Abstract

We present integrated Laser Speckle Contrast Imaging (LSCI) and Sidestream Dark Field (SDF) flowmetry to provide real-time, non-invasive and quantitative measurements of speckle decorrelation times related to microcirculatory flow. Using a multi exposure acquisition scheme, precise speckle decorrelation times were obtained. Applying SDF-LSCI in vitro and in vivo allows direct comparison between speckle contrast decorrelation and flow velocities, while imaging the phantom and microcirculation architecture. This resulted in a novel analysis approach that distinguishes decorrelation due to flow from other additive decorrelation sources.

© 2013 Optical Society of America

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2011 (3)

2010 (6)

A. B. Parthasarathy, S. M. Kazmi, A. K. Dunn, “Quantitative imaging of ischemic stroke through thinned skull in mice with Multi Exposure Speckle Imaging,” Biomed. Opt. Express 1(1), 246–259 (2010).
[CrossRef] [PubMed]

R. Bezemer, E. Klijn, M. Khalilzada, A. Lima, M. Heger, J. van Bommel, C. Ince, “Validation of near-infrared laser speckle imaging for assessing microvascular (re) perfusion,” Microvasc. Res. 79(2), 139–143 (2010).
[CrossRef] [PubMed]

T. Durduran, R. Choe, W. Baker, A. Yodh, “Diffuse optics for tissue monitoring and tomography,” Rep. Prog. Phys. 73(7), 076701 (2010).
[CrossRef]

D. A. Boas, A. K. Dunn, “Laser speckle contrast imaging in biomedical optics,” J. Biomed. Opt. 15, 011109 (2010).

J. Qiu, P. Li, W. Luo, J. Wang, H. Zhang, Q. Luo, “Spatiotemporal laser speckle contrast analysis for blood flow imaging with maximized speckle contrast,” J. Biomed. Opt. 15, 016003 (2010).

D. M. de Bruin, R. H. Bremmer, V. M. Kodach, R. de Kinkelder, J. van Marle, T. G. van Leeuwen, D. J. Faber, “Optical phantoms of varying geometry based on thin building blocks with controlled optical properties,” J. Biomed. Opt. 15(2), 025001 (2010).
[CrossRef] [PubMed]

2009 (1)

M. Draijer, E. Hondebrink, T. Leeuwen, W. Steenbergen, “Review of laser speckle contrast techniques for visualizing tissue perfusion,” Lasers Med. Sci. 24(4), 639–651 (2009).
[CrossRef] [PubMed]

2008 (6)

2007 (2)

P. T. Goedhart, M. Khalilzada, R. Bezemer, J. Merza, C. Ince, “Sidestream Dark Field (SDF) imaging: a novel stroboscopic LED ring-based imaging modality for clinical assessment of the microcirculation,” Opt. Express 15(23), 15101–15114 (2007).
[CrossRef] [PubMed]

Z. Wang, S. Hughes, S. Dayasundara, R. S. Menon, “Theoretical and experimental optimization of laser speckle contrast imaging for high specificity to brain microcirculation,” J. Cereb. Blood Flow Metab. 27(2), 258–269 (2007).
[CrossRef] [PubMed]

2006 (1)

2005 (1)

R. Bandyopadhyay, A. Gittings, S. Suh, P. Dixon, D. Durian, “Speckle-visibility spectroscopy: A tool to study time-varying dynamics,” Rev. sci. Instrum. 76, 093110 (2005).

2004 (2)

H. Cheng, Q. Luo, Q. Liu, Q. Lu, H. Gong, S. Zeng, “Laser speckle imaging of blood flow in microcirculation,” Phys. Med. Biol. 49(7), 1347–1357 (2004).
[CrossRef] [PubMed]

Y. Sakr, M. J. Dubois, D. De Backer, J. Creteur, J. L. Vincent, “Persistent microcirculatory alterations are associated with organ failure and death in patients with septic shock,” Crit. Care Med. 32(9), 1825–1831 (2004).
[CrossRef] [PubMed]

2003 (1)

H. Cheng, Q. Luo, S. Zeng, S. Chen, J. Cen, H. Gong, “Modified laser speckle imaging method with improved spatial resolution,” J. Biomed. Opt. 8(3), 559–564 (2003).
[CrossRef] [PubMed]

2001 (2)

K. R. Mathura, G. J. Bouma, C. Ince, “Abnormal microcirculation in brain tumours during surgery,” Lancet 358(9294), 1698–1699 (2001).
[CrossRef] [PubMed]

A. K. Dunn, H. Bolay, M. A. Moskowitz, D. A. Boas, “Dynamic imaging of cerebral blood flow using laser speckle,” J. Cereb. Blood Flow Metab. 21(3), 195–201 (2001).
[CrossRef] [PubMed]

1999 (1)

J. D. Briers, G. Richards, X. W. He, “Capillary blood flow monitoring using laser speckle contrast analysis (LASCA),” J. Biomed. Opt. 4(1), 164–175 (1999).
[CrossRef] [PubMed]

1998 (1)

J. M. Brown, A. J. Giaccia, “The unique physiology of solid tumors: opportunities (and problems) for cancer therapy,” Cancer Res. 58(7), 1408–1416 (1998).
[PubMed]

1997 (1)

B. Fagrell, M. Intaglietta, “Microcirculation: its significance in clinical and molecular medicine,” J. Intern. Med. 241(5), 349–362 (1997).
[CrossRef] [PubMed]

1994 (2)

1986 (1)

1984 (1)

C. W. Song, “Effect of local hyperthermia on blood flow and microenvironment: a review,” Cancer Res. 44(10Suppl), 4721s–4730s (1984).
[PubMed]

1981 (2)

A. Fercher, J. Briers, “Flow visualization by means of single-exposure speckle photography,” Opt. Commun. 37(5), 326–330 (1981).
[CrossRef]

R. Bonner, R. Nossal, “Model for laser Doppler measurements of blood flow in tissue,” Appl. Opt. 20(12), 2097–2107 (1981).
[CrossRef] [PubMed]

1976 (1)

J. W. Goodman, “Some fundamental properties of speckle,” J. Opt. Soc. Am. A 66(11), 1145–1150 (1976).
[CrossRef]

Alexander, T. L.

