Abstract

A multi-functional imaging system capable of determining relative changes in blood flow, hemoglobin concentration, and morphological features of the blood vasculature is demonstrated. The system combines two non-invasive imaging techniques, a dual-wavelength laser speckle contrast imaging (2-LSI) and an optical microangiography (OMAG) system. 2-LSI is used to monitor the changes in the dynamic blood flow and the changes in the concentration of oxygenated (HbO), deoxygenated (Hb) and total hemoglobin (HbT). The OMAG system is used to acquire high resolution images of the functional blood vessel network. The vessel area density (VAD) is used to quantify the blood vessel network morphology, specifically the capillary recruitment. The proposed multi-functional system is employed to assess the blood perfusion status from a mouse pinna before and immediately after a burn injury. To our knowledge, this is the first non-invasive, non-contact and multifunctional imaging modality that can simultaneously measure variations of several blood perfusion parameters.

© 2012 OSA

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2011 (7)

R. K. K. Wang and L. An, “Multifunctional imaging of human retina and choroid with 1050-nm spectral domain optical coherence tomography at 92-kHz line scan rate,” J. Biomed. Opt.16(5), 050503 (2011).
[CrossRef] [PubMed]

L. An and R. K. Wang, “Full range complex ultrahigh sensitive optical microangiography,” Opt. Lett.36(6), 831–833 (2011).
[CrossRef] [PubMed]

H. M. Subhash, V. Davila, H. Sun, A. T. Nguyen-Huynh, X. R. Shi, A. L. Nuttall, and R. K. K. Wang, “Volumetric in vivo imaging of microvascular perfusion within the intact cochlea in mice using ultra-high sensitive optical microangiography,” IEEE Trans. Med. Imaging30(2), 224–230 (2011).
[CrossRef] [PubMed]

J. Qin, J. Y. Jiang, L. An, D. Gareau, and R. K. Wang, “In vivo volumetric imaging of microcirculation within human skin under psoriatic conditions using optical microangiography,” Lasers Surg. Med.43(2), 122–129 (2011).
[CrossRef] [PubMed]

Y. L. Jia, J. Qin, Z. W. Zhi, and R. K. K. Wang, “Ultrahigh sensitive optical microangiography reveals depth-resolved microcirculation and its longitudinal response to prolonged ischemic event within skeletal muscles in mice,” J. Biomed. Opt.16(8), 086004 (2011).
[CrossRef] [PubMed]

M. E. Seaman, S. M. Peirce, and K. Kelly, “Rapid analysis of vessel elements (RAVE): a tool for studying physiologic, pathologic and tumor angiogenesis,” PLoS ONE6(6), e20807 (2011).
[CrossRef] [PubMed]

C. Mayeur, S. Campard, C. Richard, and J. L. Teboul, “Comparison of four different vascular occlusion tests for assessing reactive hyperemia using near-infrared spectroscopy,” Crit. Care Med.39(4), 695–701 (2011).
[CrossRef] [PubMed]

2010 (5)

D. A. Boas and A. K. Dunn, “Laser speckle contrast imaging in biomedical optics,” J. Biomed. Opt.15(1), 011109 (2010).
[CrossRef] [PubMed]

L. An, J. Qin, and R. K. Wang, “Ultrahigh sensitive optical microangiography for in vivo imaging of microcirculations within human skin tissue beds,” Opt. Express18(8), 8220–8228 (2010).
[CrossRef] [PubMed]

A. C. Sull, L. N. Vuong, L. L. Price, V. J. Srinivasan, I. Gorczynska, J. G. Fujimoto, J. S. Schuman, and J. S. Duker, “Comparison of spectral/Fourier domain optical coherence tomography instruments for assessment of normal macular thickness,” Retina30(2), 235–245 (2010).
[CrossRef] [PubMed]

D. Attwell, A. M. Buchan, S. Charpak, M. Lauritzen, B. A. Macvicar, and E. A. Newman, “Glial and neuronal control of brain blood flow,” Nature468(7321), 232–243 (2010).
[CrossRef] [PubMed]

S. R. Nirmala, S. Dandapat, and P. M. Bora, “Wavelet weighted blood vessel distortion measure for retinal images,” Biomed. Signal Process. Control5(4), 282–291 (2010).
[CrossRef]

2009 (2)

B. J. Vakoc, R. M. Lanning, J. A. Tyrrell, T. P. Padera, L. A. Bartlett, T. Stylianopoulos, L. L. Munn, G. J. Tearney, D. Fukumura, R. K. Jain, and B. E. Bouma, “Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging,” Nat. Med.15(10), 1219–1223 (2009).
[CrossRef] [PubMed]

Z. Luo, Z. Yuan, Y. Pan, and C. Du, “Simultaneous imaging of cortical hemodynamics and blood oxygenation change during cerebral ischemia using dual-wavelength laser speckle contrast imaging,” Opt. Lett.34(9), 1480–1482 (2009).
[CrossRef] [PubMed]

2008 (3)

2007 (4)

L. An and R. K. Wang, “Use of a scanner to modulate spatial interferograms for in vivo full-range Fourier-domain optical coherence tomography,” Opt. Lett.32(23), 3423–3425 (2007).
[CrossRef] [PubMed]

