Abstract

The integrity of the blood brain barrier (BBB) can contribute to the development of many brain disorders. We evaluate laser speckle contrast imaging (LSCI) as an intrinsic modality for monitoring BBB disruptions through simultaneous fluorescence and LSCI with vertical cavity surface emitting lasers (VCSELs). We demonstrated that drug-induced BBB opening was associated with a relative change of the arterial and venous blood velocities. Cross-sectional flow velocity ratio (veins/arteries) decreased significantly in rats treated with BBB-opening drugs, ≤0.81 of initial values.

© 2013 OSA

Full Article  |  PDF Article

References

  • View by:
  • |
  • |
  • |

  1. N. J. Abbott, A. A. K. Patabendige, D. E. M. Dolman, S. R. Yusof, and D. J. Begley, “Structure and function of the blood-brain barrier,” Neurobiol. Dis.37(1), 13–25 (2010).
  2. R. N. Kalaria, “The Blood-Brain Barrier and Cerebrovascular Pathology in Alzheimer’s Disease,” Ann. N. Y. Acad. Sci.893, 113–125 (1999).
  3. M. B. Shlosberg, D. Kaufer, and A. Friedman, “Blood-brain barrier breakdown as a therapeutic target in traumatic brain injury,” Nat. Rev. Neurol.6, 10 (2010).
  4. O. Tomkins, I. Shelef, I. Kaizerman, A. Eliushin, Z. Afawi, A. Misk, M. Gidon, A. Cohen, D. Zumsteg, and A. Friedman, “Blood-brain barrier disruption in post-traumatic epilepsy,” J. Neurol. Neurosurg. Psychiatry79(7), 774–777 (2008).
  5. E. Seiffert, J. P. Dreier, S. Ivens, I. Bechmann, O. Tomkins, U. Heinemann, and A. Friedman, “Lasting Blood-Brain Barrier Disruption Induces Epileptic Focus in the Rat Somatosensory Cortex,” J. Neurosci.24(36), 7829–7836 (2004).
  6. W. H. Oldendorf, “Blood-Brain Barrier Permeability to Drugs,” Annu. Rev. Pharmacol.14(1), 239–248 (1974).
  7. W. M. Pardridge, “CNS Drug Design Based on Principles of Blood-Brain Barrier Transport,” J. Neurochem.70(5), 1781–1792 (1998).
  8. M. Kinoshita, N. McDannold, F. A. Jolesz, and K. Hynynen, “Noninvasive localized delivery of Herceptin to the mouse brain by MRI-guided focused ultrasound-induced blood-brain barrier disruption,” Proc. Natl. Acad. Sci. U.S.A.103(31), 11719–11723 (2006).
  9. S. I. Rapoport, “Osmotic Opening of the Blood-Brain Barrier: Principles, Mechanism, and Therapeutic Applications,” Cell. Mol. Neurobiol.20(2), 217–230 (2000).
  10. N. Sheikov, N. McDannold, N. Vykhodtseva, F. Jolesz, and K. Hynynen, “Cellular mechanisms of the blood-brain barrier opening induced by ultrasound in presence of microbubbles,” Ultrasound Med. Biol.30(7), 979–989 (2004).
  11. Q. Jiang, J. R. Ewing, G. L. Ding, L. Zhang, Z. G. Zhang, L. Li, P. Whitton, M. Lu, J. Hu, Q. J. Li, R. A. Knight, and M. Chopp, “Quantitative evaluation of BBB permeability after embolic stroke in rat using MRI,” J. Cereb. Blood Flow Metab.25(5), 583–592 (2005).
  12. P. S. Tofts and A. G. Kermode, “Measurement of the blood-brain barrier permeability and leakage space using dynamic MR imaging. 1. Fundamental concepts,” Magn. Reson. Med.17(2), 357–367 (1991).
  13. S. Taheri, E. Candelario-Jalil, E. Y. Estrada, and G. A. Rosenberg, “Spatiotemporal Correlations between Blood-Brain Barrier Permeability and Apparent Diffusion Coefficient in a Rat Model of Ischemic Stroke,” PLoS ONE4(8), e6597 (2009).
  14. M. Wintermark, J. Hom, J. Dankbaar, J. Bredno, and M. Olszewski, “Blood-brain barrier permeability: quantification with computed tomography and application in acute ischemic stroke,” Dear Friends53, 3 (2009).
  15. L. Ruiz-Valdepeñas, J. A. Martínez-Orgado, C. Benito, A. Millán, R. M. Tolón, and J. Romero, “Cannabidiol reduces lipopolysaccharide-induced vascular changes and inflammation in the mouse brain: an intravital microscopy study,” J. Neuroinflammation8(1), 5 (2011).
  16. D.-E. Kim, D. Schellingerhout, F. A. Jaffer, R. Weissleder, and C. H. Tung, “Near-infrared fluorescent imaging of cerebral thrombi and blood-brain barrier disruption in a mouse model of cerebral venous sinus thrombosis,” J. Cereb. Blood Flow Metab.25(2), 226–233 (2005).
  17. E. E. Cho, J. Drazic, M. Ganguly, B. Stefanovic, and K. Hynynen, “Two-photon fluorescence microscopy study of cerebrovascular dynamics in ultrasound-induced blood-brain barrier opening,” J. Cereb. Blood Flow Metab.31(9), 1852–1862 (2011).
  18. O. Prager, Y. Chassidim, C. Klein, H. Levi, I. Shelef, and A. Friedman, “Dynamic in vivo imaging of cerebral blood flow and blood-brain barrier permeability,” Neuroimage49(1), 337–344 (2010).
  19. D. A. Boas and A. K. Dunn, “Laser speckle contrast imaging in biomedical optics,” J. Biomed. Opt.15(1), 011109 (2010).
  20. A. Ponticorvo and A. K. Dunn, “How to build a Laser Speckle Contrast Imaging (LSCI) system to monitor blood flow,” J. Vis. Exp. (45): (2010).
  21. S. Yuan, A. Devor, D. A. Boas, and A. K. Dunn, “Determination of optimal exposure time for imaging of blood flow changes with laser speckle contrast imaging,” Appl. Opt.44(10), 1823–1830 (2005).
  22. P. Miao, H. Lu, Q. Liu, Y. Li, and S. Tong, “Laser speckle contrast imaging of cerebral blood flow in freely moving animals,” J. Biomed. Opt.16(9), 090502 (2011).
  23. Y. Atchia, H. Levy, S. Dufour, and O. Levi, “Rapid multiexposure in vivo brain imaging system using vertical cavity surface emitting lasers as a light source,” Appl. Opt.52(7), C64–C71 (2013).
  24. 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).
  25. I. Sigal, Y. Atchia, R. Gad, A. M. Caravaca, D. Conkey, R. Piestun, and O. Levi, “Laser Speckle Contrast Imaging with Extended Depth of Field for Brain Imaging Applications,” in CLEO: Science and Innovations, Imaging & Microscopy I (Optical Society of America, 2013), paper CTu2M.
  26. A. K. Dunn, “Laser Speckle Contrast Imaging of Cerebral Blood Flow,” Ann. Biomed. Eng.40(2), 367–377 (2012).
  27. J. D. Briers, “Laser Doppler, speckle and related techniques for blood perfusion mapping and imaging,” Physiol. Meas.22(4), R35–R66 (2001).
  28. L. M. Richards, E. L. Towle, D. J. Fox, and A. K. Dunn, “Laser Speckle Imaging of Cerebral Blood Flow,” in Optical Methods and Instrumentation in Brain Imaging and Therapy (Springer New York, 2013), pp. 117–136.
  29. M. Kaiser, A. Yafi, M. Cinat, B. Choi, and A. J. Durkin, “Noninvasive assessment of burn wound severity using optical technology: a review of current and future modalities,” Burns37(3), 377–386 (2011).
  30. H. Levy, D. Ringuette, and O. Levi, “Rapid monitoring of cerebral ischemia dynamics using laser-based optical imaging of blood oxygenation and flow,” Biomed. Opt. Express3(4), 777–791 (2012).
  31. E. A. Munro, H. Levy, D. Ringuette, T. D. O’Sullivan, and O. Levi, “Multi-modality optical neural imaging using coherence control of VCSELs,” Opt. Express19(11), 10747–10761 (2011).
  32. M. B. Bouchard, B. R. Chen, S. A. Burgess, and E. M. Hillman, “Ultra-fast multispectral optical imaging of cortical oxygenation, blood flow, and intracellular calcium dynamics,” Opt. Express17(18), 15670–15678 (2009).
  33. J. Greenwood, J. Adu, A. J. Davey, N. J. Abbott, and M. W. Bradbury, “The effect of bile salts on the permeability and ultrastructure of the perfused, energy-depleted, rat blood-brain barrier,” J. Cereb. Blood Flow Metab.11(4), 644–654 (1991).
  34. H. Ichikawa and K. Itoh, “Blood-arachnoid barrier disruption in experimental rat meningitis detected using gadolinium-enhancement ratio imaging,” Brain Res.1390, 142–149 (2011).
  35. A. Saria and J. M. Lundberg, “Evans blue fluorescence: quantitative and morphological evaluation of vascular permeability in animal tissues,” J. Neurosci. Methods8(1), 41–49 (1983).
  36. A. Y. Shih, J. D. Driscoll, P. J. Drew, N. Nishimura, C. B. Schaffer, and D. Kleinfeld, “Two-photon microscopy as a tool to study blood flow and neurovascular coupling in the rodent brain,” J. Cereb. Blood Flow Metab.32(7), 1277–1309 (2012).
  37. H. P. Rani, T. W. Sheu, T. M. Chang, and P. C. Liang, “Numerical investigation of non-Newtonian microcirculatory blood flow in hepatic lobule,” J. Biomech.39(3), 551–563 (2006).
  38. L. Grinberg, V. Morozov, D. Fedosov, J. A. Insley, M. E. Papka, K. Kumaran, and G. E. Karniadakis, “A new computational paradigm in multiscale simulations: Application to brain blood flow,” in High Performance Computing, Networking, Storage and Analysis (SC), 2011International Conference for(IEEE, 2011), pp. 1–12.
  39. S. Lorthois, F. Cassot, and F. Lauwers, “Simulation study of brain blood flow regulation by intra-cortical arterioles in an anatomically accurate large human vascular network. Part II: flow variations induced by global or localized modifications of arteriolar diameters,” Neuroimage54(4), 2840–2853 (2011).
  40. S. Lorthois, F. Cassot, and F. Lauwers, “Simulation study of brain blood flow regulation by intra-cortical arterioles in an anatomically accurate large human vascular network: Part I: methodology and baseline flow,” Neuroimage54(2), 1031–1042 (2011).
  41. R. Byron Bird and P. J. Carreau, “A nonlinear viscoelastic model for polymer solutions and melts—I,” Chem. Eng. Sci.23(5), 427–434 (1968).
  42. Y. I. Cho and K. R. Kensey, “Effects of the non-Newtonian viscosity of blood on flows in a diseased arterial vessel. Part 1: Steady flows,” Biorheology28(3-4), 241–262 (1991).
  43. A. Sequeira and J. Janela, “An overview of some mathematical models of blood rheology,” in A Portrait of State-of-the-Art Research at the Technical University of Lisbon(Springer, 2007), pp. 65–87.
  44. B. M. Johnston, P. R. Johnston, S. Corney, and D. Kilpatrick, “Non-Newtonian blood flow in human right coronary arteries: steady state simulations,” J. Biomech.37(5), 709–720 (2004).
  45. K. P. Ivanov, M. K. Kalinina, and Y. I. Levkovich, “Blood flow velocity in capillaries of brain and muscles and its physiological significance,” Microvasc. Res.22(2), 143–155 (1981).
  46. S. M. Stieger, C. F. Caskey, R. H. Adamson, S. Qin, F.-R. E. Curry, E. R. Wisner, and K. W. Ferrara, “Enhancement of vascular permeability with low-frequency contrast-enhanced ultrasound in the chorioallantoic membrane model,” Radiology243(1), 112–121 (2007).
  47. S. Lorthois and F. Lauwers, “Control of brain blood flow by capillaries: a simulation study in an anatomically accurate large human vascular network,” Comput. Methods Biomech. Biomed. Engin. 15(sup1), 66–68 (2012).
  48. M. E. van Raaij, L. Lindvere, A. Dorr, J. He, B. Sahota, F. S. Foster, and B. Stefanovic, “Quantification of blood flow and volume in arterioles and venules of the rat cerebral cortex using functional micro-ultrasound,” Neuroimage63(3), 1030–1037 (2012).
  49. N. Nishimura, N. L. Rosidi, C. Iadecola, and C. B. Schaffer, “Limitations of collateral flow after occlusion of a single cortical penetrating arteriole,” J. Cereb. Blood Flow Metab.30(12), 1914–1927 (2010).
  50. J. Nguyen, N. Nishimura, R. N. Fetcho, C. Iadecola, and C. B. Schaffer, “Occlusion of cortical ascending venules causes blood flow decreases, reversals in flow direction, and vessel dilation in upstream capillaries,” J. Cereb. Blood Flow Metab.31(11), 2243–2254 (2011).
  51. M. B. Lawrence, L. V. McIntire, and S. G. Eskin, “Effect of flow on polymorphonuclear leukocyte/endothelial cell adhesion,” Blood70(5), 1284–1290 (1987).
  52. C. Skilbeck, S. M. Westwood, P. G. Walker, T. David, and G. B. Nash, “Population of the vessel wall by leukocytes binding to P-selectin in a model of disturbed arterial flow,” Arterioscler. Thromb. Vasc. Biol.21(8), 1294–1300 (2001).
  53. B. Arvin, L. F. Neville, F. C. Barone, and G. Z. Feuerstein, “The role of inflammation and cytokines in brain injury,” Neurosci. Biobehav. Rev.20(3), 445–452 (1996).
  54. K. Miyamoto, Y. Ogura, M. Hamada, H. Nishiwaki, N. Hiroshiba, and Y. Honda, “In vivo quantification of leukocyte behavior in the retina during endotoxin-induced uveitis,” Invest. Ophthalmol. Vis. Sci.37(13), 2708–2715 (1996).
  55. M. Bohatschek, A. Werner, and G. Raivich, “Systemic LPS injection leads to granulocyte influx into normal and injured brain: effects of ICAM-1 deficiency,” Exp. Neurol.172(1), 137–152 (2001).
  56. N. Parashurama, T. D. O’Sullivan, A. De La Zerda, P. El Kalassi, S. Cho, H. Liu, R. Teed, H. Levy, J. Rosenberg, Z. Cheng, O. Levi, J. S. Harris, and S. S. Gambhir, “Continuous sensing of tumor-targeted molecular probes with a vertical cavity surface emitting laser-based biosensor,” J. Biomed. Opt.17(11), 117004 (2012).

