Abstract

We developed section-illumination photoacoustic microscopy capable of dynamic in vivo imaging of microvessels as small as 30μm in diameter. The section illumination improved the elevational resolution while an ultrasound array provided the in-plane axial and lateral resolutions. Using the imaging system, we monitored the wash-in dynamics of Evans Blue in the microcirculation of mouse ears at 249Hz 2D and 0.5Hz 3D image acquisition rates. Such observation allowed us to differentiate the arterioles from the venules. In the future, the technology may be used to study angiogenesis, diabetes-induced vascular complications, and pharmacokinetics.

© 2010 Optical Society of America

Full Article  |  PDF Article

References

  • View by:
  • |
  • |
  • |

  1. M. J. Leahya, J. G. Enfielda, N. T. Clancya, J. O’Dohertya, P. McNamaraa, and G. E. Nilsson, Med. Laser Appl. 22, 105 (2007).
    [CrossRef]
  2. M. D. Stern, Nature 254, 56 (1975).
    [CrossRef] [PubMed]
  3. W. Groner, J. W. Winkelman, A. G. Harris, C. Ince, G. J. Bouma, K. Messmer, and R. G. Nadeau, Nat. Med. 5, 1209 (1999).
    [CrossRef] [PubMed]
  4. A. F. DeVries, J. Griebel, C. Kremser, W. Judmaier, T. Gneiting, A. Kreczy, D. Ofner, K. P. Pfeiffer, G. Brix, and P. Lukas, Cancer Res. 61, 2513 (2001).
    [PubMed]
  5. M. Cutolo, A. Sulli, C. Pizzorni, and S. Accardo, J. Rheumatol. 27, 155 (2000).
    [PubMed]
  6. D. E. Goertz, J. L. Yu, R. S. Kerbel, P. N. Burns, and F. S. Foster, Ultrasound Med. Biol. 29, 39 (2003).
    [CrossRef] [PubMed]
  7. K. Maslov, H. F. Zhang, S. Hu, and L. V. Wang, Opt. Lett. 33, 929 (2008).
    [CrossRef] [PubMed]
  8. L. V. Wang, Nat. Photonics 3, 503 (2009).
    [CrossRef]
  9. L. Song, K. Maslov, R. Bitton, K. K. Shung, and L. V. Wang, J. Biomed. Opt. 13, 054028 (2008).
    [CrossRef] [PubMed]
  10. R. J. Zemp, L. Song, R. Bitton, K. K. Shung, and L. V. Wang, Opt. Express 16, 7915 (2008).
    [CrossRef] [PubMed]
  11. L. Song, K. Maslov, K. K. Shung, and L. V. Wang, J. Biomed. Opt. 15, 021303 (2010).
    [CrossRef] [PubMed]
  12. L. Song, C. Kim, K. Maslov, K. K. Shung, and L. V. Wang, Med. Phys. 36, 3724 (2009).
    [CrossRef] [PubMed]
  13. S. Hu, K. Maslov, and L. V. Wang, Opt. Express 17, 7688 (2009).
    [CrossRef] [PubMed]

2010 (1)

L. Song, K. Maslov, K. K. Shung, and L. V. Wang, J. Biomed. Opt. 15, 021303 (2010).
[CrossRef] [PubMed]

2009 (3)

L. Song, C. Kim, K. Maslov, K. K. Shung, and L. V. Wang, Med. Phys. 36, 3724 (2009).
[CrossRef] [PubMed]

S. Hu, K. Maslov, and L. V. Wang, Opt. Express 17, 7688 (2009).
[CrossRef] [PubMed]

L. V. Wang, Nat. Photonics 3, 503 (2009).
[CrossRef]

2008 (3)

2007 (1)

M. J. Leahya, J. G. Enfielda, N. T. Clancya, J. O’Dohertya, P. McNamaraa, and G. E. Nilsson, Med. Laser Appl. 22, 105 (2007).
[CrossRef]

2003 (1)

D. E. Goertz, J. L. Yu, R. S. Kerbel, P. N. Burns, and F. S. Foster, Ultrasound Med. Biol. 29, 39 (2003).
[CrossRef] [PubMed]

2001 (1)

