Abstract

The analysis of speckle contrast in a time-integrated speckle pattern enables visualization of superficial blood flow in exposed vasculature, a method we call laser speckle imaging (LSI). With current methods, LSI does not enable visualization of subsurface or small vasculature, because of optical scattering by stationary structures. In this work we propose a new technique called photothermal LSI to improve the visualization of blood vessels. A 595 nm laser pulse was used to excite blood in both in vitro and in vivo samples. The high absorption coefficient of blood at this wavelength results in efficient conversion of optical energy to thermal energy, resulting in an increase in the local temperature and hence increased scatterer motion, and thus a transient decrease in speckle contrast. As a result, we found that photothermal LSI was able to visualize blood vessels that were hidden when imaged with a conventional LSI system.

© 2014 Optical Society of America

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References

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  1. A. F. Fercher and J. D. Briers, Opt. Commun. 37, 326 (1981).
    [CrossRef]
  2. A. K. Dunn, T. Bolay, M. A. Moskowitz, and D. A. Boas, J. Cereb. Bl. F. Metab. 21, 195 (2001).
    [CrossRef]
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    [CrossRef]
  4. P. C. Li, S. L. Ni, L. Zhang, S. Q. Zeng, and Q. M. Luo, Opt. Lett. 31, 1824 (2006).
    [CrossRef]
  5. R. Liu, J. Qin, and R. K. K. Wang, J. Biomed. Opt. 18, 060508 (2013).
    [CrossRef]
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    [CrossRef]
  7. B. C. Li, B. Majaron, J. A. Viator, T. E. Milner, Z. P. Chen, Y. H. Zhao, H. W. Ren, and J. S. Nelson, J. Biomed. Opt. 9, 961 (2004).
    [CrossRef]
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    [CrossRef]
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    [CrossRef]

2013 (2)

2011 (2)

O. Yang, D. Cuccia, and B. Choi, J. Biomed. Opt. 16, 016009 (2011).
[CrossRef]

A. J. Moy, S. M. White, E. S. Indrawan, J. Lotfi, M. J. Nudelman, S. J. Costantini, N. Agarwal, W. Jia, K. M. Kelly, B. S. Sorg, and B. Choi, Microvasc. Res. 82, 199 (2011).
[CrossRef]

2010 (2)

J. Kim, J. Oh, and B. Choi, J. Biomed. Opt. 15, 011110 (2010).
[CrossRef]

J. J. Qiu, P. C. Li, W. H. Luo, J. Wang, H. Y. Zhang, and Q. M. Luo, J. Biomed. Opt. 15, 016003 (2010).
[CrossRef]

2006 (1)

2004 (2)

B. C. Li, B. Majaron, J. A. Viator, T. E. Milner, Z. P. Chen, Y. H. Zhao, H. W. Ren, and J. S. Nelson, J. Biomed. Opt. 9, 961 (2004).
[CrossRef]

V. S. Kalambur, H. Mahaseth, J. C. Bischof, M. C. Kiebik, T. E. Welch, A. Vilback, D. J. Swanlund, R. P. Hebbel, J. D. Belcher, and G. M. Vercellotti, Am. J. Hematol. 77, 117 (2004).
[CrossRef]

2001 (2)

B. Choi and A. J. Welch, Lasers Surg. Med. 29, 351 (2001).
[CrossRef]

A. K. Dunn, T. Bolay, M. A. Moskowitz, and D. A. Boas, J. Cereb. Bl. F. Metab. 21, 195 (2001).
[CrossRef]

1992 (1)

S. A. Prahl, I. A. Vitkin, U. Burggemann, B. C. Wilson, and R. R. Anderson, Phys. Med. Biol. 37, 1203 (1992).
[CrossRef]

1981 (1)

A. F. Fercher and J. D. Briers, Opt. Commun. 37, 326 (1981).
[CrossRef]

Agarwal, N.