2013 (1)

2012 (5)

A. K. Dunn, “Laser Speckle Contrast Imaging of Cerebral Blood Flow,” Ann. Biomed. Eng.40(2), 367–377 (2012).

H. Levy, D. Ringuette, and O. Levi, “Rapid monitoring of cerebral ischemia dynamics using laser-based optical imaging of blood oxygenation and flow,” Biomed. Opt. Express3(4), 777–791 (2012).

A. Y. Shih, J. D. Driscoll, P. J. Drew, N. Nishimura, C. B. Schaffer, and D. Kleinfeld, “Two-photon microscopy as a tool to study blood flow and neurovascular coupling in the rodent brain,” J. Cereb. Blood Flow Metab.32(7), 1277–1309 (2012).

M. E. van Raaij, L. Lindvere, A. Dorr, J. He, B. Sahota, F. S. Foster, and B. Stefanovic, “Quantification of blood flow and volume in arterioles and venules of the rat cerebral cortex using functional micro-ultrasound,” Neuroimage63(3), 1030–1037 (2012).

N. Parashurama, T. D. O’Sullivan, A. De La Zerda, P. El Kalassi, S. Cho, H. Liu, R. Teed, H. Levy, J. Rosenberg, Z. Cheng, O. Levi, J. S. Harris, and S. S. Gambhir, “Continuous sensing of tumor-targeted molecular probes with a vertical cavity surface emitting laser-based biosensor,” J. Biomed. Opt.17(11), 117004 (2012).

2011 (9)

J. Nguyen, N. Nishimura, R. N. Fetcho, C. Iadecola, and C. B. Schaffer, “Occlusion of cortical ascending venules causes blood flow decreases, reversals in flow direction, and vessel dilation in upstream capillaries,” J. Cereb. Blood Flow Metab.31(11), 2243–2254 (2011).

S. Lorthois, F. Cassot, and F. Lauwers, “Simulation study of brain blood flow regulation by intra-cortical arterioles in an anatomically accurate large human vascular network. Part II: flow variations induced by global or localized modifications of arteriolar diameters,” Neuroimage54(4), 2840–2853 (2011).

S. Lorthois, F. Cassot, and F. Lauwers, “Simulation study of brain blood flow regulation by intra-cortical arterioles in an anatomically accurate large human vascular network: Part I: methodology and baseline flow,” Neuroimage54(2), 1031–1042 (2011).

E. A. Munro, H. Levy, D. Ringuette, T. D. O’Sullivan, and O. Levi, “Multi-modality optical neural imaging using coherence control of VCSELs,” Opt. Express19(11), 10747–10761 (2011).

P. Miao, H. Lu, Q. Liu, Y. Li, and S. Tong, “Laser speckle contrast imaging of cerebral blood flow in freely moving animals,” J. Biomed. Opt.16(9), 090502 (2011).

M. Kaiser, A. Yafi, M. Cinat, B. Choi, and A. J. Durkin, “Noninvasive assessment of burn wound severity using optical technology: a review of current and future modalities,” Burns37(3), 377–386 (2011).

H. Ichikawa and K. Itoh, “Blood-arachnoid barrier disruption in experimental rat meningitis detected using gadolinium-enhancement ratio imaging,” Brain Res.1390, 142–149 (2011).

E. E. Cho, J. Drazic, M. Ganguly, B. Stefanovic, and K. Hynynen, “Two-photon fluorescence microscopy study of cerebrovascular dynamics in ultrasound-induced blood-brain barrier opening,” J. Cereb. Blood Flow Metab.31(9), 1852–1862 (2011).

L. Ruiz-Valdepeñas, J. A. Martínez-Orgado, C. Benito, A. Millán, R. M. Tolón, and J. Romero, “Cannabidiol reduces lipopolysaccharide-induced vascular changes and inflammation in the mouse brain: an intravital microscopy study,” J. Neuroinflammation8(1), 5 (2011).

2010 (5)

M. B. Shlosberg, D. Kaufer, and A. Friedman, “Blood-brain barrier breakdown as a therapeutic target in traumatic brain injury,” Nat. Rev. Neurol.6, 10 (2010).

N. J. Abbott, A. A. K. Patabendige, D. E. M. Dolman, S. R. Yusof, and D. J. Begley, “Structure and function of the blood-brain barrier,” Neurobiol. Dis.37(1), 13–25 (2010).

O. Prager, Y. Chassidim, C. Klein, H. Levi, I. Shelef, and A. Friedman, “Dynamic in vivo imaging of cerebral blood flow and blood-brain barrier permeability,” Neuroimage49(1), 337–344 (2010).

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

N. Nishimura, N. L. Rosidi, C. Iadecola, and C. B. Schaffer, “Limitations of collateral flow after occlusion of a single cortical penetrating arteriole,” J. Cereb. Blood Flow Metab.30(12), 1914–1927 (2010).

2009 (3)

M. B. Bouchard, B. R. Chen, S. A. Burgess, and E. M. Hillman, “Ultra-fast multispectral optical imaging of cortical oxygenation, blood flow, and intracellular calcium dynamics,” Opt. Express17(18), 15670–15678 (2009).

S. Taheri, E. Candelario-Jalil, E. Y. Estrada, and G. A. Rosenberg, “Spatiotemporal Correlations between Blood-Brain Barrier Permeability and Apparent Diffusion Coefficient in a Rat Model of Ischemic Stroke,” PLoS ONE4(8), e6597 (2009).

M. Wintermark, J. Hom, J. Dankbaar, J. Bredno, and M. Olszewski, “Blood-brain barrier permeability: quantification with computed tomography and application in acute ischemic stroke,” Dear Friends53, 3 (2009).

2008 (1)

O. Tomkins, I. Shelef, I. Kaizerman, A. Eliushin, Z. Afawi, A. Misk, M. Gidon, A. Cohen, D. Zumsteg, and A. Friedman, “Blood-brain barrier disruption in post-traumatic epilepsy,” J. Neurol. Neurosurg. Psychiatry79(7), 774–777 (2008).

2007 (1)

S. M. Stieger, C. F. Caskey, R. H. Adamson, S. Qin, F.-R. E. Curry, E. R. Wisner, and K. W. Ferrara, “Enhancement of vascular permeability with low-frequency contrast-enhanced ultrasound in the chorioallantoic membrane model,” Radiology243(1), 112–121 (2007).

2006 (2)

H. P. Rani, T. W. Sheu, T. M. Chang, and P. C. Liang, “Numerical investigation of non-Newtonian microcirculatory blood flow in hepatic lobule,” J. Biomech.39(3), 551–563 (2006).

M. Kinoshita, N. McDannold, F. A. Jolesz, and K. Hynynen, “Noninvasive localized delivery of Herceptin to the mouse brain by MRI-guided focused ultrasound-induced blood-brain barrier disruption,” Proc. Natl. Acad. Sci. U.S.A.103(31), 11719–11723 (2006).

2005 (3)

D.-E. Kim, D. Schellingerhout, F. A. Jaffer, R. Weissleder, and C. H. Tung, “Near-infrared fluorescent imaging of cerebral thrombi and blood-brain barrier disruption in a mouse model of cerebral venous sinus thrombosis,” J. Cereb. Blood Flow Metab.25(2), 226–233 (2005).

Q. Jiang, J. R. Ewing, G. L. Ding, L. Zhang, Z. G. Zhang, L. Li, P. Whitton, M. Lu, J. Hu, Q. J. Li, R. A. Knight, and M. Chopp, “Quantitative evaluation of BBB permeability after embolic stroke in rat using MRI,” J. Cereb. Blood Flow Metab.25(5), 583–592 (2005).

S. Yuan, A. Devor, D. A. Boas, and A. K. Dunn, “Determination of optimal exposure time for imaging of blood flow changes with laser speckle contrast imaging,” Appl. Opt.44(10), 1823–1830 (2005).

2004 (3)

N. Sheikov, N. McDannold, N. Vykhodtseva, F. Jolesz, and K. Hynynen, “Cellular mechanisms of the blood-brain barrier opening induced by ultrasound in presence of microbubbles,” Ultrasound Med. Biol.30(7), 979–989 (2004).

E. Seiffert, J. P. Dreier, S. Ivens, I. Bechmann, O. Tomkins, U. Heinemann, and A. Friedman, “Lasting Blood-Brain Barrier Disruption Induces Epileptic Focus in the Rat Somatosensory Cortex,” J. Neurosci.24(36), 7829–7836 (2004).

B. M. Johnston, P. R. Johnston, S. Corney, and D. Kilpatrick, “Non-Newtonian blood flow in human right coronary arteries: steady state simulations,” J. Biomech.37(5), 709–720 (2004).

2001 (4)

M. Bohatschek, A. Werner, and G. Raivich, “Systemic LPS injection leads to granulocyte influx into normal and injured brain: effects of ICAM-1 deficiency,” Exp. Neurol.172(1), 137–152 (2001).

C. Skilbeck, S. M. Westwood, P. G. Walker, T. David, and G. B. Nash, “Population of the vessel wall by leukocytes binding to P-selectin in a model of disturbed arterial flow,” Arterioscler. Thromb. Vasc. Biol.21(8), 1294–1300 (2001).

J. D. Briers, “Laser Doppler, speckle and related techniques for blood perfusion mapping and imaging,” Physiol. Meas.22(4), R35–R66 (2001).

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).

2000 (1)

S. I. Rapoport, “Osmotic Opening of the Blood-Brain Barrier: Principles, Mechanism, and Therapeutic Applications,” Cell. Mol. Neurobiol.20(2), 217–230 (2000).

1999 (1)

R. N. Kalaria, “The Blood-Brain Barrier and Cerebrovascular Pathology in Alzheimer’s Disease,” Ann. N. Y. Acad. Sci.893, 113–125 (1999).

1998 (1)

W. M. Pardridge, “CNS Drug Design Based on Principles of Blood-Brain Barrier Transport,” J. Neurochem.70(5), 1781–1792 (1998).

1996 (2)

B. Arvin, L. F. Neville, F. C. Barone, and G. Z. Feuerstein, “The role of inflammation and cytokines in brain injury,” Neurosci. Biobehav. Rev.20(3), 445–452 (1996).

K. Miyamoto, Y. Ogura, M. Hamada, H. Nishiwaki, N. Hiroshiba, and Y. Honda, “In vivo quantification of leukocyte behavior in the retina during endotoxin-induced uveitis,” Invest. Ophthalmol. Vis. Sci.37(13), 2708–2715 (1996).

1991 (3)

Y. I. Cho and K. R. Kensey, “Effects of the non-Newtonian viscosity of blood on flows in a diseased arterial vessel. Part 1: Steady flows,” Biorheology28(3-4), 241–262 (1991).

P. S. Tofts and A. G. Kermode, “Measurement of the blood-brain barrier permeability and leakage space using dynamic MR imaging. 1. Fundamental concepts,” Magn. Reson. Med.17(2), 357–367 (1991).

J. Greenwood, J. Adu, A. J. Davey, N. J. Abbott, and M. W. Bradbury, “The effect of bile salts on the permeability and ultrastructure of the perfused, energy-depleted, rat blood-brain barrier,” J. Cereb. Blood Flow Metab.11(4), 644–654 (1991).

1987 (1)

M. B. Lawrence, L. V. McIntire, and S. G. Eskin, “Effect of flow on polymorphonuclear leukocyte/endothelial cell adhesion,” Blood70(5), 1284–1290 (1987).

1983 (1)

A. Saria and J. M. Lundberg, “Evans blue fluorescence: quantitative and morphological evaluation of vascular permeability in animal tissues,” J. Neurosci. Methods8(1), 41–49 (1983).

