Abstract

Optically activated cavitation in a nanoemulsion contrast agent is proposed for therapeutic applications. With a 56°C boiling point perfluorohexane core and highly absorptive gold nanospheres at the oil–water interface, cavitation nuclei in the core can be efficiently induced with a laser fluence below medical safety limits (70mJ/cm2 at 1064 nm). This agent is also sensitive to ultrasound (US) exposure and can induce inertial cavitation at a pressure within the medical diagnostic range. Images from a high-speed camera demonstrate bubble formation in these nanoemulsions. The potential of using this contrast agent for blood clot disruption is demonstrated in an in vitro study. The possibility of simultaneous laser and US excitation to reduce the cavitation threshold for therapeutic applications is also discussed.

© 2014 Optical Society of America

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References

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  1. Y. A. Pishchalnikov, O. A. Sapozhnikov, M. R. Bailey, J. C. Williams, R. O. Cleveland, T. Colonius, L. A. Crum, A. P. Evan, and J. A. McAteer, J. Endourol. 17, 435 (2003).
    [CrossRef]
  2. J. E. Kennedy, Nat. Rev. Cancer 5, 321 (2005).
  3. A. Gasselhuber, M. R. Dreher, A. Partanen, P. S. Yarmolenko, D. Woods, B. J. Wood, and D. Haemmerich, Int. J. Hyperthermia 28, 337 (2012).
    [CrossRef]
  4. C. H. Farny, T. Wu, R. G. Holt, T. W. Murray, and R. A. Roy, Acoust. Res. Lett. Online 6, 138 (2005).
    [CrossRef]
  5. J. R. McLaughlan, R. A. Roy, H. Ju, and T. W. Murray, Opt. Lett. 35, 2127 (2010).
    [CrossRef]
  6. H. Ju, R. A. Roy, and T. W. Murray, Biomed. Opt. Express 4, 66 (2013).
    [CrossRef]
  7. A. de la Zerda, J. W. Kim, E. I. Galanzha, S. S. Gambhir, and V. P. Zharov, Contrast Media Mol. Imag. 6, 346 (2011).
    [CrossRef]
  8. K. Wilson, K. Homan, and S. Emelianov, Nat. Commun. 3, 618 (2012).
    [CrossRef]
  9. K. Larson-Smith and D. C. Pozzo, Langmuir 28, 11725 (2012).
    [CrossRef]
  10. C.-W. Wei, M. Lombardo, K. Larson-Smith, I. Pelivanov, C. Perez, J. Xia, T. Matula, D. Pozzo, and M. O’Donnell, Appl. Phys. Lett. 104, 033701 (2014).
    [CrossRef]
  11. K. Larson-Smith and D. C. Pozzo, Soft Matter 7, 5339 (2011).
    [CrossRef]
  12. K. M. Weigandt, N. White, D. Chung, E. Ellingson, Y. Wang, X. Fu, and D. C. Pozzo, Biophys. J. 103, 2399 (2012).
    [CrossRef]
  13. American National Standard for the Safe Use of Lasers in Health Care Facilities, (American National Standards Institute, New York, NY, 2007).
  14. M. Mleczko and G. Schmitz, in Proceedings of IEEE International Ultrasonics Symposium (IEEE, 2008), pp. 1686–1689.
  15. A. Burgess, Y. Huang, A. C. Waspe, M. Ganguly, D. E. Goertz, and K. Hynynen, PLoS ONE 7, e42311 (2012).
    [CrossRef]
  16. V. Kumar, A. K. Abbas, N. Fausto, and J. Aster, Robbins & Cotran Pathologic Basis of Disease (Saunders, 2009).