R. K. Wang, “Three-dimensional optical micro-angiography maps directional blood perfusion deep within microcirculation tissue beds in vivo,” Phys. Med. Biol.52(23), N531–N537 (2007).
[CrossRef] [PubMed]

V. Provitera, M. Nolano, N. Pappone, E. Lubrano, A. Stancanelli, B. Lanzillo, and L. Santoro, “Axonal degeneration in systemic sclerosis can be reverted by factors improving tissue oxygenation,” Rheumatology (Oxford)46(11), 1739–1741 (2007).
[CrossRef] [PubMed]

E. Tibiriçá, E. Rodrigues, R. A. Cobas, and M. B. Gomes, “Endothelial function in patients with type 1 diabetes evaluated by skin capillary recruitment,” Microvasc. Res.73(2), 107–112 (2007).
[CrossRef] [PubMed]

2006 (3)

R. K. K. Wang and Z. H. Ma, “Real-time flow imaging by removing texture pattern artifacts in spectral-domain optical Doppler tomography,” Opt. Lett.31(20), 3001–3003 (2006).
[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]

H. F. Zhang, K. Maslov, G. Stoica, and L. V. Wang, “Imaging acute thermal burns by photoacoustic microscopy,” J. Biomed. Opt.11(5), 054033 (2006).
[CrossRef] [PubMed]

2005 (2)

C. W. Du, A. P. Koretsky, I. Izrailtyan, and H. Benveniste, “Simultaneous detection of blood volume, oxygenation, and intracellular calcium changes during cerebral ischemia and reperfusion in vivo using diffuse reflectance and fluorescence,” J. Cereb. Blood Flow Metab.25(8), 1078–1092 (2005).
[CrossRef] [PubMed]

L. Pascarella, G. W. Schmid Schönbein, and J. J. Bergan, “Microcirculation and venous ulcers: a review,” Ann. Vasc. Surg.19(6), 921–927 (2005).
[CrossRef] [PubMed]

2004 (3)

C. Ayata, A. K. Dunn, Y. Gursoy-OZdemir, Z. H. Huang, D. A. Boas, and M. A. Moskowitz, “Laser speckle flowmetry for the study of cerebrovascular physiology in normal and ischemic mouse cortex,” J. Cereb. Blood Flow Metab.24(7), 744–755 (2004).
[CrossRef] [PubMed]

M. Wojtkowski, V. J. Srinivasan, T. H. Ko, J. G. Fujimoto, A. Kowalczyk, and J. S. Duker, “Ultrahigh-resolution, high-speed, Fourier domain optical coherence tomography and methods for dispersion compensation,” Opt. Express12(11), 2404–2422 (2004).
[CrossRef] [PubMed]

H. Schulte, A. Sollevi, and M. Segerdahl, “The distribution of hyperaemia induced by skin burn injury is not correlated with the development of secondary punctate hyperalgesia,” J. Pain5(4), 212–217 (2004).
[CrossRef] [PubMed]

2003 (2)

T. Kusaka, Y. Hisamatsu, K. Kawada, K. Okubo, H. Okada, M. Namba, T. Imai, K. Isobe, and S. Itoh, “Measurement of cerebral optical pathlength as a function of oxygenation using near-infrared time-resolved spectroscopy in a piglet model of hypoxia,” Opt. Rev.10(5), 466–469 (2003).
[CrossRef]

A. K. Dunn, A. Devor, H. Bolay, M. L. Andermann, M. A. Moskowitz, A. M. Dale, and D. A. Boas, “Simultaneous imaging of total cerebral hemoglobin concentration, oxygenation, and blood flow during functional activation,” Opt. Lett.28(1), 28–30 (2003).
[CrossRef] [PubMed]

2002 (2)

D. De Backer, J. Creteur, J. C. Preiser, M. J. Dubois, and J. L. Vincent, “Microvascular blood flow is altered in patients with sepsis,” Am. J. Respir. Crit. Care Med.166(1), 98–104 (2002).
[CrossRef] [PubMed]

G. Ciuffetti, L. Pasqualini, M. Pirro, R. Lombardini, M. De Sio, G. Schillaci, and E. Mannarino, “Blood rheology in men with essential hypertension and capillary rarefaction,” J. Hum. Hypertens.16(8), 533–537 (2002).
[CrossRef] [PubMed]

2001 (2)

M. Jones, J. Berwick, D. Johnston, and J. Mayhew, “Concurrent optical imaging spectroscopy and laser-Doppler flowmetry: the relationship between blood flow, oxygenation, and volume in rodent barrel cortex,” Neuroimage13(6), 1002–1015 (2001).
[CrossRef] [PubMed]

A. K. Dunn, H. Bolay, M. A. Moskowitz, and 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)

K. Parthasarathi and H. H. Lipowsky, “Capillary recruitment in response to tissue hypoxia and its dependence on red blood cell deformability,” Am. J. Physiol.277(6 Pt 2), H2145–H2157 (1999).
[PubMed]

1998 (2)

S. A. Boppart, B. E. Bouma, C. Pitris, J. F. Southern, M. E. Brezinski, and J. G. Fujimoto, “In vivo cellular optical coherence tomography imaging,” Nat. Med.4(7), 861–865 (1998).
[CrossRef] [PubMed]

C. M. Wacker, A. W. Hartlep, M. Bock, S. Pfleger, G. Beck, G. van Kaick, L. R. Schad, and W. R. Bauer, “BOLD-MRI of the heart in patients with coronary artery disease: evidence for imaging of capillary recruitment in myocardium supplied by the stenotic artery,” Circulation98, 371–9999 (1998).