1981 (1)

K. P. Ivanov, M. K. Kalinina, and Y. I. Levkovich, “Blood flow velocity in capillaries of brain and muscles and its physiological significance,” Microvasc. Res.22(2), 143–155 (1981).

1974 (1)

W. H. Oldendorf, “Blood-Brain Barrier Permeability to Drugs,” Annu. Rev. Pharmacol.14(1), 239–248 (1974).

1968 (1)

R. Byron Bird and P. J. Carreau, “A nonlinear viscoelastic model for polymer solutions and melts—I,” Chem. Eng. Sci.23(5), 427–434 (1968).

Abbott, N. J.

N. J. Abbott, A. A. K. Patabendige, D. E. M. Dolman, S. R. Yusof, and D. J. Begley, “Structure and function of the blood-brain barrier,” Neurobiol. Dis.37(1), 13–25 (2010).

J. Greenwood, J. Adu, A. J. Davey, N. J. Abbott, and M. W. Bradbury, “The effect of bile salts on the permeability and ultrastructure of the perfused, energy-depleted, rat blood-brain barrier,” J. Cereb. Blood Flow Metab.11(4), 644–654 (1991).

Adamson, R. H.

S. M. Stieger, C. F. Caskey, R. H. Adamson, S. Qin, F.-R. E. Curry, E. R. Wisner, and K. W. Ferrara, “Enhancement of vascular permeability with low-frequency contrast-enhanced ultrasound in the chorioallantoic membrane model,” Radiology243(1), 112–121 (2007).

Adu, J.

J. Greenwood, J. Adu, A. J. Davey, N. J. Abbott, and M. W. Bradbury, “The effect of bile salts on the permeability and ultrastructure of the perfused, energy-depleted, rat blood-brain barrier,” J. Cereb. Blood Flow Metab.11(4), 644–654 (1991).

Afawi, Z.

O. Tomkins, I. Shelef, I. Kaizerman, A. Eliushin, Z. Afawi, A. Misk, M. Gidon, A. Cohen, D. Zumsteg, and A. Friedman, “Blood-brain barrier disruption in post-traumatic epilepsy,” J. Neurol. Neurosurg. Psychiatry79(7), 774–777 (2008).

Arvin, B.

B. Arvin, L. F. Neville, F. C. Barone, and G. Z. Feuerstein, “The role of inflammation and cytokines in brain injury,” Neurosci. Biobehav. Rev.20(3), 445–452 (1996).

Atchia, Y.

Barone, F. C.

B. Arvin, L. F. Neville, F. C. Barone, and G. Z. Feuerstein, “The role of inflammation and cytokines in brain injury,” Neurosci. Biobehav. Rev.20(3), 445–452 (1996).

Bechmann, I.

E. Seiffert, J. P. Dreier, S. Ivens, I. Bechmann, O. Tomkins, U. Heinemann, and A. Friedman, “Lasting Blood-Brain Barrier Disruption Induces Epileptic Focus in the Rat Somatosensory Cortex,” J. Neurosci.24(36), 7829–7836 (2004).

Begley, D. J.

N. J. Abbott, A. A. K. Patabendige, D. E. M. Dolman, S. R. Yusof, and D. J. Begley, “Structure and function of the blood-brain barrier,” Neurobiol. Dis.37(1), 13–25 (2010).

Benito, C.

L. Ruiz-Valdepeñas, J. A. Martínez-Orgado, C. Benito, A. Millán, R. M. Tolón, and J. Romero, “Cannabidiol reduces lipopolysaccharide-induced vascular changes and inflammation in the mouse brain: an intravital microscopy study,” J. Neuroinflammation8(1), 5 (2011).

Boas, D. A.

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

S. Yuan, A. Devor, D. A. Boas, and A. K. Dunn, “Determination of optimal exposure time for imaging of blood flow changes with laser speckle contrast imaging,” Appl. Opt.44(10), 1823–1830 (2005).

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).

Bohatschek, M.

M. Bohatschek, A. Werner, and G. Raivich, “Systemic LPS injection leads to granulocyte influx into normal and injured brain: effects of ICAM-1 deficiency,” Exp. Neurol.172(1), 137–152 (2001).

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).

Bouchard, M. B.

Bradbury, M. W.

J. Greenwood, J. Adu, A. J. Davey, N. J. Abbott, and M. W. Bradbury, “The effect of bile salts on the permeability and ultrastructure of the perfused, energy-depleted, rat blood-brain barrier,” J. Cereb. Blood Flow Metab.11(4), 644–654 (1991).

Bredno, J.

M. Wintermark, J. Hom, J. Dankbaar, J. Bredno, and M. Olszewski, “Blood-brain barrier permeability: quantification with computed tomography and application in acute ischemic stroke,” Dear Friends53, 3 (2009).

Briers, J. D.

J. D. Briers, “Laser Doppler, speckle and related techniques for blood perfusion mapping and imaging,” Physiol. Meas.22(4), R35–R66 (2001).

Burgess, S. A.

Byron Bird, R.

R. Byron Bird and P. J. Carreau, “A nonlinear viscoelastic model for polymer solutions and melts—I,” Chem. Eng. Sci.23(5), 427–434 (1968).

Candelario-Jalil, E.

S. Taheri, E. Candelario-Jalil, E. Y. Estrada, and G. A. Rosenberg, “Spatiotemporal Correlations between Blood-Brain Barrier Permeability and Apparent Diffusion Coefficient in a Rat Model of Ischemic Stroke,” PLoS ONE4(8), e6597 (2009).

Carreau, P. J.

R. Byron Bird and P. J. Carreau, “A nonlinear viscoelastic model for polymer solutions and melts—I,” Chem. Eng. Sci.23(5), 427–434 (1968).

Caskey, C. F.

S. M. Stieger, C. F. Caskey, R. H. Adamson, S. Qin, F.-R. E. Curry, E. R. Wisner, and K. W. Ferrara, “Enhancement of vascular permeability with low-frequency contrast-enhanced ultrasound in the chorioallantoic membrane model,” Radiology243(1), 112–121 (2007).

Cassot, F.

S. Lorthois, F. Cassot, and F. Lauwers, “Simulation study of brain blood flow regulation by intra-cortical arterioles in an anatomically accurate large human vascular network. Part II: flow variations induced by global or localized modifications of arteriolar diameters,” Neuroimage54(4), 2840–2853 (2011).

S. Lorthois, F. Cassot, and F. Lauwers, “Simulation study of brain blood flow regulation by intra-cortical arterioles in an anatomically accurate large human vascular network: Part I: methodology and baseline flow,” Neuroimage54(2), 1031–1042 (2011).

Chang, T. M.

H. P. Rani, T. W. Sheu, T. M. Chang, and P. C. Liang, “Numerical investigation of non-Newtonian microcirculatory blood flow in hepatic lobule,” J. Biomech.39(3), 551–563 (2006).

Chassidim, Y.

O. Prager, Y. Chassidim, C. Klein, H. Levi, I. Shelef, and A. Friedman, “Dynamic in vivo imaging of cerebral blood flow and blood-brain barrier permeability,” Neuroimage49(1), 337–344 (2010).

Chen, B. R.

Cheng, Z.

N. Parashurama, T. D. O’Sullivan, A. De La Zerda, P. El Kalassi, S. Cho, H. Liu, R. Teed, H. Levy, J. Rosenberg, Z. Cheng, O. Levi, J. S. Harris, and S. S. Gambhir, “Continuous sensing of tumor-targeted molecular probes with a vertical cavity surface emitting laser-based biosensor,” J. Biomed. Opt.17(11), 117004 (2012).

Cho, E. E.

E. E. Cho, J. Drazic, M. Ganguly, B. Stefanovic, and K. Hynynen, “Two-photon fluorescence microscopy study of cerebrovascular dynamics in ultrasound-induced blood-brain barrier opening,” J. Cereb. Blood Flow Metab.31(9), 1852–1862 (2011).

Cho, S.

N. Parashurama, T. D. O’Sullivan, A. De La Zerda, P. El Kalassi, S. Cho, H. Liu, R. Teed, H. Levy, J. Rosenberg, Z. Cheng, O. Levi, J. S. Harris, and S. S. Gambhir, “Continuous sensing of tumor-targeted molecular probes with a vertical cavity surface emitting laser-based biosensor,” J. Biomed. Opt.17(11), 117004 (2012).

Cho, Y. I.

Y. I. Cho and K. R. Kensey, “Effects of the non-Newtonian viscosity of blood on flows in a diseased arterial vessel. Part 1: Steady flows,” Biorheology28(3-4), 241–262 (1991).

Choi, B.

M. Kaiser, A. Yafi, M. Cinat, B. Choi, and A. J. Durkin, “Noninvasive assessment of burn wound severity using optical technology: a review of current and future modalities,” Burns37(3), 377–386 (2011).

Chopp, M.

Q. Jiang, J. R. Ewing, G. L. Ding, L. Zhang, Z. G. Zhang, L. Li, P. Whitton, M. Lu, J. Hu, Q. J. Li, R. A. Knight, and M. Chopp, “Quantitative evaluation of BBB permeability after embolic stroke in rat using MRI,” J. Cereb. Blood Flow Metab.25(5), 583–592 (2005).

Cinat, M.

M. Kaiser, A. Yafi, M. Cinat, B. Choi, and A. J. Durkin, “Noninvasive assessment of burn wound severity using optical technology: a review of current and future modalities,” Burns37(3), 377–386 (2011).

Cohen, A.

O. Tomkins, I. Shelef, I. Kaizerman, A. Eliushin, Z. Afawi, A. Misk, M. Gidon, A. Cohen, D. Zumsteg, and A. Friedman, “Blood-brain barrier disruption in post-traumatic epilepsy,” J. Neurol. Neurosurg. Psychiatry79(7), 774–777 (2008).

Corney, S.

B. M. Johnston, P. R. Johnston, S. Corney, and D. Kilpatrick, “Non-Newtonian blood flow in human right coronary arteries: steady state simulations,” J. Biomech.37(5), 709–720 (2004).

Curry, F.-R. E.

S. M. Stieger, C. F. Caskey, R. H. Adamson, S. Qin, F.-R. E. Curry, E. R. Wisner, and K. W. Ferrara, “Enhancement of vascular permeability with low-frequency contrast-enhanced ultrasound in the chorioallantoic membrane model,” Radiology243(1), 112–121 (2007).

Dankbaar, J.

M. Wintermark, J. Hom, J. Dankbaar, J. Bredno, and M. Olszewski, “Blood-brain barrier permeability: quantification with computed tomography and application in acute ischemic stroke,” Dear Friends53, 3 (2009).

Davey, A. J.

J. Greenwood, J. Adu, A. J. Davey, N. J. Abbott, and M. W. Bradbury, “The effect of bile salts on the permeability and ultrastructure of the perfused, energy-depleted, rat blood-brain barrier,” J. Cereb. Blood Flow Metab.11(4), 644–654 (1991).

David, T.

C. Skilbeck, S. M. Westwood, P. G. Walker, T. David, and G. B. Nash, “Population of the vessel wall by leukocytes binding to P-selectin in a model of disturbed arterial flow,” Arterioscler. Thromb. Vasc. Biol.21(8), 1294–1300 (2001).

De La Zerda, A.

N. Parashurama, T. D. O’Sullivan, A. De La Zerda, P. El Kalassi, S. Cho, H. Liu, R. Teed, H. Levy, J. Rosenberg, Z. Cheng, O. Levi, J. S. Harris, and S. S. Gambhir, “Continuous sensing of tumor-targeted molecular probes with a vertical cavity surface emitting laser-based biosensor,” J. Biomed. Opt.17(11), 117004 (2012).

Devor, A.

Ding, G. L.

Q. Jiang, J. R. Ewing, G. L. Ding, L. Zhang, Z. G. Zhang, L. Li, P. Whitton, M. Lu, J. Hu, Q. J. Li, R. A. Knight, and M. Chopp, “Quantitative evaluation of BBB permeability after embolic stroke in rat using MRI,” J. Cereb. Blood Flow Metab.25(5), 583–592 (2005).

Dolman, D. E. M.

N. J. Abbott, A. A. K. Patabendige, D. E. M. Dolman, S. R. Yusof, and D. J. Begley, “Structure and function of the blood-brain barrier,” Neurobiol. Dis.37(1), 13–25 (2010).

Dorr, A.

M. E. van Raaij, L. Lindvere, A. Dorr, J. He, B. Sahota, F. S. Foster, and B. Stefanovic, “Quantification of blood flow and volume in arterioles and venules of the rat cerebral cortex using functional micro-ultrasound,” Neuroimage63(3), 1030–1037 (2012).

Drazic, J.

E. E. Cho, J. Drazic, M. Ganguly, B. Stefanovic, and K. Hynynen, “Two-photon fluorescence microscopy study of cerebrovascular dynamics in ultrasound-induced blood-brain barrier opening,” J. Cereb. Blood Flow Metab.31(9), 1852–1862 (2011).

Dreier, J. P.

E. Seiffert, J. P. Dreier, S. Ivens, I. Bechmann, O. Tomkins, U. Heinemann, and A. Friedman, “Lasting Blood-Brain Barrier Disruption Induces Epileptic Focus in the Rat Somatosensory Cortex,” J. Neurosci.24(36), 7829–7836 (2004).

