Abstract

Absolute measurements of cerebral blood flow (CBF) are an important endpoint in studies of cerebral pathophysiology. Currently no accepted method exists for in vivo longitudinal monitoring of CBF with high resolution in rats and mice. Using three-dimensional Doppler Optical Coherence Tomography and cranial window preparations, we present methods and algorithms for regional CBF measurements in the rat cortex. Towards this end, we develop and validate a quantitative statistical model to describe the effect of static tissue on velocity sensitivity. This model is used to design scanning protocols and algorithms for sensitive 3D flow measurements and angiography of the cortex. We also introduce a method of absolute flow calculation that does not require explicit knowledge of vessel angles. We show that OCT estimates of absolute CBF values in rats agree with prior measures by autoradiography, suggesting that Doppler OCT can perform absolute flow measurements in animal models.

© 2010 OSA

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    [PubMed]
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    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
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  9. R. Bonner and R. Nossal, “Model for laser Doppler measurements of blood flow in tissue,” Appl. Opt. 20(12), 2097–2107 (1981).
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  11. J. A. Izatt, M. D. Kulkarni, S. Yazdanfar, J. K. Barton, and A. J. Welch, “In vivo bidirectional color Doppler flow imaging of picoliter blood volumes using optical coherence tomography,” Opt. Lett. 22(18), 1439–1441 (1997).
    [CrossRef]
  12. R. A. Leitgeb, L. Schmetterer, W. Drexler, A. F. Fercher, R. J. Zawadzki, and T. Bajraszewski, “Real-time assessment of retinal blood flow with ultrafast acquisition by color Doppler Fourier domain optical coherence tomography,” Opt. Express 11(23), 3116–3121 (2003).
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  15. R. K. Wang, S. L. Jacques, Z. Ma, S. Hurst, S. R. Hanson, and A. Gruber, “Three dimensional optical angiography,” Opt. Express 15(7), 4083–4097 (2007).
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  16. H. Ren, T. Sun, D. J. MacDonald, M. J. Cobb, and X. Li, “Real-time in vivo blood-flow imaging by moving-scatterer-sensitive spectral-domain optical Doppler tomography,” Opt. Lett. 31(7), 927–929 (2006).
    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
  19. 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).
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    [CrossRef] [PubMed]
  21. D. Kleinfeld and K. R. Delaney, “Distributed representation of vibrissa movement in the upper layers of somatosensory cortex revealed with voltage-sensitive dyes,” J. Comp. Neurol. 375(1), 89–108 (1996).
    [CrossRef] [PubMed]
  22. M. A. Choma, A. K. Ellerbee, C. H. Yang, T. L. Creazzo, and J. A. Izatt, “Spectral-domain phase microscopy,” Opt. Lett. 30(10), 1162–1164 (2005).
    [CrossRef] [PubMed]
  23. B. Park, M. C. Pierce, B. Cense, S. H. Yun, M. Mujat, G. Tearney, B. Bouma, and J. de Boer, “Real-time fiber-based multi-functional spectral-domain optical coherence tomography at 1.3 microm,” Opt. Express 13(11), 3931–3944 (2005).
    [CrossRef] [PubMed]
  24. S. Yazdanfar, C. Yang, M. Sarunic, and J. Izatt, “Frequency estimation precision in Doppler optical coherence tomography using the Cramer-Rao lower bound,” Opt. Express 13(2), 410–416 (2005).
    [CrossRef] [PubMed]
  25. S. Makita, Y. Hong, M. Yamanari, T. Yatagai, and Y. Yasuno, “Optical coherence angiography,” Opt. Express 14(17), 7821–7840 (2006).
    [CrossRef] [PubMed]
  26. B. J. Vakoc, G. J. Tearney, and B. E. Bouma, “Statistical properties of phase-decorrelation in phase-resolved Doppler optical coherence tomography,” IEEE Trans. Med. Imaging 28(6), 814–821 (2009).
    [CrossRef] [PubMed]
  27. J. M. Schmitt, S. H. Xiang, and K. M. Yung, “Speckle in optical coherence tomography,” J. Biomed. Opt. 4(1), 95–105 (1999).
    [CrossRef]
  28. S. H. Yun, G. Tearney, J. de Boer, and B. Bouma, “Motion artifacts in optical coherence tomography with frequency-domain ranging,” Opt. Express 12(13), 2977–2998 (2004).
    [CrossRef] [PubMed]
  29. J. Walther and E. Koch, “Transverse motion as a source of noise and reduced correlation of the Doppler phase shift in spectral domain OCT,” Opt. Express 17(22), 19698–19713 (2009).
    [CrossRef] [PubMed]
  30. M. Szkulmowski, A. Szkulmowska, T. Bajraszewski, A. Kowalczyk, and M. Wojtkowski, “Flow velocity estimation using joint Spectral and Time domain Optical Coherence Tomography,” Opt. Express 16(9), 6008–6025 (2008).
    [CrossRef] [PubMed]
  31. C. Kasai, K. Namekawa, A. Koyano, and R. Omoto, “Real-Time Two-Dimensional Blood-Flow Imaging Using an Auto-Correlation Technique,” IEEE Trans. Sonics Ultrason. 32, 458–464 (1985).
  32. V. X. D. Yang, M. L. Gordon, A. Mok, Y. H. Zhao, Z. P. Chen, R. S. C. Cobbold, B. C. Wilson, and I. A. Vitkin, “Improved phase-resolved optical Doppler tomography using the Kasai velocity estimator and histogram segmentation,” Opt. Commun. 208(4-6), 209–214 (2002).
    [CrossRef]
  33. N. Nishimura, C. B. Schaffer, B. Friedman, P. D. Lyden, and D. Kleinfeld, “Penetrating arterioles are a bottleneck in the perfusion of neocortex,” Proc. Natl. Acad. Sci. U.S.A. 104(1), 365–370 (2007).
    [CrossRef]
  34. Y. Wang, B. A. Bower, J. A. Izatt, O. Tan, and D. Huang, “In vivo total retinal blood flow measurement by Fourier domain Doppler optical coherence tomography,” J. Biomed. Opt. 12(4), 041215 (2007).
    [CrossRef] [PubMed]
  35. R. K. Wang and Z. 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]
  36. R. Michaely, A. H. Bachmann, M. L. Villiger, C. Blatter, T. Lasser, and R. A. Leitgeb, “Vectorial reconstruction of retinal blood flow in three dimensions measured with high resolution resonant Doppler Fourier domain optical coherence tomography,” J. Biomed. Opt. 12(4), 041213 (2007).
    [CrossRef] [PubMed]
  37. A. Pellicer, F. Gayá, R. Madero, J. Quero, and F. Cabañas, “Noninvasive continuous monitoring of the effects of head position on brain hemodynamics in ventilated infants,” Pediatrics 109(3), 434–440 (2002).
    [CrossRef] [PubMed]
  38. Y. Nakao, Y. Itoh, T. Y. Kuang, M. Cook, J. Jehle, and L. Sokoloff, “Effects of anesthesia on functional activation of cerebral blood flow and metabolism,” Proc. Natl. Acad. Sci. U.S.A. 98(13), 7593–7598 (2001).
    [CrossRef] [PubMed]
  39. R. K. K. Wang and S. Hurst, “Mapping of cerebro-vascular blood perfusion in mice with skin and skull intact by Optical Micro-AngioGraphy at 1.3 mum wavelength,” Opt. Express 15(18), 11402–11412 (2007).
    [CrossRef] [PubMed]
  40. Y. Yasuno, T. Endo, S. Makita, G. Aoki, M. Itoh, and T. Yatagai, “Three-dimensional line-field Fourier domain optical coherence tomography for in vivo dermatological investigation,” J. Biomed. Opt. 11(1), 014014 (2006).
    [CrossRef] [PubMed]
  41. V. J. Srinivasan, J. Y. Jiang, M. A. Yaseen, H. Radhakrishnan, W. Wu, S. Barry, A. E. Cable, and D. A. Boas, “Rapid volumetric angiography of cortical microvasculature with optical coherence tomography,” Opt. Lett. 35(1), 43–45 (2010).
    [CrossRef] [PubMed]