2014 (1)

C.-W. Wei, M. Lombardo, K. Larson-Smith, I. Pelivanov, C. Perez, J. Xia, T. Matula, D. Pozzo, and M. O’Donnell, Appl. Phys. Lett. 104, 033701 (2014).
[CrossRef]

2013 (1)

2012 (5)

K. M. Weigandt, N. White, D. Chung, E. Ellingson, Y. Wang, X. Fu, and D. C. Pozzo, Biophys. J. 103, 2399 (2012).
[CrossRef]

A. Burgess, Y. Huang, A. C. Waspe, M. Ganguly, D. E. Goertz, and K. Hynynen, PLoS ONE 7, e42311 (2012).
[CrossRef]

K. Wilson, K. Homan, and S. Emelianov, Nat. Commun. 3, 618 (2012).
[CrossRef]

K. Larson-Smith and D. C. Pozzo, Langmuir 28, 11725 (2012).
[CrossRef]

A. Gasselhuber, M. R. Dreher, A. Partanen, P. S. Yarmolenko, D. Woods, B. J. Wood, and D. Haemmerich, Int. J. Hyperthermia 28, 337 (2012).
[CrossRef]

2011 (2)

K. Larson-Smith and D. C. Pozzo, Soft Matter 7, 5339 (2011).
[CrossRef]

A. de la Zerda, J. W. Kim, E. I. Galanzha, S. S. Gambhir, and V. P. Zharov, Contrast Media Mol. Imag. 6, 346 (2011).
[CrossRef]

2010 (1)

2005 (2)

C. H. Farny, T. Wu, R. G. Holt, T. W. Murray, and R. A. Roy, Acoust. Res. Lett. Online 6, 138 (2005).
[CrossRef]

J. E. Kennedy, Nat. Rev. Cancer 5, 321 (2005).

2003 (1)

Y. A. Pishchalnikov, O. A. Sapozhnikov, M. R. Bailey, J. C. Williams, R. O. Cleveland, T. Colonius, L. A. Crum, A. P. Evan, and J. A. McAteer, J. Endourol. 17, 435 (2003).
[CrossRef]

Abbas, A. K.

V. Kumar, A. K. Abbas, N. Fausto, and J. Aster, Robbins & Cotran Pathologic Basis of Disease (Saunders, 2009).

Aster, J.

V. Kumar, A. K. Abbas, N. Fausto, and J. Aster, Robbins & Cotran Pathologic Basis of Disease (Saunders, 2009).

Bailey, M. R.

Y. A. Pishchalnikov, O. A. Sapozhnikov, M. R. Bailey, J. C. Williams, R. O. Cleveland, T. Colonius, L. A. Crum, A. P. Evan, and J. A. McAteer, J. Endourol. 17, 435 (2003).
[CrossRef]

Burgess, A.

A. Burgess, Y. Huang, A. C. Waspe, M. Ganguly, D. E. Goertz, and K. Hynynen, PLoS ONE 7, e42311 (2012).
[CrossRef]

Chung, D.

K. M. Weigandt, N. White, D. Chung, E. Ellingson, Y. Wang, X. Fu, and D. C. Pozzo, Biophys. J. 103, 2399 (2012).
[CrossRef]

Cleveland, R. O.

Y. A. Pishchalnikov, O. A. Sapozhnikov, M. R. Bailey, J. C. Williams, R. O. Cleveland, T. Colonius, L. A. Crum, A. P. Evan, and J. A. McAteer, J. Endourol. 17, 435 (2003).
[CrossRef]

Colonius, T.

Y. A. Pishchalnikov, O. A. Sapozhnikov, M. R. Bailey, J. C. Williams, R. O. Cleveland, T. Colonius, L. A. Crum, A. P. Evan, and J. A. McAteer, J. Endourol. 17, 435 (2003).
[CrossRef]

Crum, L. A.

Y. A. Pishchalnikov, O. A. Sapozhnikov, M. R. Bailey, J. C. Williams, R. O. Cleveland, T. Colonius, L. A. Crum, A. P. Evan, and J. A. McAteer, J. Endourol. 17, 435 (2003).
[CrossRef]

de la Zerda, A.

A. de la Zerda, J. W. Kim, E. I. Galanzha, S. S. Gambhir, and V. P. Zharov, Contrast Media Mol. Imag. 6, 346 (2011).
[CrossRef]

Dreher, M. R.