Drew, P. J.

A. Y. Shih, J. D. Driscoll, P. J. Drew, N. Nishimura, C. B. Schaffer, and D. Kleinfeld, “Two-photon microscopy as a tool to study blood flow and neurovascular coupling in the rodent brain,” J. Cereb. Blood Flow Metab.32(7), 1277–1309 (2012).

Driscoll, J. D.

A. Y. Shih, J. D. Driscoll, P. J. Drew, N. Nishimura, C. B. Schaffer, and D. Kleinfeld, “Two-photon microscopy as a tool to study blood flow and neurovascular coupling in the rodent brain,” J. Cereb. Blood Flow Metab.32(7), 1277–1309 (2012).

Dufour, S.

Dunn, A. K.

A. K. Dunn, “Laser Speckle Contrast Imaging of Cerebral Blood Flow,” Ann. Biomed. Eng.40(2), 367–377 (2012).

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

S. Yuan, A. Devor, D. A. Boas, and A. K. Dunn, “Determination of optimal exposure time for imaging of blood flow changes with laser speckle contrast imaging,” Appl. Opt.44(10), 1823–1830 (2005).

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).

Durkin, A. J.

M. Kaiser, A. Yafi, M. Cinat, B. Choi, and A. J. Durkin, “Noninvasive assessment of burn wound severity using optical technology: a review of current and future modalities,” Burns37(3), 377–386 (2011).

El Kalassi, P.

N. Parashurama, T. D. O’Sullivan, A. De La Zerda, P. El Kalassi, S. Cho, H. Liu, R. Teed, H. Levy, J. Rosenberg, Z. Cheng, O. Levi, J. S. Harris, and S. S. Gambhir, “Continuous sensing of tumor-targeted molecular probes with a vertical cavity surface emitting laser-based biosensor,” J. Biomed. Opt.17(11), 117004 (2012).

Eliushin, A.

O. Tomkins, I. Shelef, I. Kaizerman, A. Eliushin, Z. Afawi, A. Misk, M. Gidon, A. Cohen, D. Zumsteg, and A. Friedman, “Blood-brain barrier disruption in post-traumatic epilepsy,” J. Neurol. Neurosurg. Psychiatry79(7), 774–777 (2008).

Eskin, S. G.

M. B. Lawrence, L. V. McIntire, and S. G. Eskin, “Effect of flow on polymorphonuclear leukocyte/endothelial cell adhesion,” Blood70(5), 1284–1290 (1987).

Estrada, E. Y.

S. Taheri, E. Candelario-Jalil, E. Y. Estrada, and G. A. Rosenberg, “Spatiotemporal Correlations between Blood-Brain Barrier Permeability and Apparent Diffusion Coefficient in a Rat Model of Ischemic Stroke,” PLoS ONE4(8), e6597 (2009).

Ewing, J. R.

Q. Jiang, J. R. Ewing, G. L. Ding, L. Zhang, Z. G. Zhang, L. Li, P. Whitton, M. Lu, J. Hu, Q. J. Li, R. A. Knight, and M. Chopp, “Quantitative evaluation of BBB permeability after embolic stroke in rat using MRI,” J. Cereb. Blood Flow Metab.25(5), 583–592 (2005).

Ferrara, K. W.

S. M. Stieger, C. F. Caskey, R. H. Adamson, S. Qin, F.-R. E. Curry, E. R. Wisner, and K. W. Ferrara, “Enhancement of vascular permeability with low-frequency contrast-enhanced ultrasound in the chorioallantoic membrane model,” Radiology243(1), 112–121 (2007).

Fetcho, R. N.

J. Nguyen, N. Nishimura, R. N. Fetcho, C. Iadecola, and C. B. Schaffer, “Occlusion of cortical ascending venules causes blood flow decreases, reversals in flow direction, and vessel dilation in upstream capillaries,” J. Cereb. Blood Flow Metab.31(11), 2243–2254 (2011).

Feuerstein, G. Z.

B. Arvin, L. F. Neville, F. C. Barone, and G. Z. Feuerstein, “The role of inflammation and cytokines in brain injury,” Neurosci. Biobehav. Rev.20(3), 445–452 (1996).

Foster, F. S.

M. E. van Raaij, L. Lindvere, A. Dorr, J. He, B. Sahota, F. S. Foster, and B. Stefanovic, “Quantification of blood flow and volume in arterioles and venules of the rat cerebral cortex using functional micro-ultrasound,” Neuroimage63(3), 1030–1037 (2012).

Friedman, A.

O. Prager, Y. Chassidim, C. Klein, H. Levi, I. Shelef, and A. Friedman, “Dynamic in vivo imaging of cerebral blood flow and blood-brain barrier permeability,” Neuroimage49(1), 337–344 (2010).

M. B. Shlosberg, D. Kaufer, and A. Friedman, “Blood-brain barrier breakdown as a therapeutic target in traumatic brain injury,” Nat. Rev. Neurol.6, 10 (2010).

O. Tomkins, I. Shelef, I. Kaizerman, A. Eliushin, Z. Afawi, A. Misk, M. Gidon, A. Cohen, D. Zumsteg, and A. Friedman, “Blood-brain barrier disruption in post-traumatic epilepsy,” J. Neurol. Neurosurg. Psychiatry79(7), 774–777 (2008).

E. Seiffert, J. P. Dreier, S. Ivens, I. Bechmann, O. Tomkins, U. Heinemann, and A. Friedman, “Lasting Blood-Brain Barrier Disruption Induces Epileptic Focus in the Rat Somatosensory Cortex,” J. Neurosci.24(36), 7829–7836 (2004).

Gambhir, S. S.

N. Parashurama, T. D. O’Sullivan, A. De La Zerda, P. El Kalassi, S. Cho, H. Liu, R. Teed, H. Levy, J. Rosenberg, Z. Cheng, O. Levi, J. S. Harris, and S. S. Gambhir, “Continuous sensing of tumor-targeted molecular probes with a vertical cavity surface emitting laser-based biosensor,” J. Biomed. Opt.17(11), 117004 (2012).

Ganguly, M.

E. E. Cho, J. Drazic, M. Ganguly, B. Stefanovic, and K. Hynynen, “Two-photon fluorescence microscopy study of cerebrovascular dynamics in ultrasound-induced blood-brain barrier opening,” J. Cereb. Blood Flow Metab.31(9), 1852–1862 (2011).

Gidon, M.

O. Tomkins, I. Shelef, I. Kaizerman, A. Eliushin, Z. Afawi, A. Misk, M. Gidon, A. Cohen, D. Zumsteg, and A. Friedman, “Blood-brain barrier disruption in post-traumatic epilepsy,” J. Neurol. Neurosurg. Psychiatry79(7), 774–777 (2008).

Greenwood, J.

J. Greenwood, J. Adu, A. J. Davey, N. J. Abbott, and M. W. Bradbury, “The effect of bile salts on the permeability and ultrastructure of the perfused, energy-depleted, rat blood-brain barrier,” J. Cereb. Blood Flow Metab.11(4), 644–654 (1991).

Hamada, M.

K. Miyamoto, Y. Ogura, M. Hamada, H. Nishiwaki, N. Hiroshiba, and Y. Honda, “In vivo quantification of leukocyte behavior in the retina during endotoxin-induced uveitis,” Invest. Ophthalmol. Vis. Sci.37(13), 2708–2715 (1996).

Harris, J. S.

N. Parashurama, T. D. O’Sullivan, A. De La Zerda, P. El Kalassi, S. Cho, H. Liu, R. Teed, H. Levy, J. Rosenberg, Z. Cheng, O. Levi, J. S. Harris, and S. S. Gambhir, “Continuous sensing of tumor-targeted molecular probes with a vertical cavity surface emitting laser-based biosensor,” J. Biomed. Opt.17(11), 117004 (2012).

He, J.

M. E. van Raaij, L. Lindvere, A. Dorr, J. He, B. Sahota, F. S. Foster, and B. Stefanovic, “Quantification of blood flow and volume in arterioles and venules of the rat cerebral cortex using functional micro-ultrasound,” Neuroimage63(3), 1030–1037 (2012).

Heinemann, U.

E. Seiffert, J. P. Dreier, S. Ivens, I. Bechmann, O. Tomkins, U. Heinemann, and A. Friedman, “Lasting Blood-Brain Barrier Disruption Induces Epileptic Focus in the Rat Somatosensory Cortex,” J. Neurosci.24(36), 7829–7836 (2004).

Hillman, E. M.

Hiroshiba, N.

K. Miyamoto, Y. Ogura, M. Hamada, H. Nishiwaki, N. Hiroshiba, and Y. Honda, “In vivo quantification of leukocyte behavior in the retina during endotoxin-induced uveitis,” Invest. Ophthalmol. Vis. Sci.37(13), 2708–2715 (1996).

Hom, J.

M. Wintermark, J. Hom, J. Dankbaar, J. Bredno, and M. Olszewski, “Blood-brain barrier permeability: quantification with computed tomography and application in acute ischemic stroke,” Dear Friends53, 3 (2009).

Honda, Y.

K. Miyamoto, Y. Ogura, M. Hamada, H. Nishiwaki, N. Hiroshiba, and Y. Honda, “In vivo quantification of leukocyte behavior in the retina during endotoxin-induced uveitis,” Invest. Ophthalmol. Vis. Sci.37(13), 2708–2715 (1996).

Hu, J.

Q. Jiang, J. R. Ewing, G. L. Ding, L. Zhang, Z. G. Zhang, L. Li, P. Whitton, M. Lu, J. Hu, Q. J. Li, R. A. Knight, and M. Chopp, “Quantitative evaluation of BBB permeability after embolic stroke in rat using MRI,” J. Cereb. Blood Flow Metab.25(5), 583–592 (2005).

Hynynen, K.

E. E. Cho, J. Drazic, M. Ganguly, B. Stefanovic, and K. Hynynen, “Two-photon fluorescence microscopy study of cerebrovascular dynamics in ultrasound-induced blood-brain barrier opening,” J. Cereb. Blood Flow Metab.31(9), 1852–1862 (2011).

M. Kinoshita, N. McDannold, F. A. Jolesz, and K. Hynynen, “Noninvasive localized delivery of Herceptin to the mouse brain by MRI-guided focused ultrasound-induced blood-brain barrier disruption,” Proc. Natl. Acad. Sci. U.S.A.103(31), 11719–11723 (2006).

N. Sheikov, N. McDannold, N. Vykhodtseva, F. Jolesz, and K. Hynynen, “Cellular mechanisms of the blood-brain barrier opening induced by ultrasound in presence of microbubbles,” Ultrasound Med. Biol.30(7), 979–989 (2004).

Iadecola, C.

J. Nguyen, N. Nishimura, R. N. Fetcho, C. Iadecola, and C. B. Schaffer, “Occlusion of cortical ascending venules causes blood flow decreases, reversals in flow direction, and vessel dilation in upstream capillaries,” J. Cereb. Blood Flow Metab.31(11), 2243–2254 (2011).

N. Nishimura, N. L. Rosidi, C. Iadecola, and C. B. Schaffer, “Limitations of collateral flow after occlusion of a single cortical penetrating arteriole,” J. Cereb. Blood Flow Metab.30(12), 1914–1927 (2010).

Ichikawa, H.

H. Ichikawa and K. Itoh, “Blood-arachnoid barrier disruption in experimental rat meningitis detected using gadolinium-enhancement ratio imaging,” Brain Res.1390, 142–149 (2011).

Itoh, K.

H. Ichikawa and K. Itoh, “Blood-arachnoid barrier disruption in experimental rat meningitis detected using gadolinium-enhancement ratio imaging,” Brain Res.1390, 142–149 (2011).

Ivanov, K. P.

K. P. Ivanov, M. K. Kalinina, and Y. I. Levkovich, “Blood flow velocity in capillaries of brain and muscles and its physiological significance,” Microvasc. Res.22(2), 143–155 (1981).

Ivens, S.

E. Seiffert, J. P. Dreier, S. Ivens, I. Bechmann, O. Tomkins, U. Heinemann, and A. Friedman, “Lasting Blood-Brain Barrier Disruption Induces Epileptic Focus in the Rat Somatosensory Cortex,” J. Neurosci.24(36), 7829–7836 (2004).

Jaffer, F. A.

D.-E. Kim, D. Schellingerhout, F. A. Jaffer, R. Weissleder, and C. H. Tung, “Near-infrared fluorescent imaging of cerebral thrombi and blood-brain barrier disruption in a mouse model of cerebral venous sinus thrombosis,” J. Cereb. Blood Flow Metab.25(2), 226–233 (2005).

Jiang, Q.

Q. Jiang, J. R. Ewing, G. L. Ding, L. Zhang, Z. G. Zhang, L. Li, P. Whitton, M. Lu, J. Hu, Q. J. Li, R. A. Knight, and M. Chopp, “Quantitative evaluation of BBB permeability after embolic stroke in rat using MRI,” J. Cereb. Blood Flow Metab.25(5), 583–592 (2005).

Johnston, B. M.

