Abstract

Since the photoacoustic effect relies only on the absorbed optical energy, the back-reflected photons from samples in optical-resolution photoacoustic microscopy are usually discarded. By employing a 2 × 2 single-mode fiber optical coupler in a laser-scanning optical-resolution photoacoustic microscope for delivering the illuminating laser light and collecting the back reflected photons, a fiber-optic confocal microscope is integrated with the photoacoustic microscope. Thus, simultaneous multimodal imaging can be achieved with a single light source and images from the two modalities are intrinsically registered. Such capabilities are demonstrated in imaging both phantoms and small animals in vivo.

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    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
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2009 (6)

E. Z. Zhang, J. G. Laufer, R. B. Pedley, and P. C. Beard, “In vivo high-resolution 3D photoacoustic imaging of superficial vascular anatomy,” Phys. Med. Biol. 54(4), 1035–1046 (2009).
[CrossRef] [PubMed]

Z. X. Xie, S. L. Jiao, H. F. Zhang, and C. A. Puliafito, “Laser-scanning optical-resolution photoacoustic microscopy,” Opt. Lett. 34(12), 1771–1773 (2009).
[CrossRef] [PubMed]

L. V. Wang, “Multiscale photoacoustic microscopy and computed tomography,” Nat. Photonics 3(9), 503–509 (2009).
[CrossRef]

K. H. Song, C. H. Kim, C. M. Cobley, Y. N. Xia, and L. V. Wang, “Near-infrared gold nanocages as a new class of tracers for photoacoustic sentinel lymph node mapping on a rat model,” Nano Lett. 9(1), 183–188 (2009).
[CrossRef]

J. Laufer, E. Zhang, G. Raivich, and P. Beard, “Three-dimensional noninvasive imaging of the vasculature in the mouse brain using a high resolution photoacoustic scanner,” Appl. Opt. 48(10), D299–D306 (2009).
[CrossRef] [PubMed]

S. L. Jiao, Z. X. Xie, H. F. Zhang, and C. A. Puliafito, “Simultaneous multimodal imaging with integrated photoacoustic microscopy and optical coherence tomography,” Opt. Lett. 34(19), 2961–2963 (2009).
[CrossRef] [PubMed]

2008 (3)

S. Schmitz-Valckenberg, M. Fleckenstein, A. P. Göbel, K. Sehmi, F. W. Fitzke, F. G. Holz, and A. Tufail, “Evaluation of autofluorescence imaging with the scanning laser ophthalmoscope and the fundus camera in age-related geographic atrophy,” Am. J. Ophthalmol. 146(2), 183–192 (2008).
[CrossRef] [PubMed]

K. Maslov, H. F. Zhang, S. Hu, and L. V. Wang, “Optical-resolution photoacoustic microscopy for in vivo imaging of single capillaries,” Opt. Lett. 33(9), 929–931 (2008).
[CrossRef] [PubMed]

A. De La Zerda, C. Zavaleta, S. Keren, S. Vaithilingam, S. Bodapati, Z. Liu, J. Levi, B. R. Smith, T. J. Ma, O. Oralkan, Z. Cheng, X. Y. Chen, H. J. Dai, B. T. Khuri-Yakub, and S. S. Gambhir, “Carbon nanotubes as photoacoustic molecular imaging agents in living mice,” Nat. Nanotechnol. 3(9), 557–562 (2008).
[CrossRef] [PubMed]

2006 (2)

H. F. Zhang, K. Maslov, G. Stoica, and L. V. Wang, “Functional photoacoustic microscopy for high-resolution and noninvasive in vivo imaging,” Nat. Biotechnol. 24(7), 848–851 (2006).
[CrossRef] [PubMed]

E. Salomatina, B. Jiang, J. Novak, and A. N. Yaroslavsky, “Optical properties of normal and cancerous human skin in the visible and near-infrared spectral range,” J. Biomed. Opt. 11(6), 064026 (2006).
[CrossRef]

2005 (1)

1992 (1)

1987 (1)

Beard, P.

Beard, P. C.