A. F. DeVries, J. Griebel, C. Kremser, W. Judmaier, T. Gneiting, A. Kreczy, D. Ofner, K. P. Pfeiffer, G. Brix, and P. Lukas, Cancer Res. 61, 2513 (2001).
[PubMed]

2000 (1)

M. Cutolo, A. Sulli, C. Pizzorni, and S. Accardo, J. Rheumatol. 27, 155 (2000).
[PubMed]

1999 (1)

W. Groner, J. W. Winkelman, A. G. Harris, C. Ince, G. J. Bouma, K. Messmer, and R. G. Nadeau, Nat. Med. 5, 1209 (1999).
[CrossRef] [PubMed]

1975 (1)

M. D. Stern, Nature 254, 56 (1975).
[CrossRef] [PubMed]

Accardo, S.

M. Cutolo, A. Sulli, C. Pizzorni, and S. Accardo, J. Rheumatol. 27, 155 (2000).
[PubMed]

Bitton, R.

L. Song, K. Maslov, R. Bitton, K. K. Shung, and L. V. Wang, J. Biomed. Opt. 13, 054028 (2008).
[CrossRef] [PubMed]

R. J. Zemp, L. Song, R. Bitton, K. K. Shung, and L. V. Wang, Opt. Express 16, 7915 (2008).
[CrossRef] [PubMed]

Bouma, G. J.

W. Groner, J. W. Winkelman, A. G. Harris, C. Ince, G. J. Bouma, K. Messmer, and R. G. Nadeau, Nat. Med. 5, 1209 (1999).
[CrossRef] [PubMed]

Brix, G.

A. F. DeVries, J. Griebel, C. Kremser, W. Judmaier, T. Gneiting, A. Kreczy, D. Ofner, K. P. Pfeiffer, G. Brix, and P. Lukas, Cancer Res. 61, 2513 (2001).
[PubMed]

Burns, P. N.

D. E. Goertz, J. L. Yu, R. S. Kerbel, P. N. Burns, and F. S. Foster, Ultrasound Med. Biol. 29, 39 (2003).
[CrossRef] [PubMed]

Clancya, N. T.

M. J. Leahya, J. G. Enfielda, N. T. Clancya, J. O’Dohertya, P. McNamaraa, and G. E. Nilsson, Med. Laser Appl. 22, 105 (2007).
[CrossRef]

Cutolo, M.

M. Cutolo, A. Sulli, C. Pizzorni, and S. Accardo, J. Rheumatol. 27, 155 (2000).
[PubMed]

DeVries, A. F.

A. F. DeVries, J. Griebel, C. Kremser, W. Judmaier, T. Gneiting, A. Kreczy, D. Ofner, K. P. Pfeiffer, G. Brix, and P. Lukas, Cancer Res. 61, 2513 (2001).
[PubMed]

Enfielda, J. G.

M. J. Leahya, J. G. Enfielda, N. T. Clancya, J. O’Dohertya, P. McNamaraa, and G. E. Nilsson, Med. Laser Appl. 22, 105 (2007).
[CrossRef]

Foster, F. S.

D. E. Goertz, J. L. Yu, R. S. Kerbel, P. N. Burns, and F. S. Foster, Ultrasound Med. Biol. 29, 39 (2003).
[CrossRef] [PubMed]

Gneiting, T.

A. F. DeVries, J. Griebel, C. Kremser, W. Judmaier, T. Gneiting, A. Kreczy, D. Ofner, K. P. Pfeiffer, G. Brix, and P. Lukas, Cancer Res. 61, 2513 (2001).
[PubMed]

Goertz, D. E.

D. E. Goertz, J. L. Yu, R. S. Kerbel, P. N. Burns, and F. S. Foster, Ultrasound Med. Biol. 29, 39 (2003).
[CrossRef] [PubMed]

Griebel, J.

A. F. DeVries, J. Griebel, C. Kremser, W. Judmaier, T. Gneiting, A. Kreczy, D. Ofner, K. P. Pfeiffer, G. Brix, and P. Lukas, Cancer Res. 61, 2513 (2001).
[PubMed]

Groner, W.

W. Groner, J. W. Winkelman, A. G. Harris, C. Ince, G. J. Bouma, K. Messmer, and R. G. Nadeau, Nat. Med. 5, 1209 (1999).
[CrossRef] [PubMed]

Harris, A. G.