B. M. Johnston, P. R. Johnston, S. Corney, and D. Kilpatrick, “Non-Newtonian blood flow in human right coronary arteries: steady state simulations,” J. Biomech.37(5), 709–720 (2004).

Johnston, P. R.

B. M. Johnston, P. R. Johnston, S. Corney, and D. Kilpatrick, “Non-Newtonian blood flow in human right coronary arteries: steady state simulations,” J. Biomech.37(5), 709–720 (2004).

Jolesz, F.

N. Sheikov, N. McDannold, N. Vykhodtseva, F. Jolesz, and K. Hynynen, “Cellular mechanisms of the blood-brain barrier opening induced by ultrasound in presence of microbubbles,” Ultrasound Med. Biol.30(7), 979–989 (2004).

Jolesz, F. A.

M. Kinoshita, N. McDannold, F. A. Jolesz, and K. Hynynen, “Noninvasive localized delivery of Herceptin to the mouse brain by MRI-guided focused ultrasound-induced blood-brain barrier disruption,” Proc. Natl. Acad. Sci. U.S.A.103(31), 11719–11723 (2006).

Kaiser, M.

M. Kaiser, A. Yafi, M. Cinat, B. Choi, and A. J. Durkin, “Noninvasive assessment of burn wound severity using optical technology: a review of current and future modalities,” Burns37(3), 377–386 (2011).

Kaizerman, I.

O. Tomkins, I. Shelef, I. Kaizerman, A. Eliushin, Z. Afawi, A. Misk, M. Gidon, A. Cohen, D. Zumsteg, and A. Friedman, “Blood-brain barrier disruption in post-traumatic epilepsy,” J. Neurol. Neurosurg. Psychiatry79(7), 774–777 (2008).

Kalaria, R. N.

R. N. Kalaria, “The Blood-Brain Barrier and Cerebrovascular Pathology in Alzheimer’s Disease,” Ann. N. Y. Acad. Sci.893, 113–125 (1999).

Kalinina, M. K.

K. P. Ivanov, M. K. Kalinina, and Y. I. Levkovich, “Blood flow velocity in capillaries of brain and muscles and its physiological significance,” Microvasc. Res.22(2), 143–155 (1981).

Kaufer, D.

M. B. Shlosberg, D. Kaufer, and A. Friedman, “Blood-brain barrier breakdown as a therapeutic target in traumatic brain injury,” Nat. Rev. Neurol.6, 10 (2010).

Kensey, K. R.

Y. I. Cho and K. R. Kensey, “Effects of the non-Newtonian viscosity of blood on flows in a diseased arterial vessel. Part 1: Steady flows,” Biorheology28(3-4), 241–262 (1991).

Kermode, A. G.

P. S. Tofts and A. G. Kermode, “Measurement of the blood-brain barrier permeability and leakage space using dynamic MR imaging. 1. Fundamental concepts,” Magn. Reson. Med.17(2), 357–367 (1991).

Kilpatrick, D.

B. M. Johnston, P. R. Johnston, S. Corney, and D. Kilpatrick, “Non-Newtonian blood flow in human right coronary arteries: steady state simulations,” J. Biomech.37(5), 709–720 (2004).

Kim, D.-E.

D.-E. Kim, D. Schellingerhout, F. A. Jaffer, R. Weissleder, and C. H. Tung, “Near-infrared fluorescent imaging of cerebral thrombi and blood-brain barrier disruption in a mouse model of cerebral venous sinus thrombosis,” J. Cereb. Blood Flow Metab.25(2), 226–233 (2005).

Kinoshita, M.

M. Kinoshita, N. McDannold, F. A. Jolesz, and K. Hynynen, “Noninvasive localized delivery of Herceptin to the mouse brain by MRI-guided focused ultrasound-induced blood-brain barrier disruption,” Proc. Natl. Acad. Sci. U.S.A.103(31), 11719–11723 (2006).

Klein, C.

O. Prager, Y. Chassidim, C. Klein, H. Levi, I. Shelef, and A. Friedman, “Dynamic in vivo imaging of cerebral blood flow and blood-brain barrier permeability,” Neuroimage49(1), 337–344 (2010).

Kleinfeld, D.

A. Y. Shih, J. D. Driscoll, P. J. Drew, N. Nishimura, C. B. Schaffer, and D. Kleinfeld, “Two-photon microscopy as a tool to study blood flow and neurovascular coupling in the rodent brain,” J. Cereb. Blood Flow Metab.32(7), 1277–1309 (2012).

Knight, R. A.

Q. Jiang, J. R. Ewing, G. L. Ding, L. Zhang, Z. G. Zhang, L. Li, P. Whitton, M. Lu, J. Hu, Q. J. Li, R. A. Knight, and M. Chopp, “Quantitative evaluation of BBB permeability after embolic stroke in rat using MRI,” J. Cereb. Blood Flow Metab.25(5), 583–592 (2005).

Lauwers, F.

S. Lorthois, F. Cassot, and F. Lauwers, “Simulation study of brain blood flow regulation by intra-cortical arterioles in an anatomically accurate large human vascular network: Part I: methodology and baseline flow,” Neuroimage54(2), 1031–1042 (2011).

S. Lorthois, F. Cassot, and F. Lauwers, “Simulation study of brain blood flow regulation by intra-cortical arterioles in an anatomically accurate large human vascular network. Part II: flow variations induced by global or localized modifications of arteriolar diameters,” Neuroimage54(4), 2840–2853 (2011).

Lawrence, M. B.

M. B. Lawrence, L. V. McIntire, and S. G. Eskin, “Effect of flow on polymorphonuclear leukocyte/endothelial cell adhesion,” Blood70(5), 1284–1290 (1987).

Levi, H.

O. Prager, Y. Chassidim, C. Klein, H. Levi, I. Shelef, and A. Friedman, “Dynamic in vivo imaging of cerebral blood flow and blood-brain barrier permeability,” Neuroimage49(1), 337–344 (2010).

Levi, O.

Levkovich, Y. I.

K. P. Ivanov, M. K. Kalinina, and Y. I. Levkovich, “Blood flow velocity in capillaries of brain and muscles and its physiological significance,” Microvasc. Res.22(2), 143–155 (1981).

Levy, H.

Li, L.

Q. Jiang, J. R. Ewing, G. L. Ding, L. Zhang, Z. G. Zhang, L. Li, P. Whitton, M. Lu, J. Hu, Q. J. Li, R. A. Knight, and M. Chopp, “Quantitative evaluation of BBB permeability after embolic stroke in rat using MRI,” J. Cereb. Blood Flow Metab.25(5), 583–592 (2005).

Li, Q. J.

Q. Jiang, J. R. Ewing, G. L. Ding, L. Zhang, Z. G. Zhang, L. Li, P. Whitton, M. Lu, J. Hu, Q. J. Li, R. A. Knight, and M. Chopp, “Quantitative evaluation of BBB permeability after embolic stroke in rat using MRI,” J. Cereb. Blood Flow Metab.25(5), 583–592 (2005).

Li, Y.

P. Miao, H. Lu, Q. Liu, Y. Li, and S. Tong, “Laser speckle contrast imaging of cerebral blood flow in freely moving animals,” J. Biomed. Opt.16(9), 090502 (2011).

Liang, P. C.

H. P. Rani, T. W. Sheu, T. M. Chang, and P. C. Liang, “Numerical investigation of non-Newtonian microcirculatory blood flow in hepatic lobule,” J. Biomech.39(3), 551–563 (2006).

Lindvere, L.

M. E. van Raaij, L. Lindvere, A. Dorr, J. He, B. Sahota, F. S. Foster, and B. Stefanovic, “Quantification of blood flow and volume in arterioles and venules of the rat cerebral cortex using functional micro-ultrasound,” Neuroimage63(3), 1030–1037 (2012).

Liu, H.

N. Parashurama, T. D. O’Sullivan, A. De La Zerda, P. El Kalassi, S. Cho, H. Liu, R. Teed, H. Levy, J. Rosenberg, Z. Cheng, O. Levi, J. S. Harris, and S. S. Gambhir, “Continuous sensing of tumor-targeted molecular probes with a vertical cavity surface emitting laser-based biosensor,” J. Biomed. Opt.17(11), 117004 (2012).

Liu, Q.

P. Miao, H. Lu, Q. Liu, Y. Li, and S. Tong, “Laser speckle contrast imaging of cerebral blood flow in freely moving animals,” J. Biomed. Opt.16(9), 090502 (2011).

Lorthois, S.

S. Lorthois, F. Cassot, and F. Lauwers, “Simulation study of brain blood flow regulation by intra-cortical arterioles in an anatomically accurate large human vascular network. Part II: flow variations induced by global or localized modifications of arteriolar diameters,” Neuroimage54(4), 2840–2853 (2011).

S. Lorthois, F. Cassot, and F. Lauwers, “Simulation study of brain blood flow regulation by intra-cortical arterioles in an anatomically accurate large human vascular network: Part I: methodology and baseline flow,” Neuroimage54(2), 1031–1042 (2011).

Lu, H.

P. Miao, H. Lu, Q. Liu, Y. Li, and S. Tong, “Laser speckle contrast imaging of cerebral blood flow in freely moving animals,” J. Biomed. Opt.16(9), 090502 (2011).

Lu, M.

Q. Jiang, J. R. Ewing, G. L. Ding, L. Zhang, Z. G. Zhang, L. Li, P. Whitton, M. Lu, J. Hu, Q. J. Li, R. A. Knight, and M. Chopp, “Quantitative evaluation of BBB permeability after embolic stroke in rat using MRI,” J. Cereb. Blood Flow Metab.25(5), 583–592 (2005).

Lundberg, J. M.

A. Saria and J. M. Lundberg, “Evans blue fluorescence: quantitative and morphological evaluation of vascular permeability in animal tissues,” J. Neurosci. Methods8(1), 41–49 (1983).

Martínez-Orgado, J. A.

L. Ruiz-Valdepeñas, J. A. Martínez-Orgado, C. Benito, A. Millán, R. M. Tolón, and J. Romero, “Cannabidiol reduces lipopolysaccharide-induced vascular changes and inflammation in the mouse brain: an intravital microscopy study,” J. Neuroinflammation8(1), 5 (2011).

McDannold, N.

M. Kinoshita, N. McDannold, F. A. Jolesz, and K. Hynynen, “Noninvasive localized delivery of Herceptin to the mouse brain by MRI-guided focused ultrasound-induced blood-brain barrier disruption,” Proc. Natl. Acad. Sci. U.S.A.103(31), 11719–11723 (2006).

N. Sheikov, N. McDannold, N. Vykhodtseva, F. Jolesz, and K. Hynynen, “Cellular mechanisms of the blood-brain barrier opening induced by ultrasound in presence of microbubbles,” Ultrasound Med. Biol.30(7), 979–989 (2004).

McIntire, L. V.

M. B. Lawrence, L. V. McIntire, and S. G. Eskin, “Effect of flow on polymorphonuclear leukocyte/endothelial cell adhesion,” Blood70(5), 1284–1290 (1987).

Miao, P.

P. Miao, H. Lu, Q. Liu, Y. Li, and S. Tong, “Laser speckle contrast imaging of cerebral blood flow in freely moving animals,” J. Biomed. Opt.16(9), 090502 (2011).

Millán, A.

L. Ruiz-Valdepeñas, J. A. Martínez-Orgado, C. Benito, A. Millán, R. M. Tolón, and J. Romero, “Cannabidiol reduces lipopolysaccharide-induced vascular changes and inflammation in the mouse brain: an intravital microscopy study,” J. Neuroinflammation8(1), 5 (2011).

Misk, A.

O. Tomkins, I. Shelef, I. Kaizerman, A. Eliushin, Z. Afawi, A. Misk, M. Gidon, A. Cohen, D. Zumsteg, and A. Friedman, “Blood-brain barrier disruption in post-traumatic epilepsy,” J. Neurol. Neurosurg. Psychiatry79(7), 774–777 (2008).

Miyamoto, K.

K. Miyamoto, Y. Ogura, M. Hamada, H. Nishiwaki, N. Hiroshiba, and Y. Honda, “In vivo quantification of leukocyte behavior in the retina during endotoxin-induced uveitis,” Invest. Ophthalmol. Vis. Sci.37(13), 2708–2715 (1996).

Moskowitz, M. A.

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).

Munro, E. A.

Nash, G. B.

C. Skilbeck, S. M. Westwood, P. G. Walker, T. David, and G. B. Nash, “Population of the vessel wall by leukocytes binding to P-selectin in a model of disturbed arterial flow,” Arterioscler. Thromb. Vasc. Biol.21(8), 1294–1300 (2001).

Neville, L. F.

B. Arvin, L. F. Neville, F. C. Barone, and G. Z. Feuerstein, “The role of inflammation and cytokines in brain injury,” Neurosci. Biobehav. Rev.20(3), 445–452 (1996).

Nguyen, J.

J. Nguyen, N. Nishimura, R. N. Fetcho, C. Iadecola, and C. B. Schaffer, “Occlusion of cortical ascending venules causes blood flow decreases, reversals in flow direction, and vessel dilation in upstream capillaries,” J. Cereb. Blood Flow Metab.31(11), 2243–2254 (2011).

Nishimura, N.