E. Z. Zhang, J. G. Laufer, R. B. Pedley, and P. C. Beard, “In vivo high-resolution 3D photoacoustic imaging of superficial vascular anatomy,” Phys. Med. Biol. 54(4), 1035–1046 (2009).
[CrossRef] [PubMed]

Bodapati, S.

A. De La Zerda, C. Zavaleta, S. Keren, S. Vaithilingam, S. Bodapati, Z. Liu, J. Levi, B. R. Smith, T. J. Ma, O. Oralkan, Z. Cheng, X. Y. Chen, H. J. Dai, B. T. Khuri-Yakub, and S. S. Gambhir, “Carbon nanotubes as photoacoustic molecular imaging agents in living mice,” Nat. Nanotechnol. 3(9), 557–562 (2008).
[CrossRef] [PubMed]

Chen, X. Y.

A. De La Zerda, C. Zavaleta, S. Keren, S. Vaithilingam, S. Bodapati, Z. Liu, J. Levi, B. R. Smith, T. J. Ma, O. Oralkan, Z. Cheng, X. Y. Chen, H. J. Dai, B. T. Khuri-Yakub, and S. S. Gambhir, “Carbon nanotubes as photoacoustic molecular imaging agents in living mice,” Nat. Nanotechnol. 3(9), 557–562 (2008).
[CrossRef] [PubMed]

Cheng, Z.

A. De La Zerda, C. Zavaleta, S. Keren, S. Vaithilingam, S. Bodapati, Z. Liu, J. Levi, B. R. Smith, T. J. Ma, O. Oralkan, Z. Cheng, X. Y. Chen, H. J. Dai, B. T. Khuri-Yakub, and S. S. Gambhir, “Carbon nanotubes as photoacoustic molecular imaging agents in living mice,” Nat. Nanotechnol. 3(9), 557–562 (2008).
[CrossRef] [PubMed]

Cobley, C. M.

K. H. Song, C. H. Kim, C. M. Cobley, Y. N. Xia, and L. V. Wang, “Near-infrared gold nanocages as a new class of tracers for photoacoustic sentinel lymph node mapping on a rat model,” Nano Lett. 9(1), 183–188 (2009).
[CrossRef]

Dabbs, T.

Dai, H. J.

A. De La Zerda, C. Zavaleta, S. Keren, S. Vaithilingam, S. Bodapati, Z. Liu, J. Levi, B. R. Smith, T. J. Ma, O. Oralkan, Z. Cheng, X. Y. Chen, H. J. Dai, B. T. Khuri-Yakub, and S. S. Gambhir, “Carbon nanotubes as photoacoustic molecular imaging agents in living mice,” Nat. Nanotechnol. 3(9), 557–562 (2008).
[CrossRef] [PubMed]

De La Zerda, A.

A. De La Zerda, C. Zavaleta, S. Keren, S. Vaithilingam, S. Bodapati, Z. Liu, J. Levi, B. R. Smith, T. J. Ma, O. Oralkan, Z. Cheng, X. Y. Chen, H. J. Dai, B. T. Khuri-Yakub, and S. S. Gambhir, “Carbon nanotubes as photoacoustic molecular imaging agents in living mice,” Nat. Nanotechnol. 3(9), 557–562 (2008).
[CrossRef] [PubMed]

Delori, F. C.

Fitzke, F. W.

S. Schmitz-Valckenberg, M. Fleckenstein, A. P. Göbel, K. Sehmi, F. W. Fitzke, F. G. Holz, and A. Tufail, “Evaluation of autofluorescence imaging with the scanning laser ophthalmoscope and the fundus camera in age-related geographic atrophy,” Am. J. Ophthalmol. 146(2), 183–192 (2008).
[CrossRef] [PubMed]

Fleckenstein, M.

S. Schmitz-Valckenberg, M. Fleckenstein, A. P. Göbel, K. Sehmi, F. W. Fitzke, F. G. Holz, and A. Tufail, “Evaluation of autofluorescence imaging with the scanning laser ophthalmoscope and the fundus camera in age-related geographic atrophy,” Am. J. Ophthalmol. 146(2), 183–192 (2008).
[CrossRef] [PubMed]

Gambhir, S. S.

