Abstract

Optical coherence tomography (OCT) has recently been used to produce 3D angiography of microvasculature and blood flow maps of large vessels in the rodent brain in-vivo. However, use of this optical method for the study of cerebrovascular disease has not been fully explored. Recent developments in neurodegenerative diseases has linked common cardiovascular risk factors to neurodegenerative risk factors hinting at a vascular hypothesis for the development of the latter. Tools for studying cerebral blood flow and the myogenic tone of cerebral vasculature have thus far been either highly invasive or required ex-vivo preparations therefore not preserving the delicate in-vivo conditions. We propose a novel technique for reconstructing the flow profile over a single cardiac cycle in order to evaluate flow pulsatility and vessel compliance. A vascular model is used to simulate changes in vascular compliance and interpret OCT results. Comparison between atherosclerotic and wild type mice show a trend towards increased compliance in the smaller arterioles of the brain (diameter < 80μm) in the disease model. These results are consistent with previously published ex-vivo work confirming the ability of OCT to investigate vascular dysfunction.

© 2011 OSA

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    [CrossRef] [PubMed]
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    [CrossRef] [PubMed]
  17. C. Kasai, K. Namekawa, A. Koyano, and R. Omoto, “Real-time two-dimensional blood flow imaging using an autocorrelation technique,” IEEE Trans. Sonics Ultrason.32, 458–464 (1985).
  18. D. Boas, S. Jones, A. Devor, T. Huppert, and A. Dale, “A vascular anatomical network model of the spatio-temporal response to brain activation,” Neuroimage40, 1116–1129 (2008).
    [CrossRef] [PubMed]
  19. A. Pries, D. Neuhaus, and P. Gaehtgens, “Blood viscosity in tube flow: dependence on diameter and hematocrit,” Am. J. Physiol. Heart Circ. Physiol.263, H1770–H1778 (1992).
  20. A. Drouin, V. Bolduc, N. Thorin-Trescases, É. Bélanger, P. Fernandes, E. Baraghis, F. Lesage, M. Gillis, L. Villeneuve, E. Hamel, G. Ferland, and E. Thorin, “Catechin treatment improves cerebrovascular flow-mediated dilation and learning abilities in atherosclerotic mice,” Am. J. Physiol. Heart Circ. Physiol.300, H1032–H1043 (2011).
    [CrossRef]

2011 (1)

A. Drouin, V. Bolduc, N. Thorin-Trescases, É. Bélanger, P. Fernandes, E. Baraghis, F. Lesage, M. Gillis, L. Villeneuve, E. Hamel, G. Ferland, and E. Thorin, “Catechin treatment improves cerebrovascular flow-mediated dilation and learning abilities in atherosclerotic mice,” Am. J. Physiol. Heart Circ. Physiol.300, H1032–H1043 (2011).
[CrossRef]

2010 (3)

2009 (2)

E. Helzner, J. Luchsinger, N. Scarmeas, S. Cosentino, A. Brickman, M. Glymour, and Y. Stern, “Contribution of vascular risk factors to the progression in alzheimer disease,” Arch. Neurol.66, 343 (2009).
[CrossRef] [PubMed]

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

2008 (3)

Q. Fang, S. Sakadzic, L. Ruvinskaya, A. Devor, A. M. Dale, and D. A. Boas, “Oxygen advection and diffusion in a three-dimensional vascular anatomical network,” Opt. Express16, 17530–17541 (2008).
[CrossRef] [PubMed]

D. Boas, S. Jones, A. Devor, T. Huppert, and A. Dale, “A vascular anatomical network model of the spatio-temporal response to brain activation,” Neuroimage40, 1116–1129 (2008).
[CrossRef] [PubMed]

T. Murphy, P. Li, K. Betts, and R. Liu, “Two-photon imaging of stroke onset in vivo reveals that nmda-receptor independent ischemic depolarization is the major cause of rapid reversible damage to dendrites and spines,” J. Neurosci.28, 1756–1772 (2008).
[CrossRef]

2007 (1)

2006 (2)

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

C. Schaffer, B. Friedman, N. Nishimura, L. Schroeder, P. Tsai, F. Ebner, P. Lyden, and D. Kleinfeld, “Two-photon imaging of cortical surface microvessels reveals a robust redistribution in blood flow after vascular occlusion,” PLoS Biol.4, e22 (2006).
[CrossRef]

2004 (3)

J. C. de la Torre, “Is alzheimer’s disease a neurodegenerative or a vascular disorder? data, dogma, and dialectics,” Lancet Neurol.3, 184–190 (2004).
[CrossRef] [PubMed]

C. Iadecola, “Neurovascular regulation in the normal brain and in alzheimer’s disease,” Nat. Rev. Neurosci.5, 347–360 (2004).
[CrossRef] [PubMed]

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

2003 (1)

L. Hebert, P. Scherr, J. Bienias, D. Bennett, and D. Evans, “Alzheimer disease in the us population: prevalence estimates using the 2000 census,” Arch. Neurol.60, 1119–1122 (2003).
[CrossRef] [PubMed]

2001 (1)

N. van Popele, D. Grobbee, M. Bots, R. Asmar, J. Topouchian, R. Reneman, A. Hoeks, D. van der Kuip, A. Hofman, and J. Witteman, “Association between arterial stiffness and atherosclerosis: the rotterdam study,” Stroke32, 454–460 (2001).
[CrossRef] [PubMed]

1992 (1)

A. Pries, D. Neuhaus, and P. Gaehtgens, “Blood viscosity in tube flow: dependence on diameter and hematocrit,” Am. J. Physiol. Heart Circ. Physiol.263, H1770–H1778 (1992).