A. Y. Shih, J. D. Driscoll, P. J. Drew, N. Nishimura, C. B. Schaffer, and D. Kleinfeld, “Two-photon microscopy as a tool to study blood flow and neurovascular coupling in the rodent brain,” J. Cereb. Blood Flow Metab.32(7), 1277–1309 (2012).

J. Nguyen, N. Nishimura, R. N. Fetcho, C. Iadecola, and C. B. Schaffer, “Occlusion of cortical ascending venules causes blood flow decreases, reversals in flow direction, and vessel dilation in upstream capillaries,” J. Cereb. Blood Flow Metab.31(11), 2243–2254 (2011).

N. Nishimura, N. L. Rosidi, C. Iadecola, and C. B. Schaffer, “Limitations of collateral flow after occlusion of a single cortical penetrating arteriole,” J. Cereb. Blood Flow Metab.30(12), 1914–1927 (2010).

Nishiwaki, H.

K. Miyamoto, Y. Ogura, M. Hamada, H. Nishiwaki, N. Hiroshiba, and Y. Honda, “In vivo quantification of leukocyte behavior in the retina during endotoxin-induced uveitis,” Invest. Ophthalmol. Vis. Sci.37(13), 2708–2715 (1996).

O’Sullivan, T. D.

N. Parashurama, T. D. O’Sullivan, A. De La Zerda, P. El Kalassi, S. Cho, H. Liu, R. Teed, H. Levy, J. Rosenberg, Z. Cheng, O. Levi, J. S. Harris, and S. S. Gambhir, “Continuous sensing of tumor-targeted molecular probes with a vertical cavity surface emitting laser-based biosensor,” J. Biomed. Opt.17(11), 117004 (2012).

E. A. Munro, H. Levy, D. Ringuette, T. D. O’Sullivan, and O. Levi, “Multi-modality optical neural imaging using coherence control of VCSELs,” Opt. Express19(11), 10747–10761 (2011).

Ogura, Y.

K. Miyamoto, Y. Ogura, M. Hamada, H. Nishiwaki, N. Hiroshiba, and Y. Honda, “In vivo quantification of leukocyte behavior in the retina during endotoxin-induced uveitis,” Invest. Ophthalmol. Vis. Sci.37(13), 2708–2715 (1996).

Oldendorf, W. H.

W. H. Oldendorf, “Blood-Brain Barrier Permeability to Drugs,” Annu. Rev. Pharmacol.14(1), 239–248 (1974).

Olszewski, M.

M. Wintermark, J. Hom, J. Dankbaar, J. Bredno, and M. Olszewski, “Blood-brain barrier permeability: quantification with computed tomography and application in acute ischemic stroke,” Dear Friends53, 3 (2009).

Parashurama, N.

N. Parashurama, T. D. O’Sullivan, A. De La Zerda, P. El Kalassi, S. Cho, H. Liu, R. Teed, H. Levy, J. Rosenberg, Z. Cheng, O. Levi, J. S. Harris, and S. S. Gambhir, “Continuous sensing of tumor-targeted molecular probes with a vertical cavity surface emitting laser-based biosensor,” J. Biomed. Opt.17(11), 117004 (2012).

Pardridge, W. M.

W. M. Pardridge, “CNS Drug Design Based on Principles of Blood-Brain Barrier Transport,” J. Neurochem.70(5), 1781–1792 (1998).

Patabendige, A. A. K.

N. J. Abbott, A. A. K. Patabendige, D. E. M. Dolman, S. R. Yusof, and D. J. Begley, “Structure and function of the blood-brain barrier,” Neurobiol. Dis.37(1), 13–25 (2010).

Prager, O.

O. Prager, Y. Chassidim, C. Klein, H. Levi, I. Shelef, and A. Friedman, “Dynamic in vivo imaging of cerebral blood flow and blood-brain barrier permeability,” Neuroimage49(1), 337–344 (2010).

Qin, S.

S. M. Stieger, C. F. Caskey, R. H. Adamson, S. Qin, F.-R. E. Curry, E. R. Wisner, and K. W. Ferrara, “Enhancement of vascular permeability with low-frequency contrast-enhanced ultrasound in the chorioallantoic membrane model,” Radiology243(1), 112–121 (2007).

Raivich, G.

M. Bohatschek, A. Werner, and G. Raivich, “Systemic LPS injection leads to granulocyte influx into normal and injured brain: effects of ICAM-1 deficiency,” Exp. Neurol.172(1), 137–152 (2001).

Rani, H. P.

H. P. Rani, T. W. Sheu, T. M. Chang, and P. C. Liang, “Numerical investigation of non-Newtonian microcirculatory blood flow in hepatic lobule,” J. Biomech.39(3), 551–563 (2006).

Rapoport, S. I.

S. I. Rapoport, “Osmotic Opening of the Blood-Brain Barrier: Principles, Mechanism, and Therapeutic Applications,” Cell. Mol. Neurobiol.20(2), 217–230 (2000).

Ringuette, D.

Romero, J.

L. Ruiz-Valdepeñas, J. A. Martínez-Orgado, C. Benito, A. Millán, R. M. Tolón, and J. Romero, “Cannabidiol reduces lipopolysaccharide-induced vascular changes and inflammation in the mouse brain: an intravital microscopy study,” J. Neuroinflammation8(1), 5 (2011).

Rosenberg, G. A.

S. Taheri, E. Candelario-Jalil, E. Y. Estrada, and G. A. Rosenberg, “Spatiotemporal Correlations between Blood-Brain Barrier Permeability and Apparent Diffusion Coefficient in a Rat Model of Ischemic Stroke,” PLoS ONE4(8), e6597 (2009).

Rosenberg, J.

N. Parashurama, T. D. O’Sullivan, A. De La Zerda, P. El Kalassi, S. Cho, H. Liu, R. Teed, H. Levy, J. Rosenberg, Z. Cheng, O. Levi, J. S. Harris, and S. S. Gambhir, “Continuous sensing of tumor-targeted molecular probes with a vertical cavity surface emitting laser-based biosensor,” J. Biomed. Opt.17(11), 117004 (2012).

Rosidi, N. L.

N. Nishimura, N. L. Rosidi, C. Iadecola, and C. B. Schaffer, “Limitations of collateral flow after occlusion of a single cortical penetrating arteriole,” J. Cereb. Blood Flow Metab.30(12), 1914–1927 (2010).

Ruiz-Valdepeñas, L.

L. Ruiz-Valdepeñas, J. A. Martínez-Orgado, C. Benito, A. Millán, R. M. Tolón, and J. Romero, “Cannabidiol reduces lipopolysaccharide-induced vascular changes and inflammation in the mouse brain: an intravital microscopy study,” J. Neuroinflammation8(1), 5 (2011).

Sahota, B.

M. E. van Raaij, L. Lindvere, A. Dorr, J. He, B. Sahota, F. S. Foster, and B. Stefanovic, “Quantification of blood flow and volume in arterioles and venules of the rat cerebral cortex using functional micro-ultrasound,” Neuroimage63(3), 1030–1037 (2012).

Saria, A.

A. Saria and J. M. Lundberg, “Evans blue fluorescence: quantitative and morphological evaluation of vascular permeability in animal tissues,” J. Neurosci. Methods8(1), 41–49 (1983).

Schaffer, C. B.

A. Y. Shih, J. D. Driscoll, P. J. Drew, N. Nishimura, C. B. Schaffer, and D. Kleinfeld, “Two-photon microscopy as a tool to study blood flow and neurovascular coupling in the rodent brain,” J. Cereb. Blood Flow Metab.32(7), 1277–1309 (2012).

J. Nguyen, N. Nishimura, R. N. Fetcho, C. Iadecola, and C. B. Schaffer, “Occlusion of cortical ascending venules causes blood flow decreases, reversals in flow direction, and vessel dilation in upstream capillaries,” J. Cereb. Blood Flow Metab.31(11), 2243–2254 (2011).

N. Nishimura, N. L. Rosidi, C. Iadecola, and C. B. Schaffer, “Limitations of collateral flow after occlusion of a single cortical penetrating arteriole,” J. Cereb. Blood Flow Metab.30(12), 1914–1927 (2010).

Schellingerhout, D.

D.-E. Kim, D. Schellingerhout, F. A. Jaffer, R. Weissleder, and C. H. Tung, “Near-infrared fluorescent imaging of cerebral thrombi and blood-brain barrier disruption in a mouse model of cerebral venous sinus thrombosis,” J. Cereb. Blood Flow Metab.25(2), 226–233 (2005).

Seiffert, E.

E. Seiffert, J. P. Dreier, S. Ivens, I. Bechmann, O. Tomkins, U. Heinemann, and A. Friedman, “Lasting Blood-Brain Barrier Disruption Induces Epileptic Focus in the Rat Somatosensory Cortex,” J. Neurosci.24(36), 7829–7836 (2004).

Sheikov, N.

N. Sheikov, N. McDannold, N. Vykhodtseva, F. Jolesz, and K. Hynynen, “Cellular mechanisms of the blood-brain barrier opening induced by ultrasound in presence of microbubbles,” Ultrasound Med. Biol.30(7), 979–989 (2004).

Shelef, I.

O. Prager, Y. Chassidim, C. Klein, H. Levi, I. Shelef, and A. Friedman, “Dynamic in vivo imaging of cerebral blood flow and blood-brain barrier permeability,” Neuroimage49(1), 337–344 (2010).

O. Tomkins, I. Shelef, I. Kaizerman, A. Eliushin, Z. Afawi, A. Misk, M. Gidon, A. Cohen, D. Zumsteg, and A. Friedman, “Blood-brain barrier disruption in post-traumatic epilepsy,” J. Neurol. Neurosurg. Psychiatry79(7), 774–777 (2008).

Sheu, T. W.

H. P. Rani, T. W. Sheu, T. M. Chang, and P. C. Liang, “Numerical investigation of non-Newtonian microcirculatory blood flow in hepatic lobule,” J. Biomech.39(3), 551–563 (2006).

Shih, A. Y.

A. Y. Shih, J. D. Driscoll, P. J. Drew, N. Nishimura, C. B. Schaffer, and D. Kleinfeld, “Two-photon microscopy as a tool to study blood flow and neurovascular coupling in the rodent brain,” J. Cereb. Blood Flow Metab.32(7), 1277–1309 (2012).

Shlosberg, M. B.

M. B. Shlosberg, D. Kaufer, and A. Friedman, “Blood-brain barrier breakdown as a therapeutic target in traumatic brain injury,” Nat. Rev. Neurol.6, 10 (2010).

Skilbeck, C.

C. Skilbeck, S. M. Westwood, P. G. Walker, T. David, and G. B. Nash, “Population of the vessel wall by leukocytes binding to P-selectin in a model of disturbed arterial flow,” Arterioscler. Thromb. Vasc. Biol.21(8), 1294–1300 (2001).

Stefanovic, B.

M. E. van Raaij, L. Lindvere, A. Dorr, J. He, B. Sahota, F. S. Foster, and B. Stefanovic, “Quantification of blood flow and volume in arterioles and venules of the rat cerebral cortex using functional micro-ultrasound,” Neuroimage63(3), 1030–1037 (2012).

E. E. Cho, J. Drazic, M. Ganguly, B. Stefanovic, and K. Hynynen, “Two-photon fluorescence microscopy study of cerebrovascular dynamics in ultrasound-induced blood-brain barrier opening,” J. Cereb. Blood Flow Metab.31(9), 1852–1862 (2011).

Stieger, S. M.

S. M. Stieger, C. F. Caskey, R. H. Adamson, S. Qin, F.-R. E. Curry, E. R. Wisner, and K. W. Ferrara, “Enhancement of vascular permeability with low-frequency contrast-enhanced ultrasound in the chorioallantoic membrane model,” Radiology243(1), 112–121 (2007).

Taheri, S.

S. Taheri, E. Candelario-Jalil, E. Y. Estrada, and G. A. Rosenberg, “Spatiotemporal Correlations between Blood-Brain Barrier Permeability and Apparent Diffusion Coefficient in a Rat Model of Ischemic Stroke,” PLoS ONE4(8), e6597 (2009).

Teed, R.

N. Parashurama, T. D. O’Sullivan, A. De La Zerda, P. El Kalassi, S. Cho, H. Liu, R. Teed, H. Levy, J. Rosenberg, Z. Cheng, O. Levi, J. S. Harris, and S. S. Gambhir, “Continuous sensing of tumor-targeted molecular probes with a vertical cavity surface emitting laser-based biosensor,” J. Biomed. Opt.17(11), 117004 (2012).

Tofts, P. S.

P. S. Tofts and A. G. Kermode, “Measurement of the blood-brain barrier permeability and leakage space using dynamic MR imaging. 1. Fundamental concepts,” Magn. Reson. Med.17(2), 357–367 (1991).

Tolón, R. M.

L. Ruiz-Valdepeñas, J. A. Martínez-Orgado, C. Benito, A. Millán, R. M. Tolón, and J. Romero, “Cannabidiol reduces lipopolysaccharide-induced vascular changes and inflammation in the mouse brain: an intravital microscopy study,” J. Neuroinflammation8(1), 5 (2011).

Tomkins, O.