A. Gasselhuber, M. R. Dreher, A. Partanen, P. S. Yarmolenko, D. Woods, B. J. Wood, and D. Haemmerich, Int. J. Hyperthermia 28, 337 (2012).
[CrossRef]

Ellingson, E.

K. M. Weigandt, N. White, D. Chung, E. Ellingson, Y. Wang, X. Fu, and D. C. Pozzo, Biophys. J. 103, 2399 (2012).
[CrossRef]

Emelianov, S.

K. Wilson, K. Homan, and S. Emelianov, Nat. Commun. 3, 618 (2012).
[CrossRef]

Evan, A. P.

Y. A. Pishchalnikov, O. A. Sapozhnikov, M. R. Bailey, J. C. Williams, R. O. Cleveland, T. Colonius, L. A. Crum, A. P. Evan, and J. A. McAteer, J. Endourol. 17, 435 (2003).
[CrossRef]

Farny, C. H.

C. H. Farny, T. Wu, R. G. Holt, T. W. Murray, and R. A. Roy, Acoust. Res. Lett. Online 6, 138 (2005).
[CrossRef]

Fausto, N.

V. Kumar, A. K. Abbas, N. Fausto, and J. Aster, Robbins & Cotran Pathologic Basis of Disease (Saunders, 2009).

Fu, X.

K. M. Weigandt, N. White, D. Chung, E. Ellingson, Y. Wang, X. Fu, and D. C. Pozzo, Biophys. J. 103, 2399 (2012).
[CrossRef]

Galanzha, E. I.

A. de la Zerda, J. W. Kim, E. I. Galanzha, S. S. Gambhir, and V. P. Zharov, Contrast Media Mol. Imag. 6, 346 (2011).
[CrossRef]

Gambhir, S. S.

A. de la Zerda, J. W. Kim, E. I. Galanzha, S. S. Gambhir, and V. P. Zharov, Contrast Media Mol. Imag. 6, 346 (2011).
[CrossRef]

Ganguly, M.

A. Burgess, Y. Huang, A. C. Waspe, M. Ganguly, D. E. Goertz, and K. Hynynen, PLoS ONE 7, e42311 (2012).
[CrossRef]

Gasselhuber, A.

A. Gasselhuber, M. R. Dreher, A. Partanen, P. S. Yarmolenko, D. Woods, B. J. Wood, and D. Haemmerich, Int. J. Hyperthermia 28, 337 (2012).
[CrossRef]

Goertz, D. E.

A. Burgess, Y. Huang, A. C. Waspe, M. Ganguly, D. E. Goertz, and K. Hynynen, PLoS ONE 7, e42311 (2012).
[CrossRef]

Haemmerich, D.

A. Gasselhuber, M. R. Dreher, A. Partanen, P. S. Yarmolenko, D. Woods, B. J. Wood, and D. Haemmerich, Int. J. Hyperthermia 28, 337 (2012).
[CrossRef]

Holt, R. G.

C. H. Farny, T. Wu, R. G. Holt, T. W. Murray, and R. A. Roy, Acoust. Res. Lett. Online 6, 138 (2005).
[CrossRef]

Homan, K.

K. Wilson, K. Homan, and S. Emelianov, Nat. Commun. 3, 618 (2012).
[CrossRef]

Huang, Y.

A. Burgess, Y. Huang, A. C. Waspe, M. Ganguly, D. E. Goertz, and K. Hynynen, PLoS ONE 7, e42311 (2012).
[CrossRef]

Hynynen, K.

A. Burgess, Y. Huang, A. C. Waspe, M. Ganguly, D. E. Goertz, and K. Hynynen, PLoS ONE 7, e42311 (2012).
[CrossRef]

Ju, H.

Kennedy, J. E.

J. E. Kennedy, Nat. Rev. Cancer 5, 321 (2005).

Kim, J. W.

A. de la Zerda, J. W. Kim, E. I. Galanzha, S. S. Gambhir, and V. P. Zharov, Contrast Media Mol. Imag. 6, 346 (2011).
[CrossRef]

Kumar, V.