1985 (1)

C. Kasai, K. Namekawa, A. Koyano, and R. Omoto, “Real-time two-dimensional blood flow imaging using an autocorrelation technique,” IEEE Trans. Sonics Ultrason.32, 458–464 (1985).

An, L.

Y. Jia, L. An, and R. Wang, “Label-free and highly sensitive optical imaging of detailed microcirculation within meninges and cortex in mice with the cranium left intact,” J. Biomed. Opt.15, 030510 (2010).
[CrossRef] [PubMed]

Asmar, R.

N. van Popele, D. Grobbee, M. Bots, R. Asmar, J. Topouchian, R. Reneman, A. Hoeks, D. van der Kuip, A. Hofman, and J. Witteman, “Association between arterial stiffness and atherosclerosis: the rotterdam study,” Stroke32, 454–460 (2001).
[CrossRef] [PubMed]

Baraghis, E.

A. Drouin, V. Bolduc, N. Thorin-Trescases, É. Bélanger, P. Fernandes, E. Baraghis, F. Lesage, M. Gillis, L. Villeneuve, E. Hamel, G. Ferland, and E. Thorin, “Catechin treatment improves cerebrovascular flow-mediated dilation and learning abilities in atherosclerotic mice,” Am. J. Physiol. Heart Circ. Physiol.300, H1032–H1043 (2011).
[CrossRef]

Barry, S.

Bartlett, L.

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

Bélanger, É.

A. Drouin, V. Bolduc, N. Thorin-Trescases, É. Bélanger, P. Fernandes, E. Baraghis, F. Lesage, M. Gillis, L. Villeneuve, E. Hamel, G. Ferland, and E. Thorin, “Catechin treatment improves cerebrovascular flow-mediated dilation and learning abilities in atherosclerotic mice,” Am. J. Physiol. Heart Circ. Physiol.300, H1032–H1043 (2011).
[CrossRef]

Bennett, D.

L. Hebert, P. Scherr, J. Bienias, D. Bennett, and D. Evans, “Alzheimer disease in the us population: prevalence estimates using the 2000 census,” Arch. Neurol.60, 1119–1122 (2003).
[CrossRef] [PubMed]

Betts, K.

T. Murphy, P. Li, K. Betts, and R. Liu, “Two-photon imaging of stroke onset in vivo reveals that nmda-receptor independent ischemic depolarization is the major cause of rapid reversible damage to dendrites and spines,” J. Neurosci.28, 1756–1772 (2008).
[CrossRef]

Bienias, J.

L. Hebert, P. Scherr, J. Bienias, D. Bennett, and D. Evans, “Alzheimer disease in the us population: prevalence estimates using the 2000 census,” Arch. Neurol.60, 1119–1122 (2003).
[CrossRef] [PubMed]

Boas, D.

D. Boas, S. Jones, A. Devor, T. Huppert, and A. Dale, “A vascular anatomical network model of the spatio-temporal response to brain activation,” Neuroimage40, 1116–1129 (2008).
[CrossRef] [PubMed]

Boas, D. A.

Bolduc, V.

A. Drouin, V. Bolduc, N. Thorin-Trescases, É. Bélanger, P. Fernandes, E. Baraghis, F. Lesage, M. Gillis, L. Villeneuve, E. Hamel, G. Ferland, and E. Thorin, “Catechin treatment improves cerebrovascular flow-mediated dilation and learning abilities in atherosclerotic mice,” Am. J. Physiol. Heart Circ. Physiol.300, H1032–H1043 (2011).
[CrossRef]

V. Bolduc, A. Drouin, M. Gillis, N. Duquette, N. Thorin-Trescases, I. Frayne-Robillard, C. Des Rosiers, J. Tardif, and E. Thorin, “Heart rate-associated mechanical stress impairs carotid but not cerebral artery compliance in dyslipidemic atherosclerotic mice,” Am. J. Physiol. Heart Circ. Physiol. 10.1152/ajpheart.00706.2011 (Sept.2011).
[CrossRef] [PubMed]

Bots, M.

N. van Popele, D. Grobbee, M. Bots, R. Asmar, J. Topouchian, R. Reneman, A. Hoeks, D. van der Kuip, A. Hofman, and J. Witteman, “Association between arterial stiffness and atherosclerosis: the rotterdam study,” Stroke32, 454–460 (2001).
[CrossRef] [PubMed]

Brickman, A.

E. Helzner, J. Luchsinger, N. Scarmeas, S. Cosentino, A. Brickman, M. Glymour, and Y. Stern, “Contribution of vascular risk factors to the progression in alzheimer disease,” Arch. Neurol.66, 343 (2009).
[CrossRef] [PubMed]

Cable, A. E.

Cobb, M.

Cosentino, S.

E. Helzner, J. Luchsinger, N. Scarmeas, S. Cosentino, A. Brickman, M. Glymour, and Y. Stern, “Contribution of vascular risk factors to the progression in alzheimer disease,” Arch. Neurol.66, 343 (2009).
[CrossRef] [PubMed]

Dale, A.