Andrews, M.

Atasever, B.

J. G. G. Dobbe, G. J. Streekstra, B. Atasever, R. van Zijderveld, C. Ince, “Measurement of functional microcirculatory geometry and velocity distributions using automated image analysis,” Med. Biol. Eng. Comput. 46(7), 659–670 (2008).
[CrossRef] [PubMed]

Baker, W.

T. Durduran, R. Choe, W. Baker, A. Yodh, “Diffuse optics for tissue monitoring and tomography,” Rep. Prog. Phys. 73(7), 076701 (2010).
[CrossRef]

Bandyopadhyay, R.

R. Bandyopadhyay, A. Gittings, S. Suh, P. Dixon, D. Durian, “Speckle-visibility spectroscopy: A tool to study time-varying dynamics,” Rev. sci. Instrum. 76, 093110 (2005).

Bezemer, R.

R. Bezemer, E. Klijn, M. Khalilzada, A. Lima, M. Heger, J. van Bommel, C. Ince, “Validation of near-infrared laser speckle imaging for assessing microvascular (re) perfusion,” Microvasc. Res. 79(2), 139–143 (2010).
[CrossRef] [PubMed]

P. T. Goedhart, M. Khalilzada, R. Bezemer, J. Merza, C. Ince, “Sidestream Dark Field (SDF) imaging: a novel stroboscopic LED ring-based imaging modality for clinical assessment of the microcirculation,” Opt. Express 15(23), 15101–15114 (2007).
[CrossRef] [PubMed]

Bicout, D.

D. Bicout, G. Maret, “Multiple light scattering in Taylor-Couette flow,” Physica A 210(1-2), 87–112 (1994).
[CrossRef]

Boas, D. A.

D. A. Boas, A. K. Dunn, “Laser speckle contrast imaging in biomedical optics,” J. Biomed. Opt. 15, 011109 (2010).

A. K. Dunn, H. Bolay, M. A. Moskowitz, D. A. Boas, “Dynamic imaging of cerebral blood flow using laser speckle,” J. Cereb. Blood Flow Metab. 21(3), 195–201 (2001).
[CrossRef] [PubMed]

Bolay, H.

A. K. Dunn, H. Bolay, M. A. Moskowitz, D. A. Boas, “Dynamic imaging of cerebral blood flow using laser speckle,” J. Cereb. Blood Flow Metab. 21(3), 195–201 (2001).
[CrossRef] [PubMed]

Bonner, R.

Bouma, G. J.

K. R. Mathura, G. J. Bouma, C. Ince, “Abnormal microcirculation in brain tumours during surgery,” Lancet 358(9294), 1698–1699 (2001).
[CrossRef] [PubMed]

Bremmer, R. H.

D. M. de Bruin, R. H. Bremmer, V. M. Kodach, R. de Kinkelder, J. van Marle, T. G. van Leeuwen, D. J. Faber, “Optical phantoms of varying geometry based on thin building blocks with controlled optical properties,” J. Biomed. Opt. 15(2), 025001 (2010).
[CrossRef] [PubMed]

Briers, J.

A. Fercher, J. Briers, “Flow visualization by means of single-exposure speckle photography,” Opt. Commun. 37(5), 326–330 (1981).
[CrossRef]

Briers, J. D.

J. D. Briers, G. Richards, X. W. He, “Capillary blood flow monitoring using laser speckle contrast analysis (LASCA),” J. Biomed. Opt. 4(1), 164–175 (1999).
[CrossRef] [PubMed]

Brown, J. M.

J. M. Brown, A. J. Giaccia, “The unique physiology of solid tumors: opportunities (and problems) for cancer therapy,” Cancer Res. 58(7), 1408–1416 (1998).
[PubMed]

Buck, A.

Cen, J.

H. Cheng, Q. Luo, S. Zeng, S. Chen, J. Cen, H. Gong, “Modified laser speckle imaging method with improved spatial resolution,” J. Biomed. Opt. 8(3), 559–564 (2003).
[CrossRef] [PubMed]

Chen, S.

H. Cheng, Q. Luo, S. Zeng, S. Chen, J. Cen, H. Gong, “Modified laser speckle imaging method with improved spatial resolution,” J. Biomed. Opt. 8(3), 559–564 (2003).
[CrossRef] [PubMed]

Cheng, H.

H. Cheng, Q. Luo, Q. Liu, Q. Lu, H. Gong, S. Zeng, “Laser speckle imaging of blood flow in microcirculation,” Phys. Med. Biol. 49(7), 1347–1357 (2004).
[CrossRef] [PubMed]

H. Cheng, Q. Luo, S. Zeng, S. Chen, J. Cen, H. Gong, “Modified laser speckle imaging method with improved spatial resolution,” J. Biomed. Opt. 8(3), 559–564 (2003).
[CrossRef] [PubMed]

Choe, R.

T. Durduran, R. Choe, W. Baker, A. Yodh, “Diffuse optics for tissue monitoring and tomography,” Rep. Prog. Phys. 73(7), 076701 (2010).
[CrossRef]

Choi, B.

Creteur, J.