2010

V. J. Srinivasan, J. Y. Jiang, M. A. Yaseen, H. Radhakrishnan, W. Wu, S. Barry, A. E. Cable, and D. A. Boas, “Rapid volumetric angiography of cortical microvasculature with optical coherence tomography,” Opt. Lett. 35(1), 43–45 (2010).
[CrossRef] [PubMed]

2009

R. K. Wang and L. An, “Doppler optical micro-angiography for volumetric imaging of vascular perfusion in vivo,” Opt. Express 17(11), 8926–8940 (2009).
[CrossRef] [PubMed]

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]

V. J. Srinivasan, S. Sakadzić, I. Gorczynska, S. Ruvinskaya, W. Wu, J. G. Fujimoto, and D. A. Boas, “Depth-resolved microscopy of cortical hemodynamics with optical coherence tomography,” Opt. Lett. 34(20), 3086–3088 (2009).
[CrossRef] [PubMed]

B. J. Vakoc, G. J. Tearney, and B. E. Bouma, “Statistical properties of phase-decorrelation in phase-resolved Doppler optical coherence tomography,” IEEE Trans. Med. Imaging 28(6), 814–821 (2009).
[CrossRef] [PubMed]

J. Walther and E. Koch, “Transverse motion as a source of noise and reduced correlation of the Doppler phase shift in spectral domain OCT,” Opt. Express 17(22), 19698–19713 (2009).
[CrossRef] [PubMed]

2008

M. Szkulmowski, A. Szkulmowska, T. Bajraszewski, A. Kowalczyk, and M. Wojtkowski, “Flow velocity estimation using joint Spectral and Time domain Optical Coherence Tomography,” Opt. Express 16(9), 6008–6025 (2008).
[CrossRef] [PubMed]

Y. K. Tao, A. M. Davis, and J. A. Izatt, “Single-pass volumetric bidirectional blood flow imaging spectral domain optical coherence tomography using a modified Hilbert transform,” Opt. Express 16(16), 12350–12361 (2008).
[CrossRef] [PubMed]

2007

R. K. Wang, S. L. Jacques, Z. Ma, S. Hurst, S. R. Hanson, and A. Gruber, “Three dimensional optical angiography,” Opt. Express 15(7), 4083–4097 (2007).
[CrossRef] [PubMed]

N. Nishimura, C. B. Schaffer, B. Friedman, P. D. Lyden, and D. Kleinfeld, “Penetrating arterioles are a bottleneck in the perfusion of neocortex,” Proc. Natl. Acad. Sci. U.S.A. 104(1), 365–370 (2007).
[CrossRef]

Y. Wang, B. A. Bower, J. A. Izatt, O. Tan, and D. Huang, “In vivo total retinal blood flow measurement by Fourier domain Doppler optical coherence tomography,” J. Biomed. Opt. 12(4), 041215 (2007).
[CrossRef] [PubMed]

R. Michaely, A. H. Bachmann, M. L. Villiger, C. Blatter, T. Lasser, and R. A. Leitgeb, “Vectorial reconstruction of retinal blood flow in three dimensions measured with high resolution resonant Doppler Fourier domain optical coherence tomography,” J. Biomed. Opt. 12(4), 041213 (2007).
[CrossRef] [PubMed]

R. K. K. Wang and S. Hurst, “Mapping of cerebro-vascular blood perfusion in mice with skin and skull intact by Optical Micro-AngioGraphy at 1.3 mum wavelength,” Opt. Express 15(18), 11402–11412 (2007).
[CrossRef] [PubMed]

2006

Y. Yasuno, T. Endo, S. Makita, G. Aoki, M. Itoh, and T. Yatagai, “Three-dimensional line-field Fourier domain optical coherence tomography for in vivo dermatological investigation,” J. Biomed. Opt. 11(1), 014014 (2006).
[CrossRef] [PubMed]

R. K. Wang and Z. 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. Ren, T. Sun, D. J. MacDonald, M. J. Cobb, and X. Li, “Real-time in vivo blood-flow imaging by moving-scatterer-sensitive spectral-domain optical Doppler tomography,” Opt. Lett. 31(7), 927–929 (2006).
[CrossRef] [PubMed]

S. Makita, Y. Hong, M. Yamanari, T. Yatagai, and Y. Yasuno, “Optical coherence angiography,” Opt. Express 14(17), 7821–7840 (2006).
[CrossRef] [PubMed]

H. Girouard and C. Iadecola, “Neurovascular coupling in the normal brain and in hypertension, stroke, and Alzheimer disease,” J. Appl. Physiol. 100(1), 328–335 (2006).
[CrossRef]

2005

M. A. Choma, A. K. Ellerbee, C. H. Yang, T. L. Creazzo, and J. A. Izatt, “Spectral-domain phase microscopy,” Opt. Lett. 30(10), 1162–1164 (2005).
[CrossRef] [PubMed]

B. Park, M. C. Pierce, B. Cense, S. H. Yun, M. Mujat, G. Tearney, B. Bouma, and J. de Boer, “Real-time fiber-based multi-functional spectral-domain optical coherence tomography at 1.3 microm,” Opt. Express 13(11), 3931–3944 (2005).
[CrossRef] [PubMed]

S. Yazdanfar, C. Yang, M. Sarunic, and J. Izatt, “Frequency estimation precision in Doppler optical coherence tomography using the Cramer-Rao lower bound,” Opt. Express 13(2), 410–416 (2005).
[CrossRef] [PubMed]

2004

S. H. Yun, G. Tearney, J. de Boer, and B. Bouma, “Motion artifacts in optical coherence tomography with frequency-domain ranging,” Opt. Express 12(13), 2977–2998 (2004).
[CrossRef] [PubMed]

2003

R. A. Leitgeb, L. Schmetterer, W. Drexler, A. F. Fercher, R. J. Zawadzki, and T. Bajraszewski, “Real-time assessment of retinal blood flow with ultrafast acquisition by color Doppler Fourier domain optical coherence tomography,” Opt. Express 11(23), 3116–3121 (2003).
[CrossRef] [PubMed]

B. R. White, M. C. Pierce, N. Nassif, B. Cense, B. H. Park, G. J. Tearney, B. E. Bouma, T. C. Chen, and J. F. de Boer, “In vivo dynamic human retinal blood flow imaging using ultra-high-speed spectral domain optical coherence tomography,” Opt. Express 11(25), 3490–3497 (2003).
[CrossRef] [PubMed]

2002

V. X. D. Yang, M. L. Gordon, A. Mok, Y. H. Zhao, Z. P. Chen, R. S. C. Cobbold, B. C. Wilson, and I. A. Vitkin, “Improved phase-resolved optical Doppler tomography using the Kasai velocity estimator and histogram segmentation,” Opt. Commun. 208(4-6), 209–214 (2002).
[CrossRef]

A. Pellicer, F. Gayá, R. Madero, J. Quero, and F. Cabañas, “Noninvasive continuous monitoring of the effects of head position on brain hemodynamics in ventilated infants,” Pediatrics 109(3), 434–440 (2002).
[CrossRef] [PubMed]