D. Boas, S. Jones, A. Devor, T. Huppert, and A. Dale, “A vascular anatomical network model of the spatio-temporal response to brain activation,” Neuroimage40, 1116–1129 (2008).
[CrossRef] [PubMed]

Dale, A. M.

de la Torre, J. C.

J. C. de la Torre, “Is alzheimer’s disease a neurodegenerative or a vascular disorder? data, dogma, and dialectics,” Lancet Neurol.3, 184–190 (2004).
[CrossRef] [PubMed]

Des Rosiers, C.

V. Bolduc, A. Drouin, M. Gillis, N. Duquette, N. Thorin-Trescases, I. Frayne-Robillard, C. Des Rosiers, J. Tardif, and E. Thorin, “Heart rate-associated mechanical stress impairs carotid but not cerebral artery compliance in dyslipidemic atherosclerotic mice,” Am. J. Physiol. Heart Circ. Physiol. 10.1152/ajpheart.00706.2011 (Sept.2011).
[CrossRef] [PubMed]

Devor, A.

D. Boas, S. Jones, A. Devor, T. Huppert, and A. Dale, “A vascular anatomical network model of the spatio-temporal response to brain activation,” Neuroimage40, 1116–1129 (2008).
[CrossRef] [PubMed]

Q. Fang, S. Sakadzic, L. Ruvinskaya, A. Devor, A. M. Dale, and D. A. Boas, “Oxygen advection and diffusion in a three-dimensional vascular anatomical network,” Opt. Express16, 17530–17541 (2008).
[CrossRef] [PubMed]

Drouin, A.

A. Drouin, V. Bolduc, N. Thorin-Trescases, É. Bélanger, P. Fernandes, E. Baraghis, F. Lesage, M. Gillis, L. Villeneuve, E. Hamel, G. Ferland, and E. Thorin, “Catechin treatment improves cerebrovascular flow-mediated dilation and learning abilities in atherosclerotic mice,” Am. J. Physiol. Heart Circ. Physiol.300, H1032–H1043 (2011).
[CrossRef]

V. Bolduc, A. Drouin, M. Gillis, N. Duquette, N. Thorin-Trescases, I. Frayne-Robillard, C. Des Rosiers, J. Tardif, and E. Thorin, “Heart rate-associated mechanical stress impairs carotid but not cerebral artery compliance in dyslipidemic atherosclerotic mice,” Am. J. Physiol. Heart Circ. Physiol. 10.1152/ajpheart.00706.2011 (Sept.2011).
[CrossRef] [PubMed]

Duker, J.

Duquette, N.

V. Bolduc, A. Drouin, M. Gillis, N. Duquette, N. Thorin-Trescases, I. Frayne-Robillard, C. Des Rosiers, J. Tardif, and E. Thorin, “Heart rate-associated mechanical stress impairs carotid but not cerebral artery compliance in dyslipidemic atherosclerotic mice,” Am. J. Physiol. Heart Circ. Physiol. 10.1152/ajpheart.00706.2011 (Sept.2011).
[CrossRef] [PubMed]

Ebner, F.

C. Schaffer, B. Friedman, N. Nishimura, L. Schroeder, P. Tsai, F. Ebner, P. Lyden, and D. Kleinfeld, “Two-photon imaging of cortical surface microvessels reveals a robust redistribution in blood flow after vascular occlusion,” PLoS Biol.4, e22 (2006).
[CrossRef]

Evans, D.

L. Hebert, P. Scherr, J. Bienias, D. Bennett, and D. Evans, “Alzheimer disease in the us population: prevalence estimates using the 2000 census,” Arch. Neurol.60, 1119–1122 (2003).
[CrossRef] [PubMed]

Fang, Q.

Ferland, G.

A. Drouin, V. Bolduc, N. Thorin-Trescases, É. Bélanger, P. Fernandes, E. Baraghis, F. Lesage, M. Gillis, L. Villeneuve, E. Hamel, G. Ferland, and E. Thorin, “Catechin treatment improves cerebrovascular flow-mediated dilation and learning abilities in atherosclerotic mice,” Am. J. Physiol. Heart Circ. Physiol.300, H1032–H1043 (2011).
[CrossRef]

Fernandes, P.

A. Drouin, V. Bolduc, N. Thorin-Trescases, É. Bélanger, P. Fernandes, E. Baraghis, F. Lesage, M. Gillis, L. Villeneuve, E. Hamel, G. Ferland, and E. Thorin, “Catechin treatment improves cerebrovascular flow-mediated dilation and learning abilities in atherosclerotic mice,” Am. J. Physiol. Heart Circ. Physiol.300, H1032–H1043 (2011).
[CrossRef]

Frayne-Robillard, I.

V. Bolduc, A. Drouin, M. Gillis, N. Duquette, N. Thorin-Trescases, I. Frayne-Robillard, C. Des Rosiers, J. Tardif, and E. Thorin, “Heart rate-associated mechanical stress impairs carotid but not cerebral artery compliance in dyslipidemic atherosclerotic mice,” Am. J. Physiol. Heart Circ. Physiol. 10.1152/ajpheart.00706.2011 (Sept.2011).
[CrossRef] [PubMed]

Friedman, B.

C. Schaffer, B. Friedman, N. Nishimura, L. Schroeder, P. Tsai, F. Ebner, P. Lyden, and D. Kleinfeld, “Two-photon imaging of cortical surface microvessels reveals a robust redistribution in blood flow after vascular occlusion,” PLoS Biol.4, e22 (2006).
[CrossRef]

Fujimoto, J.