Y. Sakr, M. J. Dubois, D. De Backer, J. Creteur, J. L. Vincent, “Persistent microcirculatory alterations are associated with organ failure and death in patients with septic shock,” Crit. Care Med. 32(9), 1825–1831 (2004).
[CrossRef] [PubMed]

Dayasundara, S.

Z. Wang, S. Hughes, S. Dayasundara, R. S. Menon, “Theoretical and experimental optimization of laser speckle contrast imaging for high specificity to brain microcirculation,” J. Cereb. Blood Flow Metab. 27(2), 258–269 (2007).
[CrossRef] [PubMed]

De Backer, D.

Y. Sakr, M. J. Dubois, D. De Backer, J. Creteur, J. L. Vincent, “Persistent microcirculatory alterations are associated with organ failure and death in patients with septic shock,” Crit. Care Med. 32(9), 1825–1831 (2004).
[CrossRef] [PubMed]

de Bruin, D. M.

D. M. de Bruin, R. H. Bremmer, V. M. Kodach, R. de Kinkelder, J. van Marle, T. G. van Leeuwen, D. J. Faber, “Optical phantoms of varying geometry based on thin building blocks with controlled optical properties,” J. Biomed. Opt. 15(2), 025001 (2010).
[CrossRef] [PubMed]

de Kinkelder, R.

D. M. de Bruin, R. H. Bremmer, V. M. Kodach, R. de Kinkelder, J. van Marle, T. G. van Leeuwen, D. J. Faber, “Optical phantoms of varying geometry based on thin building blocks with controlled optical properties,” J. Biomed. Opt. 15(2), 025001 (2010).
[CrossRef] [PubMed]

Dixon, P.

R. Bandyopadhyay, A. Gittings, S. Suh, P. Dixon, D. Durian, “Speckle-visibility spectroscopy: A tool to study time-varying dynamics,” Rev. sci. Instrum. 76, 093110 (2005).

Dobbe, J. G. G.

J. G. G. Dobbe, G. J. Streekstra, B. Atasever, R. van Zijderveld, C. Ince, “Measurement of functional microcirculatory geometry and velocity distributions using automated image analysis,” Med. Biol. Eng. Comput. 46(7), 659–670 (2008).
[CrossRef] [PubMed]

Draijer, M.

M. Draijer, E. Hondebrink, T. Leeuwen, W. Steenbergen, “Review of laser speckle contrast techniques for visualizing tissue perfusion,” Lasers Med. Sci. 24(4), 639–651 (2009).
[CrossRef] [PubMed]

Dubois, M. J.

Y. Sakr, M. J. Dubois, D. De Backer, J. Creteur, J. L. Vincent, “Persistent microcirculatory alterations are associated with organ failure and death in patients with septic shock,” Crit. Care Med. 32(9), 1825–1831 (2004).
[CrossRef] [PubMed]

Duncan, D. D.

Dunn, A. K.

A. B. Parthasarathy, S. M. Kazmi, A. K. Dunn, “Quantitative imaging of ischemic stroke through thinned skull in mice with Multi Exposure Speckle Imaging,” Biomed. Opt. Express 1(1), 246–259 (2010).
[CrossRef] [PubMed]

D. A. Boas, A. K. Dunn, “Laser speckle contrast imaging in biomedical optics,” J. Biomed. Opt. 15, 011109 (2010).

A. B. Parthasarathy, W. J. Tom, A. Gopal, X. Zhang, A. K. Dunn, “Robust flow measurement with multi-exposure speckle imaging,” Opt. Express 16(3), 1975–1989 (2008).
[CrossRef] [PubMed]

A. K. Dunn, H. Bolay, M. A. Moskowitz, D. A. Boas, “Dynamic imaging of cerebral blood flow using laser speckle,” J. Cereb. Blood Flow Metab. 21(3), 195–201 (2001).
[CrossRef] [PubMed]

Durduran, T.

T. Durduran, R. Choe, W. Baker, A. Yodh, “Diffuse optics for tissue monitoring and tomography,” Rep. Prog. Phys. 73(7), 076701 (2010).
[CrossRef]

Durian, D.

R. Bandyopadhyay, A. Gittings, S. Suh, P. Dixon, D. Durian, “Speckle-visibility spectroscopy: A tool to study time-varying dynamics,” Rev. sci. Instrum. 76, 093110 (2005).

Faber, D. J.

V. M. Kodach, D. J. Faber, J. van Marle, T. G. van Leeuwen, J. Kalkman, “Determination of the scattering anisotropy with optical coherence tomography,” Opt. Express 19(7), 6131–6140 (2011).
[CrossRef] [PubMed]

D. M. de Bruin, R. H. Bremmer, V. M. Kodach, R. de Kinkelder, J. van Marle, T. G. van Leeuwen, D. J. Faber, “Optical phantoms of varying geometry based on thin building blocks with controlled optical properties,” J. Biomed. Opt. 15(2), 025001 (2010).
[CrossRef] [PubMed]

Fagrell, B.

B. Fagrell, M. Intaglietta, “Microcirculation: its significance in clinical and molecular medicine,” J. Intern. Med. 241(5), 349–362 (1997).
[CrossRef] [PubMed]

Fercher, A.

A. Fercher, J. Briers, “Flow visualization by means of single-exposure speckle photography,” Opt. Commun. 37(5), 326–330 (1981).
[CrossRef]

Giaccia, A. J.

J. M. Brown, A. J. Giaccia, “The unique physiology of solid tumors: opportunities (and problems) for cancer therapy,” Cancer Res. 58(7), 1408–1416 (1998).
[PubMed]

Gittings, A.