1997 (3)

J. P. Noon, B. R. Walker, D. J. Webb, A. C. Shore, D. W. Holton, H. V. Edwards, and G. C. M. Watt, “Impaired microvascular dilatation and capillary rarefaction in young adults with a predisposition to high blood pressure,” J. Clin. Invest.99(8), 1873–1879 (1997).
[CrossRef] [PubMed]

M. Ferrari, T. Binzoni, and V. Quaresima, “Oxidative metabolism in muscle,” Philos. Trans. R. Soc. Lond. B Biol. Sci.352(1354), 677–683 (1997).
[CrossRef] [PubMed]

D. L. Crandall, G. J. Hausman, and J. G. Kral, “A review of the microcirculation of adipose tissue: anatomic, metabolic, and angiogenic perspectives,” Microcirculation4(2), 211–232 (1997).
[CrossRef] [PubMed]

1995 (1)

A. F. Fercher, C. K. Hitzenberger, G. Kamp, and S. Y. Elzaiat, “Measurement of Intraocular Distances by Backscattering Spectral Interferometry,” Opt. Commun.117(1-2), 43–48 (1995).
[CrossRef]

1991 (1)

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

1990 (2)

F. S. Sutherland, E. Stefansson, D. L. Hatchell, and H. Reiser, “Retinal oxygen consumption in vitro. The effect of diabetes mellitus, oxygen and glucose,” Acta Ophthalmol. (Copenh.)68(6), 715–720 (1990).
[CrossRef] [PubMed]

S. Trojan and J. Kapitola, “Reaktivní hyperémie mozku potkana po výskové hypoxii [Reactive hyperemia in the brain of rats after high altitude hypoxia],” Sb. Lek.92(4), 97–102 (1990).
[PubMed]

1988 (2)

S. Wray, M. Cope, D. T. Delpy, J. S. Wyatt, and E. O. R. Reynolds, “Characterization of the near infrared absorption spectra of cytochrome aa3 and haemoglobin for the non-invasive monitoring of cerebral oxygenation,” Biochim. Biophys. Acta933(1), 184–192 (1988).
[CrossRef] [PubMed]

J. A. Eyre, T. J. H. Essex, P. A. Flecknell, P. H. Bartholomew, and J. I. Sinclair, “A comparison of measurements of cerebral blood flow in the rabbit using laser Doppler spectroscopy and radionuclide labelled microspheres,” Clin. Phys. Physiol. Meas.9(1), 65–74 (1988).
[CrossRef] [PubMed]

1987 (1)

J. S. Wyatt, M. Cope, D. T. Delpy, S. Wray, C. Richardson, and E. O. R. Reynolds, “Responses of cerebral vasculature to changes in arterial carbon-dioxide tension measured by near-infrared spectroscopy in newborn-infants,” Pediatr. Res.22(2), 230–9999 (1987).
[CrossRef]

1981 (2)

A. F. Fercher and J. D. Briers, “Flow Visualization by Means of Single-Exposure Speckle Photography,” Opt. Commun.37(5), 326–330 (1981).
[CrossRef]

P. M. Hutchins, V. L. Roddick, and J. W. Dusseau, “Correlation of blood-pressure and rarefaction of small arterioles in back-crossed spontaneously hypertensive rats,” Microvasc. Res.21, 246–9999 (1981).

1979 (1)

W. W. Wagner, L. P. Latham, and R. L. Capen, “Capillary recruitment during airway hypoxia: role of pulmonary artery pressure,” J. Appl. Physiol.47(2), 383–387 (1979).
[PubMed]

1977 (1)

J. Schrader, F. J. Haddy, and E. Gerlach, “Release of adenosine, inosine and hypoxanthine from the isolated guinea pig heart during hypoxia, flow-autoregulation and reactive hyperemia,” Pflugers Arch.369(1), 1–6 (1977).
[CrossRef] [PubMed]

1974 (1)

S. C. Bondy, R. A. W. Lehman, and J. L. Purdy, “Visual attention affects brain blood flow,” Nature248(5447), 440–441 (1974).
[CrossRef] [PubMed]

1964 (1)

G. Bell and A. M. Harper, “Measurement of regional blood flow through skin from clearance of krypton-85,” Nature202(4933), 704–705 (1964).
[CrossRef] [PubMed]

1959 (1)

D. G. Crawford, H. M. Fairchild, and A. C. Guyton, “Oxygen lack as a possible cause of reactive hyperemia,” Am. J. Physiol.197, 613–616 (1959).
[PubMed]

1951 (1)

P. Horstmann, “The oxygen consumption in diabetes mellitus,” Acta Med. Scand.139(4), 326–330 (1951).
[CrossRef] [PubMed]

An, L.

Andermann, M. L.

Attwell, D.

D. Attwell, A. M. Buchan, S. Charpak, M. Lauritzen, B. A. Macvicar, and E. A. Newman, “Glial and neuronal control of brain blood flow,” Nature468(7321), 232–243 (2010).
[CrossRef] [PubMed]

Ayata, C.