W. Groner, J. W. Winkelman, A. G. Harris, C. Ince, G. J. Bouma, K. Messmer, and R. G. Nadeau, Nat. Med. 5, 1209 (1999).
[CrossRef] [PubMed]

Hu, S.

Ince, C.

W. Groner, J. W. Winkelman, A. G. Harris, C. Ince, G. J. Bouma, K. Messmer, and R. G. Nadeau, Nat. Med. 5, 1209 (1999).
[CrossRef] [PubMed]

Judmaier, W.

A. F. DeVries, J. Griebel, C. Kremser, W. Judmaier, T. Gneiting, A. Kreczy, D. Ofner, K. P. Pfeiffer, G. Brix, and P. Lukas, Cancer Res. 61, 2513 (2001).
[PubMed]

Kerbel, R. S.

D. E. Goertz, J. L. Yu, R. S. Kerbel, P. N. Burns, and F. S. Foster, Ultrasound Med. Biol. 29, 39 (2003).
[CrossRef] [PubMed]

Kim, C.

L. Song, C. Kim, K. Maslov, K. K. Shung, and L. V. Wang, Med. Phys. 36, 3724 (2009).
[CrossRef] [PubMed]

Kreczy, A.

A. F. DeVries, J. Griebel, C. Kremser, W. Judmaier, T. Gneiting, A. Kreczy, D. Ofner, K. P. Pfeiffer, G. Brix, and P. Lukas, Cancer Res. 61, 2513 (2001).
[PubMed]

Kremser, C.

A. F. DeVries, J. Griebel, C. Kremser, W. Judmaier, T. Gneiting, A. Kreczy, D. Ofner, K. P. Pfeiffer, G. Brix, and P. Lukas, Cancer Res. 61, 2513 (2001).
[PubMed]

Leahya, M. J.

M. J. Leahya, J. G. Enfielda, N. T. Clancya, J. O’Dohertya, P. McNamaraa, and G. E. Nilsson, Med. Laser Appl. 22, 105 (2007).
[CrossRef]

Lukas, P.

A. F. DeVries, J. Griebel, C. Kremser, W. Judmaier, T. Gneiting, A. Kreczy, D. Ofner, K. P. Pfeiffer, G. Brix, and P. Lukas, Cancer Res. 61, 2513 (2001).
[PubMed]

Maslov, K.

L. Song, K. Maslov, K. K. Shung, and L. V. Wang, J. Biomed. Opt. 15, 021303 (2010).
[CrossRef] [PubMed]

S. Hu, K. Maslov, and L. V. Wang, Opt. Express 17, 7688 (2009).
[CrossRef] [PubMed]

L. Song, C. Kim, K. Maslov, K. K. Shung, and L. V. Wang, Med. Phys. 36, 3724 (2009).
[CrossRef] [PubMed]

L. Song, K. Maslov, R. Bitton, K. K. Shung, and L. V. Wang, J. Biomed. Opt. 13, 054028 (2008).
[CrossRef] [PubMed]

K. Maslov, H. F. Zhang, S. Hu, and L. V. Wang, Opt. Lett. 33, 929 (2008).
[CrossRef] [PubMed]

McNamaraa, P.

M. J. Leahya, J. G. Enfielda, N. T. Clancya, J. O’Dohertya, P. McNamaraa, and G. E. Nilsson, Med. Laser Appl. 22, 105 (2007).
[CrossRef]

Messmer, K.

W. Groner, J. W. Winkelman, A. G. Harris, C. Ince, G. J. Bouma, K. Messmer, and R. G. Nadeau, Nat. Med. 5, 1209 (1999).
[CrossRef] [PubMed]

Nadeau, R. G.

W. Groner, J. W. Winkelman, A. G. Harris, C. Ince, G. J. Bouma, K. Messmer, and R. G. Nadeau, Nat. Med. 5, 1209 (1999).
[CrossRef] [PubMed]

Nilsson, G. E.

M. J. Leahya, J. G. Enfielda, N. T. Clancya, J. O’Dohertya, P. McNamaraa, and G. E. Nilsson, Med. Laser Appl. 22, 105 (2007).
[CrossRef]

O’Dohertya, J.