R. Bandyopadhyay, A. Gittings, S. Suh, P. Dixon, D. Durian, “Speckle-visibility spectroscopy: A tool to study time-varying dynamics,” Rev. sci. Instrum. 76, 093110 (2005).

Goedhart, P. T.

Gong, H.

H. Cheng, Q. Luo, Q. Liu, Q. Lu, H. Gong, S. Zeng, “Laser speckle imaging of blood flow in microcirculation,” Phys. Med. Biol. 49(7), 1347–1357 (2004).
[CrossRef] [PubMed]

H. Cheng, Q. Luo, S. Zeng, S. Chen, J. Cen, H. Gong, “Modified laser speckle imaging method with improved spatial resolution,” J. Biomed. Opt. 8(3), 559–564 (2003).
[CrossRef] [PubMed]

Goodman, J. W.

J. W. Goodman, “Some fundamental properties of speckle,” J. Opt. Soc. Am. A 66(11), 1145–1150 (1976).
[CrossRef]

Gopal, A.

Guizar-Iturbide, I.

Harvey, J. E.

He, X. W.

J. D. Briers, G. Richards, X. W. He, “Capillary blood flow monitoring using laser speckle contrast analysis (LASCA),” J. Biomed. Opt. 4(1), 164–175 (1999).
[CrossRef] [PubMed]

Heger, M.

R. Bezemer, E. Klijn, M. Khalilzada, A. Lima, M. Heger, J. van Bommel, C. Ince, “Validation of near-infrared laser speckle imaging for assessing microvascular (re) perfusion,” Microvasc. Res. 79(2), 139–143 (2010).
[CrossRef] [PubMed]

Hirst, E.

Hondebrink, E.

M. Draijer, E. Hondebrink, T. Leeuwen, W. Steenbergen, “Review of laser speckle contrast techniques for visualizing tissue perfusion,” Lasers Med. Sci. 24(4), 639–651 (2009).
[CrossRef] [PubMed]

Hughes, S.

Z. Wang, S. Hughes, S. Dayasundara, R. S. Menon, “Theoretical and experimental optimization of laser speckle contrast imaging for high specificity to brain microcirculation,” J. Cereb. Blood Flow Metab. 27(2), 258–269 (2007).
[CrossRef] [PubMed]

Ikram, M.

H. Ullah, A. Mariampillai, M. Ikram, I. Vitkin, “Can temporal analysis of optical coherence tomography statistics report on dextrorotatory-glucose levels in blood?” Laser Phys. 21(11), 1962–1971 (2011).
[CrossRef]

Ince, C.

R. Bezemer, E. Klijn, M. Khalilzada, A. Lima, M. Heger, J. van Bommel, C. Ince, “Validation of near-infrared laser speckle imaging for assessing microvascular (re) perfusion,” Microvasc. Res. 79(2), 139–143 (2010).
[CrossRef] [PubMed]

J. G. G. Dobbe, G. J. Streekstra, B. Atasever, R. van Zijderveld, C. Ince, “Measurement of functional microcirculatory geometry and velocity distributions using automated image analysis,” Med. Biol. Eng. Comput. 46(7), 659–670 (2008).
[CrossRef] [PubMed]

P. T. Goedhart, M. Khalilzada, R. Bezemer, J. Merza, C. Ince, “Sidestream Dark Field (SDF) imaging: a novel stroboscopic LED ring-based imaging modality for clinical assessment of the microcirculation,” Opt. Express 15(23), 15101–15114 (2007).
[CrossRef] [PubMed]

K. R. Mathura, G. J. Bouma, C. Ince, “Abnormal microcirculation in brain tumours during surgery,” Lancet 358(9294), 1698–1699 (2001).
[CrossRef] [PubMed]

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B. Fagrell, M. Intaglietta, “Microcirculation: its significance in clinical and molecular medicine,” J. Intern. Med. 241(5), 349–362 (1997).
[CrossRef] [PubMed]

Kalkman, J.

Kazmi, S. M.

Khalilzada, M.

R. Bezemer, E. Klijn, M. Khalilzada, A. Lima, M. Heger, J. van Bommel, C. Ince, “Validation of near-infrared laser speckle imaging for assessing microvascular (re) perfusion,” Microvasc. Res. 79(2), 139–143 (2010).
[CrossRef] [PubMed]

P. T. Goedhart, M. Khalilzada, R. Bezemer, J. Merza, C. Ince, “Sidestream Dark Field (SDF) imaging: a novel stroboscopic LED ring-based imaging modality for clinical assessment of the microcirculation,” Opt. Express 15(23), 15101–15114 (2007).
[CrossRef] [PubMed]

Kirkpatrick, S. J.

Klijn, E.

R. Bezemer, E. Klijn, M. Khalilzada, A. Lima, M. Heger, J. van Bommel, C. Ince, “Validation of near-infrared laser speckle imaging for assessing microvascular (re) perfusion,” Microvasc. Res. 79(2), 139–143 (2010).
[CrossRef] [PubMed]

Kodach, V. M.

V. M. Kodach, D. J. Faber, J. van Marle, T. G. van Leeuwen, J. Kalkman, “Determination of the scattering anisotropy with optical coherence tomography,” Opt. Express 19(7), 6131–6140 (2011).
[CrossRef] [PubMed]

D. M. de Bruin, R. H. Bremmer, V. M. Kodach, R. de Kinkelder, J. van Marle, T. G. van Leeuwen, D. J. Faber, “Optical phantoms of varying geometry based on thin building blocks with controlled optical properties,” J. Biomed. Opt. 15(2), 025001 (2010).
[CrossRef] [PubMed]

Leeuwen, T.