C. Ayata, A. K. Dunn, Y. Gursoy-OZdemir, Z. H. Huang, D. A. Boas, and M. A. Moskowitz, “Laser speckle flowmetry for the study of cerebrovascular physiology in normal and ischemic mouse cortex,” J. Cereb. Blood Flow Metab.24(7), 744–755 (2004).
[CrossRef] [PubMed]

Bartholomew, P. H.

J. A. Eyre, T. J. H. Essex, P. A. Flecknell, P. H. Bartholomew, and J. I. Sinclair, “A comparison of measurements of cerebral blood flow in the rabbit using laser Doppler spectroscopy and radionuclide labelled microspheres,” Clin. Phys. Physiol. Meas.9(1), 65–74 (1988).
[CrossRef] [PubMed]

Bartlett, L. A.

B. J. Vakoc, R. M. Lanning, J. A. Tyrrell, T. P. Padera, L. A. Bartlett, T. Stylianopoulos, L. L. Munn, G. J. Tearney, D. Fukumura, R. K. Jain, and B. E. Bouma, “Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging,” Nat. Med.15(10), 1219–1223 (2009).
[CrossRef] [PubMed]

Bauer, W. R.

C. M. Wacker, A. W. Hartlep, M. Bock, S. Pfleger, G. Beck, G. van Kaick, L. R. Schad, and W. R. Bauer, “BOLD-MRI of the heart in patients with coronary artery disease: evidence for imaging of capillary recruitment in myocardium supplied by the stenotic artery,” Circulation98, 371–9999 (1998).

Beck, G.

C. M. Wacker, A. W. Hartlep, M. Bock, S. Pfleger, G. Beck, G. van Kaick, L. R. Schad, and W. R. Bauer, “BOLD-MRI of the heart in patients with coronary artery disease: evidence for imaging of capillary recruitment in myocardium supplied by the stenotic artery,” Circulation98, 371–9999 (1998).

Bell, G.

G. Bell and A. M. Harper, “Measurement of regional blood flow through skin from clearance of krypton-85,” Nature202(4933), 704–705 (1964).
[CrossRef] [PubMed]

Benveniste, H.

C. W. Du, A. P. Koretsky, I. Izrailtyan, and H. Benveniste, “Simultaneous detection of blood volume, oxygenation, and intracellular calcium changes during cerebral ischemia and reperfusion in vivo using diffuse reflectance and fluorescence,” J. Cereb. Blood Flow Metab.25(8), 1078–1092 (2005).
[CrossRef] [PubMed]

Bergan, J. J.

L. Pascarella, G. W. Schmid Schönbein, and J. J. Bergan, “Microcirculation and venous ulcers: a review,” Ann. Vasc. Surg.19(6), 921–927 (2005).
[CrossRef] [PubMed]

Berwick, J.

M. Jones, J. Berwick, D. Johnston, and J. Mayhew, “Concurrent optical imaging spectroscopy and laser-Doppler flowmetry: the relationship between blood flow, oxygenation, and volume in rodent barrel cortex,” Neuroimage13(6), 1002–1015 (2001).
[CrossRef] [PubMed]

Binzoni, T.

M. Ferrari, T. Binzoni, and V. Quaresima, “Oxidative metabolism in muscle,” Philos. Trans. R. Soc. Lond. B Biol. Sci.352(1354), 677–683 (1997).
[CrossRef] [PubMed]

Boas, D. A.

D. A. Boas and A. K. Dunn, “Laser speckle contrast imaging in biomedical optics,” J. Biomed. Opt.15(1), 011109 (2010).
[CrossRef] [PubMed]

C. Ayata, A. K. Dunn, Y. Gursoy-OZdemir, Z. H. Huang, D. A. Boas, and M. A. Moskowitz, “Laser speckle flowmetry for the study of cerebrovascular physiology in normal and ischemic mouse cortex,” J. Cereb. Blood Flow Metab.24(7), 744–755 (2004).
[CrossRef] [PubMed]

A. K. Dunn, A. Devor, H. Bolay, M. L. Andermann, M. A. Moskowitz, A. M. Dale, and D. A. Boas, “Simultaneous imaging of total cerebral hemoglobin concentration, oxygenation, and blood flow during functional activation,” Opt. Lett.28(1), 28–30 (2003).
[CrossRef] [PubMed]

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

Bock, M.

C. M. Wacker, A. W. Hartlep, M. Bock, S. Pfleger, G. Beck, G. van Kaick, L. R. Schad, and W. R. Bauer, “BOLD-MRI of the heart in patients with coronary artery disease: evidence for imaging of capillary recruitment in myocardium supplied by the stenotic artery,” Circulation98, 371–9999 (1998).

Bolay, H.

Bondy, S. C.

S. C. Bondy, R. A. W. Lehman, and J. L. Purdy, “Visual attention affects brain blood flow,” Nature248(5447), 440–441 (1974).
[CrossRef] [PubMed]

Boppart, S. A.

S. A. Boppart, B. E. Bouma, C. Pitris, J. F. Southern, M. E. Brezinski, and J. G. Fujimoto, “In vivo cellular optical coherence tomography imaging,” Nat. Med.4(7), 861–865 (1998).
[CrossRef] [PubMed]

Bora, P. M.