O. Tomkins, I. Shelef, I. Kaizerman, A. Eliushin, Z. Afawi, A. Misk, M. Gidon, A. Cohen, D. Zumsteg, and A. Friedman, “Blood-brain barrier disruption in post-traumatic epilepsy,” J. Neurol. Neurosurg. Psychiatry79(7), 774–777 (2008).

E. Seiffert, J. P. Dreier, S. Ivens, I. Bechmann, O. Tomkins, U. Heinemann, and A. Friedman, “Lasting Blood-Brain Barrier Disruption Induces Epileptic Focus in the Rat Somatosensory Cortex,” J. Neurosci.24(36), 7829–7836 (2004).

Tong, S.

P. Miao, H. Lu, Q. Liu, Y. Li, and S. Tong, “Laser speckle contrast imaging of cerebral blood flow in freely moving animals,” J. Biomed. Opt.16(9), 090502 (2011).

Tung, C. H.

D.-E. Kim, D. Schellingerhout, F. A. Jaffer, R. Weissleder, and C. H. Tung, “Near-infrared fluorescent imaging of cerebral thrombi and blood-brain barrier disruption in a mouse model of cerebral venous sinus thrombosis,” J. Cereb. Blood Flow Metab.25(2), 226–233 (2005).

van Raaij, M. E.

M. E. van Raaij, L. Lindvere, A. Dorr, J. He, B. Sahota, F. S. Foster, and B. Stefanovic, “Quantification of blood flow and volume in arterioles and venules of the rat cerebral cortex using functional micro-ultrasound,” Neuroimage63(3), 1030–1037 (2012).

Vykhodtseva, N.

N. Sheikov, N. McDannold, N. Vykhodtseva, F. Jolesz, and K. Hynynen, “Cellular mechanisms of the blood-brain barrier opening induced by ultrasound in presence of microbubbles,” Ultrasound Med. Biol.30(7), 979–989 (2004).

Walker, P. G.

C. Skilbeck, S. M. Westwood, P. G. Walker, T. David, and G. B. Nash, “Population of the vessel wall by leukocytes binding to P-selectin in a model of disturbed arterial flow,” Arterioscler. Thromb. Vasc. Biol.21(8), 1294–1300 (2001).

Weissleder, R.

D.-E. Kim, D. Schellingerhout, F. A. Jaffer, R. Weissleder, and C. H. Tung, “Near-infrared fluorescent imaging of cerebral thrombi and blood-brain barrier disruption in a mouse model of cerebral venous sinus thrombosis,” J. Cereb. Blood Flow Metab.25(2), 226–233 (2005).

Werner, A.

M. Bohatschek, A. Werner, and G. Raivich, “Systemic LPS injection leads to granulocyte influx into normal and injured brain: effects of ICAM-1 deficiency,” Exp. Neurol.172(1), 137–152 (2001).

Westwood, S. M.

C. Skilbeck, S. M. Westwood, P. G. Walker, T. David, and G. B. Nash, “Population of the vessel wall by leukocytes binding to P-selectin in a model of disturbed arterial flow,” Arterioscler. Thromb. Vasc. Biol.21(8), 1294–1300 (2001).

Whitton, P.

Q. Jiang, J. R. Ewing, G. L. Ding, L. Zhang, Z. G. Zhang, L. Li, P. Whitton, M. Lu, J. Hu, Q. J. Li, R. A. Knight, and M. Chopp, “Quantitative evaluation of BBB permeability after embolic stroke in rat using MRI,” J. Cereb. Blood Flow Metab.25(5), 583–592 (2005).

Wintermark, M.

M. Wintermark, J. Hom, J. Dankbaar, J. Bredno, and M. Olszewski, “Blood-brain barrier permeability: quantification with computed tomography and application in acute ischemic stroke,” Dear Friends53, 3 (2009).

Wisner, E. R.

S. M. Stieger, C. F. Caskey, R. H. Adamson, S. Qin, F.-R. E. Curry, E. R. Wisner, and K. W. Ferrara, “Enhancement of vascular permeability with low-frequency contrast-enhanced ultrasound in the chorioallantoic membrane model,” Radiology243(1), 112–121 (2007).

Yafi, A.

M. Kaiser, A. Yafi, M. Cinat, B. Choi, and A. J. Durkin, “Noninvasive assessment of burn wound severity using optical technology: a review of current and future modalities,” Burns37(3), 377–386 (2011).

Yuan, S.

Yusof, S. R.

N. J. Abbott, A. A. K. Patabendige, D. E. M. Dolman, S. R. Yusof, and D. J. Begley, “Structure and function of the blood-brain barrier,” Neurobiol. Dis.37(1), 13–25 (2010).

Zhang, L.

Q. Jiang, J. R. Ewing, G. L. Ding, L. Zhang, Z. G. Zhang, L. Li, P. Whitton, M. Lu, J. Hu, Q. J. Li, R. A. Knight, and M. Chopp, “Quantitative evaluation of BBB permeability after embolic stroke in rat using MRI,” J. Cereb. Blood Flow Metab.25(5), 583–592 (2005).

Zhang, Z. G.

Q. Jiang, J. R. Ewing, G. L. Ding, L. Zhang, Z. G. Zhang, L. Li, P. Whitton, M. Lu, J. Hu, Q. J. Li, R. A. Knight, and M. Chopp, “Quantitative evaluation of BBB permeability after embolic stroke in rat using MRI,” J. Cereb. Blood Flow Metab.25(5), 583–592 (2005).

Zumsteg, D.

O. Tomkins, I. Shelef, I. Kaizerman, A. Eliushin, Z. Afawi, A. Misk, M. Gidon, A. Cohen, D. Zumsteg, and A. Friedman, “Blood-brain barrier disruption in post-traumatic epilepsy,” J. Neurol. Neurosurg. Psychiatry79(7), 774–777 (2008).

Ann. Biomed. Eng. (1)

A. K. Dunn, “Laser Speckle Contrast Imaging of Cerebral Blood Flow,” Ann. Biomed. Eng.40(2), 367–377 (2012).

Ann. N. Y. Acad. Sci. (1)

R. N. Kalaria, “The Blood-Brain Barrier and Cerebrovascular Pathology in Alzheimer’s Disease,” Ann. N. Y. Acad. Sci.893, 113–125 (1999).

Annu. Rev. Pharmacol. (1)

W. H. Oldendorf, “Blood-Brain Barrier Permeability to Drugs,” Annu. Rev. Pharmacol.14(1), 239–248 (1974).

Appl. Opt. (2)

Arterioscler. Thromb. Vasc. Biol. (1)

C. Skilbeck, S. M. Westwood, P. G. Walker, T. David, and G. B. Nash, “Population of the vessel wall by leukocytes binding to P-selectin in a model of disturbed arterial flow,” Arterioscler. Thromb. Vasc. Biol.21(8), 1294–1300 (2001).

Biomed. Opt. Express (1)

Biorheology (1)

Y. I. Cho and K. R. Kensey, “Effects of the non-Newtonian viscosity of blood on flows in a diseased arterial vessel. Part 1: Steady flows,” Biorheology28(3-4), 241–262 (1991).

Blood (1)

M. B. Lawrence, L. V. McIntire, and S. G. Eskin, “Effect of flow on polymorphonuclear leukocyte/endothelial cell adhesion,” Blood70(5), 1284–1290 (1987).

Brain Res. (1)

H. Ichikawa and K. Itoh, “Blood-arachnoid barrier disruption in experimental rat meningitis detected using gadolinium-enhancement ratio imaging,” Brain Res.1390, 142–149 (2011).

Burns (1)

M. Kaiser, A. Yafi, M. Cinat, B. Choi, and A. J. Durkin, “Noninvasive assessment of burn wound severity using optical technology: a review of current and future modalities,” Burns37(3), 377–386 (2011).

Cell. Mol. Neurobiol. (1)

S. I. Rapoport, “Osmotic Opening of the Blood-Brain Barrier: Principles, Mechanism, and Therapeutic Applications,” Cell. Mol. Neurobiol.20(2), 217–230 (2000).

Chem. Eng. Sci. (1)

R. Byron Bird and P. J. Carreau, “A nonlinear viscoelastic model for polymer solutions and melts—I,” Chem. Eng. Sci.23(5), 427–434 (1968).

Dear Friends (1)

M. Wintermark, J. Hom, J. Dankbaar, J. Bredno, and M. Olszewski, “Blood-brain barrier permeability: quantification with computed tomography and application in acute ischemic stroke,” Dear Friends53, 3 (2009).

Exp. Neurol. (1)

M. Bohatschek, A. Werner, and G. Raivich, “Systemic LPS injection leads to granulocyte influx into normal and injured brain: effects of ICAM-1 deficiency,” Exp. Neurol.172(1), 137–152 (2001).

Invest. Ophthalmol. Vis. Sci. (1)

K. Miyamoto, Y. Ogura, M. Hamada, H. Nishiwaki, N. Hiroshiba, and Y. Honda, “In vivo quantification of leukocyte behavior in the retina during endotoxin-induced uveitis,” Invest. Ophthalmol. Vis. Sci.37(13), 2708–2715 (1996).

J. Biomech. (2)

B. M. Johnston, P. R. Johnston, S. Corney, and D. Kilpatrick, “Non-Newtonian blood flow in human right coronary arteries: steady state simulations,” J. Biomech.37(5), 709–720 (2004).

H. P. Rani, T. W. Sheu, T. M. Chang, and P. C. Liang, “Numerical investigation of non-Newtonian microcirculatory blood flow in hepatic lobule,” J. Biomech.39(3), 551–563 (2006).

J. Biomed. Opt. (3)

P. Miao, H. Lu, Q. Liu, Y. Li, and S. Tong, “Laser speckle contrast imaging of cerebral blood flow in freely moving animals,” J. Biomed. Opt.16(9), 090502 (2011).

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

N. Parashurama, T. D. O’Sullivan, A. De La Zerda, P. El Kalassi, S. Cho, H. Liu, R. Teed, H. Levy, J. Rosenberg, Z. Cheng, O. Levi, J. S. Harris, and S. S. Gambhir, “Continuous sensing of tumor-targeted molecular probes with a vertical cavity surface emitting laser-based biosensor,” J. Biomed. Opt.17(11), 117004 (2012).

J. Cereb. Blood Flow Metab. (8)

N. Nishimura, N. L. Rosidi, C. Iadecola, and C. B. Schaffer, “Limitations of collateral flow after occlusion of a single cortical penetrating arteriole,” J. Cereb. Blood Flow Metab.30(12), 1914–1927 (2010).

J. Nguyen, N. Nishimura, R. N. Fetcho, C. Iadecola, and C. B. Schaffer, “Occlusion of cortical ascending venules causes blood flow decreases, reversals in flow direction, and vessel dilation in upstream capillaries,” J. Cereb. Blood Flow Metab.31(11), 2243–2254 (2011).

D.-E. Kim, D. Schellingerhout, F. A. Jaffer, R. Weissleder, and C. H. Tung, “Near-infrared fluorescent imaging of cerebral thrombi and blood-brain barrier disruption in a mouse model of cerebral venous sinus thrombosis,” J. Cereb. Blood Flow Metab.25(2), 226–233 (2005).

E. E. Cho, J. Drazic, M. Ganguly, B. Stefanovic, and K. Hynynen, “Two-photon fluorescence microscopy study of cerebrovascular dynamics in ultrasound-induced blood-brain barrier opening,” J. Cereb. Blood Flow Metab.31(9), 1852–1862 (2011).

Q. Jiang, J. R. Ewing, G. L. Ding, L. Zhang, Z. G. Zhang, L. Li, P. Whitton, M. Lu, J. Hu, Q. J. Li, R. A. Knight, and M. Chopp, “Quantitative evaluation of BBB permeability after embolic stroke in rat using MRI,” J. Cereb. Blood Flow Metab.25(5), 583–592 (2005).

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).

J. Greenwood, J. Adu, A. J. Davey, N. J. Abbott, and M. W. Bradbury, “The effect of bile salts on the permeability and ultrastructure of the perfused, energy-depleted, rat blood-brain barrier,” J. Cereb. Blood Flow Metab.11(4), 644–654 (1991).

A. Y. Shih, J. D. Driscoll, P. J. Drew, N. Nishimura, C. B. Schaffer, and D. Kleinfeld, “Two-photon microscopy as a tool to study blood flow and neurovascular coupling in the rodent brain,” J. Cereb. Blood Flow Metab.32(7), 1277–1309 (2012).

J. Neurochem. (1)

W. M. Pardridge, “CNS Drug Design Based on Principles of Blood-Brain Barrier Transport,” J. Neurochem.70(5), 1781–1792 (1998).

J. Neuroinflammation (1)

L. Ruiz-Valdepeñas, J. A. Martínez-Orgado, C. Benito, A. Millán, R. M. Tolón, and J. Romero, “Cannabidiol reduces lipopolysaccharide-induced vascular changes and inflammation in the mouse brain: an intravital microscopy study,” J. Neuroinflammation8(1), 5 (2011).

J. Neurol. Neurosurg. Psychiatry (1)

O. Tomkins, I. Shelef, I. Kaizerman, A. Eliushin, Z. Afawi, A. Misk, M. Gidon, A. Cohen, D. Zumsteg, and A. Friedman, “Blood-brain barrier disruption in post-traumatic epilepsy,” J. Neurol. Neurosurg. Psychiatry79(7), 774–777 (2008).