2001

Y. Nakao, Y. Itoh, T. Y. Kuang, M. Cook, J. Jehle, and L. Sokoloff, “Effects of anesthesia on functional activation of cerebral blood flow and metabolism,” Proc. Natl. Acad. Sci. U.S.A. 98(13), 7593–7598 (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

F. Calamante, D. L. Thomas, G. S. Pell, J. Wiersma, and R. Turner, “Measuring cerebral blood flow using magnetic resonance imaging techniques,” J. Cereb. Blood Flow Metab. 19(7), 701–735 (1999).
[CrossRef] [PubMed]

J. M. Schmitt, S. H. Xiang, and K. M. Yung, “Speckle in optical coherence tomography,” J. Biomed. Opt. 4(1), 95–105 (1999).
[CrossRef]

1998

D. Kleinfeld, P. P. Mitra, F. Helmchen, and W. Denk, “Fluctuations and stimulus-induced changes in blood flow observed in individual capillaries in layers 2 through 4 of rat neocortex,” Proc. Natl. Acad. Sci. U.S.A. 95(26), 15741–15746 (1998).
[CrossRef] [PubMed]

1997

Z. Chen, T. E. Milner, D. Dave, and J. S. Nelson, “Optical Doppler tomographic imaging of fluid flow velocity in highly scattering media,” Opt. Lett. 22(1), 64–66 (1997).
[CrossRef] [PubMed]

J. A. Izatt, M. D. Kulkarni, S. Yazdanfar, J. K. Barton, and A. J. Welch, “In vivo bidirectional color Doppler flow imaging of picoliter blood volumes using optical coherence tomography,” Opt. Lett. 22(18), 1439–1441 (1997).
[CrossRef]

1996

D. Kleinfeld and K. R. Delaney, “Distributed representation of vibrissa movement in the upper layers of somatosensory cortex revealed with voltage-sensitive dyes,” J. Comp. Neurol. 375(1), 89–108 (1996).
[CrossRef] [PubMed]

1995

M. Lauritzen and M. Fabricius, “Real time laser-Doppler perfusion imaging of cortical spreading depression in rat neocortex,” Neuroreport 6(9), 1271–1273 (1995).
[CrossRef] [PubMed]

1994

W. D. Heiss, R. Graf, K. Wienhard, J. Löttgen, R. Saito, T. Fujita, G. Rosner, and R. Wagner, “Dynamic penumbra demonstrated by sequential multitracer PET after middle cerebral artery occlusion in cats,” J. Cereb. Blood Flow Metab. 14(6), 892–902 (1994).
[CrossRef] [PubMed]

J. A. Izatt, M. R. Hee, G. M. Owen, E. A. Swanson, and J. G. Fujimoto, “Optical coherence microscopy in scattering media,” Opt. Lett. 19(8), 590–592 (1994).
[CrossRef] [PubMed]

1985

C. Kasai, K. Namekawa, A. Koyano, and R. Omoto, “Real-Time Two-Dimensional Blood-Flow Imaging Using an Auto-Correlation Technique,” IEEE Trans. Sonics Ultrason. 32, 458–464 (1985).

1981

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

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

1978

O. Sakurada, C. Kennedy, J. Jehle, J. D. Brown, G. L. Carbin, and L. Sokoloff, “Measurement of local cerebral blood flow with iodo [14C] antipyrine,” Am. J. Physiol. 234(1), H59–H66 (1978).
[PubMed]

An, L.

R. K. Wang and L. An, “Doppler optical micro-angiography for volumetric imaging of vascular perfusion in vivo,” Opt. Express 17(11), 8926–8940 (2009).
[CrossRef] [PubMed]

Aoki, G.

Y. Yasuno, T. Endo, S. Makita, G. Aoki, M. Itoh, and T. Yatagai, “Three-dimensional line-field Fourier domain optical coherence tomography for in vivo dermatological investigation,” J. Biomed. Opt. 11(1), 014014 (2006).
[CrossRef] [PubMed]

Bachmann, A. H.

R. Michaely, A. H. Bachmann, M. L. Villiger, C. Blatter, T. Lasser, and R. A. Leitgeb, “Vectorial reconstruction of retinal blood flow in three dimensions measured with high resolution resonant Doppler Fourier domain optical coherence tomography,” J. Biomed. Opt. 12(4), 041213 (2007).
[CrossRef] [PubMed]

Bajraszewski, T.

M. Szkulmowski, A. Szkulmowska, T. Bajraszewski, A. Kowalczyk, and M. Wojtkowski, “Flow velocity estimation using joint Spectral and Time domain Optical Coherence Tomography,” Opt. Express 16(9), 6008–6025 (2008).
[CrossRef] [PubMed]

R. A. Leitgeb, L. Schmetterer, W. Drexler, A. F. Fercher, R. J. Zawadzki, and T. Bajraszewski, “Real-time assessment of retinal blood flow with ultrafast acquisition by color Doppler Fourier domain optical coherence tomography,” Opt. Express 11(23), 3116–3121 (2003).
[CrossRef] [PubMed]

Barry, S.

V. J. Srinivasan, J. Y. Jiang, M. A. Yaseen, H. Radhakrishnan, W. Wu, S. Barry, A. E. Cable, and D. A. Boas, “Rapid volumetric angiography of cortical microvasculature with optical coherence tomography,” Opt. Lett. 35(1), 43–45 (2010).
[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]

Barton, J. K.

J. A. Izatt, M. D. Kulkarni, S. Yazdanfar, J. K. Barton, and A. J. Welch, “In vivo bidirectional color Doppler flow imaging of picoliter blood volumes using optical coherence tomography,” Opt. Lett. 22(18), 1439–1441 (1997).
[CrossRef]

Blatter, C.

R. Michaely, A. H. Bachmann, M. L. Villiger, C. Blatter, T. Lasser, and R. A. Leitgeb, “Vectorial reconstruction of retinal blood flow in three dimensions measured with high resolution resonant Doppler Fourier domain optical coherence tomography,” J. Biomed. Opt. 12(4), 041213 (2007).
[CrossRef] [PubMed]

Boas, D. A.

V. J. Srinivasan, J. Y. Jiang, M. A. Yaseen, H. Radhakrishnan, W. Wu, S. Barry, A. E. Cable, and D. A. Boas, “Rapid volumetric angiography of cortical microvasculature with optical coherence tomography,” Opt. Lett. 35(1), 43–45 (2010).
[CrossRef] [PubMed]

V. J. Srinivasan, S. Sakadzić, I. Gorczynska, S. Ruvinskaya, W. Wu, J. G. Fujimoto, and D. A. Boas, “Depth-resolved microscopy of cortical hemodynamics with optical coherence tomography,” Opt. Lett. 34(20), 3086–3088 (2009).
[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]

Bolay, H.

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]

Bonner, R.

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

Bouma, B.

B. Park, M. C. Pierce, B. Cense, S. H. Yun, M. Mujat, G. Tearney, B. Bouma, and J. de Boer, “Real-time fiber-based multi-functional spectral-domain optical coherence tomography at 1.3 microm,” Opt. Express 13(11), 3931–3944 (2005).
[CrossRef] [PubMed]

S. H. Yun, G. Tearney, J. de Boer, and B. Bouma, “Motion artifacts in optical coherence tomography with frequency-domain ranging,” Opt. Express 12(13), 2977–2998 (2004).
[CrossRef] [PubMed]

Bouma, B. E.

