Abstract

Three-dimensional laser-induced photoacoustic tomography, also referred to as optoacoustic tomography, is developed to image animal brain structures noninvasively with the skin and skull intact. This imaging modality combines the advantages of optical contrast and ultrasonic resolution. The distribution of optical absorption in a mouse brain is imaged successfully. The intrinsic optical contrast reveals not only blood vessels but also other detailed brain structures, such as the cerebellum, hippocampus, and ventriculi lateralis. The spatial resolution is primarily diffraction limited by the received photoacoustic waves. Imaged structures of the brain at different depths match the corresponding histological pictures well.

© 2003 Optical Society of America

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    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
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    [CrossRef]
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    [CrossRef] [PubMed]
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    [CrossRef]
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    [CrossRef]
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    [CrossRef]
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    [CrossRef]

2003 (2)

M. Xu and L. V. Wang, Phys. Rev. E 67, 056605 (2003).
[CrossRef]

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

2001 (2)

J. K. Barton, G. Frangineas, H. Pummer, and J. F. Black, Photochem. Photobiol. 73, 642 (2001).
[CrossRef] [PubMed]

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]

2000 (1)

G. D. Rosen, A. G. Williams, J. A. Capra, M. T. Connolly, B. Cruz, L. Lu, D. C. Airey, K. Kulkarni, andR. W. Williams (2000), The Mouse Brain Library@ www.mbl.org.

1999 (2)

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 (1)

1997 (2)

A. Villringer and B. Chance, Trends Neurosci. 20, 435 (1997).
[CrossRef] [PubMed]

G. Gratton, M. Fabiani, P. M. Corballis, D. C. Hood, M. R. Goodman Wood, J. Hirsch, K. Kim, D. Friedman, and E. Gratton, Neuroimage 6, 168 (1997).
[CrossRef] [PubMed]

1993 (3)

B. Chance, Z. Zhuang, C. UnAh, C. Alter, and L. Lipton, Proc. Natl. Acad. Sci. USA 90, 3770 (1993).
[CrossRef]

A. Villringer, J. Planck, C. Hoch, L. Schleinkofer, and U. Dirnagl, Neurosci. Lett. 154, 101 (1993).
[CrossRef] [PubMed]

P. VanderZee, M. Essenpreis, and D. T. Delpy, Proc. SPIE 1888, 454 (1993).
[CrossRef]

1992 (1)

M. M. Haglund, G. A. Ojemann, and D. W. Hochman, Nature 358, 668 (1992).
[CrossRef] [PubMed]

1990 (1)

R. D. Frostig, E. E. Lieke, D. Y. Ts'o, and A. Grinvald, Proc. Natl. Acad. Sci. USA 87, 6082 (1990).
[CrossRef]

1986 (1)

A. Grinvald, E. Lieke, R. D. Frostig, C. D. Gilbert, and T. N. Wiesel, Nature 324, 361 (1986).
[CrossRef] [PubMed]

Airey, D. C.

G. D. Rosen, A. G. Williams, J. A. Capra, M. T. Connolly, B. Cruz, L. Lu, D. C. Airey, K. Kulkarni, andR. W. Williams (2000), The Mouse Brain Library@ www.mbl.org.

Alter, C.

B. Chance, Z. Zhuang, C. UnAh, C. Alter, and L. Lipton, Proc. Natl. Acad. Sci. USA 90, 3770 (1993).
[CrossRef]

Barton, J. K.

J. K. Barton, G. Frangineas, H. Pummer, and J. F. Black, Photochem. Photobiol. 73, 642 (2001).
[CrossRef] [PubMed]

Black, J. F.

J. K. Barton, G. Frangineas, H. Pummer, and J. F. Black, Photochem. Photobiol. 73, 642 (2001).
[CrossRef] [PubMed]

Capra, J. A.

G. D. Rosen, A. G. Williams, J. A. Capra, M. T. Connolly, B. Cruz, L. Lu, D. C. Airey, K. Kulkarni, andR. W. Williams (2000), The Mouse Brain Library@ www.mbl.org.

Chance, B.

A. Villringer and B. Chance, Trends Neurosci. 20, 435 (1997).
[CrossRef] [PubMed]

B. Chance, Z. Zhuang, C. UnAh, C. Alter, and L. Lipton, Proc. Natl. Acad. Sci. USA 90, 3770 (1993).
[CrossRef]

Connolly, M. T.

G. D. Rosen, A. G. Williams, J. A. Capra, M. T. Connolly, B. Cruz, L. Lu, D. C. Airey, K. Kulkarni, andR. W. Williams (2000), The Mouse Brain Library@ www.mbl.org.

Corballis, P. M.

G. Gratton, M. Fabiani, P. M. Corballis, D. C. Hood, M. R. Goodman Wood, J. Hirsch, K. Kim, D. Friedman, and E. Gratton, Neuroimage 6, 168 (1997).
[CrossRef] [PubMed]

Cruz, B.