A. J. Moy, S. M. White, E. S. Indrawan, J. Lotfi, M. J. Nudelman, S. J. Costantini, N. Agarwal, W. Jia, K. M. Kelly, B. S. Sorg, and B. Choi, Microvasc. Res. 82, 199 (2011).
[CrossRef]

Anderson, R. R.

S. A. Prahl, I. A. Vitkin, U. Burggemann, B. C. Wilson, and R. R. Anderson, Phys. Med. Biol. 37, 1203 (1992).
[CrossRef]

Belcher, J. D.

V. S. Kalambur, H. Mahaseth, J. C. Bischof, M. C. Kiebik, T. E. Welch, A. Vilback, D. J. Swanlund, R. P. Hebbel, J. D. Belcher, and G. M. Vercellotti, Am. J. Hematol. 77, 117 (2004).
[CrossRef]

Bischof, J. C.

V. S. Kalambur, H. Mahaseth, J. C. Bischof, M. C. Kiebik, T. E. Welch, A. Vilback, D. J. Swanlund, R. P. Hebbel, J. D. Belcher, and G. M. Vercellotti, Am. J. Hematol. 77, 117 (2004).
[CrossRef]

Boas, D. A.

A. K. Dunn, T. Bolay, M. A. Moskowitz, and D. A. Boas, J. Cereb. Bl. F. Metab. 21, 195 (2001).
[CrossRef]

Bolay, T.

A. K. Dunn, T. Bolay, M. A. Moskowitz, and D. A. Boas, J. Cereb. Bl. F. Metab. 21, 195 (2001).
[CrossRef]

Briers, J. D.

A. F. Fercher and J. D. Briers, Opt. Commun. 37, 326 (1981).
[CrossRef]

Burggemann, U.

S. A. Prahl, I. A. Vitkin, U. Burggemann, B. C. Wilson, and R. R. Anderson, Phys. Med. Biol. 37, 1203 (1992).
[CrossRef]

Chen, Z. P.

B. C. Li, B. Majaron, J. A. Viator, T. E. Milner, Z. P. Chen, Y. H. Zhao, H. W. Ren, and J. S. Nelson, J. Biomed. Opt. 9, 961 (2004).
[CrossRef]

Choi, B.

T. B. Rice, E. Kwan, C. K. Hayakawa, A. J. Durkin, B. Choi, and B. J. Tromberg, Biomed. Opt. Express 4, 2880 (2013).
[CrossRef]

A. J. Moy, S. M. White, E. S. Indrawan, J. Lotfi, M. J. Nudelman, S. J. Costantini, N. Agarwal, W. Jia, K. M. Kelly, B. S. Sorg, and B. Choi, Microvasc. Res. 82, 199 (2011).
[CrossRef]

O. Yang, D. Cuccia, and B. Choi, J. Biomed. Opt. 16, 016009 (2011).
[CrossRef]

J. Kim, J. Oh, and B. Choi, J. Biomed. Opt. 15, 011110 (2010).
[CrossRef]

B. Choi and A. J. Welch, Lasers Surg. Med. 29, 351 (2001).
[CrossRef]

Costantini, S. J.

A. J. Moy, S. M. White, E. S. Indrawan, J. Lotfi, M. J. Nudelman, S. J. Costantini, N. Agarwal, W. Jia, K. M. Kelly, B. S. Sorg, and B. Choi, Microvasc. Res. 82, 199 (2011).
[CrossRef]

Cuccia, D.

O. Yang, D. Cuccia, and B. Choi, J. Biomed. Opt. 16, 016009 (2011).
[CrossRef]

Dunn, A. K.

A. K. Dunn, T. Bolay, M. A. Moskowitz, and D. A. Boas, J. Cereb. Bl. F. Metab. 21, 195 (2001).
[CrossRef]

Durkin, A. J.

Fercher, A. F.

A. F. Fercher and J. D. Briers, Opt. Commun. 37, 326 (1981).
[CrossRef]

Hayakawa, C. K.

Hebbel, R. P.