B. J. Vakoc, G. J. Tearney, and B. E. Bouma, “Statistical properties of phase-decorrelation in phase-resolved Doppler optical coherence tomography,” IEEE Trans. Med. Imaging 28(6), 814–821 (2009).
[CrossRef] [PubMed]

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]

B. R. White, M. C. Pierce, N. Nassif, B. Cense, B. H. Park, G. J. Tearney, B. E. Bouma, T. C. Chen, and J. F. de Boer, “In vivo dynamic human retinal blood flow imaging using ultra-high-speed spectral domain optical coherence tomography,” Opt. Express 11(25), 3490–3497 (2003).
[CrossRef] [PubMed]

Bower, B. A.

Y. Wang, B. A. Bower, J. A. Izatt, O. Tan, and D. Huang, “In vivo total retinal blood flow measurement by Fourier domain Doppler optical coherence tomography,” J. Biomed. Opt. 12(4), 041215 (2007).
[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]

Brown, J. D.

O. Sakurada, C. Kennedy, J. Jehle, J. D. Brown, G. L. Carbin, and L. Sokoloff, “Measurement of local cerebral blood flow with iodo [14C] antipyrine,” Am. J. Physiol. 234(1), H59–H66 (1978).
[PubMed]

Cabañas, F.

A. Pellicer, F. Gayá, R. Madero, J. Quero, and F. Cabañas, “Noninvasive continuous monitoring of the effects of head position on brain hemodynamics in ventilated infants,” Pediatrics 109(3), 434–440 (2002).
[CrossRef] [PubMed]

Cable, A. E.

V. J. Srinivasan, J. Y. Jiang, M. A. Yaseen, H. Radhakrishnan, W. Wu, S. Barry, A. E. Cable, and D. A. Boas, “Rapid volumetric angiography of cortical microvasculature with optical coherence tomography,” Opt. Lett. 35(1), 43–45 (2010).
[CrossRef] [PubMed]

Calamante, F.

F. Calamante, D. L. Thomas, G. S. Pell, J. Wiersma, and R. Turner, “Measuring cerebral blood flow using magnetic resonance imaging techniques,” J. Cereb. Blood Flow Metab. 19(7), 701–735 (1999).
[CrossRef] [PubMed]

Carbin, G. L.

O. Sakurada, C. Kennedy, J. Jehle, J. D. Brown, G. L. Carbin, and L. Sokoloff, “Measurement of local cerebral blood flow with iodo [14C] antipyrine,” Am. J. Physiol. 234(1), H59–H66 (1978).
[PubMed]

Cense, B.

B. Park, M. C. Pierce, B. Cense, S. H. Yun, M. Mujat, G. Tearney, B. Bouma, and J. de Boer, “Real-time fiber-based multi-functional spectral-domain optical coherence tomography at 1.3 microm,” Opt. Express 13(11), 3931–3944 (2005).
[CrossRef] [PubMed]

B. R. White, M. C. Pierce, N. Nassif, B. Cense, B. H. Park, G. J. Tearney, B. E. Bouma, T. C. Chen, and J. F. de Boer, “In vivo dynamic human retinal blood flow imaging using ultra-high-speed spectral domain optical coherence tomography,” Opt. Express 11(25), 3490–3497 (2003).
[CrossRef] [PubMed]

Chen, T. C.

B. R. White, M. C. Pierce, N. Nassif, B. Cense, B. H. Park, G. J. Tearney, B. E. Bouma, T. C. Chen, and J. F. de Boer, “In vivo dynamic human retinal blood flow imaging using ultra-high-speed spectral domain optical coherence tomography,” Opt. Express 11(25), 3490–3497 (2003).
[CrossRef] [PubMed]

Chen, Z.

Z. Chen, T. E. Milner, D. Dave, and J. S. Nelson, “Optical Doppler tomographic imaging of fluid flow velocity in highly scattering media,” Opt. Lett. 22(1), 64–66 (1997).
[CrossRef] [PubMed]

Chen, Z. P.

V. X. D. Yang, M. L. Gordon, A. Mok, Y. H. Zhao, Z. P. Chen, R. S. C. Cobbold, B. C. Wilson, and I. A. Vitkin, “Improved phase-resolved optical Doppler tomography using the Kasai velocity estimator and histogram segmentation,” Opt. Commun. 208(4-6), 209–214 (2002).
[CrossRef]

Choma, M. A.

M. A. Choma, A. K. Ellerbee, C. H. Yang, T. L. Creazzo, and J. A. Izatt, “Spectral-domain phase microscopy,” Opt. Lett. 30(10), 1162–1164 (2005).
[CrossRef] [PubMed]

Cobb, M. J.

H. Ren, T. Sun, D. J. MacDonald, M. J. Cobb, and X. Li, “Real-time in vivo blood-flow imaging by moving-scatterer-sensitive spectral-domain optical Doppler tomography,” Opt. Lett. 31(7), 927–929 (2006).
[CrossRef] [PubMed]

Cobbold, R. S. C.

V. X. D. Yang, M. L. Gordon, A. Mok, Y. H. Zhao, Z. P. Chen, R. S. C. Cobbold, B. C. Wilson, and I. A. Vitkin, “Improved phase-resolved optical Doppler tomography using the Kasai velocity estimator and histogram segmentation,” Opt. Commun. 208(4-6), 209–214 (2002).
[CrossRef]

Cook, M.

Y. Nakao, Y. Itoh, T. Y. Kuang, M. Cook, J. Jehle, and L. Sokoloff, “Effects of anesthesia on functional activation of cerebral blood flow and metabolism,” Proc. Natl. Acad. Sci. U.S.A. 98(13), 7593–7598 (2001).
[CrossRef] [PubMed]

Creazzo, T. L.

M. A. Choma, A. K. Ellerbee, C. H. Yang, T. L. Creazzo, and J. A. Izatt, “Spectral-domain phase microscopy,” Opt. Lett. 30(10), 1162–1164 (2005).
[CrossRef] [PubMed]

Dave, D.

Z. Chen, T. E. Milner, D. Dave, and J. S. Nelson, “Optical Doppler tomographic imaging of fluid flow velocity in highly scattering media,” Opt. Lett. 22(1), 64–66 (1997).
[CrossRef] [PubMed]

Davis, A. M.

Y. K. Tao, A. M. Davis, and J. A. Izatt, “Single-pass volumetric bidirectional blood flow imaging spectral domain optical coherence tomography using a modified Hilbert transform,” Opt. Express 16(16), 12350–12361 (2008).
[CrossRef] [PubMed]

de Boer, J.

B. Park, M. C. Pierce, B. Cense, S. H. Yun, M. Mujat, G. Tearney, B. Bouma, and J. de Boer, “Real-time fiber-based multi-functional spectral-domain optical coherence tomography at 1.3 microm,” Opt. Express 13(11), 3931–3944 (2005).
[CrossRef] [PubMed]

S. H. Yun, G. Tearney, J. de Boer, and B. Bouma, “Motion artifacts in optical coherence tomography with frequency-domain ranging,” Opt. Express 12(13), 2977–2998 (2004).
[CrossRef] [PubMed]

de Boer, J. F.

B. R. White, M. C. Pierce, N. Nassif, B. Cense, B. H. Park, G. J. Tearney, B. E. Bouma, T. C. Chen, and J. F. de Boer, “In vivo dynamic human retinal blood flow imaging using ultra-high-speed spectral domain optical coherence tomography,” Opt. Express 11(25), 3490–3497 (2003).
[CrossRef] [PubMed]

Delaney, K. R.

D. Kleinfeld and K. R. Delaney, “Distributed representation of vibrissa movement in the upper layers of somatosensory cortex revealed with voltage-sensitive dyes,” J. Comp. Neurol. 375(1), 89–108 (1996).
[CrossRef] [PubMed]

Denk, W.