G. D. Rosen, A. G. Williams, J. A. Capra, M. T. Connolly, B. Cruz, L. Lu, D. C. Airey, K. Kulkarni, andR. W. Williams (2000), The Mouse Brain Library@ www.mbl.org.

de Mul, F. F. M.

Dekker, A.

Delpy, D. T.

P. VanderZee, M. Essenpreis, and D. T. Delpy, Proc. SPIE 1888, 454 (1993).
[CrossRef]

Dirnagl, U.

A. Villringer, J. Planck, C. Hoch, L. Schleinkofer, and U. Dirnagl, Neurosci. Lett. 154, 101 (1993).
[CrossRef] [PubMed]

Esenaliev, R. O.

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

Essenpreis, M.

P. VanderZee, M. Essenpreis, and D. T. Delpy, Proc. SPIE 1888, 454 (1993).
[CrossRef]

Fabiani, M.

G. Gratton, M. Fabiani, P. M. Corballis, D. C. Hood, M. R. Goodman Wood, J. Hirsch, K. Kim, D. Friedman, and E. Gratton, Neuroimage 6, 168 (1997).
[CrossRef] [PubMed]

Frangineas, G.

J. K. Barton, G. Frangineas, H. Pummer, and J. F. Black, Photochem. Photobiol. 73, 642 (2001).
[CrossRef] [PubMed]

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]

Friedman, D.

G. Gratton, M. Fabiani, P. M. Corballis, D. C. Hood, M. R. Goodman Wood, J. Hirsch, K. Kim, D. Friedman, and E. Gratton, Neuroimage 6, 168 (1997).
[CrossRef] [PubMed]

Frostig, R. D.

R. D. Frostig, E. E. Lieke, D. Y. Ts'o, and A. Grinvald, Proc. Natl. Acad. Sci. USA 87, 6082 (1990).
[CrossRef]

A. Grinvald, E. Lieke, R. D. Frostig, C. D. Gilbert, and T. N. Wiesel, Nature 324, 361 (1986).
[CrossRef] [PubMed]

Gilbert, C. D.

A. Grinvald, E. Lieke, R. D. Frostig, C. D. Gilbert, and T. N. Wiesel, Nature 324, 361 (1986).
[CrossRef] [PubMed]

Goodman Wood, M. R.

G. Gratton, M. Fabiani, P. M. Corballis, D. C. Hood, M. R. Goodman Wood, J. Hirsch, K. Kim, D. Friedman, and E. Gratton, Neuroimage 6, 168 (1997).
[CrossRef] [PubMed]

Gratton, E.

G. Gratton, M. Fabiani, P. M. Corballis, D. C. Hood, M. R. Goodman Wood, J. Hirsch, K. Kim, D. Friedman, and E. Gratton, Neuroimage 6, 168 (1997).
[CrossRef] [PubMed]

Gratton, G.

G. Gratton, M. Fabiani, P. M. Corballis, D. C. Hood, M. R. Goodman Wood, J. Hirsch, K. Kim, D. Friedman, and E. Gratton, Neuroimage 6, 168 (1997).
[CrossRef] [PubMed]

Grinvald, A.

R. D. Frostig, E. E. Lieke, D. Y. Ts'o, and A. Grinvald, Proc. Natl. Acad. Sci. USA 87, 6082 (1990).
[CrossRef]

A. Grinvald, E. Lieke, R. D. Frostig, C. D. Gilbert, and T. N. Wiesel, Nature 324, 361 (1986).
[CrossRef] [PubMed]

Haglund, M. M.

M. M. Haglund, G. A. Ojemann, and D. W. Hochman, Nature 358, 668 (1992).
[CrossRef] [PubMed]

Hirsch, J.

G. Gratton, M. Fabiani, P. M. Corballis, D. C. Hood, M. R. Goodman Wood, J. Hirsch, K. Kim, D. Friedman, and E. Gratton, Neuroimage 6, 168 (1997).
[CrossRef] [PubMed]

Hoch, C.

A. Villringer, J. Planck, C. Hoch, L. Schleinkofer, and U. Dirnagl, Neurosci. Lett. 154, 101 (1993).
[CrossRef] [PubMed]

Hochman, D. W.

M. M. Haglund, G. A. Ojemann, and D. W. Hochman, Nature 358, 668 (1992).
[CrossRef] [PubMed]

Hoelen, C. G. A.

Hood, D. C.

G. Gratton, M. Fabiani, P. M. Corballis, D. C. Hood, M. R. Goodman Wood, J. Hirsch, K. Kim, D. Friedman, and E. Gratton, Neuroimage 6, 168 (1997).
[CrossRef] [PubMed]

Karabutov, A. A.

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

Kim, K.