A. De La Zerda, C. Zavaleta, S. Keren, S. Vaithilingam, S. Bodapati, Z. Liu, J. Levi, B. R. Smith, T. J. Ma, O. Oralkan, Z. Cheng, X. Y. Chen, H. J. Dai, B. T. Khuri-Yakub, and S. S. Gambhir, “Carbon nanotubes as photoacoustic molecular imaging agents in living mice,” Nat. Nanotechnol. 3(9), 557–562 (2008).
[CrossRef] [PubMed]

Glass, M.

Göbel, A. P.

S. Schmitz-Valckenberg, M. Fleckenstein, A. P. Göbel, K. Sehmi, F. W. Fitzke, F. G. Holz, and A. Tufail, “Evaluation of autofluorescence imaging with the scanning laser ophthalmoscope and the fundus camera in age-related geographic atrophy,” Am. J. Ophthalmol. 146(2), 183–192 (2008).
[CrossRef] [PubMed]

Gregori, G.

Holz, F. G.

S. Schmitz-Valckenberg, M. Fleckenstein, A. P. Göbel, K. Sehmi, F. W. Fitzke, F. G. Holz, and A. Tufail, “Evaluation of autofluorescence imaging with the scanning laser ophthalmoscope and the fundus camera in age-related geographic atrophy,” Am. J. Ophthalmol. 146(2), 183–192 (2008).
[CrossRef] [PubMed]

Hu, S.

Huang, X.

Hughes, G. W.

Jiang, B.

E. Salomatina, B. Jiang, J. Novak, and A. N. Yaroslavsky, “Optical properties of normal and cancerous human skin in the visible and near-infrared spectral range,” J. Biomed. Opt. 11(6), 064026 (2006).
[CrossRef]

Jiao, S.

Jiao, S. L.

Keren, S.

A. De La Zerda, C. Zavaleta, S. Keren, S. Vaithilingam, S. Bodapati, Z. Liu, J. Levi, B. R. Smith, T. J. Ma, O. Oralkan, Z. Cheng, X. Y. Chen, H. J. Dai, B. T. Khuri-Yakub, and S. S. Gambhir, “Carbon nanotubes as photoacoustic molecular imaging agents in living mice,” Nat. Nanotechnol. 3(9), 557–562 (2008).
[CrossRef] [PubMed]

Khuri-Yakub, B. T.

A. De La Zerda, C. Zavaleta, S. Keren, S. Vaithilingam, S. Bodapati, Z. Liu, J. Levi, B. R. Smith, T. J. Ma, O. Oralkan, Z. Cheng, X. Y. Chen, H. J. Dai, B. T. Khuri-Yakub, and S. S. Gambhir, “Carbon nanotubes as photoacoustic molecular imaging agents in living mice,” Nat. Nanotechnol. 3(9), 557–562 (2008).
[CrossRef] [PubMed]

Kim, C. H.

K. H. Song, C. H. Kim, C. M. Cobley, Y. N. Xia, and L. V. Wang, “Near-infrared gold nanocages as a new class of tracers for photoacoustic sentinel lymph node mapping on a rat model,” Nano Lett. 9(1), 183–188 (2009).
[CrossRef]

Knighton, R.

Laufer, J.

Laufer, J. G.

E. Z. Zhang, J. G. Laufer, R. B. Pedley, and P. C. Beard, “In vivo high-resolution 3D photoacoustic imaging of superficial vascular anatomy,” Phys. Med. Biol. 54(4), 1035–1046 (2009).
[CrossRef] [PubMed]

Levi, J.

A. De La Zerda, C. Zavaleta, S. Keren, S. Vaithilingam, S. Bodapati, Z. Liu, J. Levi, B. R. Smith, T. J. Ma, O. Oralkan, Z. Cheng, X. Y. Chen, H. J. Dai, B. T. Khuri-Yakub, and S. S. Gambhir, “Carbon nanotubes as photoacoustic molecular imaging agents in living mice,” Nat. Nanotechnol. 3(9), 557–562 (2008).
[CrossRef] [PubMed]

Liu, Z.