M. J. Leahya, J. G. Enfielda, N. T. Clancya, J. O’Dohertya, P. McNamaraa, and G. E. Nilsson, Med. Laser Appl. 22, 105 (2007).
[CrossRef]

Ofner, D.

A. F. DeVries, J. Griebel, C. Kremser, W. Judmaier, T. Gneiting, A. Kreczy, D. Ofner, K. P. Pfeiffer, G. Brix, and P. Lukas, Cancer Res. 61, 2513 (2001).
[PubMed]

Pfeiffer, K. P.

A. F. DeVries, J. Griebel, C. Kremser, W. Judmaier, T. Gneiting, A. Kreczy, D. Ofner, K. P. Pfeiffer, G. Brix, and P. Lukas, Cancer Res. 61, 2513 (2001).
[PubMed]

Pizzorni, C.

M. Cutolo, A. Sulli, C. Pizzorni, and S. Accardo, J. Rheumatol. 27, 155 (2000).
[PubMed]

Shung, K. K.

L. Song, K. Maslov, K. K. Shung, and L. V. Wang, J. Biomed. Opt. 15, 021303 (2010).
[CrossRef] [PubMed]

L. Song, C. Kim, K. Maslov, K. K. Shung, and L. V. Wang, Med. Phys. 36, 3724 (2009).
[CrossRef] [PubMed]

R. J. Zemp, L. Song, R. Bitton, K. K. Shung, and L. V. Wang, Opt. Express 16, 7915 (2008).
[CrossRef] [PubMed]

L. Song, K. Maslov, R. Bitton, K. K. Shung, and L. V. Wang, J. Biomed. Opt. 13, 054028 (2008).
[CrossRef] [PubMed]

Song, L.

L. Song, K. Maslov, K. K. Shung, and L. V. Wang, J. Biomed. Opt. 15, 021303 (2010).
[CrossRef] [PubMed]

L. Song, C. Kim, K. Maslov, K. K. Shung, and L. V. Wang, Med. Phys. 36, 3724 (2009).
[CrossRef] [PubMed]

R. J. Zemp, L. Song, R. Bitton, K. K. Shung, and L. V. Wang, Opt. Express 16, 7915 (2008).
[CrossRef] [PubMed]

L. Song, K. Maslov, R. Bitton, K. K. Shung, and L. V. Wang, J. Biomed. Opt. 13, 054028 (2008).
[CrossRef] [PubMed]

Stern, M. D.

M. D. Stern, Nature 254, 56 (1975).
[CrossRef] [PubMed]

Sulli, A.

M. Cutolo, A. Sulli, C. Pizzorni, and S. Accardo, J. Rheumatol. 27, 155 (2000).
[PubMed]

Wang, L. V.

L. Song, K. Maslov, K. K. Shung, and L. V. Wang, J. Biomed. Opt. 15, 021303 (2010).
[CrossRef] [PubMed]

S. Hu, K. Maslov, and L. V. Wang, Opt. Express 17, 7688 (2009).
[CrossRef] [PubMed]

L. V. Wang, Nat. Photonics 3, 503 (2009).
[CrossRef]

L. Song, C. Kim, K. Maslov, K. K. Shung, and L. V. Wang, Med. Phys. 36, 3724 (2009).
[CrossRef] [PubMed]

R. J. Zemp, L. Song, R. Bitton, K. K. Shung, and L. V. Wang, Opt. Express 16, 7915 (2008).
[CrossRef] [PubMed]

L. Song, K. Maslov, R. Bitton, K. K. Shung, and L. V. Wang, J. Biomed. Opt. 13, 054028 (2008).
[CrossRef] [PubMed]

K. Maslov, H. F. Zhang, S. Hu, and L. V. Wang, Opt. Lett. 33, 929 (2008).
[CrossRef] [PubMed]

Winkelman, J. W.

W. Groner, J. W. Winkelman, A. G. Harris, C. Ince, G. J. Bouma, K. Messmer, and R. G. Nadeau, Nat. Med. 5, 1209 (1999).
[CrossRef] [PubMed]

Yu, J. L.

D. E. Goertz, J. L. Yu, R. S. Kerbel, P. N. Burns, and F. S. Foster, Ultrasound Med. Biol. 29, 39 (2003).
[CrossRef] [PubMed]

Zemp, R. J.

