Abstract

Optical contrast agents have been widely applied to enhance the sensitivity and specificity of optical imaging with near-infrared (NIR) light. However, because of the overwhelming scattering of light in biological tissues, the spatial resolution of traditional optical imaging degrades drastically as the imaging depth increases. Here, for the first time to our knowledge, we present noninvasive photoacoustic angiography of animal brains in vivo with NIR light and an optical contrast agent. When indocyanine green polyethylene glycol, a novel absorption dye with prolonged clearance, is injected into the circulatory system of a rat, it obviously enhances the absorption contrast between the blood vessels and the background tissues. Because NIR light can penetrate deep into the brain tissues through the skin and skull, we are able to successfully reconstruct the vascular distribution in the rat brain from the photoacoustic signals. On the basis of differential optical absorption with and without contrast enhancement, a photoacoustic angiograph of a rat brain is acquired that matches the anatomical photograph well and exhibits high spatial resolution and a much-reduced background. This new technology demonstrates the potential for dynamic and molecular biomedical imaging.

© 2004 Optical Society of America

Full Article  |  PDF Article

References

  • View by:
  • |
  • |
  • |

  1. Y.-L. He, H. Tanigami, H. Ueyama, T. Mashimo, and I. Yoshiya, Crit. Care Med. 26, 1446 (1998).
    [PubMed]
  2. J. Caesar, S. Shaldon, L. Chiandussi, L. Guevara, and S. Sherlock, Clin. Sci. 21, 43 (1961).
    [PubMed]
  3. B. F. Hochheim, Arch. Ophthalmol. 86, 564 (1971).
    [CrossRef]
  4. M. M. Haglund, M. S. Berger, and D. W. Hochman, Neurosurgery 38, 308 (1996).
    [CrossRef] [PubMed]
  5. C. G. A. Hoelen, F. F. M. de Mul, R. Pongers, and A. Dekker, Opt. Lett. 23, 648 (1998).
    [CrossRef]
  6. R. A. Kruger, D. R. Reinecke, and G. A. Kruger, Med. Phys. 26, 1832 (1999).
    [CrossRef] [PubMed]
  7. R. O. Esenaliev, A. A. Karabutov, and A. A. Oraevsky, IEEE J. Sel. Top. Quantum Electron. 5, 981 (1999).
    [CrossRef]
  8. K. P. Köstli, D. Frauchiger, J. J. Niederhauser, G. Paltauf, H. P. Weber, and M. Frenz, IEEE J. Sel. Top. Quantum Electron. 7, 918 (2001).
    [CrossRef]
  9. X. Wang, Y. Pang, G. Ku, X. Xie, G. Stoica, and L. V. Wang, Nat. Biotechnol. 21, 803 (2003).
    [CrossRef] [PubMed]
  10. X. Wang, Y. Pang, G. Ku, G. Stoica, and L. V. Wang, Opt. Lett. 28, 1739 (2003).
    [CrossRef] [PubMed]
  11. M. Xu and L. V. Wang, IEEE Trans. Med. Imaging 21, 814 (2002).
    [CrossRef] [PubMed]
  12. S. Zalipsky, E. Brandeis, M. S. Newman, and M. C. Woodle, FEBS Lett. 353, 71 (1994).
    [CrossRef] [PubMed]

2003

X. Wang, Y. Pang, G. Ku, X. Xie, G. Stoica, and L. V. Wang, Nat. Biotechnol. 21, 803 (2003).
[CrossRef] [PubMed]

X. Wang, Y. Pang, G. Ku, G. Stoica, and L. V. Wang, Opt. Lett. 28, 1739 (2003).
[CrossRef] [PubMed]

2002

M. Xu and L. V. Wang, IEEE Trans. Med. Imaging 21, 814 (2002).
[CrossRef] [PubMed]

2001

K. P. Köstli, D. Frauchiger, J. J. Niederhauser, G. Paltauf, H. P. Weber, and M. Frenz, IEEE J. Sel. Top. Quantum Electron. 7, 918 (2001).
[CrossRef]