J. Neurosci. (1)

E. Seiffert, J. P. Dreier, S. Ivens, I. Bechmann, O. Tomkins, U. Heinemann, and A. Friedman, “Lasting Blood-Brain Barrier Disruption Induces Epileptic Focus in the Rat Somatosensory Cortex,” J. Neurosci.24(36), 7829–7836 (2004).

J. Neurosci. Methods (1)

A. Saria and J. M. Lundberg, “Evans blue fluorescence: quantitative and morphological evaluation of vascular permeability in animal tissues,” J. Neurosci. Methods8(1), 41–49 (1983).

Magn. Reson. Med. (1)

P. S. Tofts and A. G. Kermode, “Measurement of the blood-brain barrier permeability and leakage space using dynamic MR imaging. 1. Fundamental concepts,” Magn. Reson. Med.17(2), 357–367 (1991).

Microvasc. Res. (1)

K. P. Ivanov, M. K. Kalinina, and Y. I. Levkovich, “Blood flow velocity in capillaries of brain and muscles and its physiological significance,” Microvasc. Res.22(2), 143–155 (1981).

Nat. Rev. Neurol. (1)

M. B. Shlosberg, D. Kaufer, and A. Friedman, “Blood-brain barrier breakdown as a therapeutic target in traumatic brain injury,” Nat. Rev. Neurol.6, 10 (2010).

Neurobiol. Dis. (1)

N. J. Abbott, A. A. K. Patabendige, D. E. M. Dolman, S. R. Yusof, and D. J. Begley, “Structure and function of the blood-brain barrier,” Neurobiol. Dis.37(1), 13–25 (2010).

Neuroimage (4)

O. Prager, Y. Chassidim, C. Klein, H. Levi, I. Shelef, and A. Friedman, “Dynamic in vivo imaging of cerebral blood flow and blood-brain barrier permeability,” Neuroimage49(1), 337–344 (2010).

S. Lorthois, F. Cassot, and F. Lauwers, “Simulation study of brain blood flow regulation by intra-cortical arterioles in an anatomically accurate large human vascular network. Part II: flow variations induced by global or localized modifications of arteriolar diameters,” Neuroimage54(4), 2840–2853 (2011).

S. Lorthois, F. Cassot, and F. Lauwers, “Simulation study of brain blood flow regulation by intra-cortical arterioles in an anatomically accurate large human vascular network: Part I: methodology and baseline flow,” Neuroimage54(2), 1031–1042 (2011).

M. E. van Raaij, L. Lindvere, A. Dorr, J. He, B. Sahota, F. S. Foster, and B. Stefanovic, “Quantification of blood flow and volume in arterioles and venules of the rat cerebral cortex using functional micro-ultrasound,” Neuroimage63(3), 1030–1037 (2012).

Neurosci. Biobehav. Rev. (1)

B. Arvin, L. F. Neville, F. C. Barone, and G. Z. Feuerstein, “The role of inflammation and cytokines in brain injury,” Neurosci. Biobehav. Rev.20(3), 445–452 (1996).

Opt. Express (2)

Physiol. Meas. (1)

J. D. Briers, “Laser Doppler, speckle and related techniques for blood perfusion mapping and imaging,” Physiol. Meas.22(4), R35–R66 (2001).

PLoS ONE (1)

S. Taheri, E. Candelario-Jalil, E. Y. Estrada, and G. A. Rosenberg, “Spatiotemporal Correlations between Blood-Brain Barrier Permeability and Apparent Diffusion Coefficient in a Rat Model of Ischemic Stroke,” PLoS ONE4(8), e6597 (2009).

Proc. Natl. Acad. Sci. U.S.A. (1)

M. Kinoshita, N. McDannold, F. A. Jolesz, and K. Hynynen, “Noninvasive localized delivery of Herceptin to the mouse brain by MRI-guided focused ultrasound-induced blood-brain barrier disruption,” Proc. Natl. Acad. Sci. U.S.A.103(31), 11719–11723 (2006).

Radiology (1)

S. M. Stieger, C. F. Caskey, R. H. Adamson, S. Qin, F.-R. E. Curry, E. R. Wisner, and K. W. Ferrara, “Enhancement of vascular permeability with low-frequency contrast-enhanced ultrasound in the chorioallantoic membrane model,” Radiology243(1), 112–121 (2007).

Ultrasound Med. Biol. (1)

N. Sheikov, N. McDannold, N. Vykhodtseva, F. Jolesz, and K. Hynynen, “Cellular mechanisms of the blood-brain barrier opening induced by ultrasound in presence of microbubbles,” Ultrasound Med. Biol.30(7), 979–989 (2004).

Other (6)

A. Ponticorvo and A. K. Dunn, “How to build a Laser Speckle Contrast Imaging (LSCI) system to monitor blood flow,” J. Vis. Exp. (45): (2010).

L. M. Richards, E. L. Towle, D. J. Fox, and A. K. Dunn, “Laser Speckle Imaging of Cerebral Blood Flow,” in Optical Methods and Instrumentation in Brain Imaging and Therapy (Springer New York, 2013), pp. 117–136.

I. Sigal, Y. Atchia, R. Gad, A. M. Caravaca, D. Conkey, R. Piestun, and O. Levi, “Laser Speckle Contrast Imaging with Extended Depth of Field for Brain Imaging Applications,” in CLEO: Science and Innovations, Imaging & Microscopy I (Optical Society of America, 2013), paper CTu2M.

L. Grinberg, V. Morozov, D. Fedosov, J. A. Insley, M. E. Papka, K. Kumaran, and G. E. Karniadakis, “A new computational paradigm in multiscale simulations: Application to brain blood flow,” in High Performance Computing, Networking, Storage and Analysis (SC), 2011International Conference for(IEEE, 2011), pp. 1–12.

S. Lorthois and F. Lauwers, “Control of brain blood flow by capillaries: a simulation study in an anatomically accurate large human vascular network,” Comput. Methods Biomech. Biomed. Engin. 15(sup1), 66–68 (2012).

A. Sequeira and J. Janela, “An overview of some mathematical models of blood rheology,” in A Portrait of State-of-the-Art Research at the Technical University of Lisbon(Springer, 2007), pp. 65–87.

Cited By

OSA participates in CrossRef's Cited-By Linking service. Citing articles from OSA journals and other participating publishers are listed here.

Alert me when this article is cited.


Figures (12)

Fig. 1
Fig. 1

(a) Hypothetical illustration of the blood flowing through an artery (or arteriole), capillaries and a vein (or venule), subsequently, in the condition of intact BBB. (b) Same representation for a compromised blood brain barrier, wherein the venous output (red arrow) is decreased. The input and output blood volumes are represented by white and red arrows, respectively. (c) Hypothetical transverse velocity profile along the dotted line (b) and definition of the different parameters measured and analyzed in this study. The maximal velocity amplitude is represented by the vertical arrow, the vessel diameter (full width at half maximum) is represented by the horizontal arrow, and the area under the transverse velocity profile is represented by the shaded area.

Fig. 2
Fig. 2

Schematics of (a) the imaging experimental setup and (b) the illumination and image acquisition sequences.

Fig. 3
Fig. 3

Simulated geometry of an 80 μm artery diving into the cortex tissue, branching into 5-20μm capillaries, and uniting into a surfacing 200 μm vein.

Fig. 4
Fig. 4

DOC-induced BBB opening signature in the blood velocity map. (a) Fluorescence intensity and blood relative velocity maps before and after DOC application. (b) Relative changes of flow velocity after DOC application. (c) Relative blood velocity profiles were traced for an artery (upper) and a vein (lower) before and after DOC application. The DOC fluorescence and relative velocity images were recorded 30 minutes after the drug application. Initial profiles are traced in black and the final ones are traced in grey. Locations of the profiles shown in (c) are highlighted in panel (a) by the black bars.

Fig. 5
Fig. 5

LPS-induced BBB opening signature in the blood velocity map. (a) Fluorescence intensity and blood relative velocity maps before and after LPS application. (b) Relative changes of flow velocity after LPS application. (c) Relative blood velocity profiles were traced for an artery (upper) and a vein (lower) before and after LPS application. The LPS fluorescence and relative velocity images were recorded 2 hours after the drug application because LPS effect was slower. Initial profiles are traced in black and the final ones are traced in grey. Locations of the profiles shown in (c) are highlighted in panel (a) by the black bars.

Fig. 6
Fig. 6

BBB opening and permeability change effects on the vascular output/input ratio. To compare the veins and arteries hemodynamics before and after drug-induced BBB disruption, three parameters were measured in veins and arteries: the vessel diameter, the maximum relative flow and the profile area. These parameters were normalized to initial values and used to calculate the output/input ratios, i.e. the relative change in veins divided by the relative change in arteries for each measured parameters. Output/Input ratios for different parameters: the vessel diameter (width at half maximum of the velocity profile), the maximum relative velocity (the maximum of the velocity profile) and the transverse profile area (the area under the relative velocity profile curve) are shown in control animals (white, n = 5 rats (14 arteries and 20 veins)), in animals treated with DOC (dark blue, n = 6 rats (21 arteries and 26 veins)) and in animal treated with LPS (pale blue, n = 4 rats (11 arteries and 15 veins)). For each animal, the ratio was normalized according to the initial values (* = p < 0.05).

Fig. 7
Fig. 7

Simultaneous observation of fluorescence and blood flow velocity maps in treated and untreated hemispheres. (a) Schematic representation of the surgical procedures. (b) Fluorescence (top) and relative velocity (bottom) maps for untreated “control” hemisphere (left two panels) and treated hemisphere (right two panels) as they appear 60 minutes after DOC application on the right treated hemisphere. (c) Temporal evolution of the relative flow velocity in different tissue compartments for the treated (bold lines) and untreated hemispheres. Artery (black), vein (grey) and extravascular tissue (dotted lines) are presented. The regions over which the relative velocities were averaged are highlighted in panel b. (d) Time course of the normalized integrated transverse output/input profile ratio (bar graph, data shown as mean ± SE) and for the ratio calculated from the vessels shown in (b)-(c) (thick bold time traces). (e) Extravascular fluorescence accumulation for a treated and control regions. Note that in panels (c)-(e), the DOC application duration is represented by a grey zone. (f) Mean output/input ratio 10 minutes after DOC application (n = 5 rats, ** = p < 0.01, data shown as mean ± SD).

Fig. 8
Fig. 8

Simulated effects of a localized leakage on velocity maps. a-b) Velocity maps without (a) and with (b) leaky boundary conditions. The arrow in (b) shows the location of the leaking zone. (c) Velocity changes calculated as 100∙(vf - vi)/ vi, where vf is the final velocity (with leak) and vi stands for the initial velocity (no leak). (d) Initial (black curve) and final (grey curve) transverse velocity profile of the simulated vein. (e-g) Initial and final transverse velocity profiles of different simulated arteries or arterioles. Lines along which the profiles were taken (corresponding to locations i, ii, iii) are marked in panel (b).

Fig. 9
Fig. 9

Small permeability changes in vessels due to DOC application to a live rat brain. (a) Fluorescence intensity and blood flow relative velocity maps before and after DOC application. In some discrete locations, an accumulation of fluorescent dye is observed in the extravascular region (white arrow). There is a slight change in the blood velocity map (top), correlated with the observed small changes in intensity outside the vessels in the fluorescence map (bottom) (b) Relative changes of velocity after DOC application. (c) Transverse relative blood velocity profiles for an artery (upper) and a vein (bottom) before and after DOC application. Initial profiles blood velocity profiles (black) and the final blood velocity profiles (grey) after DOC application are overlaid in the figure. Spatial Locations of the plotted profiles are highlighted in black in (a), top left panel.

Fig. 10
Fig. 10

Time course of the normalized integrated transverse output/input profile ratio (N = 2 rats, data shown as mean ± SE). Grey bars represent the treated hemisphere and white bars the untreated hemisphere. DOC application period is marked with a grey box.

Fig. 11
Fig. 11

Overlay of simulated (colored map) and measured vessel morphology maps (grey level map). The color-coded velocities are in [mm/sec].

Fig. 12
Fig. 12

Simulated effects of a localized clog on velocity maps. a-b) Velocity maps without (a) and with (b) an occlusion. The arrow in (b) shows the location of the clogged zone (smaller diameter over a length of 20 µm). (c) Velocity changes calculated as 100*(( vf - vi)/ vi) where vf is the final velocity (with an occlusion) and vi stands for the initial velocity. (d) Initial (black dots) and final (grey cross) transverse velocity profile of a simulated vein. (e) Initial and final transverse velocity profiles of the simulated artery. Lines along which the profiles were taken are marked in panel (b).

Tables (1)

Tables Icon

Table 1 Measured and simulated velocity values for the vessels marked by a number in Fig. 11. Velocities were measured with the time of flight technique under green LED illumination along the lines highlighted in Fig. 11. Given the challenges in translating the vessel morphology accurately into COMSOL, the simulations did not converge for a portion of the vessels.

Equations (2)

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

η( γ ˙ )= η +( η 0 η ) [ 1+ ( λ γ ˙ ) 2 ] n1 2
ρ u t +ρ( u ) u = σ + f

Metrics