Fujimoto, J. G.

Fukumura, D.

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

Gaehtgens, P.

A. Pries, D. Neuhaus, and P. Gaehtgens, “Blood viscosity in tube flow: dependence on diameter and hematocrit,” Am. J. Physiol. Heart Circ. Physiol.263, H1770–H1778 (1992).

Gillis, M.

A. Drouin, V. Bolduc, N. Thorin-Trescases, É. Bélanger, P. Fernandes, E. Baraghis, F. Lesage, M. Gillis, L. Villeneuve, E. Hamel, G. Ferland, and E. Thorin, “Catechin treatment improves cerebrovascular flow-mediated dilation and learning abilities in atherosclerotic mice,” Am. J. Physiol. Heart Circ. Physiol.300, H1032–H1043 (2011).
[CrossRef]

V. Bolduc, A. Drouin, M. Gillis, N. Duquette, N. Thorin-Trescases, I. Frayne-Robillard, C. Des Rosiers, J. Tardif, and E. Thorin, “Heart rate-associated mechanical stress impairs carotid but not cerebral artery compliance in dyslipidemic atherosclerotic mice,” Am. J. Physiol. Heart Circ. Physiol. 10.1152/ajpheart.00706.2011 (Sept.2011).
[CrossRef] [PubMed]

Glymour, M.

E. Helzner, J. Luchsinger, N. Scarmeas, S. Cosentino, A. Brickman, M. Glymour, and Y. Stern, “Contribution of vascular risk factors to the progression in alzheimer disease,” Arch. Neurol.66, 343 (2009).
[CrossRef] [PubMed]

Gorczynska, I.

Grobbee, D.

N. van Popele, D. Grobbee, M. Bots, R. Asmar, J. Topouchian, R. Reneman, A. Hoeks, D. van der Kuip, A. Hofman, and J. Witteman, “Association between arterial stiffness and atherosclerosis: the rotterdam study,” Stroke32, 454–460 (2001).
[CrossRef] [PubMed]

Gruber, A.

Hamel, E.

A. Drouin, V. Bolduc, N. Thorin-Trescases, É. Bélanger, P. Fernandes, E. Baraghis, F. Lesage, M. Gillis, L. Villeneuve, E. Hamel, G. Ferland, and E. Thorin, “Catechin treatment improves cerebrovascular flow-mediated dilation and learning abilities in atherosclerotic mice,” Am. J. Physiol. Heart Circ. Physiol.300, H1032–H1043 (2011).
[CrossRef]

Hanson, S. R.

Hebert, L.

L. Hebert, P. Scherr, J. Bienias, D. Bennett, and D. Evans, “Alzheimer disease in the us population: prevalence estimates using the 2000 census,” Arch. Neurol.60, 1119–1122 (2003).
[CrossRef] [PubMed]

Helzner, E.

E. Helzner, J. Luchsinger, N. Scarmeas, S. Cosentino, A. Brickman, M. Glymour, and Y. Stern, “Contribution of vascular risk factors to the progression in alzheimer disease,” Arch. Neurol.66, 343 (2009).
[CrossRef] [PubMed]

Hoeks, A.

N. van Popele, D. Grobbee, M. Bots, R. Asmar, J. Topouchian, R. Reneman, A. Hoeks, D. van der Kuip, A. Hofman, and J. Witteman, “Association between arterial stiffness and atherosclerosis: the rotterdam study,” Stroke32, 454–460 (2001).
[CrossRef] [PubMed]

Hofman, A.

N. van Popele, D. Grobbee, M. Bots, R. Asmar, J. Topouchian, R. Reneman, A. Hoeks, D. van der Kuip, A. Hofman, and J. Witteman, “Association between arterial stiffness and atherosclerosis: the rotterdam study,” Stroke32, 454–460 (2001).
[CrossRef] [PubMed]

Huppert, T.

D. Boas, S. Jones, A. Devor, T. Huppert, and A. Dale, “A vascular anatomical network model of the spatio-temporal response to brain activation,” Neuroimage40, 1116–1129 (2008).
[CrossRef] [PubMed]

Hurst, S.

Iadecola, C.

C. Iadecola, “Neurovascular regulation in the normal brain and in alzheimer’s disease,” Nat. Rev. Neurosci.5, 347–360 (2004).
[CrossRef] [PubMed]

Jacques, S. L.

Jain, R.

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

Jia, Y.

Y. Jia, L. An, and R. Wang, “Label-free and highly sensitive optical imaging of detailed microcirculation within meninges and cortex in mice with the cranium left intact,” J. Biomed. Opt.15, 030510 (2010).
[CrossRef] [PubMed]

Jiang, J. Y.

Jones, S.

D. Boas, S. Jones, A. Devor, T. Huppert, and A. Dale, “A vascular anatomical network model of the spatio-temporal response to brain activation,” Neuroimage40, 1116–1129 (2008).
[CrossRef] [PubMed]

Kasai, C.

C. Kasai, K. Namekawa, A. Koyano, and R. Omoto, “Real-time two-dimensional blood flow imaging using an autocorrelation technique,” IEEE Trans. Sonics Ultrason.32, 458–464 (1985).

Kleinfeld, D.