D. Kleinfeld, P. P. Mitra, F. Helmchen, and W. Denk, “Fluctuations and stimulus-induced changes in blood flow observed in individual capillaries in layers 2 through 4 of rat neocortex,” Proc. Natl. Acad. Sci. U.S.A. 95(26), 15741–15746 (1998).
[CrossRef] [PubMed]

Drexler, W.

R. A. Leitgeb, L. Schmetterer, W. Drexler, A. F. Fercher, R. J. Zawadzki, and T. Bajraszewski, “Real-time assessment of retinal blood flow with ultrafast acquisition by color Doppler Fourier domain optical coherence tomography,” Opt. Express 11(23), 3116–3121 (2003).
[CrossRef] [PubMed]

Dunn, A. K.

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]

Ellerbee, A. K.

M. A. Choma, A. K. Ellerbee, C. H. Yang, T. L. Creazzo, and J. A. Izatt, “Spectral-domain phase microscopy,” Opt. Lett. 30(10), 1162–1164 (2005).
[CrossRef] [PubMed]

Endo, T.

Y. Yasuno, T. Endo, S. Makita, G. Aoki, M. Itoh, and T. Yatagai, “Three-dimensional line-field Fourier domain optical coherence tomography for in vivo dermatological investigation,” J. Biomed. Opt. 11(1), 014014 (2006).
[CrossRef] [PubMed]

Fabricius, M.

M. Lauritzen and M. Fabricius, “Real time laser-Doppler perfusion imaging of cortical spreading depression in rat neocortex,” Neuroreport 6(9), 1271–1273 (1995).
[CrossRef] [PubMed]

Fercher, A. F.

R. A. Leitgeb, L. Schmetterer, W. Drexler, A. F. Fercher, R. J. Zawadzki, and T. Bajraszewski, “Real-time assessment of retinal blood flow with ultrafast acquisition by color Doppler Fourier domain optical coherence tomography,” Opt. Express 11(23), 3116–3121 (2003).
[CrossRef] [PubMed]

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

Friedman, B.

N. Nishimura, C. B. Schaffer, B. Friedman, P. D. Lyden, and D. Kleinfeld, “Penetrating arterioles are a bottleneck in the perfusion of neocortex,” Proc. Natl. Acad. Sci. U.S.A. 104(1), 365–370 (2007).
[CrossRef]

Fujimoto, J. G.

V. J. Srinivasan, S. Sakadzić, I. Gorczynska, S. Ruvinskaya, W. Wu, J. G. Fujimoto, and D. A. Boas, “Depth-resolved microscopy of cortical hemodynamics with optical coherence tomography,” Opt. Lett. 34(20), 3086–3088 (2009).
[CrossRef] [PubMed]

J. A. Izatt, M. R. Hee, G. M. Owen, E. A. Swanson, and J. G. Fujimoto, “Optical coherence microscopy in scattering media,” Opt. Lett. 19(8), 590–592 (1994).
[CrossRef] [PubMed]

Fujita, T.

W. D. Heiss, R. Graf, K. Wienhard, J. Löttgen, R. Saito, T. Fujita, G. Rosner, and R. Wagner, “Dynamic penumbra demonstrated by sequential multitracer PET after middle cerebral artery occlusion in cats,” J. Cereb. Blood Flow Metab. 14(6), 892–902 (1994).
[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]

Gayá, F.

A. Pellicer, F. Gayá, R. Madero, J. Quero, and F. Cabañas, “Noninvasive continuous monitoring of the effects of head position on brain hemodynamics in ventilated infants,” Pediatrics 109(3), 434–440 (2002).
[CrossRef] [PubMed]

Girouard, H.

H. Girouard and C. Iadecola, “Neurovascular coupling in the normal brain and in hypertension, stroke, and Alzheimer disease,” J. Appl. Physiol. 100(1), 328–335 (2006).
[CrossRef]

Gorczynska, I.

V. J. Srinivasan, S. Sakadzić, I. Gorczynska, S. Ruvinskaya, W. Wu, J. G. Fujimoto, and D. A. Boas, “Depth-resolved microscopy of cortical hemodynamics with optical coherence tomography,” Opt. Lett. 34(20), 3086–3088 (2009).
[CrossRef] [PubMed]

Gordon, M. L.

V. X. D. Yang, M. L. Gordon, A. Mok, Y. H. Zhao, Z. P. Chen, R. S. C. Cobbold, B. C. Wilson, and I. A. Vitkin, “Improved phase-resolved optical Doppler tomography using the Kasai velocity estimator and histogram segmentation,” Opt. Commun. 208(4-6), 209–214 (2002).
[CrossRef]

Graf, R.

W. D. Heiss, R. Graf, K. Wienhard, J. Löttgen, R. Saito, T. Fujita, G. Rosner, and R. Wagner, “Dynamic penumbra demonstrated by sequential multitracer PET after middle cerebral artery occlusion in cats,” J. Cereb. Blood Flow Metab. 14(6), 892–902 (1994).
[CrossRef] [PubMed]

Gruber, A.

R. K. Wang, S. L. Jacques, Z. Ma, S. Hurst, S. R. Hanson, and A. Gruber, “Three dimensional optical angiography,” Opt. Express 15(7), 4083–4097 (2007).
[CrossRef] [PubMed]

Hanson, S. R.

R. K. Wang, S. L. Jacques, Z. Ma, S. Hurst, S. R. Hanson, and A. Gruber, “Three dimensional optical angiography,” Opt. Express 15(7), 4083–4097 (2007).
[CrossRef] [PubMed]

Hee, M. R.

J. A. Izatt, M. R. Hee, G. M. Owen, E. A. Swanson, and J. G. Fujimoto, “Optical coherence microscopy in scattering media,” Opt. Lett. 19(8), 590–592 (1994).
[CrossRef] [PubMed]

Heiss, W. D.

W. D. Heiss, R. Graf, K. Wienhard, J. Löttgen, R. Saito, T. Fujita, G. Rosner, and R. Wagner, “Dynamic penumbra demonstrated by sequential multitracer PET after middle cerebral artery occlusion in cats,” J. Cereb. Blood Flow Metab. 14(6), 892–902 (1994).
[CrossRef] [PubMed]

Helmchen, F.

D. Kleinfeld, P. P. Mitra, F. Helmchen, and W. Denk, “Fluctuations and stimulus-induced changes in blood flow observed in individual capillaries in layers 2 through 4 of rat neocortex,” Proc. Natl. Acad. Sci. U.S.A. 95(26), 15741–15746 (1998).
[CrossRef] [PubMed]

Hong, Y.

S. Makita, Y. Hong, M. Yamanari, T. Yatagai, and Y. Yasuno, “Optical coherence angiography,” Opt. Express 14(17), 7821–7840 (2006).
[CrossRef] [PubMed]

Huang, D.

Y. Wang, B. A. Bower, J. A. Izatt, O. Tan, and D. Huang, “In vivo total retinal blood flow measurement by Fourier domain Doppler optical coherence tomography,” J. Biomed. Opt. 12(4), 041215 (2007).
[CrossRef] [PubMed]

Hurst, S.

R. K. K. Wang and S. Hurst, “Mapping of cerebro-vascular blood perfusion in mice with skin and skull intact by Optical Micro-AngioGraphy at 1.3 mum wavelength,” Opt. Express 15(18), 11402–11412 (2007).
[CrossRef] [PubMed]

R. K. Wang, S. L. Jacques, Z. Ma, S. Hurst, S. R. Hanson, and A. Gruber, “Three dimensional optical angiography,” Opt. Express 15(7), 4083–4097 (2007).
[CrossRef] [PubMed]

Iadecola, C.