S. R. Nirmala, S. Dandapat, and P. M. Bora, “Wavelet weighted blood vessel distortion measure for retinal images,” Biomed. Signal Process. Control5(4), 282–291 (2010).
[CrossRef]

Bouma, B. E.

B. J. Vakoc, R. M. Lanning, J. A. Tyrrell, T. P. Padera, L. A. Bartlett, T. Stylianopoulos, L. L. Munn, G. J. Tearney, D. Fukumura, R. K. Jain, and B. E. Bouma, “Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging,” Nat. Med.15(10), 1219–1223 (2009).
[CrossRef] [PubMed]

S. A. Boppart, B. E. Bouma, C. Pitris, J. F. Southern, M. E. Brezinski, and J. G. Fujimoto, “In vivo cellular optical coherence tomography imaging,” Nat. Med.4(7), 861–865 (1998).
[CrossRef] [PubMed]

Brezinski, M. E.

S. A. Boppart, B. E. Bouma, C. Pitris, J. F. Southern, M. E. Brezinski, and J. G. Fujimoto, “In vivo cellular optical coherence tomography imaging,” Nat. Med.4(7), 861–865 (1998).
[CrossRef] [PubMed]

Briers, J. D.

A. F. Fercher and J. D. Briers, “Flow Visualization by Means of Single-Exposure Speckle Photography,” Opt. Commun.37(5), 326–330 (1981).
[CrossRef]

Buchan, A. M.

D. Attwell, A. M. Buchan, S. Charpak, M. Lauritzen, B. A. Macvicar, and E. A. Newman, “Glial and neuronal control of brain blood flow,” Nature468(7321), 232–243 (2010).
[CrossRef] [PubMed]

Campard, S.

C. Mayeur, S. Campard, C. Richard, and J. L. Teboul, “Comparison of four different vascular occlusion tests for assessing reactive hyperemia using near-infrared spectroscopy,” Crit. Care Med.39(4), 695–701 (2011).
[CrossRef] [PubMed]

Capen, R. L.

W. W. Wagner, L. P. Latham, and R. L. Capen, “Capillary recruitment during airway hypoxia: role of pulmonary artery pressure,” J. Appl. Physiol.47(2), 383–387 (1979).
[PubMed]

Chang, W.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Charpak, S.

D. Attwell, A. M. Buchan, S. Charpak, M. Lauritzen, B. A. Macvicar, and E. A. Newman, “Glial and neuronal control of brain blood flow,” Nature468(7321), 232–243 (2010).
[CrossRef] [PubMed]

Ciuffetti, G.

G. Ciuffetti, L. Pasqualini, M. Pirro, R. Lombardini, M. De Sio, G. Schillaci, and E. Mannarino, “Blood rheology in men with essential hypertension and capillary rarefaction,” J. Hum. Hypertens.16(8), 533–537 (2002).
[CrossRef] [PubMed]

Cobas, R. A.

E. Tibiriçá, E. Rodrigues, R. A. Cobas, and M. B. Gomes, “Endothelial function in patients with type 1 diabetes evaluated by skin capillary recruitment,” Microvasc. Res.73(2), 107–112 (2007).
[CrossRef] [PubMed]

Cope, M.

S. Wray, M. Cope, D. T. Delpy, J. S. Wyatt, and E. O. R. Reynolds, “Characterization of the near infrared absorption spectra of cytochrome aa3 and haemoglobin for the non-invasive monitoring of cerebral oxygenation,” Biochim. Biophys. Acta933(1), 184–192 (1988).
[CrossRef] [PubMed]

J. S. Wyatt, M. Cope, D. T. Delpy, S. Wray, C. Richardson, and E. O. R. Reynolds, “Responses of cerebral vasculature to changes in arterial carbon-dioxide tension measured by near-infrared spectroscopy in newborn-infants,” Pediatr. Res.22(2), 230–9999 (1987).
[CrossRef]

Crandall, D. L.

D. L. Crandall, G. J. Hausman, and J. G. Kral, “A review of the microcirculation of adipose tissue: anatomic, metabolic, and angiogenic perspectives,” Microcirculation4(2), 211–232 (1997).
[CrossRef] [PubMed]

Crawford, D. G.

D. G. Crawford, H. M. Fairchild, and A. C. Guyton, “Oxygen lack as a possible cause of reactive hyperemia,” Am. J. Physiol.197, 613–616 (1959).
[PubMed]

Creteur, J.

D. De Backer, J. Creteur, J. C. Preiser, M. J. Dubois, and J. L. Vincent, “Microvascular blood flow is altered in patients with sepsis,” Am. J. Respir. Crit. Care Med.166(1), 98–104 (2002).
[CrossRef] [PubMed]

Dale, A. M.

Dandapat, S.

S. R. Nirmala, S. Dandapat, and P. M. Bora, “Wavelet weighted blood vessel distortion measure for retinal images,” Biomed. Signal Process. Control5(4), 282–291 (2010).
[CrossRef]

Davila, V.

H. M. Subhash, V. Davila, H. Sun, A. T. Nguyen-Huynh, X. R. Shi, A. L. Nuttall, and R. K. K. Wang, “Volumetric in vivo imaging of microvascular perfusion within the intact cochlea in mice using ultra-high sensitive optical microangiography,” IEEE Trans. Med. Imaging30(2), 224–230 (2011).
[CrossRef] [PubMed]

De Backer, D.