C. Schaffer, B. Friedman, N. Nishimura, L. Schroeder, P. Tsai, F. Ebner, P. Lyden, and D. Kleinfeld, “Two-photon imaging of cortical surface microvessels reveals a robust redistribution in blood flow after vascular occlusion,” PLoS Biol.4, e22 (2006).
[CrossRef]

Ko, T.

Kowalczyk, A.

Koyano, A.

C. Kasai, K. Namekawa, A. Koyano, and R. Omoto, “Real-time two-dimensional blood flow imaging using an autocorrelation technique,” IEEE Trans. Sonics Ultrason.32, 458–464 (1985).

Lanning, R.

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

Lesage, F.

A. Drouin, V. Bolduc, N. Thorin-Trescases, É. Bélanger, P. Fernandes, E. Baraghis, F. Lesage, M. Gillis, L. Villeneuve, E. Hamel, G. Ferland, and E. Thorin, “Catechin treatment improves cerebrovascular flow-mediated dilation and learning abilities in atherosclerotic mice,” Am. J. Physiol. Heart Circ. Physiol.300, H1032–H1043 (2011).
[CrossRef]

Li, P.

T. Murphy, P. Li, K. Betts, and R. Liu, “Two-photon imaging of stroke onset in vivo reveals that nmda-receptor independent ischemic depolarization is the major cause of rapid reversible damage to dendrites and spines,” J. Neurosci.28, 1756–1772 (2008).
[CrossRef]

Li, X.

Liu, R.

T. Murphy, P. Li, K. Betts, and R. Liu, “Two-photon imaging of stroke onset in vivo reveals that nmda-receptor independent ischemic depolarization is the major cause of rapid reversible damage to dendrites and spines,” J. Neurosci.28, 1756–1772 (2008).
[CrossRef]

Luchsinger, J.

E. Helzner, J. Luchsinger, N. Scarmeas, S. Cosentino, A. Brickman, M. Glymour, and Y. Stern, “Contribution of vascular risk factors to the progression in alzheimer disease,” Arch. Neurol.66, 343 (2009).
[CrossRef] [PubMed]

Lyden, P.

C. Schaffer, B. Friedman, N. Nishimura, L. Schroeder, P. Tsai, F. Ebner, P. Lyden, and D. Kleinfeld, “Two-photon imaging of cortical surface microvessels reveals a robust redistribution in blood flow after vascular occlusion,” PLoS Biol.4, e22 (2006).
[CrossRef]

Ma, Z.

MacDonald, D.

Munn, L.

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

Murphy, T.

T. Murphy, P. Li, K. Betts, and R. Liu, “Two-photon imaging of stroke onset in vivo reveals that nmda-receptor independent ischemic depolarization is the major cause of rapid reversible damage to dendrites and spines,” J. Neurosci.28, 1756–1772 (2008).
[CrossRef]

Namekawa, K.

C. Kasai, K. Namekawa, A. Koyano, and R. Omoto, “Real-time two-dimensional blood flow imaging using an autocorrelation technique,” IEEE Trans. Sonics Ultrason.32, 458–464 (1985).

Neuhaus, D.

A. Pries, D. Neuhaus, and P. Gaehtgens, “Blood viscosity in tube flow: dependence on diameter and hematocrit,” Am. J. Physiol. Heart Circ. Physiol.263, H1770–H1778 (1992).

Nishimura, N.

C. Schaffer, B. Friedman, N. Nishimura, L. Schroeder, P. Tsai, F. Ebner, P. Lyden, and D. Kleinfeld, “Two-photon imaging of cortical surface microvessels reveals a robust redistribution in blood flow after vascular occlusion,” PLoS Biol.4, e22 (2006).
[CrossRef]

Omoto, R.

C. Kasai, K. Namekawa, A. Koyano, and R. Omoto, “Real-time two-dimensional blood flow imaging using an autocorrelation technique,” IEEE Trans. Sonics Ultrason.32, 458–464 (1985).

Padera, T.

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

Pries, A.

A. Pries, D. Neuhaus, and P. Gaehtgens, “Blood viscosity in tube flow: dependence on diameter and hematocrit,” Am. J. Physiol. Heart Circ. Physiol.263, H1770–H1778 (1992).

Radhakrishnan, H.

Ren, H.

Reneman, R.

N. van Popele, D. Grobbee, M. Bots, R. Asmar, J. Topouchian, R. Reneman, A. Hoeks, D. van der Kuip, A. Hofman, and J. Witteman, “Association between arterial stiffness and atherosclerosis: the rotterdam study,” Stroke32, 454–460 (2001).
[CrossRef] [PubMed]

Ruvinskaya, L.

Ruvinskaya, S.

Sakadzic, S.

Sakadžic, S.

Scarmeas, N.

E. Helzner, J. Luchsinger, N. Scarmeas, S. Cosentino, A. Brickman, M. Glymour, and Y. Stern, “Contribution of vascular risk factors to the progression in alzheimer disease,” Arch. Neurol.66, 343 (2009).
[CrossRef] [PubMed]

Schaffer, C.

C. Schaffer, B. Friedman, N. Nishimura, L. Schroeder, P. Tsai, F. Ebner, P. Lyden, and D. Kleinfeld, “Two-photon imaging of cortical surface microvessels reveals a robust redistribution in blood flow after vascular occlusion,” PLoS Biol.4, e22 (2006).
[CrossRef]

Scherr, P.