H. Girouard and C. Iadecola, “Neurovascular coupling in the normal brain and in hypertension, stroke, and Alzheimer disease,” J. Appl. Physiol. 100(1), 328–335 (2006).
[CrossRef]

Itoh, M.

Y. Yasuno, T. Endo, S. Makita, G. Aoki, M. Itoh, and T. Yatagai, “Three-dimensional line-field Fourier domain optical coherence tomography for in vivo dermatological investigation,” J. Biomed. Opt. 11(1), 014014 (2006).
[CrossRef] [PubMed]

Itoh, Y.

Y. Nakao, Y. Itoh, T. Y. Kuang, M. Cook, J. Jehle, and L. Sokoloff, “Effects of anesthesia on functional activation of cerebral blood flow and metabolism,” Proc. Natl. Acad. Sci. U.S.A. 98(13), 7593–7598 (2001).
[CrossRef] [PubMed]

Izatt, J.

S. Yazdanfar, C. Yang, M. Sarunic, and J. Izatt, “Frequency estimation precision in Doppler optical coherence tomography using the Cramer-Rao lower bound,” Opt. Express 13(2), 410–416 (2005).
[CrossRef] [PubMed]

Izatt, J. A.

Y. K. Tao, A. M. Davis, and J. A. Izatt, “Single-pass volumetric bidirectional blood flow imaging spectral domain optical coherence tomography using a modified Hilbert transform,” Opt. Express 16(16), 12350–12361 (2008).
[CrossRef] [PubMed]

Y. Wang, B. A. Bower, J. A. Izatt, O. Tan, and D. Huang, “In vivo total retinal blood flow measurement by Fourier domain Doppler optical coherence tomography,” J. Biomed. Opt. 12(4), 041215 (2007).
[CrossRef] [PubMed]

M. A. Choma, A. K. Ellerbee, C. H. Yang, T. L. Creazzo, and J. A. Izatt, “Spectral-domain phase microscopy,” Opt. Lett. 30(10), 1162–1164 (2005).
[CrossRef] [PubMed]

J. A. Izatt, M. D. Kulkarni, S. Yazdanfar, J. K. Barton, and A. J. Welch, “In vivo bidirectional color Doppler flow imaging of picoliter blood volumes using optical coherence tomography,” Opt. Lett. 22(18), 1439–1441 (1997).
[CrossRef]

J. A. Izatt, M. R. Hee, G. M. Owen, E. A. Swanson, and J. G. Fujimoto, “Optical coherence microscopy in scattering media,” Opt. Lett. 19(8), 590–592 (1994).
[CrossRef] [PubMed]

Jacques, S. L.

R. K. Wang, S. L. Jacques, Z. Ma, S. Hurst, S. R. Hanson, and A. Gruber, “Three dimensional optical angiography,” Opt. Express 15(7), 4083–4097 (2007).
[CrossRef] [PubMed]

Jain, R. K.

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]

Jehle, J.

Y. Nakao, Y. Itoh, T. Y. Kuang, M. Cook, J. Jehle, and L. Sokoloff, “Effects of anesthesia on functional activation of cerebral blood flow and metabolism,” Proc. Natl. Acad. Sci. U.S.A. 98(13), 7593–7598 (2001).
[CrossRef] [PubMed]

O. Sakurada, C. Kennedy, J. Jehle, J. D. Brown, G. L. Carbin, and L. Sokoloff, “Measurement of local cerebral blood flow with iodo [14C] antipyrine,” Am. J. Physiol. 234(1), H59–H66 (1978).
[PubMed]

Jiang, J. Y.

V. J. Srinivasan, J. Y. Jiang, M. A. Yaseen, H. Radhakrishnan, W. Wu, S. Barry, A. E. Cable, and D. A. Boas, “Rapid volumetric angiography of cortical microvasculature with optical coherence tomography,” Opt. Lett. 35(1), 43–45 (2010).
[CrossRef] [PubMed]

Kasai, C.

C. Kasai, K. Namekawa, A. Koyano, and R. Omoto, “Real-Time Two-Dimensional Blood-Flow Imaging Using an Auto-Correlation Technique,” IEEE Trans. Sonics Ultrason. 32, 458–464 (1985).

Kennedy, C.

O. Sakurada, C. Kennedy, J. Jehle, J. D. Brown, G. L. Carbin, and L. Sokoloff, “Measurement of local cerebral blood flow with iodo [14C] antipyrine,” Am. J. Physiol. 234(1), H59–H66 (1978).
[PubMed]

Kleinfeld, D.

N. Nishimura, C. B. Schaffer, B. Friedman, P. D. Lyden, and D. Kleinfeld, “Penetrating arterioles are a bottleneck in the perfusion of neocortex,” Proc. Natl. Acad. Sci. U.S.A. 104(1), 365–370 (2007).
[CrossRef]

D. Kleinfeld, P. P. Mitra, F. Helmchen, and W. Denk, “Fluctuations and stimulus-induced changes in blood flow observed in individual capillaries in layers 2 through 4 of rat neocortex,” Proc. Natl. Acad. Sci. U.S.A. 95(26), 15741–15746 (1998).
[CrossRef] [PubMed]

D. Kleinfeld and K. R. Delaney, “Distributed representation of vibrissa movement in the upper layers of somatosensory cortex revealed with voltage-sensitive dyes,” J. Comp. Neurol. 375(1), 89–108 (1996).
[CrossRef] [PubMed]

Koch, E.

J. Walther and E. Koch, “Transverse motion as a source of noise and reduced correlation of the Doppler phase shift in spectral domain OCT,” Opt. Express 17(22), 19698–19713 (2009).
[CrossRef] [PubMed]

Kowalczyk, A.

M. Szkulmowski, A. Szkulmowska, T. Bajraszewski, A. Kowalczyk, and M. Wojtkowski, “Flow velocity estimation using joint Spectral and Time domain Optical Coherence Tomography,” Opt. Express 16(9), 6008–6025 (2008).
[CrossRef] [PubMed]

Koyano, A.

C. Kasai, K. Namekawa, A. Koyano, and R. Omoto, “Real-Time Two-Dimensional Blood-Flow Imaging Using an Auto-Correlation Technique,” IEEE Trans. Sonics Ultrason. 32, 458–464 (1985).

Kuang, T. Y.

Y. Nakao, Y. Itoh, T. Y. Kuang, M. Cook, J. Jehle, and L. Sokoloff, “Effects of anesthesia on functional activation of cerebral blood flow and metabolism,” Proc. Natl. Acad. Sci. U.S.A. 98(13), 7593–7598 (2001).
[CrossRef] [PubMed]

Kulkarni, M. D.

J. A. Izatt, M. D. Kulkarni, S. Yazdanfar, J. K. Barton, and A. J. Welch, “In vivo bidirectional color Doppler flow imaging of picoliter blood volumes using optical coherence tomography,” Opt. Lett. 22(18), 1439–1441 (1997).
[CrossRef]

Lanning, R. M.

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]

Lasser, T.

R. Michaely, A. H. Bachmann, M. L. Villiger, C. Blatter, T. Lasser, and R. A. Leitgeb, “Vectorial reconstruction of retinal blood flow in three dimensions measured with high resolution resonant Doppler Fourier domain optical coherence tomography,” J. Biomed. Opt. 12(4), 041213 (2007).
[CrossRef] [PubMed]

Lauritzen, M.