V. Kumar, A. K. Abbas, N. Fausto, and J. Aster, Robbins & Cotran Pathologic Basis of Disease (Saunders, 2009).

Larson-Smith, K.

C.-W. Wei, M. Lombardo, K. Larson-Smith, I. Pelivanov, C. Perez, J. Xia, T. Matula, D. Pozzo, and M. O’Donnell, Appl. Phys. Lett. 104, 033701 (2014).
[CrossRef]

K. Larson-Smith and D. C. Pozzo, Langmuir 28, 11725 (2012).
[CrossRef]

K. Larson-Smith and D. C. Pozzo, Soft Matter 7, 5339 (2011).
[CrossRef]

Lombardo, M.

C.-W. Wei, M. Lombardo, K. Larson-Smith, I. Pelivanov, C. Perez, J. Xia, T. Matula, D. Pozzo, and M. O’Donnell, Appl. Phys. Lett. 104, 033701 (2014).
[CrossRef]

Matula, T.

C.-W. Wei, M. Lombardo, K. Larson-Smith, I. Pelivanov, C. Perez, J. Xia, T. Matula, D. Pozzo, and M. O’Donnell, Appl. Phys. Lett. 104, 033701 (2014).
[CrossRef]

McAteer, J. A.

Y. A. Pishchalnikov, O. A. Sapozhnikov, M. R. Bailey, J. C. Williams, R. O. Cleveland, T. Colonius, L. A. Crum, A. P. Evan, and J. A. McAteer, J. Endourol. 17, 435 (2003).
[CrossRef]

McLaughlan, J. R.

Mleczko, M.

M. Mleczko and G. Schmitz, in Proceedings of IEEE International Ultrasonics Symposium (IEEE, 2008), pp. 1686–1689.

Murray, T. W.

O’Donnell, M.

C.-W. Wei, M. Lombardo, K. Larson-Smith, I. Pelivanov, C. Perez, J. Xia, T. Matula, D. Pozzo, and M. O’Donnell, Appl. Phys. Lett. 104, 033701 (2014).
[CrossRef]

Partanen, A.

A. Gasselhuber, M. R. Dreher, A. Partanen, P. S. Yarmolenko, D. Woods, B. J. Wood, and D. Haemmerich, Int. J. Hyperthermia 28, 337 (2012).
[CrossRef]

Pelivanov, I.

C.-W. Wei, M. Lombardo, K. Larson-Smith, I. Pelivanov, C. Perez, J. Xia, T. Matula, D. Pozzo, and M. O’Donnell, Appl. Phys. Lett. 104, 033701 (2014).
[CrossRef]

Perez, C.

C.-W. Wei, M. Lombardo, K. Larson-Smith, I. Pelivanov, C. Perez, J. Xia, T. Matula, D. Pozzo, and M. O’Donnell, Appl. Phys. Lett. 104, 033701 (2014).
[CrossRef]

Pishchalnikov, Y. A.

Y. A. Pishchalnikov, O. A. Sapozhnikov, M. R. Bailey, J. C. Williams, R. O. Cleveland, T. Colonius, L. A. Crum, A. P. Evan, and J. A. McAteer, J. Endourol. 17, 435 (2003).
[CrossRef]

Pozzo, D.

C.-W. Wei, M. Lombardo, K. Larson-Smith, I. Pelivanov, C. Perez, J. Xia, T. Matula, D. Pozzo, and M. O’Donnell, Appl. Phys. Lett. 104, 033701 (2014).
[CrossRef]

Pozzo, D. C.

K. M. Weigandt, N. White, D. Chung, E. Ellingson, Y. Wang, X. Fu, and D. C. Pozzo, Biophys. J. 103, 2399 (2012).
[CrossRef]

K. Larson-Smith and D. C. Pozzo, Langmuir 28, 11725 (2012).
[CrossRef]

K. Larson-Smith and D. C. Pozzo, Soft Matter 7, 5339 (2011).
[CrossRef]

Roy, R. A.