1999

R. A. Kruger, D. R. Reinecke, and G. A. Kruger, Med. Phys. 26, 1832 (1999).
[CrossRef] [PubMed]

R. O. Esenaliev, A. A. Karabutov, and A. A. Oraevsky, IEEE J. Sel. Top. Quantum Electron. 5, 981 (1999).
[CrossRef]

1998

C. G. A. Hoelen, F. F. M. de Mul, R. Pongers, and A. Dekker, Opt. Lett. 23, 648 (1998).
[CrossRef]

Y.-L. He, H. Tanigami, H. Ueyama, T. Mashimo, and I. Yoshiya, Crit. Care Med. 26, 1446 (1998).
[PubMed]

1996

M. M. Haglund, M. S. Berger, and D. W. Hochman, Neurosurgery 38, 308 (1996).
[CrossRef] [PubMed]

1994

S. Zalipsky, E. Brandeis, M. S. Newman, and M. C. Woodle, FEBS Lett. 353, 71 (1994).
[CrossRef] [PubMed]

1971

B. F. Hochheim, Arch. Ophthalmol. 86, 564 (1971).
[CrossRef]

1961

J. Caesar, S. Shaldon, L. Chiandussi, L. Guevara, and S. Sherlock, Clin. Sci. 21, 43 (1961).
[PubMed]

Berger, M. S.

M. M. Haglund, M. S. Berger, and D. W. Hochman, Neurosurgery 38, 308 (1996).
[CrossRef] [PubMed]

Brandeis, E.

S. Zalipsky, E. Brandeis, M. S. Newman, and M. C. Woodle, FEBS Lett. 353, 71 (1994).
[CrossRef] [PubMed]

Caesar, J.

J. Caesar, S. Shaldon, L. Chiandussi, L. Guevara, and S. Sherlock, Clin. Sci. 21, 43 (1961).
[PubMed]

Chiandussi, L.

J. Caesar, S. Shaldon, L. Chiandussi, L. Guevara, and S. Sherlock, Clin. Sci. 21, 43 (1961).
[PubMed]

de Mul, F. F. M.

Dekker, A.

Esenaliev, R. O.

R. O. Esenaliev, A. A. Karabutov, and A. A. Oraevsky, IEEE J. Sel. Top. Quantum Electron. 5, 981 (1999).
[CrossRef]

Frauchiger, D.

K. P. Köstli, D. Frauchiger, J. J. Niederhauser, G. Paltauf, H. P. Weber, and M. Frenz, IEEE J. Sel. Top. Quantum Electron. 7, 918 (2001).
[CrossRef]

Frenz, M.

K. P. Köstli, D. Frauchiger, J. J. Niederhauser, G. Paltauf, H. P. Weber, and M. Frenz, IEEE J. Sel. Top. Quantum Electron. 7, 918 (2001).
[CrossRef]

Guevara, L.

J. Caesar, S. Shaldon, L. Chiandussi, L. Guevara, and S. Sherlock, Clin. Sci. 21, 43 (1961).
[PubMed]

Haglund, M. M.

M. M. Haglund, M. S. Berger, and D. W. Hochman, Neurosurgery 38, 308 (1996).
[CrossRef] [PubMed]

He, Y.-L.

Y.-L. He, H. Tanigami, H. Ueyama, T. Mashimo, and I. Yoshiya, Crit. Care Med. 26, 1446 (1998).
[PubMed]

Hochheim, B. F.

B. F. Hochheim, Arch. Ophthalmol. 86, 564 (1971).
[CrossRef]

Hochman, D. W.

M. M. Haglund, M. S. Berger, and D. W. Hochman, Neurosurgery 38, 308 (1996).
[CrossRef] [PubMed]

Hoelen, C. G. A.

Karabutov, A. A.

R. O. Esenaliev, A. A. Karabutov, and A. A. Oraevsky, IEEE J. Sel. Top. Quantum Electron. 5, 981 (1999).
[CrossRef]

Köstli, K. P.

K. P. Köstli, D. Frauchiger, J. J. Niederhauser, G. Paltauf, H. P. Weber, and M. Frenz, IEEE J. Sel. Top. Quantum Electron. 7, 918 (2001).
[CrossRef]

Kruger, G. A.

R. A. Kruger, D. R. Reinecke, and G. A. Kruger, Med. Phys. 26, 1832 (1999).
[CrossRef] [PubMed]

Kruger, R. A.

R. A. Kruger, D. R. Reinecke, and G. A. Kruger, Med. Phys. 26, 1832 (1999).
[CrossRef] [PubMed]

Ku, G.