A. De La Zerda, C. Zavaleta, S. Keren, S. Vaithilingam, S. Bodapati, Z. Liu, J. Levi, B. R. Smith, T. J. Ma, O. Oralkan, Z. Cheng, X. Y. Chen, H. J. Dai, B. T. Khuri-Yakub, and S. S. Gambhir, “Carbon nanotubes as photoacoustic molecular imaging agents in living mice,” Nat. Nanotechnol. 3(9), 557–562 (2008).
[CrossRef] [PubMed]

Ma, T. J.

A. De La Zerda, C. Zavaleta, S. Keren, S. Vaithilingam, S. Bodapati, Z. Liu, J. Levi, B. R. Smith, T. J. Ma, O. Oralkan, Z. Cheng, X. Y. Chen, H. J. Dai, B. T. Khuri-Yakub, and S. S. Gambhir, “Carbon nanotubes as photoacoustic molecular imaging agents in living mice,” Nat. Nanotechnol. 3(9), 557–562 (2008).
[CrossRef] [PubMed]

Maslov, K.

K. Maslov, H. F. Zhang, S. Hu, and L. V. Wang, “Optical-resolution photoacoustic microscopy for in vivo imaging of single capillaries,” Opt. Lett. 33(9), 929–931 (2008).
[CrossRef] [PubMed]

H. F. Zhang, K. Maslov, G. Stoica, and L. V. Wang, “Functional photoacoustic microscopy for high-resolution and noninvasive in vivo imaging,” Nat. Biotechnol. 24(7), 848–851 (2006).
[CrossRef] [PubMed]

Novak, J.

E. Salomatina, B. Jiang, J. Novak, and A. N. Yaroslavsky, “Optical properties of normal and cancerous human skin in the visible and near-infrared spectral range,” J. Biomed. Opt. 11(6), 064026 (2006).
[CrossRef]

Oralkan, O.

A. De La Zerda, C. Zavaleta, S. Keren, S. Vaithilingam, S. Bodapati, Z. Liu, J. Levi, B. R. Smith, T. J. Ma, O. Oralkan, Z. Cheng, X. Y. Chen, H. J. Dai, B. T. Khuri-Yakub, and S. S. Gambhir, “Carbon nanotubes as photoacoustic molecular imaging agents in living mice,” Nat. Nanotechnol. 3(9), 557–562 (2008).
[CrossRef] [PubMed]

Pedley, R. B.

E. Z. Zhang, J. G. Laufer, R. B. Pedley, and P. C. Beard, “In vivo high-resolution 3D photoacoustic imaging of superficial vascular anatomy,” Phys. Med. Biol. 54(4), 1035–1046 (2009).
[CrossRef] [PubMed]

Puliafito, C. A.

Raivich, G.

Salomatina, E.

E. Salomatina, B. Jiang, J. Novak, and A. N. Yaroslavsky, “Optical properties of normal and cancerous human skin in the visible and near-infrared spectral range,” J. Biomed. Opt. 11(6), 064026 (2006).
[CrossRef]

Schmitz-Valckenberg, S.

S. Schmitz-Valckenberg, M. Fleckenstein, A. P. Göbel, K. Sehmi, F. W. Fitzke, F. G. Holz, and A. Tufail, “Evaluation of autofluorescence imaging with the scanning laser ophthalmoscope and the fundus camera in age-related geographic atrophy,” Am. J. Ophthalmol. 146(2), 183–192 (2008).
[CrossRef] [PubMed]

Sehmi, K.

S. Schmitz-Valckenberg, M. Fleckenstein, A. P. Göbel, K. Sehmi, F. W. Fitzke, F. G. Holz, and A. Tufail, “Evaluation of autofluorescence imaging with the scanning laser ophthalmoscope and the fundus camera in age-related geographic atrophy,” Am. J. Ophthalmol. 146(2), 183–192 (2008).
[CrossRef] [PubMed]

Smith, B. R.