D. De Backer, J. Creteur, J. C. Preiser, M. J. Dubois, and J. L. Vincent, “Microvascular blood flow is altered in patients with sepsis,” Am. J. Respir. Crit. Care Med.166(1), 98–104 (2002).
[CrossRef] [PubMed]

De Sio, M.

G. Ciuffetti, L. Pasqualini, M. Pirro, R. Lombardini, M. De Sio, G. Schillaci, and E. Mannarino, “Blood rheology in men with essential hypertension and capillary rarefaction,” J. Hum. Hypertens.16(8), 533–537 (2002).
[CrossRef] [PubMed]

Delpy, D. T.

S. Wray, M. Cope, D. T. Delpy, J. S. Wyatt, and E. O. R. Reynolds, “Characterization of the near infrared absorption spectra of cytochrome aa3 and haemoglobin for the non-invasive monitoring of cerebral oxygenation,” Biochim. Biophys. Acta933(1), 184–192 (1988).
[CrossRef] [PubMed]

J. S. Wyatt, M. Cope, D. T. Delpy, S. Wray, C. Richardson, and E. O. R. Reynolds, “Responses of cerebral vasculature to changes in arterial carbon-dioxide tension measured by near-infrared spectroscopy in newborn-infants,” Pediatr. Res.22(2), 230–9999 (1987).
[CrossRef]

Devor, A.

Du, C.

Du, C. W.

C. W. Du, A. P. Koretsky, I. Izrailtyan, and H. Benveniste, “Simultaneous detection of blood volume, oxygenation, and intracellular calcium changes during cerebral ischemia and reperfusion in vivo using diffuse reflectance and fluorescence,” J. Cereb. Blood Flow Metab.25(8), 1078–1092 (2005).
[CrossRef] [PubMed]

Dubois, M. J.

D. De Backer, J. Creteur, J. C. Preiser, M. J. Dubois, and J. L. Vincent, “Microvascular blood flow is altered in patients with sepsis,” Am. J. Respir. Crit. Care Med.166(1), 98–104 (2002).
[CrossRef] [PubMed]

Duker, J. S.

A. C. Sull, L. N. Vuong, L. L. Price, V. J. Srinivasan, I. Gorczynska, J. G. Fujimoto, J. S. Schuman, and J. S. Duker, “Comparison of spectral/Fourier domain optical coherence tomography instruments for assessment of normal macular thickness,” Retina30(2), 235–245 (2010).
[CrossRef] [PubMed]

M. Wojtkowski, V. J. Srinivasan, T. H. Ko, J. G. Fujimoto, A. Kowalczyk, and J. S. Duker, “Ultrahigh-resolution, high-speed, Fourier domain optical coherence tomography and methods for dispersion compensation,” Opt. Express12(11), 2404–2422 (2004).
[CrossRef] [PubMed]

Duncan, D. D.

Dunn, A. K.

D. A. Boas and A. K. Dunn, “Laser speckle contrast imaging in biomedical optics,” J. Biomed. Opt.15(1), 011109 (2010).
[CrossRef] [PubMed]

C. Ayata, A. K. Dunn, Y. Gursoy-OZdemir, Z. H. Huang, D. A. Boas, and M. A. Moskowitz, “Laser speckle flowmetry for the study of cerebrovascular physiology in normal and ischemic mouse cortex,” J. Cereb. Blood Flow Metab.24(7), 744–755 (2004).
[CrossRef] [PubMed]

A. K. Dunn, A. Devor, H. Bolay, M. L. Andermann, M. A. Moskowitz, A. M. Dale, and D. A. Boas, “Simultaneous imaging of total cerebral hemoglobin concentration, oxygenation, and blood flow during functional activation,” Opt. Lett.28(1), 28–30 (2003).
[CrossRef] [PubMed]

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

Dusseau, J. W.

P. M. Hutchins, V. L. Roddick, and J. W. Dusseau, “Correlation of blood-pressure and rarefaction of small arterioles in back-crossed spontaneously hypertensive rats,” Microvasc. Res.21, 246–9999 (1981).

Edwards, H. V.

J. P. Noon, B. R. Walker, D. J. Webb, A. C. Shore, D. W. Holton, H. V. Edwards, and G. C. M. Watt, “Impaired microvascular dilatation and capillary rarefaction in young adults with a predisposition to high blood pressure,” J. Clin. Invest.99(8), 1873–1879 (1997).
[CrossRef] [PubMed]

Elzaiat, S. Y.

A. F. Fercher, C. K. Hitzenberger, G. Kamp, and S. Y. Elzaiat, “Measurement of Intraocular Distances by Backscattering Spectral Interferometry,” Opt. Commun.117(1-2), 43–48 (1995).
[CrossRef]

Essex, T. J. H.

J. A. Eyre, T. J. H. Essex, P. A. Flecknell, P. H. Bartholomew, and J. I. Sinclair, “A comparison of measurements of cerebral blood flow in the rabbit using laser Doppler spectroscopy and radionuclide labelled microspheres,” Clin. Phys. Physiol. Meas.9(1), 65–74 (1988).
[CrossRef] [PubMed]

Eyre, J. A.