M. Lauritzen and M. Fabricius, “Real time laser-Doppler perfusion imaging of cortical spreading depression in rat neocortex,” Neuroreport 6(9), 1271–1273 (1995).
[CrossRef] [PubMed]

Leitgeb, R. A.

R. Michaely, A. H. Bachmann, M. L. Villiger, C. Blatter, T. Lasser, and R. A. Leitgeb, “Vectorial reconstruction of retinal blood flow in three dimensions measured with high resolution resonant Doppler Fourier domain optical coherence tomography,” J. Biomed. Opt. 12(4), 041213 (2007).
[CrossRef] [PubMed]

R. A. Leitgeb, L. Schmetterer, W. Drexler, A. F. Fercher, R. J. Zawadzki, and T. Bajraszewski, “Real-time assessment of retinal blood flow with ultrafast acquisition by color Doppler Fourier domain optical coherence tomography,” Opt. Express 11(23), 3116–3121 (2003).
[CrossRef] [PubMed]

Li, X.

H. Ren, T. Sun, D. J. MacDonald, M. J. Cobb, and X. Li, “Real-time in vivo blood-flow imaging by moving-scatterer-sensitive spectral-domain optical Doppler tomography,” Opt. Lett. 31(7), 927–929 (2006).
[CrossRef] [PubMed]

Löttgen, J.

W. D. Heiss, R. Graf, K. Wienhard, J. Löttgen, R. Saito, T. Fujita, G. Rosner, and R. Wagner, “Dynamic penumbra demonstrated by sequential multitracer PET after middle cerebral artery occlusion in cats,” J. Cereb. Blood Flow Metab. 14(6), 892–902 (1994).
[CrossRef] [PubMed]

Lyden, P. D.

N. Nishimura, C. B. Schaffer, B. Friedman, P. D. Lyden, and D. Kleinfeld, “Penetrating arterioles are a bottleneck in the perfusion of neocortex,” Proc. Natl. Acad. Sci. U.S.A. 104(1), 365–370 (2007).
[CrossRef]

Ma, Z.

R. K. Wang, S. L. Jacques, Z. Ma, S. Hurst, S. R. Hanson, and A. Gruber, “Three dimensional optical angiography,” Opt. Express 15(7), 4083–4097 (2007).
[CrossRef] [PubMed]

R. K. Wang and Z. 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]

MacDonald, D. J.

H. Ren, T. Sun, D. J. MacDonald, M. J. Cobb, and X. Li, “Real-time in vivo blood-flow imaging by moving-scatterer-sensitive spectral-domain optical Doppler tomography,” Opt. Lett. 31(7), 927–929 (2006).
[CrossRef] [PubMed]

Madero, R.

A. Pellicer, F. Gayá, R. Madero, J. Quero, and F. Cabañas, “Noninvasive continuous monitoring of the effects of head position on brain hemodynamics in ventilated infants,” Pediatrics 109(3), 434–440 (2002).
[CrossRef] [PubMed]

Makita, S.

Y. Yasuno, T. Endo, S. Makita, G. Aoki, M. Itoh, and T. Yatagai, “Three-dimensional line-field Fourier domain optical coherence tomography for in vivo dermatological investigation,” J. Biomed. Opt. 11(1), 014014 (2006).
[CrossRef] [PubMed]

S. Makita, Y. Hong, M. Yamanari, T. Yatagai, and Y. Yasuno, “Optical coherence angiography,” Opt. Express 14(17), 7821–7840 (2006).
[CrossRef] [PubMed]

Michaely, R.

R. Michaely, A. H. Bachmann, M. L. Villiger, C. Blatter, T. Lasser, and R. A. Leitgeb, “Vectorial reconstruction of retinal blood flow in three dimensions measured with high resolution resonant Doppler Fourier domain optical coherence tomography,” J. Biomed. Opt. 12(4), 041213 (2007).
[CrossRef] [PubMed]

Milner, T. E.

Z. Chen, T. E. Milner, D. Dave, and J. S. Nelson, “Optical Doppler tomographic imaging of fluid flow velocity in highly scattering media,” Opt. Lett. 22(1), 64–66 (1997).
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Mitra, P. P.

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J. A. Izatt, M. R. Hee, G. M. Owen, E. A. Swanson, and J. G. Fujimoto, “Optical coherence microscopy in scattering media,” Opt. Lett. 19(8), 590–592 (1994).
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V. X. D. Yang, M. L. Gordon, A. Mok, Y. H. Zhao, Z. P. Chen, R. S. C. Cobbold, B. C. Wilson, and I. A. Vitkin, “Improved phase-resolved optical Doppler tomography using the Kasai velocity estimator and histogram segmentation,” Opt. Commun. 208(4-6), 209–214 (2002).
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V. J. Srinivasan, J. Y. Jiang, M. A. Yaseen, H. Radhakrishnan, W. Wu, S. Barry, A. E. Cable, and D. A. Boas, “Rapid volumetric angiography of cortical microvasculature with optical coherence tomography,” Opt. Lett. 35(1), 43–45 (2010).
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V. J. Srinivasan, J. Y. Jiang, M. A. Yaseen, H. Radhakrishnan, W. Wu, S. Barry, A. E. Cable, and D. A. Boas, “Rapid volumetric angiography of cortical microvasculature with optical coherence tomography,” Opt. Lett. 35(1), 43–45 (2010).
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Y. Yasuno, T. Endo, S. Makita, G. Aoki, M. Itoh, and T. Yatagai, “Three-dimensional line-field Fourier domain optical coherence tomography for in vivo dermatological investigation,” J. Biomed. Opt. 11(1), 014014 (2006).
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S. Yazdanfar, C. Yang, M. Sarunic, and J. Izatt, “Frequency estimation precision in Doppler optical coherence tomography using the Cramer-Rao lower bound,” Opt. Express 13(2), 410–416 (2005).
[CrossRef] [PubMed]

J. A. Izatt, M. D. Kulkarni, S. Yazdanfar, J. K. Barton, and A. J. Welch, “In vivo bidirectional color Doppler flow imaging of picoliter blood volumes using optical coherence tomography,” Opt. Lett. 22(18), 1439–1441 (1997).
[CrossRef]

Yun, S. H.

B. Park, M. C. Pierce, B. Cense, S. H. Yun, M. Mujat, G. Tearney, B. Bouma, and J. de Boer, “Real-time fiber-based multi-functional spectral-domain optical coherence tomography at 1.3 microm,” Opt. Express 13(11), 3931–3944 (2005).
[CrossRef] [PubMed]

S. H. Yun, G. Tearney, J. de Boer, and B. Bouma, “Motion artifacts in optical coherence tomography with frequency-domain ranging,” Opt. Express 12(13), 2977–2998 (2004).
[CrossRef] [PubMed]

Yung, K. M.

J. M. Schmitt, S. H. Xiang, and K. M. Yung, “Speckle in optical coherence tomography,” J. Biomed. Opt. 4(1), 95–105 (1999).
[CrossRef]

Zawadzki, R. J.

R. A. Leitgeb, L. Schmetterer, W. Drexler, A. F. Fercher, R. J. Zawadzki, and T. Bajraszewski, “Real-time assessment of retinal blood flow with ultrafast acquisition by color Doppler Fourier domain optical coherence tomography,” Opt. Express 11(23), 3116–3121 (2003).
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Zhao, Y. H.

V. X. D. Yang, M. L. Gordon, A. Mok, Y. H. Zhao, Z. P. Chen, R. S. C. Cobbold, B. C. Wilson, and I. A. Vitkin, “Improved phase-resolved optical Doppler tomography using the Kasai velocity estimator and histogram segmentation,” Opt. Commun. 208(4-6), 209–214 (2002).
[CrossRef]

Am. J. Physiol.