V. S. Kalambur, H. Mahaseth, J. C. Bischof, M. C. Kiebik, T. E. Welch, A. Vilback, D. J. Swanlund, R. P. Hebbel, J. D. Belcher, and G. M. Vercellotti, Am. J. Hematol. 77, 117 (2004).
[CrossRef]

Indrawan, E. S.

A. J. Moy, S. M. White, E. S. Indrawan, J. Lotfi, M. J. Nudelman, S. J. Costantini, N. Agarwal, W. Jia, K. M. Kelly, B. S. Sorg, and B. Choi, Microvasc. Res. 82, 199 (2011).
[CrossRef]

Jia, W.

A. J. Moy, S. M. White, E. S. Indrawan, J. Lotfi, M. J. Nudelman, S. J. Costantini, N. Agarwal, W. Jia, K. M. Kelly, B. S. Sorg, and B. Choi, Microvasc. Res. 82, 199 (2011).
[CrossRef]

Kalambur, V. S.

V. S. Kalambur, H. Mahaseth, J. C. Bischof, M. C. Kiebik, T. E. Welch, A. Vilback, D. J. Swanlund, R. P. Hebbel, J. D. Belcher, and G. M. Vercellotti, Am. J. Hematol. 77, 117 (2004).
[CrossRef]

Kelly, K. M.

A. J. Moy, S. M. White, E. S. Indrawan, J. Lotfi, M. J. Nudelman, S. J. Costantini, N. Agarwal, W. Jia, K. M. Kelly, B. S. Sorg, and B. Choi, Microvasc. Res. 82, 199 (2011).
[CrossRef]

Kiebik, M. C.

V. S. Kalambur, H. Mahaseth, J. C. Bischof, M. C. Kiebik, T. E. Welch, A. Vilback, D. J. Swanlund, R. P. Hebbel, J. D. Belcher, and G. M. Vercellotti, Am. J. Hematol. 77, 117 (2004).
[CrossRef]

Kim, J.

J. Kim, J. Oh, and B. Choi, J. Biomed. Opt. 15, 011110 (2010).
[CrossRef]

Kwan, E.

Li, B. C.

B. C. Li, B. Majaron, J. A. Viator, T. E. Milner, Z. P. Chen, Y. H. Zhao, H. W. Ren, and J. S. Nelson, J. Biomed. Opt. 9, 961 (2004).
[CrossRef]

Li, P. C.

J. J. Qiu, P. C. Li, W. H. Luo, J. Wang, H. Y. Zhang, and Q. M. Luo, J. Biomed. Opt. 15, 016003 (2010).
[CrossRef]

P. C. Li, S. L. Ni, L. Zhang, S. Q. Zeng, and Q. M. Luo, Opt. Lett. 31, 1824 (2006).
[CrossRef]

Liu, R.

R. Liu, J. Qin, and R. K. K. Wang, J. Biomed. Opt. 18, 060508 (2013).
[CrossRef]

Lotfi, J.

A. J. Moy, S. M. White, E. S. Indrawan, J. Lotfi, M. J. Nudelman, S. J. Costantini, N. Agarwal, W. Jia, K. M. Kelly, B. S. Sorg, and B. Choi, Microvasc. Res. 82, 199 (2011).
[CrossRef]

Luo, Q. M.

J. J. Qiu, P. C. Li, W. H. Luo, J. Wang, H. Y. Zhang, and Q. M. Luo, J. Biomed. Opt. 15, 016003 (2010).
[CrossRef]

P. C. Li, S. L. Ni, L. Zhang, S. Q. Zeng, and Q. M. Luo, Opt. Lett. 31, 1824 (2006).
[CrossRef]

Luo, W. H.

J. J. Qiu, P. C. Li, W. H. Luo, J. Wang, H. Y. Zhang, and Q. M. Luo, J. Biomed. Opt. 15, 016003 (2010).
[CrossRef]

Mahaseth, H.

