, and S. J. Forbes, Hepatology 53, 2003 (2011).
[CrossRef]

Razansky, D.

A. Rosenthal, D. Razansky, and V. Ntziachristos, IEEE Trans. Med. Imaging 29, 1275 (2010).
[CrossRef]

A. Buehler, E. Herzog, D. Razansky, and V. Ntziachristos, Opt. Lett. 35, 2475 (2010).
[CrossRef]

D. Razansky, J. Baeten, and V. Ntziachristos, Med. Phys. 36, 939 (2009).
[CrossRef]

D. Razansky, M. Distel, C. Vinegoni, R. Ma, N. Perrimon, R. W. Koster, and V. Ntziachristos, Nat. Photonics 3, 412 (2009).
[CrossRef]

Restifo, N. P.

N. P. Restifo, M. E. Dudley, and S. A. Rosenberg, Nat. Rev. Immunol. 12, 269 (2012).
[CrossRef]

Ricles, L. M.

S. Y. Nam, L. M. Ricles, L. J. Suggs, and S. Y. Emelianov, PLoS One 7, e37267 (2012).
[CrossRef]

Robson, A. J.

J. A. Thomas, C. Pope, D. Wojtacha, A. J. Robson, T. T. Gordon-Walker, S. Hartland, P. Ramachandran, M. Van Deemter, D. A. Hume, J. P. Iredale, and S. J. Forbes, Hepatology 53, 2003 (2011).
[CrossRef]

Rosenberg, S. A.

N. P. Restifo, M. E. Dudley, and S. A. Rosenberg, Nat. Rev. Immunol. 12, 269 (2012).
[CrossRef]

Rosenthal, A.

A. Rosenthal, D. Razansky, and V. Ntziachristos, IEEE Trans. Med. Imaging 29, 1275 (2010).
[CrossRef]

Rummeny, E.

A. Taruttis, M. Wildgruber, K. Kosanke, N. Beziere, K. Licha, R. Haag, M. Aichler, A. Walch, E. Rummeny, and V. Ntziachristos, J. Photoacoustics 1, 3 (2013).
[CrossRef]

Sarantopoulos, A.

A. Sarantopoulos, G. Themelis, and V. Ntziachristos, Molecular Imaging Biol. 13, 874 (2011).
[CrossRef]

Segall, J. E.

J. Condeelis and J. E. Segall, Nat. Rev. Cancer 3, 921 (2003).
[CrossRef]

Sokolov, K. V.

Strohm, E. M.

E. M. Strohm, E. S. Berndl, and M. C. Kolios, J. Photoacoustics 1, 49 (2013).
[CrossRef]

Suggs, L. J.

S. Y. Nam, L. M. Ricles, L. J. Suggs, and S. Y. Emelianov, PLoS One 7, e37267 (2012).
[CrossRef]

Taruttis, A.

A. Taruttis, M. Wildgruber, K. Kosanke, N. Beziere, K. Licha, R. Haag, M. Aichler, A. Walch, E. Rummeny, and V. Ntziachristos, J. Photoacoustics 1, 3 (2013).
[CrossRef]

Themelis, G.

A. Sarantopoulos, G. Themelis, and V. Ntziachristos, Molecular Imaging Biol. 13, 874 (2011).
[CrossRef]

Thomas, J. A.

J. A. Thomas, C. Pope, D. Wojtacha, A. J. Robson, T. T. Gordon-Walker, S. Hartland, P. Ramachandran, M. Van Deemter, D. A. Hume, J. P. Iredale, and S. J. Forbes, Hepatology 53, 2003 (2011).
[CrossRef]

Tzoumas, S.

S. Tzoumas, N. Deliolanis, S. Morscher, and V. Ntziachristos, IEEE Trans. Med. Imaging, 33, 48 (2014).
[CrossRef]

Van Deemter, M.

J. A. Thomas, C. Pope, D. Wojtacha, A. J. Robson, T. T. Gordon-Walker, S. Hartland, P. Ramachandran, M. Van Deemter, D. A. Hume, J. P. Iredale, and S. J. Forbes, Hepatology 53, 2003 (2011).
[CrossRef]

Vinegoni, C.

D. Razansky, M. Distel, C. Vinegoni, R. Ma, N. Perrimon, R. W. Koster, and V. Ntziachristos, Nat. Photonics 3, 412 (2009).
[CrossRef]

Walch, A.

A. Taruttis, M. Wildgruber, K. Kosanke, N. Beziere, K. Licha, R. Haag, M. Aichler, A. Walch, E. Rummeny, and V. Ntziachristos, J. Photoacoustics 1, 3 (2013).
[CrossRef]

Wang, S.

H. Liu, X. Wu, S. Wang, W. Deng, L. Zan, and S. Yu, Oncol.Res. 20, 275 (2013).
[CrossRef]

Wildgruber, M.

A. Taruttis, M. Wildgruber, K. Kosanke, N. Beziere, K. Licha, R. Haag, M. Aichler, A. Walch, E. Rummeny, and V. Ntziachristos, J. Photoacoustics 1, 3 (2013).
[CrossRef]

Wojtacha, D.

J. A. Thomas, C. Pope, D. Wojtacha, A. J. Robson, T. T. Gordon-Walker, S. Hartland, P. Ramachandran, M. Van Deemter, D. A. Hume, J. P. Iredale, and S. J. Forbes, Hepatology 53, 2003 (2011).
[CrossRef]

Wu, X.