O. Sakurada, C. Kennedy, J. Jehle, J. D. Brown, G. L. Carbin, and L. Sokoloff, “Measurement of local cerebral blood flow with iodo [14C] antipyrine,” Am. J. Physiol. 234(1), H59–H66 (1978).
[PubMed]

Appl. Opt.

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

IEEE Trans. Med. Imaging

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Supplementary Material (1)

» Media 1: AVI (3602 KB)     

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Figures (7)

Fig. 1
Fig. 1

Schematic of the OCT system. (a) The optical path incorporates two steering mirrors (M1 and M2) in the beam path to achieve precise alignment of the OCT beam. (b) Zoom of the focal plane of the objective lens showing a point scatterer emitting a spherical wave. This model is used in the derivation of the point spread function. (c) Schematic of two adjacent axial scans showing how transverse scanning can lead to a Doppler shift if the axis of light propagation (green arrow) is not aligned perpendicular to the scanning direction (red arrow). Mirrors M1 and M2 were used to correct for this effect, ensuring accurate Doppler measurements and reduced phase noise. (d) Summary of parameters for scanning protocols.

Fig. 5
Fig. 5

Procedure for calculating flow without explicit calculation of vessel angle. (a) Blood vessels can be oriented at any angle φ relative to the incident light. (b) The area of the vessel in the en face (xy) transverse plane is inversely proportional to cos(φ). (c) En face cut through a 3D OCT velocity projection volume (obtained by averaging all 10 volumes in Protocol 1) at a depth of 50 µm. (d) Zoom of a venule showing the z projection of velocity over the vessel cross-section (upsampled to reduce pixellation). While the area of the vessel in the xy plane is inversely proportional to cos(φ) the z-projection of the velocity is proportional to cos(φ).

Fig. 7
Fig. 7

Absolute values of flow measurements in the rat cortex in ascending venules. (a) Locations for flow measurements (Media 1) and (b) absolute flow measurements at the designated locations. Standard errors over 10 repeated measurements are shown.

Fig. 6
Fig. 6

(a) OCT maximum intensity projection (MIP) angiogram of the rat somatosensory cortex showing comprehensive visualization of the vasculature at 12.0 µm transverse resolution. (b) zoom of arterial anasthmosis, showing visualization of surface vessels as well as capillaries below. (c) OCT MIP angiogram acquired with a 3.6 µm transverse resolution in a different animal. The transverse scanning speed was chosen to yield identical temporal power spectral densities at both resolutions. The apparent diameter of capillaries is increased as the transverse resolution is increased. In addition, due to the smaller depth of field, fewer vessels are visualized in the high transverse resolution MIP angiogram (c).

Fig. 2
Fig. 2

Slower scanning speeds improve frequency sensitivity by decreasing the width of the power spectral density of static tissue. (a) Image of scattering phantom used for autocorrelation and power spectral density measurements. (b) Measured and theoretical spatial autocorrelation functions. The theoretical spatial autocorrelation function was calculated by assuming the complex speckle pattern is formed by spatially uncorrelated (white) noise filtered by the point spread function in the focal plane. (c) Spatial autocorrelation functions at different scanning speeds are virtually identical. (d) Temporal autocorrelation functions at different scanning speeds show width inversely proportional to the scanning speed. (e) Spatial power spectral density at different scanning speeds are virtually identical. (f) Temporal power spectral densities at different scanning speeds show width proportional to the scanning speed.

Fig. 3
Fig. 3

. High-pass filtering was performed along the transverse direction to separate moving and stationary scatterers. (a) Real-valued filter kernel used for high-pass filtering and (b) Fourier transform of the filter kernel, or frequency response, for protocol 1 (0.95 µm / axial scan). (c) Filter kernel and (d) frequency response for protocol 2 (0.025 µm / axial scan).

Fig. 4
Fig. 4

. Digital high-pass filtering results in a Doppler mean frequency bias. Comparison of power spectral densities for protocol 1 (a-b) and protocol 2 (c-d) before and after digital high-pass filtering. The input center frequencies (0.0, 1.5, 3.0, 4.5, 6.0 kHz) are color coded as shown in the legends. Power spectral densities before and after high-pass filtering are shown as dotted and solid lines, respectively. The only source of decorrelation is assumed to be transverse scanning of the OCT beam. The mean frequencies of the power spectral densities before and after high-pass filtering are plotted (b) for protocol 1 (0.95 µm / axial scan), showing a significant bias in the mean frequency caused by filtering. (c-d) For the high-density scanning protocol (0.025 µm / axial scan), high-pass filtering causes a negligible bias in the mean frequency.

Equations (19)

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R t ( t ) = - P t ( f t ) e j 2 π f t t d f t , R x ( x ) = - P x ( f x ) e j 2 π f x x d f x
R t ( t ) = | R t ( t ) | e j ϕ t ( t ) , R x ( x ) = | R x ( x ) | e j ϕ x ( x )
E i ( x , y , z ) = ( 2 π 1 w i ' ) e - x 2 + y 2 w i ' 2 e - j k ( x 2 + y 2 ) 2 R i ' 2 e - j ( k z - θ ' ) , where w i ' = w i ' ( z ) = w i 1 + z 2 Z i 2 , R i ' = R i ' ( z ) = z ( 1 + Z i 2 z 2 ) , θ ' = tan - 1 ( z 2 Z i 2 ) , Z i = π n w i 2 λ
| E i ( x , y , z ) | 2 d x d y = 1
E r ( x , y , z 0 ) = K * E i * ( x 0 , 0 , z 0 ) δ ( x - x 0 , y ) .
η c ( x 0 , z 0 ) = - - E i ( x , y , z 0 ) E r * ( x , y , z 0 ) d x d y = - - K E i 2 ( x , y , z 0 ) δ ( x - x 0 , y ) d x d y = K E i 2 ( x 0 , 0 , z 0 )
h ( x ) = η c ( x , 0 ) = 2 K π w i 2 e - ( 2 x 2 w i 2 )
R x ( x ) = σ 2 h ( x ) * h * ( - x ) = 2 | K | 2 σ 2 π 3 / 2 w i 3 e - ( x 2 w i 2 ) P x ( f x ) = σ 2 | H ( f x ) | 2 = 2 | K | 2 σ 2 π w i 2 e - π 2 w i 2 f x 2
R t ( t ) = R x ( v x t ) P t ( f t ) = 1 v x P x ( f t v x )
f ¯ t , K a s a i = 1 2 π Τ tan - 1 [ Im ( A k ( z ) A k + 1 * ( z ) ) Re ( A k ( z ) A k + 1 * ( z ) ) ]
R ^ t ( T ) = | R ^ t ( T ) | e j ϕ ^ t ( T ) = A k ( z ) A k + 1 * ( z )
2 π f ¯ t , K a s a i = arg [ R ^ t ( T ) ] T = ϕ ^ t ( T ) T
R ^ t ( i T ) = A k ( z ) A k + i * ( z )
f t = f t , e s t max i m i z e s P ^ t ( f t ) = i = - N N R ^ t ( i T ) e - j 2 π f t i T
v z = f t , e s t λ 2 n
F= S v d S = S ( v n )dS
S ( v n ) d S = y z p l a n e v x ( y , z ) d y d z = y z p l a n e v z ( y , z ) tan ( φ ) d y d z
F = - x y p l a n e v z ( x , y ) d x d y
Δt~ 1 Δf t = 1 v x Δf x ~ w i v x

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