G. Gratton, M. Fabiani, P. M. Corballis, D. C. Hood, M. R. Goodman Wood, J. Hirsch, K. Kim, D. Friedman, and E. Gratton, Neuroimage 6, 168 (1997).
[CrossRef] [PubMed]

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, Nature Biotechnol. 21, 803 (2003).
[CrossRef]

Kulkarni, K.

G. D. Rosen, A. G. Williams, J. A. Capra, M. T. Connolly, B. Cruz, L. Lu, D. C. Airey, K. Kulkarni, andR. W. Williams (2000), The Mouse Brain Library@ www.mbl.org.

Lieke, E.

A. Grinvald, E. Lieke, R. D. Frostig, C. D. Gilbert, and T. N. Wiesel, Nature 324, 361 (1986).
[CrossRef] [PubMed]

Lieke, E. E.

R. D. Frostig, E. E. Lieke, D. Y. Ts'o, and A. Grinvald, Proc. Natl. Acad. Sci. USA 87, 6082 (1990).
[CrossRef]

Lipton, L.

B. Chance, Z. Zhuang, C. UnAh, C. Alter, and L. Lipton, Proc. Natl. Acad. Sci. USA 90, 3770 (1993).
[CrossRef]

Lu, L.

G. D. Rosen, A. G. Williams, J. A. Capra, M. T. Connolly, B. Cruz, L. Lu, D. C. Airey, K. Kulkarni, andR. W. Williams (2000), The Mouse Brain Library@ www.mbl.org.

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]

Ojemann, G. A.

M. M. Haglund, G. A. Ojemann, and D. W. Hochman, Nature 358, 668 (1992).
[CrossRef] [PubMed]

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, Nature Biotechnol. 21, 803 (2003).
[CrossRef]

Planck, J.

A. Villringer, J. Planck, C. Hoch, L. Schleinkofer, and U. Dirnagl, Neurosci. Lett. 154, 101 (1993).
[CrossRef] [PubMed]

Pongers, R.

Pummer, H.

J. K. Barton, G. Frangineas, H. Pummer, and J. F. Black, Photochem. Photobiol. 73, 642 (2001).
[CrossRef] [PubMed]

Reinecke, D. R.

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

Rosen, G. D.

G. D. Rosen, A. G. Williams, J. A. Capra, M. T. Connolly, B. Cruz, L. Lu, D. C. Airey, K. Kulkarni, andR. W. Williams (2000), The Mouse Brain Library@ www.mbl.org.

Schleinkofer, L.

A. Villringer, J. Planck, C. Hoch, L. Schleinkofer, and U. Dirnagl, Neurosci. Lett. 154, 101 (1993).
[CrossRef] [PubMed]

Stoica, G.

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

Ts'o, D. Y.

R. D. Frostig, E. E. Lieke, D. Y. Ts'o, and A. Grinvald, Proc. Natl. Acad. Sci. USA 87, 6082 (1990).
[CrossRef]

UnAh, C.

B. Chance, Z. Zhuang, C. UnAh, C. Alter, and L. Lipton, Proc. Natl. Acad. Sci. USA 90, 3770 (1993).
[CrossRef]

VanderZee, P.

P. VanderZee, M. Essenpreis, and D. T. Delpy, Proc. SPIE 1888, 454 (1993).
[CrossRef]

Villringer, A.

A. Villringer and B. Chance, Trends Neurosci. 20, 435 (1997).
[CrossRef] [PubMed]

A. Villringer, J. Planck, C. Hoch, L. Schleinkofer, and U. Dirnagl, Neurosci. Lett. 154, 101 (1993).
[CrossRef] [PubMed]

Wang, L. V.

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

M. Xu and L. V. Wang, Phys. Rev. E 67, 056605 (2003).
[CrossRef]

M. Xu, Y. Xu, and L. V. Wang, “Time-domain reconstruction algorithms and numerical simulations for thermoacoustic tomography in various geometries,” IEEE Trans. Biomed. Eng. (to be published).

Wang, X.

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

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]

Wiesel, T. N.

A. Grinvald, E. Lieke, R. D. Frostig, C. D. Gilbert, and T. N. Wiesel, Nature 324, 361 (1986).
[CrossRef] [PubMed]

Williams, A. G.

G. D. Rosen, A. G. Williams, J. A. Capra, M. T. Connolly, B. Cruz, L. Lu, D. C. Airey, K. Kulkarni, andR. W. Williams (2000), The Mouse Brain Library@ www.mbl.org.

Williams, R. W.

G. D. Rosen, A. G. Williams, J. A. Capra, M. T. Connolly, B. Cruz, L. Lu, D. C. Airey, K. Kulkarni, andR. W. Williams (2000), The Mouse Brain Library@ www.mbl.org.

Xie, X.

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

Xu, M.