X. Wang, Y. Pang, G. Ku, X. Xie, G. Stoica, and L. V. Wang, Nat. Biotechnol. 21, 803 (2003).
[CrossRef] [PubMed]

X. Wang, Y. Pang, G. Ku, G. Stoica, and L. V. Wang, Opt. Lett. 28, 1739 (2003).
[CrossRef] [PubMed]

Mashimo, T.

Y.-L. He, H. Tanigami, H. Ueyama, T. Mashimo, and I. Yoshiya, Crit. Care Med. 26, 1446 (1998).
[PubMed]

Newman, M. S.

S. Zalipsky, E. Brandeis, M. S. Newman, and M. C. Woodle, FEBS Lett. 353, 71 (1994).
[CrossRef] [PubMed]

Niederhauser, J. J.

K. P. Köstli, D. Frauchiger, J. J. Niederhauser, G. Paltauf, H. P. Weber, and M. Frenz, IEEE J. Sel. Top. Quantum Electron. 7, 918 (2001).
[CrossRef]

Oraevsky, A. A.

R. O. Esenaliev, A. A. Karabutov, and A. A. Oraevsky, IEEE J. Sel. Top. Quantum Electron. 5, 981 (1999).
[CrossRef]

Paltauf, G.

K. P. Köstli, D. Frauchiger, J. J. Niederhauser, G. Paltauf, H. P. Weber, and M. Frenz, IEEE J. Sel. Top. Quantum Electron. 7, 918 (2001).
[CrossRef]

Pang, Y.

X. Wang, Y. Pang, G. Ku, X. Xie, G. Stoica, and L. V. Wang, Nat. Biotechnol. 21, 803 (2003).
[CrossRef] [PubMed]

X. Wang, Y. Pang, G. Ku, G. Stoica, and L. V. Wang, Opt. Lett. 28, 1739 (2003).
[CrossRef] [PubMed]

Pongers, R.

Reinecke, D. R.

R. A. Kruger, D. R. Reinecke, and G. A. Kruger, Med. Phys. 26, 1832 (1999).
[CrossRef] [PubMed]

Shaldon, S.

J. Caesar, S. Shaldon, L. Chiandussi, L. Guevara, and S. Sherlock, Clin. Sci. 21, 43 (1961).
[PubMed]

Sherlock, S.

J. Caesar, S. Shaldon, L. Chiandussi, L. Guevara, and S. Sherlock, Clin. Sci. 21, 43 (1961).
[PubMed]

Stoica, G.

X. Wang, Y. Pang, G. Ku, X. Xie, G. Stoica, and L. V. Wang, Nat. Biotechnol. 21, 803 (2003).
[CrossRef] [PubMed]

X. Wang, Y. Pang, G. Ku, G. Stoica, and L. V. Wang, Opt. Lett. 28, 1739 (2003).
[CrossRef] [PubMed]

Tanigami, H.

Y.-L. He, H. Tanigami, H. Ueyama, T. Mashimo, and I. Yoshiya, Crit. Care Med. 26, 1446 (1998).
[PubMed]

Ueyama, H.

Y.-L. He, H. Tanigami, H. Ueyama, T. Mashimo, and I. Yoshiya, Crit. Care Med. 26, 1446 (1998).
[PubMed]

Wang, L. V.

X. Wang, Y. Pang, G. Ku, X. Xie, G. Stoica, and L. V. Wang, Nat. Biotechnol. 21, 803 (2003).
[CrossRef] [PubMed]

X. Wang, Y. Pang, G. Ku, G. Stoica, and L. V. Wang, Opt. Lett. 28, 1739 (2003).
[CrossRef] [PubMed]

M. Xu and L. V. Wang, IEEE Trans. Med. Imaging 21, 814 (2002).
[CrossRef] [PubMed]

Wang, X.

X. Wang, Y. Pang, G. Ku, G. Stoica, and L. V. Wang, Opt. Lett. 28, 1739 (2003).
[CrossRef] [PubMed]

X. Wang, Y. Pang, G. Ku, X. Xie, G. Stoica, and L. V. Wang, Nat. Biotechnol. 21, 803 (2003).
[CrossRef] [PubMed]

Weber, H. P.