M. Draijer, E. Hondebrink, T. Leeuwen, W. Steenbergen, “Review of laser speckle contrast techniques for visualizing tissue perfusion,” Lasers Med. Sci. 24(4), 639–651 (2009).
[CrossRef] [PubMed]

Li, P.

J. Qiu, P. Li, W. Luo, J. Wang, H. Zhang, Q. Luo, “Spatiotemporal laser speckle contrast analysis for blood flow imaging with maximized speckle contrast,” J. Biomed. Opt. 15, 016003 (2010).

Lima, A.

R. Bezemer, E. Klijn, M. Khalilzada, A. Lima, M. Heger, J. van Bommel, C. Ince, “Validation of near-infrared laser speckle imaging for assessing microvascular (re) perfusion,” Microvasc. Res. 79(2), 139–143 (2010).
[CrossRef] [PubMed]

Liu, Q.

H. Cheng, Q. Luo, Q. Liu, Q. Lu, H. Gong, S. Zeng, “Laser speckle imaging of blood flow in microcirculation,” Phys. Med. Biol. 49(7), 1347–1357 (2004).
[CrossRef] [PubMed]

Lu, Q.

H. Cheng, Q. Luo, Q. Liu, Q. Lu, H. Gong, S. Zeng, “Laser speckle imaging of blood flow in microcirculation,” Phys. Med. Biol. 49(7), 1347–1357 (2004).
[CrossRef] [PubMed]

Luo, Q.

J. Qiu, P. Li, W. Luo, J. Wang, H. Zhang, Q. Luo, “Spatiotemporal laser speckle contrast analysis for blood flow imaging with maximized speckle contrast,” J. Biomed. Opt. 15, 016003 (2010).

H. Cheng, Q. Luo, Q. Liu, Q. Lu, H. Gong, S. Zeng, “Laser speckle imaging of blood flow in microcirculation,” Phys. Med. Biol. 49(7), 1347–1357 (2004).
[CrossRef] [PubMed]

H. Cheng, Q. Luo, S. Zeng, S. Chen, J. Cen, H. Gong, “Modified laser speckle imaging method with improved spatial resolution,” J. Biomed. Opt. 8(3), 559–564 (2003).
[CrossRef] [PubMed]

Luo, W.

J. Qiu, P. Li, W. Luo, J. Wang, H. Zhang, Q. Luo, “Spatiotemporal laser speckle contrast analysis for blood flow imaging with maximized speckle contrast,” J. Biomed. Opt. 15, 016003 (2010).

Maret, G.

D. Bicout, G. Maret, “Multiple light scattering in Taylor-Couette flow,” Physica A 210(1-2), 87–112 (1994).
[CrossRef]

Mariampillai, A.

H. Ullah, A. Mariampillai, M. Ikram, I. Vitkin, “Can temporal analysis of optical coherence tomography statistics report on dextrorotatory-glucose levels in blood?” Laser Phys. 21(11), 1962–1971 (2011).
[CrossRef]

Martínez-Niconoff, G.

Mathura, K. R.

K. R. Mathura, G. J. Bouma, C. Ince, “Abnormal microcirculation in brain tumours during surgery,” Lancet 358(9294), 1698–1699 (2001).
[CrossRef] [PubMed]

Menon, R. S.

Z. Wang, S. Hughes, S. Dayasundara, R. S. Menon, “Theoretical and experimental optimization of laser speckle contrast imaging for high specificity to brain microcirculation,” J. Cereb. Blood Flow Metab. 27(2), 258–269 (2007).
[CrossRef] [PubMed]

Merza, J.

Moskowitz, M. A.

A. K. Dunn, H. Bolay, M. A. Moskowitz, D. A. Boas, “Dynamic imaging of cerebral blood flow using laser speckle,” J. Cereb. Blood Flow Metab. 21(3), 195–201 (2001).
[CrossRef] [PubMed]

Nossal, R.

Parthasarathy, A. B.

Qiu, J.

J. Qiu, P. Li, W. Luo, J. Wang, H. Zhang, Q. Luo, “Spatiotemporal laser speckle contrast analysis for blood flow imaging with maximized speckle contrast,” J. Biomed. Opt. 15, 016003 (2010).

Ramirez-San-Juan, J. C.

Ramos-García, R.

Richards, G.

J. D. Briers, G. Richards, X. W. He, “Capillary blood flow monitoring using laser speckle contrast analysis (LASCA),” J. Biomed. Opt. 4(1), 164–175 (1999).
[CrossRef] [PubMed]

Sakr, Y.

Y. Sakr, M. J. Dubois, D. De Backer, J. Creteur, J. L. Vincent, “Persistent microcirculatory alterations are associated with organ failure and death in patients with septic shock,” Crit. Care Med. 32(9), 1825–1831 (2004).
[CrossRef] [PubMed]

Scheffold, F.

Song, C. W.

C. W. Song, “Effect of local hyperthermia on blood flow and microenvironment: a review,” Cancer Res. 44(10Suppl), 4721s–4730s (1984).
[PubMed]

Steenbergen, W.

M. Draijer, E. Hondebrink, T. Leeuwen, W. Steenbergen, “Review of laser speckle contrast techniques for visualizing tissue perfusion,” Lasers Med. Sci. 24(4), 639–651 (2009).
[CrossRef] [PubMed]

Streekstra, G. J.

J. G. G. Dobbe, G. J. Streekstra, B. Atasever, R. van Zijderveld, C. Ince, “Measurement of functional microcirculatory geometry and velocity distributions using automated image analysis,” Med. Biol. Eng. Comput. 46(7), 659–670 (2008).
[CrossRef] [PubMed]

Suh, S.

R. Bandyopadhyay, A. Gittings, S. Suh, P. Dixon, D. Durian, “Speckle-visibility spectroscopy: A tool to study time-varying dynamics,” Rev. sci. Instrum. 76, 093110 (2005).