L. Hebert, P. Scherr, J. Bienias, D. Bennett, and D. Evans, “Alzheimer disease in the us population: prevalence estimates using the 2000 census,” Arch. Neurol.60, 1119–1122 (2003).
[CrossRef] [PubMed]

Schroeder, L.

C. Schaffer, B. Friedman, N. Nishimura, L. Schroeder, P. Tsai, F. Ebner, P. Lyden, and D. Kleinfeld, “Two-photon imaging of cortical surface microvessels reveals a robust redistribution in blood flow after vascular occlusion,” PLoS Biol.4, e22 (2006).
[CrossRef]

Srinivasan, V.

Srinivasan, V. J.

Stern, Y.

E. Helzner, J. Luchsinger, N. Scarmeas, S. Cosentino, A. Brickman, M. Glymour, and Y. Stern, “Contribution of vascular risk factors to the progression in alzheimer disease,” Arch. Neurol.66, 343 (2009).
[CrossRef] [PubMed]

Stylianopoulos, T.

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

Sun, T.

Tardif, J.

V. Bolduc, A. Drouin, M. Gillis, N. Duquette, N. Thorin-Trescases, I. Frayne-Robillard, C. Des Rosiers, J. Tardif, and E. Thorin, “Heart rate-associated mechanical stress impairs carotid but not cerebral artery compliance in dyslipidemic atherosclerotic mice,” Am. J. Physiol. Heart Circ. Physiol. 10.1152/ajpheart.00706.2011 (Sept.2011).
[CrossRef] [PubMed]

Tearney, G.

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

Thorin, E.

A. Drouin, V. Bolduc, N. Thorin-Trescases, É. Bélanger, P. Fernandes, E. Baraghis, F. Lesage, M. Gillis, L. Villeneuve, E. Hamel, G. Ferland, and E. Thorin, “Catechin treatment improves cerebrovascular flow-mediated dilation and learning abilities in atherosclerotic mice,” Am. J. Physiol. Heart Circ. Physiol.300, H1032–H1043 (2011).
[CrossRef]

V. Bolduc, A. Drouin, M. Gillis, N. Duquette, N. Thorin-Trescases, I. Frayne-Robillard, C. Des Rosiers, J. Tardif, and E. Thorin, “Heart rate-associated mechanical stress impairs carotid but not cerebral artery compliance in dyslipidemic atherosclerotic mice,” Am. J. Physiol. Heart Circ. Physiol. 10.1152/ajpheart.00706.2011 (Sept.2011).
[CrossRef] [PubMed]

Thorin-Trescases, N.

A. Drouin, V. Bolduc, N. Thorin-Trescases, É. Bélanger, P. Fernandes, E. Baraghis, F. Lesage, M. Gillis, L. Villeneuve, E. Hamel, G. Ferland, and E. Thorin, “Catechin treatment improves cerebrovascular flow-mediated dilation and learning abilities in atherosclerotic mice,” Am. J. Physiol. Heart Circ. Physiol.300, H1032–H1043 (2011).
[CrossRef]

V. Bolduc, A. Drouin, M. Gillis, N. Duquette, N. Thorin-Trescases, I. Frayne-Robillard, C. Des Rosiers, J. Tardif, and E. Thorin, “Heart rate-associated mechanical stress impairs carotid but not cerebral artery compliance in dyslipidemic atherosclerotic mice,” Am. J. Physiol. Heart Circ. Physiol. 10.1152/ajpheart.00706.2011 (Sept.2011).
[CrossRef] [PubMed]

Topouchian, J.

N. van Popele, D. Grobbee, M. Bots, R. Asmar, J. Topouchian, R. Reneman, A. Hoeks, D. van der Kuip, A. Hofman, and J. Witteman, “Association between arterial stiffness and atherosclerosis: the rotterdam study,” Stroke32, 454–460 (2001).
[CrossRef] [PubMed]

Tsai, P.

C. Schaffer, B. Friedman, N. Nishimura, L. Schroeder, P. Tsai, F. Ebner, P. Lyden, and D. Kleinfeld, “Two-photon imaging of cortical surface microvessels reveals a robust redistribution in blood flow after vascular occlusion,” PLoS Biol.4, e22 (2006).
[CrossRef]

Tyrrell, J.

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

Vakoc, B.

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

van der Kuip, D.

N. van Popele, D. Grobbee, M. Bots, R. Asmar, J. Topouchian, R. Reneman, A. Hoeks, D. van der Kuip, A. Hofman, and J. Witteman, “Association between arterial stiffness and atherosclerosis: the rotterdam study,” Stroke32, 454–460 (2001).
[CrossRef] [PubMed]

van Popele, N.

N. van Popele, D. Grobbee, M. Bots, R. Asmar, J. Topouchian, R. Reneman, A. Hoeks, D. van der Kuip, A. Hofman, and J. Witteman, “Association between arterial stiffness and atherosclerosis: the rotterdam study,” Stroke32, 454–460 (2001).
[CrossRef] [PubMed]

Villeneuve, L.

A. Drouin, V. Bolduc, N. Thorin-Trescases, É. Bélanger, P. Fernandes, E. Baraghis, F. Lesage, M. Gillis, L. Villeneuve, E. Hamel, G. Ferland, and E. Thorin, “Catechin treatment improves cerebrovascular flow-mediated dilation and learning abilities in atherosclerotic mice,” Am. J. Physiol. Heart Circ. Physiol.300, H1032–H1043 (2011).
[CrossRef]

Wang, R.