K. P. Köstli, D. Frauchiger, J. J. Niederhauser, G. Paltauf, H. P. Weber, and M. Frenz, IEEE J. Sel. Top. Quantum Electron. 7, 918 (2001).
[CrossRef]

Woodle, M. C.

S. Zalipsky, E. Brandeis, M. S. Newman, and M. C. Woodle, FEBS Lett. 353, 71 (1994).
[CrossRef] [PubMed]

Xie, X.

X. Wang, Y. Pang, G. Ku, X. Xie, G. Stoica, and L. V. Wang, Nat. Biotechnol. 21, 803 (2003).
[CrossRef] [PubMed]

Xu, M.

M. Xu and L. V. Wang, IEEE Trans. Med. Imaging 21, 814 (2002).
[CrossRef] [PubMed]

Yoshiya, I.

Y.-L. He, H. Tanigami, H. Ueyama, T. Mashimo, and I. Yoshiya, Crit. Care Med. 26, 1446 (1998).
[PubMed]

Zalipsky, S.

S. Zalipsky, E. Brandeis, M. S. Newman, and M. C. Woodle, FEBS Lett. 353, 71 (1994).
[CrossRef] [PubMed]

Arch. Ophthalmol.

B. F. Hochheim, Arch. Ophthalmol. 86, 564 (1971).
[CrossRef]

Clin. Sci.

J. Caesar, S. Shaldon, L. Chiandussi, L. Guevara, and S. Sherlock, Clin. Sci. 21, 43 (1961).
[PubMed]

Crit. Care Med.

Y.-L. He, H. Tanigami, H. Ueyama, T. Mashimo, and I. Yoshiya, Crit. Care Med. 26, 1446 (1998).
[PubMed]

FEBS Lett.

S. Zalipsky, E. Brandeis, M. S. Newman, and M. C. Woodle, FEBS Lett. 353, 71 (1994).
[CrossRef] [PubMed]

IEEE J. Sel. Top. Quantum Electron.

R. O. Esenaliev, A. A. Karabutov, and A. A. Oraevsky, IEEE J. Sel. Top. Quantum Electron. 5, 981 (1999).
[CrossRef]

K. P. Köstli, D. Frauchiger, J. J. Niederhauser, G. Paltauf, H. P. Weber, and M. Frenz, IEEE J. Sel. Top. Quantum Electron. 7, 918 (2001).
[CrossRef]

IEEE Trans. Med. Imaging

M. Xu and L. V. Wang, IEEE Trans. Med. Imaging 21, 814 (2002).
[CrossRef] [PubMed]

Med. Phys.

R. A. Kruger, D. R. Reinecke, and G. A. Kruger, Med. Phys. 26, 1832 (1999).
[CrossRef] [PubMed]

Nat. Biotechnol.

X. Wang, Y. Pang, G. Ku, X. Xie, G. Stoica, and L. V. Wang, Nat. Biotechnol. 21, 803 (2003).
[CrossRef] [PubMed]

Neurosurgery

M. M. Haglund, M. S. Berger, and D. W. Hochman, Neurosurgery 38, 308 (1996).
[CrossRef] [PubMed]

Opt. Lett.

Cited By

OSA participates in CrossRef's Cited-By Linking service. Citing articles from OSA journals and other participating publishers are listed here.

Alert me when this article is cited.


Figures (2)

Fig. 1
Fig. 1

(A) Schematic of noninvasive photoacoustic angiography in the rat brain, employing an optical contrast agent and a NIR laser. (B) Absorption spectra of ICG-PEG and native ICG. (C) Intensity of the photoacoustic signals from the blood vessels in the median fissure of the rat brain as a function of time after the intravascular injection of ICG-PEG (circles) or native ICG (triangles), which are normalized to the initial intensity of the photoacoustic signals before the injection. PA, photoacoustic.

Fig. 2
Fig. 2

Noninvasive photoacoustic images of a rat brain in vivo, employing NIR light and an optical contrast agent (ICG-PEG). (A), (B) Photoacoustic images acquired before and after the injection of ICG-PEG, respectively, where the two gray scales are the same. MF, median fissure. (C) ICG-based angiograph of the rat brain (C=B-A). (D) Open-skull photograph of the rat brain obtained after the data acquisition for photoacoustic imaging.

Metrics