Zhang, H. F.

Cancer Res. (1)

A. F. DeVries, J. Griebel, C. Kremser, W. Judmaier, T. Gneiting, A. Kreczy, D. Ofner, K. P. Pfeiffer, G. Brix, and P. Lukas, Cancer Res. 61, 2513 (2001).
[PubMed]

J. Biomed. Opt. (2)

L. Song, K. Maslov, R. Bitton, K. K. Shung, and L. V. Wang, J. Biomed. Opt. 13, 054028 (2008).
[CrossRef] [PubMed]

L. Song, K. Maslov, K. K. Shung, and L. V. Wang, J. Biomed. Opt. 15, 021303 (2010).
[CrossRef] [PubMed]

J. Rheumatol. (1)

M. Cutolo, A. Sulli, C. Pizzorni, and S. Accardo, J. Rheumatol. 27, 155 (2000).
[PubMed]

Med. Laser Appl. (1)

M. J. Leahya, J. G. Enfielda, N. T. Clancya, J. O’Dohertya, P. McNamaraa, and G. E. Nilsson, Med. Laser Appl. 22, 105 (2007).
[CrossRef]

Med. Phys. (1)

L. Song, C. Kim, K. Maslov, K. K. Shung, and L. V. Wang, Med. Phys. 36, 3724 (2009).
[CrossRef] [PubMed]

Nat. Med. (1)

W. Groner, J. W. Winkelman, A. G. Harris, C. Ince, G. J. Bouma, K. Messmer, and R. G. Nadeau, Nat. Med. 5, 1209 (1999).
[CrossRef] [PubMed]

Nat. Photonics (1)

L. V. Wang, Nat. Photonics 3, 503 (2009).
[CrossRef]

Nature (1)

M. D. Stern, Nature 254, 56 (1975).
[CrossRef] [PubMed]

Opt. Express (2)

Opt. Lett. (1)

Ultrasound Med. Biol. (1)

D. E. Goertz, J. L. Yu, R. S. Kerbel, P. N. Burns, and F. S. Foster, Ultrasound Med. Biol. 29, 39 (2003).
[CrossRef] [PubMed]

Supplementary Material (4)

» Media 1: MPG (2894 KB)     
» Media 2: MPG (1626 KB)     
» Media 3: MPG (1626 KB)     
» Media 4: MPG (4766 KB)     

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 (5)

Fig. 1
Fig. 1

Schematic of the section-illumination photoacoustic microscopy (SI-PAM) system. The widths of the slit and the aperture along the y axis are 50 μ m and 5 mm , respectively. Coordinates x, y, and z represent the lateral, elevational, and axial (depth) directions of the ultrasound array, respectively.

Fig. 2
Fig. 2

(a), (b) MAP images of two crossed 6 μ m diameter carbon fibers (CFs) acquired by PAM at 584 nm without and with section illumination, respectively. (c) Distribution of photoacoustic (PA) amplitude from the vertical carbon fiber along the dashed line in (b). (d) MAP (along the x axis) image of a 250 μ m diameter black needle inserted in a fresh pork specimen acquired by SI-PAM at 584 nm . (e) MAP image of a mouse ear microvasculature acquired by SI-PAM noninvasively in vivo (at 584 nm ). Depth ( z ) 300 μ m in total—is encoded by color. (f) Snapshot of a 3D animation (Media 1) showing the microvasculature in (e).

Fig. 3
Fig. 3

Wash-in dynamics of EB in a mouse ear microvasculature imaged by SI-PAM at 600 nm (Media 2). (a)–(h) MAP images at representative time points after EB injection.

Fig. 4
Fig. 4

Pseudocolored composite image showing arterioles and venules separated according to the wash-in dynamics of EB (Media 3).

Fig. 5
Fig. 5

Real-time B-scan imaging of the EB wash-in dynamics in a mouse ear microvasculature. (a) Control MAP image at 584 nm . (b) Control B-scan image at 584 nm corresponding to the dotted line in (a). (c) Snapshot of a B-scan movie (Media 4) of the EB wash-in dynamics acquired at 600 nm . (d) Plot of the EB wash-in dynamics in vessel 1.

Metrics