Abstract

Measuring blood cell dynamics within the capillaries of the living eye provides crucial information regarding the health of the microvascular network. To date, the study of single blood cell movement in this network has been obscured by optical aberrations, hindered by weak optical contrast, and often required injection of exogenous fluorescent dyes to perform measurements. Here we present a new strategy to non-invasively image single blood cells in the living mouse eye without contrast agents. Eye aberrations were corrected with an adaptive optics camera coupled with a fast, 15 kHz scanned beam orthogonal to a capillary of interest. Blood cells were imaged as they flowed past a near infrared imaging beam to which the eye is relatively insensitive. Optical contrast of cells was optimized using differential scatter of blood cells in the split-detector imaging configuration. Combined, these strategies provide label-free, non-invasive imaging of blood cells in the retina as they travel in single file in capillaries, enabling determination of cell flux, morphology, class, velocity, and rheology at the single cell level.

© 2016 Optical Society of America

Full Article  |  PDF Article
OSA Recommended Articles
Adaptive optics retinal imaging in the living mouse eye

Ying Geng, Alfredo Dubra, Lu Yin, William H. Merigan, Robin Sharma, Richard T. Libby, and David R. Williams
Biomed. Opt. Express 3(4) 715-734 (2012)

Comparison of adaptive optics scanning light ophthalmoscopic fluorescein angiography and offset pinhole imaging

Toco Y. P. Chui, Michael Dubow, Alexander Pinhas, Nishit Shah, Alexander Gan, Rishard Weitz, Yusufu N. Sulai, Alfredo Dubra, and Richard B. Rosen
Biomed. Opt. Express 5(4) 1173-1189 (2014)

In vivo measurement of erythrocyte velocity and retinal blood flow using adaptive optics scanning laser ophthalmoscopy

Zhangyi Zhong, Benno L. Petrig, Xiaofeng Qi, and Stephen A. Burns
Opt. Express 16(17) 12746-12756 (2008)