H. Liu, X. Wu, S. Wang, W. Deng, L. Zan, and S. Yu, Oncol.Res. 20, 275 (2013).
[CrossRef]

Yoon, S. J.

Yu, S.

H. Liu, X. Wu, S. Wang, W. Deng, L. Zan, and S. Yu, Oncol.Res. 20, 275 (2013).
[CrossRef]

Zan, L.

H. Liu, X. Wu, S. Wang, W. Deng, L. Zan, and S. Yu, Oncol.Res. 20, 275 (2013).
[CrossRef]

Biomed. Opt. Express (1)

Hepatology (1)

J. A. Thomas, C. Pope, D. Wojtacha, A. J. Robson, T. T. Gordon-Walker, S. Hartland, P. Ramachandran, M. Van Deemter, D. A. Hume, J. P. Iredale, and S. J. Forbes, Hepatology 53, 2003 (2011).
[CrossRef]

IEEE Trans. Med. Imaging (2)

S. Tzoumas, N. Deliolanis, S. Morscher, and V. Ntziachristos, IEEE Trans. Med. Imaging, 33, 48 (2014).
[CrossRef]

A. Rosenthal, D. Razansky, and V. Ntziachristos, IEEE Trans. Med. Imaging 29, 1275 (2010).
[CrossRef]

J. Photoacoustics (2)

E. M. Strohm, E. S. Berndl, and M. C. Kolios, J. Photoacoustics 1, 49 (2013).
[CrossRef]

A. Taruttis, M. Wildgruber, K. Kosanke, N. Beziere, K. Licha, R. Haag, M. Aichler, A. Walch, E. Rummeny, and V. Ntziachristos, J. Photoacoustics 1, 3 (2013).
[CrossRef]

Med. Phys. (1)

D. Razansky, J. Baeten, and V. Ntziachristos, Med. Phys. 36, 939 (2009).
[CrossRef]

Molecular Imaging Biol. (1)

A. Sarantopoulos, G. Themelis, and V. Ntziachristos, Molecular Imaging Biol. 13, 874 (2011).
[CrossRef]

Nat. Photonics (1)

D. Razansky, M. Distel, C. Vinegoni, R. Ma, N. Perrimon, R. W. Koster, and V. Ntziachristos, Nat. Photonics 3, 412 (2009).
[CrossRef]

Nat. Rev. Cancer (1)

J. Condeelis and J. E. Segall, Nat. Rev. Cancer 3, 921 (2003).
[CrossRef]

Nat. Rev. Immunol. (1)

N. P. Restifo, M. E. Dudley, and S. A. Rosenberg, Nat. Rev. Immunol. 12, 269 (2012).
[CrossRef]

Oncol.Res. (1)

H. Liu, X. Wu, S. Wang, W. Deng, L. Zan, and S. Yu, Oncol.Res. 20, 275 (2013).
[CrossRef]

Opt. Lett. (1)

Phys. Med. Biol. (1)

S. L. Jacques, Phys. Med. Biol. 58, 37 (2013).
[CrossRef]

PLoS One (1)

S. Y. Nam, L. M. Ricles, L. J. Suggs, and S. Y. Emelianov, PLoS One 7, e37267 (2012).
[CrossRef]

Semin. nephrol. (1)

D. Ferenbach and D. Kluth, Semin. nephrol. 30, 345 (2010).
[CrossRef]

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Figures (3)

Fig. 1.
Fig. 1.

In vitro optoacoustic imaging (720 nm) of DiR-labeled cells. (a) Schematic of the phantoms used in the in vitro tests. Labeled and unlabeled cells are inserted in 3 mm diameter tubes that are placed within a 20 mm diameter scattering phantom. (b) Imaging of Jurkat cells: (i)–(iii) optoacoustic signal generated by 1250, 2500, and 5000 DiR-labeled cells, respectively; and (iv) optoacoustic signal intensity comparison for different amounts of labeled cells. The bar heights indicate the mean intensity within the region of interest and the error bars indicate the standard deviation. (c) Imaging of J774A.1 cells: (i)–(iii) optoacoustic signal generated by 1250, 2500, and 5000 DiR-labeled J774A.1 cells, respectively; and (iv) optoacoustic signal intensity comparison for different amounts of labeled cells. The bar heights indicate the mean intensity within the region of interest and the error bars indicate the standard deviation.

Fig. 2.
Fig. 2.

Comparison and quantification of the absorbance of DiR-labeled cells. Single-wavelength (720 nm) optoacoustic phantom images of (a) 5000 DiR-labeled Jurkat cells and (b) J774A.1 cells, next to black India Ink of absorption coefficient 0.5cm1. (c) Comparison in terms of optoacoustic signal intensity between the ink reference and the 5000 Jurkat and J774A.1 cells. (d) Comparison of the cell diameters of Jurkat and J774A.1 cells.

Fig. 3.
Fig. 3.

Ex vivo animal study. (a) and (c) Overlay of the spectrally resolved signal stemming from the DiR-labeled J774A.1 cells (red color) onto the anatomical optoacoustic image (at 900 nm) for experiments A and B, respectively. The white arrows indicate the positions of the cell insertions. (b) and (d) Overlay of the fluorescent signal stemming from the DiR-labeled cells (green color) onto the anatomical cryoslice image for experiments A and B, respectively.

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