Thompson, O.

Tom, W. J.

Ullah, H.

H. Ullah, A. Mariampillai, M. Ikram, I. Vitkin, “Can temporal analysis of optical coherence tomography statistics report on dextrorotatory-glucose levels in blood?” Laser Phys. 21(11), 1962–1971 (2011).
[CrossRef]

van Bommel, J.

R. Bezemer, E. Klijn, M. Khalilzada, A. Lima, M. Heger, J. van Bommel, C. Ince, “Validation of near-infrared laser speckle imaging for assessing microvascular (re) perfusion,” Microvasc. Res. 79(2), 139–143 (2010).
[CrossRef] [PubMed]

van Leeuwen, T. G.

V. M. Kodach, D. J. Faber, J. van Marle, T. G. van Leeuwen, J. Kalkman, “Determination of the scattering anisotropy with optical coherence tomography,” Opt. Express 19(7), 6131–6140 (2011).
[CrossRef] [PubMed]

D. M. de Bruin, R. H. Bremmer, V. M. Kodach, R. de Kinkelder, J. van Marle, T. G. van Leeuwen, D. J. Faber, “Optical phantoms of varying geometry based on thin building blocks with controlled optical properties,” J. Biomed. Opt. 15(2), 025001 (2010).
[CrossRef] [PubMed]

van Marle, J.

V. M. Kodach, D. J. Faber, J. van Marle, T. G. van Leeuwen, J. Kalkman, “Determination of the scattering anisotropy with optical coherence tomography,” Opt. Express 19(7), 6131–6140 (2011).
[CrossRef] [PubMed]

D. M. de Bruin, R. H. Bremmer, V. M. Kodach, R. de Kinkelder, J. van Marle, T. G. van Leeuwen, D. J. Faber, “Optical phantoms of varying geometry based on thin building blocks with controlled optical properties,” J. Biomed. Opt. 15(2), 025001 (2010).
[CrossRef] [PubMed]

van Zijderveld, R.

J. G. G. Dobbe, G. J. Streekstra, B. Atasever, R. van Zijderveld, C. Ince, “Measurement of functional microcirculatory geometry and velocity distributions using automated image analysis,” Med. Biol. Eng. Comput. 46(7), 659–670 (2008).
[CrossRef] [PubMed]

Vincent, J. L.

Y. Sakr, M. J. Dubois, D. De Backer, J. Creteur, J. L. Vincent, “Persistent microcirculatory alterations are associated with organ failure and death in patients with septic shock,” Crit. Care Med. 32(9), 1825–1831 (2004).
[CrossRef] [PubMed]

Vitkin, I.

H. Ullah, A. Mariampillai, M. Ikram, I. Vitkin, “Can temporal analysis of optical coherence tomography statistics report on dextrorotatory-glucose levels in blood?” Laser Phys. 21(11), 1962–1971 (2011).
[CrossRef]

Völker, A.

Wang, J.

J. Qiu, P. Li, W. Luo, J. Wang, H. Zhang, Q. Luo, “Spatiotemporal laser speckle contrast analysis for blood flow imaging with maximized speckle contrast,” J. Biomed. Opt. 15, 016003 (2010).

Wang, R. K.

Wang, Z.

Z. Wang, S. Hughes, S. Dayasundara, R. S. Menon, “Theoretical and experimental optimization of laser speckle contrast imaging for high specificity to brain microcirculation,” J. Cereb. Blood Flow Metab. 27(2), 258–269 (2007).
[CrossRef] [PubMed]

Weber, B.

Weeks, A. R.

Wells-Gray, E. M.

Yodh, A.

T. Durduran, R. Choe, W. Baker, A. Yodh, “Diffuse optics for tissue monitoring and tomography,” Rep. Prog. Phys. 73(7), 076701 (2010).
[CrossRef]

Yoshimura, T.

Zakharov, P.

Zeng, S.

H. Cheng, Q. Luo, Q. Liu, Q. Lu, H. Gong, S. Zeng, “Laser speckle imaging of blood flow in microcirculation,” Phys. Med. Biol. 49(7), 1347–1357 (2004).
[CrossRef] [PubMed]

H. Cheng, Q. Luo, S. Zeng, S. Chen, J. Cen, H. Gong, “Modified laser speckle imaging method with improved spatial resolution,” J. Biomed. Opt. 8(3), 559–564 (2003).
[CrossRef] [PubMed]

Zhang, H.

J. Qiu, P. Li, W. Luo, J. Wang, H. Zhang, Q. Luo, “Spatiotemporal laser speckle contrast analysis for blood flow imaging with maximized speckle contrast,” J. Biomed. Opt. 15, 016003 (2010).

Zhang, X.

Appl. Opt. (2)

Biomed. Opt. Express (2)

Cancer Res. (2)

J. M. Brown, A. J. Giaccia, “The unique physiology of solid tumors: opportunities (and problems) for cancer therapy,” Cancer Res. 58(7), 1408–1416 (1998).
[PubMed]

C. W. Song, “Effect of local hyperthermia on blood flow and microenvironment: a review,” Cancer Res. 44(10Suppl), 4721s–4730s (1984).
[PubMed]

Crit. Care Med. (1)

Y. Sakr, M. J. Dubois, D. De Backer, J. Creteur, J. L. Vincent, “Persistent microcirculatory alterations are associated with organ failure and death in patients with septic shock,” Crit. Care Med. 32(9), 1825–1831 (2004).
[CrossRef] [PubMed]

J. Biomed. Opt. (5)

D. A. Boas, A. K. Dunn, “Laser speckle contrast imaging in biomedical optics,” J. Biomed. Opt. 15, 011109 (2010).

J. D. Briers, G. Richards, X. W. He, “Capillary blood flow monitoring using laser speckle contrast analysis (LASCA),” J. Biomed. Opt. 4(1), 164–175 (1999).
[CrossRef] [PubMed]

J. Qiu, P. Li, W. Luo, J. Wang, H. Zhang, Q. Luo, “Spatiotemporal laser speckle contrast analysis for blood flow imaging with maximized speckle contrast,” J. Biomed. Opt. 15, 016003 (2010).