Y. Jia, L. An, and R. Wang, “Label-free and highly sensitive optical imaging of detailed microcirculation within meninges and cortex in mice with the cranium left intact,” J. Biomed. Opt.15, 030510 (2010).
[CrossRef] [PubMed]

Wang, R. K.

Witteman, J.

N. van Popele, D. Grobbee, M. Bots, R. Asmar, J. Topouchian, R. Reneman, A. Hoeks, D. van der Kuip, A. Hofman, and J. Witteman, “Association between arterial stiffness and atherosclerosis: the rotterdam study,” Stroke32, 454–460 (2001).
[CrossRef] [PubMed]

Wojtkowski, M.

Wu, W.

Yaseen, M. A.

Am. J. Physiol. Heart Circ. Physiol. (2)

A. Pries, D. Neuhaus, and P. Gaehtgens, “Blood viscosity in tube flow: dependence on diameter and hematocrit,” Am. J. Physiol. Heart Circ. Physiol.263, H1770–H1778 (1992).

A. Drouin, V. Bolduc, N. Thorin-Trescases, É. Bélanger, P. Fernandes, E. Baraghis, F. Lesage, M. Gillis, L. Villeneuve, E. Hamel, G. Ferland, and E. Thorin, “Catechin treatment improves cerebrovascular flow-mediated dilation and learning abilities in atherosclerotic mice,” Am. J. Physiol. Heart Circ. Physiol.300, H1032–H1043 (2011).
[CrossRef]

Arch. Neurol. (2)

L. Hebert, P. Scherr, J. Bienias, D. Bennett, and D. Evans, “Alzheimer disease in the us population: prevalence estimates using the 2000 census,” Arch. Neurol.60, 1119–1122 (2003).
[CrossRef] [PubMed]

E. Helzner, J. Luchsinger, N. Scarmeas, S. Cosentino, A. Brickman, M. Glymour, and Y. Stern, “Contribution of vascular risk factors to the progression in alzheimer disease,” Arch. Neurol.66, 343 (2009).
[CrossRef] [PubMed]

IEEE Trans. Sonics Ultrason. (1)

C. Kasai, K. Namekawa, A. Koyano, and R. Omoto, “Real-time two-dimensional blood flow imaging using an autocorrelation technique,” IEEE Trans. Sonics Ultrason.32, 458–464 (1985).

J. Biomed. Opt. (1)

Y. Jia, L. An, and R. Wang, “Label-free and highly sensitive optical imaging of detailed microcirculation within meninges and cortex in mice with the cranium left intact,” J. Biomed. Opt.15, 030510 (2010).
[CrossRef] [PubMed]

J. Neurosci. (1)

T. Murphy, P. Li, K. Betts, and R. Liu, “Two-photon imaging of stroke onset in vivo reveals that nmda-receptor independent ischemic depolarization is the major cause of rapid reversible damage to dendrites and spines,” J. Neurosci.28, 1756–1772 (2008).
[CrossRef]

Lancet Neurol. (1)

J. C. de la Torre, “Is alzheimer’s disease a neurodegenerative or a vascular disorder? data, dogma, and dialectics,” Lancet Neurol.3, 184–190 (2004).
[CrossRef] [PubMed]

Nat. Med. (1)

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

Nat. Rev. Neurosci. (1)

C. Iadecola, “Neurovascular regulation in the normal brain and in alzheimer’s disease,” Nat. Rev. Neurosci.5, 347–360 (2004).
[CrossRef] [PubMed]

Neuroimage (1)

D. Boas, S. Jones, A. Devor, T. Huppert, and A. Dale, “A vascular anatomical network model of the spatio-temporal response to brain activation,” Neuroimage40, 1116–1129 (2008).
[CrossRef] [PubMed]

Opt. Express (4)

Opt. Lett. (2)

PLoS Biol. (1)

C. Schaffer, B. Friedman, N. Nishimura, L. Schroeder, P. Tsai, F. Ebner, P. Lyden, and D. Kleinfeld, “Two-photon imaging of cortical surface microvessels reveals a robust redistribution in blood flow after vascular occlusion,” PLoS Biol.4, e22 (2006).
[CrossRef]

Stroke (1)

N. van Popele, D. Grobbee, M. Bots, R. Asmar, J. Topouchian, R. Reneman, A. Hoeks, D. van der Kuip, A. Hofman, and J. Witteman, “Association between arterial stiffness and atherosclerosis: the rotterdam study,” Stroke32, 454–460 (2001).
[CrossRef] [PubMed]

Other (1)

V. Bolduc, A. Drouin, M. Gillis, N. Duquette, N. Thorin-Trescases, I. Frayne-Robillard, C. Des Rosiers, J. Tardif, and E. Thorin, “Heart rate-associated mechanical stress impairs carotid but not cerebral artery compliance in dyslipidemic atherosclerotic mice,” Am. J. Physiol. Heart Circ. Physiol. 10.1152/ajpheart.00706.2011 (Sept.2011).
[CrossRef] [PubMed]

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Figures (7)

Fig. 1
Fig. 1

Schematic of OCT system design, SLED : Super Luminescent Diode, PC : Polarization controllers, P : Dispersion compension prisms, VND : Variable Neutral Density Filter, M : Reference Mirror, G : Dual galvanometer scanners, f : sample arm telescope lenses, O : Objective, S : Sample, VPHG : Volume Phase Holographic grating, FT : F-Theta Lens, CCD : CCD Line Camera.