A. De La Zerda, C. Zavaleta, S. Keren, S. Vaithilingam, S. Bodapati, Z. Liu, J. Levi, B. R. Smith, T. J. Ma, O. Oralkan, Z. Cheng, X. Y. Chen, H. J. Dai, B. T. Khuri-Yakub, and S. S. Gambhir, “Carbon nanotubes as photoacoustic molecular imaging agents in living mice,” Nat. Nanotechnol. 3(9), 557–562 (2008).
[CrossRef] [PubMed]

Song, K. H.

K. H. Song, C. H. Kim, C. M. Cobley, Y. N. Xia, and L. V. Wang, “Near-infrared gold nanocages as a new class of tracers for photoacoustic sentinel lymph node mapping on a rat model,” Nano Lett. 9(1), 183–188 (2009).
[CrossRef]

Stoica, G.

H. F. Zhang, K. Maslov, G. Stoica, and L. V. Wang, “Functional photoacoustic microscopy for high-resolution and noninvasive in vivo imaging,” Nat. Biotechnol. 24(7), 848–851 (2006).
[CrossRef] [PubMed]

Tufail, A.

S. Schmitz-Valckenberg, M. Fleckenstein, A. P. Göbel, K. Sehmi, F. W. Fitzke, F. G. Holz, and A. Tufail, “Evaluation of autofluorescence imaging with the scanning laser ophthalmoscope and the fundus camera in age-related geographic atrophy,” Am. J. Ophthalmol. 146(2), 183–192 (2008).
[CrossRef] [PubMed]

Vaithilingam, S.

A. De La Zerda, C. Zavaleta, S. Keren, S. Vaithilingam, S. Bodapati, Z. Liu, J. Levi, B. R. Smith, T. J. Ma, O. Oralkan, Z. Cheng, X. Y. Chen, H. J. Dai, B. T. Khuri-Yakub, and S. S. Gambhir, “Carbon nanotubes as photoacoustic molecular imaging agents in living mice,” Nat. Nanotechnol. 3(9), 557–562 (2008).
[CrossRef] [PubMed]

Wang, L. V.

L. V. Wang, “Multiscale photoacoustic microscopy and computed tomography,” Nat. Photonics 3(9), 503–509 (2009).
[CrossRef]

K. H. Song, C. H. Kim, C. M. Cobley, Y. N. Xia, and L. V. Wang, “Near-infrared gold nanocages as a new class of tracers for photoacoustic sentinel lymph node mapping on a rat model,” Nano Lett. 9(1), 183–188 (2009).
[CrossRef]

K. Maslov, H. F. Zhang, S. Hu, and L. V. Wang, “Optical-resolution photoacoustic microscopy for in vivo imaging of single capillaries,” Opt. Lett. 33(9), 929–931 (2008).
[CrossRef] [PubMed]

H. F. Zhang, K. Maslov, G. Stoica, and L. V. Wang, “Functional photoacoustic microscopy for high-resolution and noninvasive in vivo imaging,” Nat. Biotechnol. 24(7), 848–851 (2006).
[CrossRef] [PubMed]

Webb, R. H.

Xia, Y. N.

K. H. Song, C. H. Kim, C. M. Cobley, Y. N. Xia, and L. V. Wang, “Near-infrared gold nanocages as a new class of tracers for photoacoustic sentinel lymph node mapping on a rat model,” Nano Lett. 9(1), 183–188 (2009).
[CrossRef]

Xie, Z. X.

Yaroslavsky, A. N.

E. Salomatina, B. Jiang, J. Novak, and A. N. Yaroslavsky, “Optical properties of normal and cancerous human skin in the visible and near-infrared spectral range,” J. Biomed. Opt. 11(6), 064026 (2006).
[CrossRef]

Zavaleta, C.

A. De La Zerda, C. Zavaleta, S. Keren, S. Vaithilingam, S. Bodapati, Z. Liu, J. Levi, B. R. Smith, T. J. Ma, O. Oralkan, Z. Cheng, X. Y. Chen, H. J. Dai, B. T. Khuri-Yakub, and S. S. Gambhir, “Carbon nanotubes as photoacoustic molecular imaging agents in living mice,” Nat. Nanotechnol. 3(9), 557–562 (2008).
[CrossRef] [PubMed]

Zhang, E.