V. S. Kalambur, H. Mahaseth, J. C. Bischof, M. C. Kiebik, T. E. Welch, A. Vilback, D. J. Swanlund, R. P. Hebbel, J. D. Belcher, and G. M. Vercellotti, Am. J. Hematol. 77, 117 (2004).
[CrossRef]

Majaron, B.

B. C. Li, B. Majaron, J. A. Viator, T. E. Milner, Z. P. Chen, Y. H. Zhao, H. W. Ren, and J. S. Nelson, J. Biomed. Opt. 9, 961 (2004).
[CrossRef]

Milner, T. E.

B. C. Li, B. Majaron, J. A. Viator, T. E. Milner, Z. P. Chen, Y. H. Zhao, H. W. Ren, and J. S. Nelson, J. Biomed. Opt. 9, 961 (2004).
[CrossRef]

Moskowitz, M. A.

A. K. Dunn, T. Bolay, M. A. Moskowitz, and D. A. Boas, J. Cereb. Bl. F. Metab. 21, 195 (2001).
[CrossRef]

Moy, A. J.

A. J. Moy, S. M. White, E. S. Indrawan, J. Lotfi, M. J. Nudelman, S. J. Costantini, N. Agarwal, W. Jia, K. M. Kelly, B. S. Sorg, and B. Choi, Microvasc. Res. 82, 199 (2011).
[CrossRef]

Nelson, J. S.

B. C. Li, B. Majaron, J. A. Viator, T. E. Milner, Z. P. Chen, Y. H. Zhao, H. W. Ren, and J. S. Nelson, J. Biomed. Opt. 9, 961 (2004).
[CrossRef]

Ni, S. L.

Nudelman, M. J.

A. J. Moy, S. M. White, E. S. Indrawan, J. Lotfi, M. J. Nudelman, S. J. Costantini, N. Agarwal, W. Jia, K. M. Kelly, B. S. Sorg, and B. Choi, Microvasc. Res. 82, 199 (2011).
[CrossRef]

Oh, J.

J. Kim, J. Oh, and B. Choi, J. Biomed. Opt. 15, 011110 (2010).
[CrossRef]

Prahl, S. A.

S. A. Prahl, I. A. Vitkin, U. Burggemann, B. C. Wilson, and R. R. Anderson, Phys. Med. Biol. 37, 1203 (1992).
[CrossRef]

Qin, J.

R. Liu, J. Qin, and R. K. K. Wang, J. Biomed. Opt. 18, 060508 (2013).
[CrossRef]

Qiu, J. J.

J. J. Qiu, P. C. Li, W. H. Luo, J. Wang, H. Y. Zhang, and Q. M. Luo, J. Biomed. Opt. 15, 016003 (2010).
[CrossRef]

Ren, H. W.

B. C. Li, B. Majaron, J. A. Viator, T. E. Milner, Z. P. Chen, Y. H. Zhao, H. W. Ren, and J. S. Nelson, J. Biomed. Opt. 9, 961 (2004).
[CrossRef]

Rice, T. B.

Sorg, B. S.

A. J. Moy, S. M. White, E. S. Indrawan, J. Lotfi, M. J. Nudelman, S. J. Costantini, N. Agarwal, W. Jia, K. M. Kelly, B. S. Sorg, and B. Choi, Microvasc. Res. 82, 199 (2011).
[CrossRef]

Swanlund, D. J.

V. S. Kalambur, H. Mahaseth, J. C. Bischof, M. C. Kiebik, T. E. Welch, A. Vilback, D. J. Swanlund, R. P. Hebbel, J. D. Belcher, and G. M. Vercellotti, Am. J. Hematol. 77, 117 (2004).
[CrossRef]

Tromberg, B. J.

Vercellotti, G. M.

V. S. Kalambur, H. Mahaseth, J. C. Bischof, M. C. Kiebik, T. E. Welch, A. Vilback, D. J. Swanlund, R. P. Hebbel, J. D. Belcher, and G. M. Vercellotti, Am. J. Hematol. 77, 117 (2004).
[CrossRef]

Viator, J. A.