Sapozhnikov, O. A.

Y. A. Pishchalnikov, O. A. Sapozhnikov, M. R. Bailey, J. C. Williams, R. O. Cleveland, T. Colonius, L. A. Crum, A. P. Evan, and J. A. McAteer, J. Endourol. 17, 435 (2003).
[CrossRef]

Schmitz, G.

M. Mleczko and G. Schmitz, in Proceedings of IEEE International Ultrasonics Symposium (IEEE, 2008), pp. 1686–1689.

Wang, Y.

K. M. Weigandt, N. White, D. Chung, E. Ellingson, Y. Wang, X. Fu, and D. C. Pozzo, Biophys. J. 103, 2399 (2012).
[CrossRef]

Waspe, A. C.

A. Burgess, Y. Huang, A. C. Waspe, M. Ganguly, D. E. Goertz, and K. Hynynen, PLoS ONE 7, e42311 (2012).
[CrossRef]

Wei, C.-W.

C.-W. Wei, M. Lombardo, K. Larson-Smith, I. Pelivanov, C. Perez, J. Xia, T. Matula, D. Pozzo, and M. O’Donnell, Appl. Phys. Lett. 104, 033701 (2014).
[CrossRef]

Weigandt, K. M.

K. M. Weigandt, N. White, D. Chung, E. Ellingson, Y. Wang, X. Fu, and D. C. Pozzo, Biophys. J. 103, 2399 (2012).
[CrossRef]

White, N.

K. M. Weigandt, N. White, D. Chung, E. Ellingson, Y. Wang, X. Fu, and D. C. Pozzo, Biophys. J. 103, 2399 (2012).
[CrossRef]

Williams, J. C.

Y. A. Pishchalnikov, O. A. Sapozhnikov, M. R. Bailey, J. C. Williams, R. O. Cleveland, T. Colonius, L. A. Crum, A. P. Evan, and J. A. McAteer, J. Endourol. 17, 435 (2003).
[CrossRef]

Wilson, K.

K. Wilson, K. Homan, and S. Emelianov, Nat. Commun. 3, 618 (2012).
[CrossRef]

Wood, B. J.

A. Gasselhuber, M. R. Dreher, A. Partanen, P. S. Yarmolenko, D. Woods, B. J. Wood, and D. Haemmerich, Int. J. Hyperthermia 28, 337 (2012).
[CrossRef]

Woods, D.

A. Gasselhuber, M. R. Dreher, A. Partanen, P. S. Yarmolenko, D. Woods, B. J. Wood, and D. Haemmerich, Int. J. Hyperthermia 28, 337 (2012).
[CrossRef]

Wu, T.

C. H. Farny, T. Wu, R. G. Holt, T. W. Murray, and R. A. Roy, Acoust. Res. Lett. Online 6, 138 (2005).
[CrossRef]

Xia, J.

C.-W. Wei, M. Lombardo, K. Larson-Smith, I. Pelivanov, C. Perez, J. Xia, T. Matula, D. Pozzo, and M. O’Donnell, Appl. Phys. Lett. 104, 033701 (2014).
[CrossRef]

Yarmolenko, P. S.

A. Gasselhuber, M. R. Dreher, A. Partanen, P. S. Yarmolenko, D. Woods, B. J. Wood, and D. Haemmerich, Int. J. Hyperthermia 28, 337 (2012).
[CrossRef]

Zharov, V. P.