M. Xu and L. V. Wang, Phys. Rev. E 67, 056605 (2003).
[CrossRef]

M. Xu, Y. Xu, and L. V. Wang, “Time-domain reconstruction algorithms and numerical simulations for thermoacoustic tomography in various geometries,” IEEE Trans. Biomed. Eng. (to be published).

Xu, Y.

M. Xu, Y. Xu, and L. V. Wang, “Time-domain reconstruction algorithms and numerical simulations for thermoacoustic tomography in various geometries,” IEEE Trans. Biomed. Eng. (to be published).

Zhuang, Z.

B. Chance, Z. Zhuang, C. UnAh, C. Alter, and L. Lipton, Proc. Natl. Acad. Sci. USA 90, 3770 (1993).
[CrossRef]

IEEE J. Sel. Top. Quantum Electron. (1)

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

IEEE J. Sel. Top. Quantum Electron. (1)

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. Biomed. Eng. (1)

M. Xu, Y. Xu, and L. V. Wang, “Time-domain reconstruction algorithms and numerical simulations for thermoacoustic tomography in various geometries,” IEEE Trans. Biomed. Eng. (to be published).

Med. Phys. (1)

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

Nature (2)

M. M. Haglund, G. A. Ojemann, and D. W. Hochman, Nature 358, 668 (1992).
[CrossRef] [PubMed]

A. Grinvald, E. Lieke, R. D. Frostig, C. D. Gilbert, and T. N. Wiesel, Nature 324, 361 (1986).
[CrossRef] [PubMed]

Nature Biotechnol. (1)

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

Neuroimage (1)

G. Gratton, M. Fabiani, P. M. Corballis, D. C. Hood, M. R. Goodman Wood, J. Hirsch, K. Kim, D. Friedman, and E. Gratton, Neuroimage 6, 168 (1997).
[CrossRef] [PubMed]

Neurosci. Lett. (1)

A. Villringer, J. Planck, C. Hoch, L. Schleinkofer, and U. Dirnagl, Neurosci. Lett. 154, 101 (1993).
[CrossRef] [PubMed]

Opt. Lett. (1)

Photochem. Photobiol. (1)

J. K. Barton, G. Frangineas, H. Pummer, and J. F. Black, Photochem. Photobiol. 73, 642 (2001).
[CrossRef] [PubMed]

Phys. Rev. E (1)

M. Xu and L. V. Wang, Phys. Rev. E 67, 056605 (2003).
[CrossRef]

Proc. Natl. Acad. Sci. USA (1)

B. Chance, Z. Zhuang, C. UnAh, C. Alter, and L. Lipton, Proc. Natl. Acad. Sci. USA 90, 3770 (1993).
[CrossRef]

Proc. Natl. Acad. Sci. USA (1)

R. D. Frostig, E. E. Lieke, D. Y. Ts'o, and A. Grinvald, Proc. Natl. Acad. Sci. USA 87, 6082 (1990).
[CrossRef]

Proc. SPIE (1)

P. VanderZee, M. Essenpreis, and D. T. Delpy, Proc. SPIE 1888, 454 (1993).
[CrossRef]

Trends Neurosci. (1)

A. Villringer and B. Chance, Trends Neurosci. 20, 435 (1997).
[CrossRef] [PubMed]

Other (1)

G. D. Rosen, A. G. Williams, J. A. Capra, M. T. Connolly, B. Cruz, L. Lu, D. C. Airey, K. Kulkarni, andR. W. Williams (2000), The Mouse Brain Library@ www.mbl.org.

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Figures (2)

Fig. 1
Fig. 1

Setup for noninvasive transdermal and transcranial 3-D PAT of a mouse brain.

Fig. 2
Fig. 2

Noninvasive 3-D PAT of a mouse brain achieved with the skin and skull intact. The images show horizontal cross sections from the dorsal to the ventral part of the brain, where the imaging depth is A, 0.5 mm; B, 2.0 mm; C, 3.5 mm; D, 5.0 mm; E, 6.5 mm; and F, 8.0 mm from the top surface of the mouse’s head, with a constant interval of 1.5 mm. The size of each image is 1.8 cm×2.5 cm. A color bar shows the magnitude of optical absorption, where the red areas (such as blood vessels) indicate tissues with comparatively higher optical absorption. Histological pictures in G and H are presented for comparison with the corresponding images in D and F. In the PAT images and histological pictures, the major characteristic tissue structures in the mouse brain are indicated. BV, blood vessel; CB, cerebellum; FLC, fissura longitudinalis cerebri; FTC, fissura transversa cerebri; HC, hippocampus; LH, left hemisphere; MC, mesencephalon; MCA, middle cerebral artery; OL, olfactory lobes; RH, right hemisphere; VL, ventriculi lateralis.

Equations (1)

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Ar=-β2c4πCPS0dS01tpr0,ttt=r0-r/c,

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