J. A. Eyre, T. J. H. Essex, P. A. Flecknell, P. H. Bartholomew, and J. I. Sinclair, “A comparison of measurements of cerebral blood flow in the rabbit using laser Doppler spectroscopy and radionuclide labelled microspheres,” Clin. Phys. Physiol. Meas.9(1), 65–74 (1988).
[CrossRef] [PubMed]

Fairchild, H. M.

D. G. Crawford, H. M. Fairchild, and A. C. Guyton, “Oxygen lack as a possible cause of reactive hyperemia,” Am. J. Physiol.197, 613–616 (1959).
[PubMed]

Fercher, A. F.

A. F. Fercher, C. K. Hitzenberger, G. Kamp, and S. Y. Elzaiat, “Measurement of Intraocular Distances by Backscattering Spectral Interferometry,” Opt. Commun.117(1-2), 43–48 (1995).
[CrossRef]

A. F. Fercher and J. D. Briers, “Flow Visualization by Means of Single-Exposure Speckle Photography,” Opt. Commun.37(5), 326–330 (1981).
[CrossRef]

Ferrari, M.

M. Ferrari, T. Binzoni, and V. Quaresima, “Oxidative metabolism in muscle,” Philos. Trans. R. Soc. Lond. B Biol. Sci.352(1354), 677–683 (1997).
[CrossRef] [PubMed]

Flecknell, P. A.

J. A. Eyre, T. J. H. Essex, P. A. Flecknell, P. H. Bartholomew, and J. I. Sinclair, “A comparison of measurements of cerebral blood flow in the rabbit using laser Doppler spectroscopy and radionuclide labelled microspheres,” Clin. Phys. Physiol. Meas.9(1), 65–74 (1988).
[CrossRef] [PubMed]

Flotte, T.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Fujimoto, J. G.

A. C. Sull, L. N. Vuong, L. L. Price, V. J. Srinivasan, I. Gorczynska, J. G. Fujimoto, J. S. Schuman, and J. S. Duker, “Comparison of spectral/Fourier domain optical coherence tomography instruments for assessment of normal macular thickness,” Retina30(2), 235–245 (2010).
[CrossRef] [PubMed]

M. Wojtkowski, V. J. Srinivasan, T. H. Ko, J. G. Fujimoto, A. Kowalczyk, and J. S. Duker, “Ultrahigh-resolution, high-speed, Fourier domain optical coherence tomography and methods for dispersion compensation,” Opt. Express12(11), 2404–2422 (2004).
[CrossRef] [PubMed]

S. A. Boppart, B. E. Bouma, C. Pitris, J. F. Southern, M. E. Brezinski, and J. G. Fujimoto, “In vivo cellular optical coherence tomography imaging,” Nat. Med.4(7), 861–865 (1998).
[CrossRef] [PubMed]

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Fukumura, D.

B. J. Vakoc, R. M. Lanning, J. A. Tyrrell, T. P. Padera, L. A. Bartlett, T. Stylianopoulos, L. L. Munn, G. J. Tearney, D. Fukumura, R. K. Jain, and B. E. Bouma, “Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging,” Nat. Med.15(10), 1219–1223 (2009).
[CrossRef] [PubMed]

Gareau, D.

J. Qin, J. Y. Jiang, L. An, D. Gareau, and R. K. Wang, “In vivo volumetric imaging of microcirculation within human skin under psoriatic conditions using optical microangiography,” Lasers Surg. Med.43(2), 122–129 (2011).
[CrossRef] [PubMed]

Gerlach, E.

J. Schrader, F. J. Haddy, and E. Gerlach, “Release of adenosine, inosine and hypoxanthine from the isolated guinea pig heart during hypoxia, flow-autoregulation and reactive hyperemia,” Pflugers Arch.369(1), 1–6 (1977).
[CrossRef] [PubMed]

Gomes, M. B.

E. Tibiriçá, E. Rodrigues, R. A. Cobas, and M. B. Gomes, “Endothelial function in patients with type 1 diabetes evaluated by skin capillary recruitment,” Microvasc. Res.73(2), 107–112 (2007).
[CrossRef] [PubMed]

Gorczynska, I.

A. C. Sull, L. N. Vuong, L. L. Price, V. J. Srinivasan, I. Gorczynska, J. G. Fujimoto, J. S. Schuman, and J. S. Duker, “Comparison of spectral/Fourier domain optical coherence tomography instruments for assessment of normal macular thickness,” Retina30(2), 235–245 (2010).
[CrossRef] [PubMed]

Gregory, K.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Gursoy-OZdemir, Y.

C. Ayata, A. K. Dunn, Y. Gursoy-OZdemir, Z. H. Huang, D. A. Boas, and M. A. Moskowitz, “Laser speckle flowmetry for the study of cerebrovascular physiology in normal and ischemic mouse cortex,” J. Cereb. Blood Flow Metab.24(7), 744–755 (2004).
[CrossRef] [PubMed]

Guyton, A. C.

D. G. Crawford, H. M. Fairchild, and A. C. Guyton, “Oxygen lack as a possible cause of reactive hyperemia,” Am. J. Physiol.197, 613–616 (1959).
[PubMed]

Haddy, F. J.