Zhang, E. Z.

E. Z. Zhang, J. G. Laufer, R. B. Pedley, and P. C. Beard, “In vivo high-resolution 3D photoacoustic imaging of superficial vascular anatomy,” Phys. Med. Biol. 54(4), 1035–1046 (2009).
[CrossRef] [PubMed]

Zhang, H. F.

Am. J. Ophthalmol. (1)

S. Schmitz-Valckenberg, M. Fleckenstein, A. P. Göbel, K. Sehmi, F. W. Fitzke, F. G. Holz, and A. Tufail, “Evaluation of autofluorescence imaging with the scanning laser ophthalmoscope and the fundus camera in age-related geographic atrophy,” Am. J. Ophthalmol. 146(2), 183–192 (2008).
[CrossRef] [PubMed]

Appl. Opt. (3)

J. Biomed. Opt. (1)

E. Salomatina, B. Jiang, J. Novak, and A. N. Yaroslavsky, “Optical properties of normal and cancerous human skin in the visible and near-infrared spectral range,” J. Biomed. Opt. 11(6), 064026 (2006).
[CrossRef]

Nano Lett. (1)

K. H. Song, C. H. Kim, C. M. Cobley, Y. N. Xia, and L. V. Wang, “Near-infrared gold nanocages as a new class of tracers for photoacoustic sentinel lymph node mapping on a rat model,” Nano Lett. 9(1), 183–188 (2009).
[CrossRef]

Nat. Biotechnol. (1)

H. F. Zhang, K. Maslov, G. Stoica, and L. V. Wang, “Functional photoacoustic microscopy for high-resolution and noninvasive in vivo imaging,” Nat. Biotechnol. 24(7), 848–851 (2006).
[CrossRef] [PubMed]

Nat. Nanotechnol. (1)

A. De La Zerda, C. Zavaleta, S. Keren, S. Vaithilingam, S. Bodapati, Z. Liu, J. Levi, B. R. Smith, T. J. Ma, O. Oralkan, Z. Cheng, X. Y. Chen, H. J. Dai, B. T. Khuri-Yakub, and S. S. Gambhir, “Carbon nanotubes as photoacoustic molecular imaging agents in living mice,” Nat. Nanotechnol. 3(9), 557–562 (2008).
[CrossRef] [PubMed]

Nat. Photonics (1)

L. V. Wang, “Multiscale photoacoustic microscopy and computed tomography,” Nat. Photonics 3(9), 503–509 (2009).
[CrossRef]

Opt. Express (1)

Opt. Lett. (3)

Phys. Med. Biol. (1)

E. Z. Zhang, J. G. Laufer, R. B. Pedley, and P. C. Beard, “In vivo high-resolution 3D photoacoustic imaging of superficial vascular anatomy,” Phys. Med. Biol. 54(4), 1035–1046 (2009).
[CrossRef] [PubMed]

Other (2)

D. A. Atchison, and G. Smith, Optics of human eye (Butterworth-Heinemann, 2000).

M. Gu, Principles of three-dimensional imaging in confocal microscopes (Word Scientific, 1996).

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Figures (4)

Fig. 1
Fig. 1

Schematic of the fused laser-scanning confocal microscopy and photoacoustic microscopy. PD: photodiode; 2×2: fiber coupler.

Fig. 2
Fig. 2

Axial resolution of the confocal microscopy. (a) schematic of the optical illumination and detection for theoretical estimation; (b) experimental measurement of axial resolution.

Fig. 3
Fig. 3

Images of a printed mesh grid using the fused PAM and FOCON. (a) LSOR-PAM image; (b) FOCON image.

Fig. 4
Fig. 4

In vivo multimodal imaging of a mouse ear. (a) LSOR-PAM image showing microvasculature; (b) FOCON image showing skin structure. SB: sebaceous gland.

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