B. C. Li, B. Majaron, J. A. Viator, T. E. Milner, Z. P. Chen, Y. H. Zhao, H. W. Ren, and J. S. Nelson, J. Biomed. Opt. 9, 961 (2004).
[CrossRef]

Vilback, A.

V. S. Kalambur, H. Mahaseth, J. C. Bischof, M. C. Kiebik, T. E. Welch, A. Vilback, D. J. Swanlund, R. P. Hebbel, J. D. Belcher, and G. M. Vercellotti, Am. J. Hematol. 77, 117 (2004).
[CrossRef]

Vitkin, I. A.

S. A. Prahl, I. A. Vitkin, U. Burggemann, B. C. Wilson, and R. R. Anderson, Phys. Med. Biol. 37, 1203 (1992).
[CrossRef]

Wang, J.

J. J. Qiu, P. C. Li, W. H. Luo, J. Wang, H. Y. Zhang, and Q. M. Luo, J. Biomed. Opt. 15, 016003 (2010).
[CrossRef]

Wang, R. K. K.

R. Liu, J. Qin, and R. K. K. Wang, J. Biomed. Opt. 18, 060508 (2013).
[CrossRef]

Welch, A. J.

B. Choi and A. J. Welch, Lasers Surg. Med. 29, 351 (2001).
[CrossRef]

Welch, T. E.

V. S. Kalambur, H. Mahaseth, J. C. Bischof, M. C. Kiebik, T. E. Welch, A. Vilback, D. J. Swanlund, R. P. Hebbel, J. D. Belcher, and G. M. Vercellotti, Am. J. Hematol. 77, 117 (2004).
[CrossRef]

White, S. M.

A. J. Moy, S. M. White, E. S. Indrawan, J. Lotfi, M. J. Nudelman, S. J. Costantini, N. Agarwal, W. Jia, K. M. Kelly, B. S. Sorg, and B. Choi, Microvasc. Res. 82, 199 (2011).
[CrossRef]

Wilson, B. C.

S. A. Prahl, I. A. Vitkin, U. Burggemann, B. C. Wilson, and R. R. Anderson, Phys. Med. Biol. 37, 1203 (1992).
[CrossRef]

Yang, O.

O. Yang, D. Cuccia, and B. Choi, J. Biomed. Opt. 16, 016009 (2011).
[CrossRef]

Zeng, S. Q.

Zhang, H. Y.

J. J. Qiu, P. C. Li, W. H. Luo, J. Wang, H. Y. Zhang, and Q. M. Luo, J. Biomed. Opt. 15, 016003 (2010).
[CrossRef]

Zhang, L.

Zhao, Y. H.

B. C. Li, B. Majaron, J. A. Viator, T. E. Milner, Z. P. Chen, Y. H. Zhao, H. W. Ren, and J. S. Nelson, J. Biomed. Opt. 9, 961 (2004).
[CrossRef]

Am. J. Hematol. (1)

V. S. Kalambur, H. Mahaseth, J. C. Bischof, M. C. Kiebik, T. E. Welch, A. Vilback, D. J. Swanlund, R. P. Hebbel, J. D. Belcher, and G. M. Vercellotti, Am. J. Hematol. 77, 117 (2004).
[CrossRef]

Biomed. Opt. Express (1)

J. Biomed. Opt. (5)

O. Yang, D. Cuccia, and B. Choi, J. Biomed. Opt. 16, 016009 (2011).
[CrossRef]

J. J. Qiu, P. C. Li, W. H. Luo, J. Wang, H. Y. Zhang, and Q. M. Luo, J. Biomed. Opt. 15, 016003 (2010).
[CrossRef]

R. Liu, J. Qin, and R. K. K. Wang, J. Biomed. Opt. 18, 060508 (2013).
[CrossRef]

J. Kim, J. Oh, and B. Choi, J. Biomed. Opt. 15, 011110 (2010).
[CrossRef]

B. C. Li, B. Majaron, J. A. Viator, T. E. Milner, Z. P. Chen, Y. H. Zhao, H. W. Ren, and J. S. Nelson, J. Biomed. Opt. 9, 961 (2004).
[CrossRef]