D. M. de Bruin, R. H. Bremmer, V. M. Kodach, R. de Kinkelder, J. van Marle, T. G. van Leeuwen, D. J. Faber, “Optical phantoms of varying geometry based on thin building blocks with controlled optical properties,” J. Biomed. Opt. 15(2), 025001 (2010).
[CrossRef] [PubMed]

H. Cheng, Q. Luo, S. Zeng, S. Chen, J. Cen, H. Gong, “Modified laser speckle imaging method with improved spatial resolution,” J. Biomed. Opt. 8(3), 559–564 (2003).
[CrossRef] [PubMed]

J. Cereb. Blood Flow Metab. (2)

A. K. Dunn, H. Bolay, M. A. Moskowitz, D. A. Boas, “Dynamic imaging of cerebral blood flow using laser speckle,” J. Cereb. Blood Flow Metab. 21(3), 195–201 (2001).
[CrossRef] [PubMed]

Z. Wang, S. Hughes, S. Dayasundara, R. S. Menon, “Theoretical and experimental optimization of laser speckle contrast imaging for high specificity to brain microcirculation,” J. Cereb. Blood Flow Metab. 27(2), 258–269 (2007).
[CrossRef] [PubMed]

J. Intern. Med. (1)

B. Fagrell, M. Intaglietta, “Microcirculation: its significance in clinical and molecular medicine,” J. Intern. Med. 241(5), 349–362 (1997).
[CrossRef] [PubMed]

J. Opt. Soc. Am. A (4)

Lancet (1)

K. R. Mathura, G. J. Bouma, C. Ince, “Abnormal microcirculation in brain tumours during surgery,” Lancet 358(9294), 1698–1699 (2001).
[CrossRef] [PubMed]

Laser Phys. (1)

H. Ullah, A. Mariampillai, M. Ikram, I. Vitkin, “Can temporal analysis of optical coherence tomography statistics report on dextrorotatory-glucose levels in blood?” Laser Phys. 21(11), 1962–1971 (2011).
[CrossRef]

Lasers Med. Sci. (1)

M. Draijer, E. Hondebrink, T. Leeuwen, W. Steenbergen, “Review of laser speckle contrast techniques for visualizing tissue perfusion,” Lasers Med. Sci. 24(4), 639–651 (2009).
[CrossRef] [PubMed]

Med. Biol. Eng. Comput. (1)

J. G. G. Dobbe, G. J. Streekstra, B. Atasever, R. van Zijderveld, C. Ince, “Measurement of functional microcirculatory geometry and velocity distributions using automated image analysis,” Med. Biol. Eng. Comput. 46(7), 659–670 (2008).
[CrossRef] [PubMed]

Microvasc. Res. (1)

R. Bezemer, E. Klijn, M. Khalilzada, A. Lima, M. Heger, J. van Bommel, C. Ince, “Validation of near-infrared laser speckle imaging for assessing microvascular (re) perfusion,” Microvasc. Res. 79(2), 139–143 (2010).
[CrossRef] [PubMed]

Opt. Commun. (1)

A. Fercher, J. Briers, “Flow visualization by means of single-exposure speckle photography,” Opt. Commun. 37(5), 326–330 (1981).
[CrossRef]

Opt. Express (4)

Opt. Lett. (2)

Phys. Med. Biol. (1)

H. Cheng, Q. Luo, Q. Liu, Q. Lu, H. Gong, S. Zeng, “Laser speckle imaging of blood flow in microcirculation,” Phys. Med. Biol. 49(7), 1347–1357 (2004).
[CrossRef] [PubMed]

Physica A (1)

D. Bicout, G. Maret, “Multiple light scattering in Taylor-Couette flow,” Physica A 210(1-2), 87–112 (1994).
[CrossRef]

Rep. Prog. Phys. (1)

T. Durduran, R. Choe, W. Baker, A. Yodh, “Diffuse optics for tissue monitoring and tomography,” Rep. Prog. Phys. 73(7), 076701 (2010).
[CrossRef]

Rev. sci. Instrum. (1)

R. Bandyopadhyay, A. Gittings, S. Suh, P. Dixon, D. Durian, “Speckle-visibility spectroscopy: A tool to study time-varying dynamics,” Rev. sci. Instrum. 76, 093110 (2005).

Other (1)

J. W. Goodman, Speckle phenomena in optics: theory and applications (Roberts and Company Publishers, Greenwood Village, CO, 2007).

Supplementary Material (3)

» Media 1: MPG (3770 KB)     
» Media 2: MPG (1622 KB)     
» Media 3: MPG (7896 KB)     

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Figures (7)

Fig. 1
Fig. 1

Modified SDF-imaging system for non-invasive imaging of subsurface microcirculation in dual mode (SDF and SDF-LSCI). Broadband green light (SDF) is highly absorbed by flowing RBCs, resulting in contrast between vessels and tissue. Red coherent light (SDF-LSCI) is scattered by tissue and moving RBCs, resulting in contrasting speckle dynamics between vessels and surrounding tissue. The optical set-up for sequential coupling of SDF light and SDF-LSCI light into the four optical illumination fibers involved 3 lenses (L1 = L2, f = 32 mm, L3, f = 10mm); two filters (F1, band pass interference filter, 550 ± 20 nm and F2, variable neutral density filter, OD 0.04 - 2.00); and a flip mirror M to swop between modes. A 5x magnifying lens system in the lens tube focuses the subsurface microcirculation image onto a CCD camera (a video can be viewed in Media 1). Details of imaging modes are illustrated in the inset (green arrows: SDF, absorption; red arrows: SDF-LSCI, speckle).