Fig. 2
Fig. 2

Reconstruction of the cardiac profile of an artery on a WT mouse. A : The first 7 reconstructed frames over the same line. B : Average of all 400 frames showing blood vessel underneath the cranium. Decorrelation causes blurring underneath the main blood vessel and reveal the position of other smaller vessels in the frame. C : The corresponding ECG signal from these frames. D : The time after ECG peak is used to place each A-line of a frame in a 3D matrix by using it’s position and time value. E : Superimposition of the 7 frames in the reconstructed matrix, with 400 frames and with proper desynchronized condition, the matrix is filled. F : After reconstruction and placement of all 400 frames, the full 3D matrix was obtained. A slice was taken at the depth indicated by the red line on figure B, this slice had dimensions of 800 μm (position along r axis) by 111 ms (time in cardiac cycle). The percent change of Doppler speed from the minimum for each position was then plotted on figure F. For the positions where the vessel was present a change up to 30% high can be observed (white spot on figure) when the blood pulse arrives from the heart. A corresponding increase in Doppler speed is also observed at the same cardiac time at other positions on the line albeit to a weaker extent, this suggests the presence of smaller vessels.

Fig. 3
Fig. 3

Calculation of flow pulsatility in a single artery on a WT mouse. A. Two perpendicular slices of the artery are measured. The images present the average flow over the whole cardiac cycle. The flow is in red-blue overlaid on the grayscale structure. The artery is directly underneath the cranium and the region of interest is circled. B. Filtered blood speed profile in the region of interest. The Doppler speed is averaged in the region of interest for each time point in the cardiac cycle. The average speed is ∼ 0.21mm/s in the X slice region of interest. The average speed in the Y slice is ∼ 73% of the speed in the X slice due to different ROI coverages. The cardiac cycle profile is identical in both slices confirming the variation is due to cardiac activity. Variation between the maximum speed (systolic) and the minimum speed (diastolic) is calculated. Variability (solid vertical lines) is the standard deviation divided by the mean.

Fig. 4
Fig. 4

Example of blood flow measurement in a branching artery A. Top projection of the measured volume presenting a branching artery, diameter is 124 μm. The artery is only slightly tilted from the horizontal plane. B. Flow passing through the selected area at different depths. The maximum flow is where the artery is completely contained within the area and corresponds to it’s quantitative flow C. Blood flow as a function of vessel diameter, results from 20 ATX and 31 WT vessels, vessels larger then 150 μm not shown. No significant difference in the blood flow distribution is observed between the two groups.

Fig. 5
Fig. 5

Blood speed change over the cardiac cycle. Only slices where the X and Y cardiac cycle profiles matched were retained. A. Variability of the blood speed over the cardiac cycle. B. Normalized blood speed change between the maximum and minimum value in the cardiac cycle. C. Compliance estimator. Error bars = SEM.

Fig. 6
Fig. 6

Angiography results from 8 different animals. First row ATX animals and second row WT animals. The black bar has length of 200 μm. The results are displayed in a log scale. Similar vessel sizes are compared between the two groups.

Fig. 7
Fig. 7

A. Vascular anatomical network simulated. The dotted lines and the red box represent respectively the larger and the smaller vessels. These are the vascular segments for which the compliance parameter is modified during the simulation. B. Effect of changes in pressure wave amplitude at the entry of the VAN. small and large vessels change their pulsatility proportionally. C. Effect of lowering the compliance (increasing the parameter βM) of small vessels while leaving the larger vessels at βA = 2, D. Effect of increasing the compliance of larger vessels (βA = 1) while leaving smaller vasculature intact. E. Effect of increasing compliance of both larger and smaller vessels (βA = βM = 1)

Tables (1)

Tables Icon

Table 1. Vascular segment parameters

Equations (15)

Equations on this page are rendered with MathJax. Learn more.

δ P = Φ 8 η L π r 4
P P A
δ P = α P A
α P A = Φ 8 η L π r 4
α P A + 𝒜 ( C I ) = Φ 8 η L π r 4
C = Δ V / Δ P A = V s V d P s A P d A
C = A s A d ( Φ s / A s 2 Φ d / A d 2 ) α π 8 η
C 8 π α = 1 η δ A A d A d ( δ Φ Φ s / ( δ A 2 A d 2 ) Φ d / A d 2 ) = 1 η A d 3 ( δ A 1 ) Φ d ( δ Φ / δ A 2 1 )
C ^ = A d 3 Φ d η δ A 2 ( δ A 1 ) ( δ Φ δ A 2 ) = A d 3 Φ d η δ A ( δ A 1 ) δ v ¯ δ A
Δ P ( t ) = R ( t ) Q ( t )
P i ( t ) P I C = ( V i ( t ) A 0 , i ) β
Δ P A = ( V i ( t d ) A 0 , i ) β + β Δ V i A 0 , i ( V i ( t d ) A 0 , i ) β 1 ( V i ( t d ) A 0 , i ) β
Δ P A = β Δ V i A 0 , i ( V i ( t d ) A 0 , i ) β 1
1 C = β A 0 , i ( V i ( t d ) A 0 , i ) β 1
P art ( t ) = P art 0 ( 1 + Δ P e ( t T offset σ T ) 2 e 1 )

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