A. de la Zerda, J. W. Kim, E. I. Galanzha, S. S. Gambhir, and V. P. Zharov, Contrast Media Mol. Imag. 6, 346 (2011).
[CrossRef]

Acoust. Res. Lett. Online (1)

C. H. Farny, T. Wu, R. G. Holt, T. W. Murray, and R. A. Roy, Acoust. Res. Lett. Online 6, 138 (2005).
[CrossRef]

Appl. Phys. Lett. (1)

C.-W. Wei, M. Lombardo, K. Larson-Smith, I. Pelivanov, C. Perez, J. Xia, T. Matula, D. Pozzo, and M. O’Donnell, Appl. Phys. Lett. 104, 033701 (2014).
[CrossRef]

Biomed. Opt. Express (1)

Biophys. J. (1)

K. M. Weigandt, N. White, D. Chung, E. Ellingson, Y. Wang, X. Fu, and D. C. Pozzo, Biophys. J. 103, 2399 (2012).
[CrossRef]

Contrast Media Mol. Imag. (1)

A. de la Zerda, J. W. Kim, E. I. Galanzha, S. S. Gambhir, and V. P. Zharov, Contrast Media Mol. Imag. 6, 346 (2011).
[CrossRef]

Int. J. Hyperthermia (1)

A. Gasselhuber, M. R. Dreher, A. Partanen, P. S. Yarmolenko, D. Woods, B. J. Wood, and D. Haemmerich, Int. J. Hyperthermia 28, 337 (2012).
[CrossRef]

J. Endourol. (1)

Y. A. Pishchalnikov, O. A. Sapozhnikov, M. R. Bailey, J. C. Williams, R. O. Cleveland, T. Colonius, L. A. Crum, A. P. Evan, and J. A. McAteer, J. Endourol. 17, 435 (2003).
[CrossRef]

Langmuir (1)

K. Larson-Smith and D. C. Pozzo, Langmuir 28, 11725 (2012).
[CrossRef]

Nat. Commun. (1)

K. Wilson, K. Homan, and S. Emelianov, Nat. Commun. 3, 618 (2012).
[CrossRef]

Nat. Rev. Cancer (1)

J. E. Kennedy, Nat. Rev. Cancer 5, 321 (2005).

Opt. Lett. (1)

PLoS ONE (1)

A. Burgess, Y. Huang, A. C. Waspe, M. Ganguly, D. E. Goertz, and K. Hynynen, PLoS ONE 7, e42311 (2012).
[CrossRef]

Soft Matter (1)

K. Larson-Smith and D. C. Pozzo, Soft Matter 7, 5339 (2011).
[CrossRef]

Other (3)

V. Kumar, A. K. Abbas, N. Fausto, and J. Aster, Robbins & Cotran Pathologic Basis of Disease (Saunders, 2009).

American National Standard for the Safe Use of Lasers in Health Care Facilities, (American National Standards Institute, New York, NY, 2007).

M. Mleczko and G. Schmitz, in Proceedings of IEEE International Ultrasonics Symposium (IEEE, 2008), pp. 1686–1689.

Supplementary Material (2)

» Media 1: AVI (14520 KB)     
» Media 2: AVI (11796 KB)     

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Figures (4)

Fig. 1.
Fig. 1.

Images by a high-speed camera, showing micrometer-sized bubble formation from NEB-GNS with one short (9 ns) laser pulse irradiation at 120 ns. The lifetime of the bubbles is about 1 μs.

Fig. 2.
Fig. 2.

(Media 1) Video of laser-induced fibrin clot disruption with NEB-GNS in a tube using a 750 nm laser with a pulse repetition rate of 20 Hz and a laser fluence of 7mJ/cm2. Two insets show corresponding PA images (left) and US pulse-echo images (right), respectively. The video was played eight times faster than real time.

Fig. 3.
Fig. 3.

(Media 2) Camera video of laser-induced fibrin clot disruption with NEB-GNS in a tube using a 1064 nm laser with a pulse width of 250 ns, a pulse repetition rate of 1 kHz, and a laser fluence of 500mJ/cm2. The video was played two times faster than real time.

Fig. 4.
Fig. 4.

Preliminary results on manipulating bubble generation by NEB-GNS with simultaneous laser–US excitation. Typical backscattered RF A-line signals and slow-time differential signals received by a broadband transducer when (a), (d) the laser was off, (b), (e) the laser pulse irradiates NEB-GNS at peak positive pressure, and (c), (f) laser pulse was at peak negative pressure.

Metrics