J. Cereb. Bl. F. Metab. (1)

A. K. Dunn, T. Bolay, M. A. Moskowitz, and D. A. Boas, J. Cereb. Bl. F. Metab. 21, 195 (2001).
[CrossRef]

Lasers Surg. Med. (1)

B. Choi and A. J. Welch, Lasers Surg. Med. 29, 351 (2001).
[CrossRef]

Microvasc. Res. (1)

A. J. Moy, S. M. White, E. S. Indrawan, J. Lotfi, M. J. Nudelman, S. J. Costantini, N. Agarwal, W. Jia, K. M. Kelly, B. S. Sorg, and B. Choi, Microvasc. Res. 82, 199 (2011).
[CrossRef]

Opt. Commun. (1)

A. F. Fercher and J. D. Briers, Opt. Commun. 37, 326 (1981).
[CrossRef]

Opt. Lett. (1)

Phys. Med. Biol. (1)

S. A. Prahl, I. A. Vitkin, U. Burggemann, B. C. Wilson, and R. R. Anderson, Phys. Med. Biol. 37, 1203 (1992).
[CrossRef]

Other (2)

S. A. Prahl, “Tabulated molar extinction coefficient for hemoglobin in water,” March4, 1998. http://omlc.ogi.edu/spectra/hemoglobin/summary.html .

P. A. Hasgall, E. Neufeld, M. C. Gosselin, A. Klingenbock, and N. Kuster, “IT’IS Database for thermal and electromagnetic parameters of biological tissues,” Version 2.4, July30, 2013, www.itis.ethz.ch/database .

Supplementary Material (2)

» Media 1: MP4 (266 KB)     
» Media 2: MP4 (481 KB)     

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Figures (3)

Fig. 1.
Fig. 1.

In vitro photothermal LSI of blood in a cuvette. (a) Photothermal LSI setup with 633 nm imaging laser light and 595 nm pulsed dye laser to excite the blood. Images are captured with a cooled CCD camera with a laser-line bandpass filter to block extraneous light. (b) Speckle contrast versus time plot illustrates distinct drop in contrast corresponding to the photothermal excitation pulse at time 0 s. The 60% decrease in contrast returns to baseline over about 0.6 s as the blood returns to room temperature.

Fig. 2.
Fig. 2.

In vitro photothermal LSI of blood flowing through a microchannel. (a) Photothermal LSI setup with blood infused into the system at 4mm/s and a 400 μm epidermal phantom placed above the microchannel. (b) Speckle contrast versus time in a region of interest above the channel shows a 60% decrease in flow occurring after the excitation pulse at time 0 s, and returning to baseline over the next 0.4s. (c) Normalized speckle flow index (SFI) in microchannel before the photothermal excitation (Media 1). (d) SFI image after the excitation pulse (Media 1) shows the blood flow in the channel clearly visible beneath the skin-simulating phantom.

Fig. 3.
Fig. 3.

In vivo photothermal LSI in a mouse dorsal window chamber model. (a) Imaging setup of the epi-illuminated reverse side of the window chamber. An 808 nm laser light is used to illuminate the epidermis for imaging, and an 800 nm longpass filter is placed on the CCD camera to block stray 595 nm excitation light. (b) Speckle contrast versus time in the region of interest highlighted in (c) and (d). The contrast drops by 80% when the excitation pulse is fired at time 0 s, and quickly returns to baseline over 0.3s. (c) Normalized SFI image before the excitation pulse (Media 2). (d) SFI image after the photothermal excitation (Media 2) shows increased motion in the vessels. The perivascular increase in the SFI is probably because of smaller vessels and capillaries that cannot be resolved with our current imaging system.

Metrics