Fig. 2
Fig. 2

Flow phantom design. Optical coherence tomography image of cross-section of flow phantom (left), and schematic drawing of flow phantom (right).

Fig. 3
Fig. 3

First and second order statistics of the speckle intensity pattern recorded using the static part of the flow phantom and an exposure time T = 1 ms. (a) Intensity probability density function (PDF) of static speckle pattern (green triangles) and plot of gamma-PDF with M = 2.2 (black line) (b) Power spectral density (PSD) of the static speckle intensity pattern showing sampling above the Nyquist frequency. FWHMPSD ≈2.5 pixel−1. (c) Normalized autocovariance of static speckle intensity pattern, full width ≈5 pixels, equivalent area ≈6 pixels, FWHMautocov. ≈2.2 pixel.

Fig. 4
Fig. 4

Validation of local region size for accurate measurement of speckle contrast K. (a) Schematic representation of local region size, where Ns is the number of pixels in the spatial dimension and Nt in the temporal dimension (total number of pixels: Ns × Ns × Nt) for which K is calculated. (b) Mean <K>, as calculated from 45 K-values selected in the processed speckle contrast image from the channel (in vitro) or vessel (in vivo) area. The dashed line represents the global K value.(c) Coefficient of variance (CV = σK/<K>), where σK is the standard deviation in the 45 K-values. Both <K> and CV are plotted versus Ns, for 4 different temporal dimensions Nt. All images were recorded at exposure time 1 ms.

Fig. 5
Fig. 5

Flow phantom speckle decorrelation results. (a) Multi exposure speckle contrast values (data points) and corresponding fit (lines) for several different flow velocities. The K values (Ns = 7, Nt = 20) are fitted to Eq. (7) for the flow data, while Eq. (6) is fitted to the Brownian motion data.(b) Fit parameter τc (plotted as 1/τc) from multi exposure speckle contrast fits for several flow velocities between 0 - 20 µm/ms (mm/s), applying a spatiotemporal (purple squares) and a spatial (orange triangles) local region, consisting of 7 × 7 × 20 and 31 × 31 pixels respectively, and its linear fit (dashed line).

Fig. 6
Fig. 6

In vivo SDF-LSCI recording and analysis procedure. (a) Typical SDF image of sublingual microcirculation. (b) Raw speckle image and (c) processed K-image (Ns = 7, Nt = 20) of same region as in (a), recorded at T = 10 ms. For each pixel and exposure time, K was estimated to enable a pixel wise multi exposure curve fit (Eq. (7)), resulting in a 1/τc map of the same region as in (a), shown in (d). In Media 2 and Media 3 the four panels are presented as a video, showing flowing RBC's (top left), raw speckle (top right) and speckle contrast (bottom left) images, and a still frame (bottom right) of the corresponding 1/τc map. Media 2 (1.6 Mb) represents SDF-LSCI at T = 10 ms, while Media 3 (7.9 Mb represents SDF-LSCI at T = 1, 2, 10, 20 and 50 ms consecutively.

Fig. 7
Fig. 7

a. In vivo SDF-LSCI results. (a) Multi exposure K-values (data points) and corresponding fit (lines) for several different flow velocities in vivo (upper curves). For comparison two in vitro multi exposure K-curves are also plotted (lower curves). Equation (7) is used as fitting model. (b) Bar plot of fit parameter τc,flow (represented as 1/τc,flow) of 19 in vivo blood vessels, corrected according to Eq. (9). The vessels were grouped in five different velocity ranges, with minimally 3 vessels per group.

Equations (9)

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g 2 ( τ ) = 1 + β M | g 1 ( τ ) | 2 ,
| g 1 ( τ ) | 2 = exp ( 2 q 2 Δ r 2 ( τ ) / 6 ) ,
| g 1 ( τ ) | 2 | g 1 , B r o w n ( τ ) | 2 × | g 1 , d i r ( τ ) | 2 = exp ( 2 τ / τ C , B r o w n ) × exp ( 2 [ τ / τ C , d i r ] 2 ) ,
K = σ i I .
K ( T ) = β M 1 / 2 [ 2 T 0 T ( 1 τ T ) | g 1 ( τ ) | 2 d τ ] 1 / 2 ,
K ( T ) = β 1 / 2 [ ρ 2 exp ( 2 x ) 1 + 2 x 2 ( x ) 2 + 4 ρ ( 1 ρ ) exp ( x ) 1 + x ( x ) 2 + ( 1 ρ ) 2 ] 1 / 2 + C n o i s e ,
K ( T ) = β 1 / 2 [ ρ 2 exp ( 2 ( x ) 2 ) 1 + 2 π x e r f ( 2 x ) 2 ( x ) 2 + 2 ρ ( 1 ρ ) exp ( ( x ) 2 ) 1 + π x e r f ( x ) ( x ) 2 + ( 1 ρ ) 2 ] 1 / 2 + C n o i s e .
g 1 , t o t a l = g 1 , f l o w g 1 , o f f s e t ,
τ c , f l o w = τ c , o f f s e t τ c , t o t a l / ( τ c , o f f s e t 2 τ c , t o t a l 2 ) 1 / 2 ,

Metrics