J. Schrader, F. J. Haddy, and E. Gerlach, “Release of adenosine, inosine and hypoxanthine from the isolated guinea pig heart during hypoxia, flow-autoregulation and reactive hyperemia,” Pflugers Arch.369(1), 1–6 (1977).
[CrossRef] [PubMed]

Harper, A. M.

G. Bell and A. M. Harper, “Measurement of regional blood flow through skin from clearance of krypton-85,” Nature202(4933), 704–705 (1964).
[CrossRef] [PubMed]

Hartlep, A. W.

C. M. Wacker, A. W. Hartlep, M. Bock, S. Pfleger, G. Beck, G. van Kaick, L. R. Schad, and W. R. Bauer, “BOLD-MRI of the heart in patients with coronary artery disease: evidence for imaging of capillary recruitment in myocardium supplied by the stenotic artery,” Circulation98, 371–9999 (1998).

Hatchell, D. L.

F. S. Sutherland, E. Stefansson, D. L. Hatchell, and H. Reiser, “Retinal oxygen consumption in vitro. The effect of diabetes mellitus, oxygen and glucose,” Acta Ophthalmol. (Copenh.)68(6), 715–720 (1990).
[CrossRef] [PubMed]

Hausman, G. J.

D. L. Crandall, G. J. Hausman, and J. G. Kral, “A review of the microcirculation of adipose tissue: anatomic, metabolic, and angiogenic perspectives,” Microcirculation4(2), 211–232 (1997).
[CrossRef] [PubMed]

Hee, M. R.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Hisamatsu, Y.

T. Kusaka, Y. Hisamatsu, K. Kawada, K. Okubo, H. Okada, M. Namba, T. Imai, K. Isobe, and S. Itoh, “Measurement of cerebral optical pathlength as a function of oxygenation using near-infrared time-resolved spectroscopy in a piglet model of hypoxia,” Opt. Rev.10(5), 466–469 (2003).
[CrossRef]

Hitzenberger, C. K.

A. F. Fercher, C. K. Hitzenberger, G. Kamp, and S. Y. Elzaiat, “Measurement of Intraocular Distances by Backscattering Spectral Interferometry,” Opt. Commun.117(1-2), 43–48 (1995).
[CrossRef]

Holton, D. W.

J. P. Noon, B. R. Walker, D. J. Webb, A. C. Shore, D. W. Holton, H. V. Edwards, and G. C. M. Watt, “Impaired microvascular dilatation and capillary rarefaction in young adults with a predisposition to high blood pressure,” J. Clin. Invest.99(8), 1873–1879 (1997).
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Retina (1)

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Rheumatology (Oxford) (1)

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Science (1)

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Figures (6)

Fig. 1
Fig. 1

Schematic diagram of the multi-functional optical imaging system. SLD: superluminescent diode, OC: optical circulator, PC: polarization controller, FL: focusing lens, LD: laser diode, CH: chopper, M: mirror, BS: beam splitter, AL: adjusting lens, C: camera, ZL: zoom lens. The insert is a photo of the mouse pinna. The smallest division on the ruler is 1 mm.

Fig. 2
Fig. 2

2-LSI diffuse reflectance and speckle contrast images of the mouse pinna. (A) Diffuse reflectance, and (B) speckle contrast image of the mouse pinna before the burn. (C) Diffuse reflectance, and (D) speckle contrast image of the mouse pinna after the burn. The circles indicate the burned area. The arrows indicate representative vessels that are affected by the burn injury. Color bar shows the speckle contrast value (K).

Fig. 3
Fig. 3

Color coded map of the relative change of blood flow (A), HbO (C), Hb (E) and HbT (G). Mean and standard deviations of the relative change of blood flow (B), HbO (D), Hb (F) and HbT (G), from the three regions of interest. The circle indicates the burned area.

Fig. 4
Fig. 4

Projection view image of the blood vessel network obtained by the OMAG method before (A) and after (B) the burn injury. The circle indicates the burned area and the arrows indicate the reference vessels from Fig. 2(B). Enlarged areas of the yellow (C) and blue (D) rectangles, where the left and right images belong to (A) and (B), respectively.

Fig. 5
Fig. 5

Vessel area density map multiplied by the black and white projection view image of the blood vessel network obtained by the OMAG method before (A) and after (B) the burn injury. The white square in (A) is the window size used to calculate the VAD. (C) Vessel area density of the dashed line in (A) and (B). (D) Mean and standard deviation of the VAD for the three ROI’s determined in Fig. 6.

Fig. 6
Fig. 6

Co-registered image of the change in blood flow image (Fig. 3A) with the projection view image of the blood vessel network obtained by the OMAG method after the injury (Fig. 4B). The color map is the same as in Fig. 3A. The grayscale of the OMAG image was inverted such that the blood vessels appear dark for better contrast.

Equations (2)

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K= σ S I = { τ C 2T [ 1exp( 2T τ c ) ] } 0.5
[ ΔHbO(t) ΔHb(t) ]= [ ε HbO λ 1 ε Hb λ 1 ε HbO λ 2 ε Hb λ 2 ] 1 [ ln( R λ 1 (0) R λ 1 (t) ) L λ 1 ln( R λ 2 (0) R λ 2 (t) ) L λ 2 ]

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