References

  • View by:
  • |
  • |
  • |

  1. D. G. Lyons, A. Parpaleix, M. Roche, and S. Charpak, “Mapping oxygen concentration in the awake mouse brain,” eLife 5, e12024 (2016).
    [Crossref] [PubMed]
  2. P. Lennie, “The Cost of Cortical Computation,” Curr. Biol. 13(6), 493–497 (2003).
    [Crossref] [PubMed]
  3. M. T. T. Wong-Riley, “Energy metabolism of the visual system,” Eye Brain 2, 99–116 (2010).
    [Crossref] [PubMed]
  4. W. H. Organization, Prevention of Blindness from Diabetes Mellitus: Report of a WHO Consultation in Geneva, Switzerland, 9–11 November 2005 (World Health Organization, 2006).
  5. D. S. Fong, L. P. Aiello, F. L. Ferris, and R. Klein, “Diabetic Retinopathy,” Diabetes Care 27(10), 2540–2553 (2004).
    [Crossref] [PubMed]
  6. R. Klein, B. E. K. Klein, S. E. Moss, M. D. Davis, and D. L. DeMets, “The Wisconsin Epidemiologic Study of Diabetic Retinopathy. III. Prevalence and Risk of Diabetic Retinopathy When Age at Diagnosis Is 30 or More Years,” Arch. Ophthalmol. 102(4), 527–532 (1984).
    [Crossref] [PubMed]
  7. R. Klein, B. E. Klein, S. E. Moss, M. D. Davis, and D. L. DeMets, “The Wisconsin epidemiologic study of diabetic retinopathy. IV. Diabetic macular edema,” Ophthalmology 91(12), 1464–1474 (1984).
    [Crossref] [PubMed]
  8. Y. Akagi-Kurashige, A. Tsujikawa, S. Ooto, Y. Makiyama, Y. Muraoka, K. Kumagai, A. Uji, S. Arichika, T. Murakami, K. Miyamoto, and N. Yoshimura, “Retinal Microstructural Changes in Eyes With Resolved Branch Retinal Vein Occlusion: An Adaptive Optics Scanning Laser Ophthalmoscopy Study,” Am. J. Ophthalmol. 157(6), 1239–1249 (2014).
    [Crossref] [PubMed]
  9. D. A. Antonetti, R. Klein, and T. W. Gardner, “Diabetic Retinopathy,” N. Engl. J. Med. 366(13), 1227–1239 (2012).
    [Crossref] [PubMed]
  10. D. G. Cogan, D. Toussaint, and T. Kuwabara, “Retinal vascular patterns. IV. Diabetic retinopathy,” Arch. Ophthalmol. 66(3), 366–378 (1961).
    [Crossref] [PubMed]
  11. J. Lee, W. Wu, F. Lesage, and D. A. Boas, “Multiple-capillary measurement of RBC speed, flux, and density with optical coherence tomography,” J. Cereb. Blood Flow Metab. 33(11), 1707–1710 (2013).
    [Crossref] [PubMed]
  12. I. H. Sarelius and B. R. Duling, “Direct measurement of microvessel hematocrit, red cell flux, velocity, and transit time,” Am. J. Physiol. 243(6), H1018–H1026 (1982).
    [PubMed]
  13. D. Kleinfeld, P. P. Mitra, F. Helmchen, and W. Denk, “Fluctuations and stimulus-induced changes in blood flow observed in individual capillaries in layers 2 through 4 of rat neocortex,” Proc. Natl. Acad. Sci. U.S.A. 95(26), 15741–15746 (1998).
    [Crossref] [PubMed]
  14. 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).
    [Crossref] [PubMed]
  15. 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).
    [Crossref] [PubMed]
  16. J. Liang, D. R. Williams, and D. T. Miller, “Supernormal vision and high-resolution retinal imaging through adaptive optics,” J. Opt. Soc. Am. A 14(11), 2884–2892 (1997).
    [Crossref] [PubMed]
  17. J. Porter, Adaptive Optics for Vision Science: Principles, Practices, Design, and Applications (John Wiley and Sons, 2006).
  18. J. L. McWhirter, H. Noguchi, and G. Gompper, “Flow-induced clustering and alignment of vesicles and red blood cells in microcapillaries,” Proc. Natl. Acad. Sci. U.S.A. 106(15), 6039–6043 (2009).
    [Crossref] [PubMed]
  19. J. A. Martin and A. Roorda, “Direct and noninvasive assessment of parafoveal capillary leukocyte velocity,” Ophthalmology 112(12), 2219–2224 (2005).
    [Crossref] [PubMed]
  20. Z. Zhong, B. L. Petrig, X. Qi, and S. A. Burns, “In vivo measurement of erythrocyte velocity and retinal blood flow using adaptive optics scanning laser ophthalmoscopy,” Opt. Express 16(17), 12746–12756 (2008).
    [Crossref] [PubMed]
  21. Z. Zhong, H. Song, T. Y. P. Chui, B. L. Petrig, and S. A. Burns, “Noninvasive measurements and analysis of blood velocity profiles in human retinal vessels,” Invest. Ophthalmol. Vis. Sci. 52(7), 4151–4157 (2011).
    [Crossref] [PubMed]
  22. J. Tam, P. Tiruveedhula, and A. Roorda, “Characterization of single-file flow through human retinal parafoveal capillaries using an adaptive optics scanning laser ophthalmoscope,” Biomed. Opt. Express 2(4), 781–793 (2011).
    [Crossref] [PubMed]
  23. P. Bedggood and A. Metha, “Direct visualization and characterization of erythrocyte flow in human retinal capillaries,” Biomed. Opt. Express 3(12), 3264–3277 (2012).
    [Crossref] [PubMed]
  24. A. de Castro, G. Huang, L. Sawides, T. Luo, and S. A. Burns, “Rapid high resolution imaging with a dual-channel scanning technique,” Opt. Lett. 41(8), 1881–1884 (2016).
    [Crossref] [PubMed]
  25. A. Dubra, Z. Harvey, B. Fischer, B. M. Dawant, and C. Lorenz, “Registration of 2D Images from Fast Scanning Ophthalmic Instruments,” in Biomedical Image Registration, Lecture Notes in Computer Science No. 6204 (Springer Berlin Heidelberg, 1), pp. 60–71.
  26. J. A. Martin and A. Roorda, “Pulsatility of Parafoveal Capillary Leukocytes,” Exp. Eye Res. 88(3), 356–360 (2009).
    [Crossref] [PubMed]
  27. C. E. Riva, S. Harino, R. D. Shonat, and B. L. Petrig, “Flicker evoked increase in optic nerve head blood flow in anesthetized cats,” Neurosci. Lett. 128(2), 291–296 (1991).
    [Crossref] [PubMed]
  28. C. E. Riva, E. Logean, and B. Falsini, “Visually evoked hemodynamical response and assessment of neurovascular coupling in the optic nerve and retina,” Prog. Retin. Eye Res. 24(2), 183–215 (2005).
    [Crossref] [PubMed]
  29. J. Schallek, H. Li, R. Kardon, Y. Kwon, M. Abramoff, P. Soliz, and D. Ts’o, “Stimulus-Evoked Intrinsic Optical Signals in the Retina: Spatial and Temporal Characteristics,” Invest. Ophthalmol. Vis. Sci. 50(10), 4865–4872 (2009).
    [Crossref] [PubMed]
  30. J. Schallek and D. Ts’o, “Blood Contrast Agents Enhance Intrinsic Signals in the Retina: Evidence for an Underlying Blood Volume Component,” Invest. Ophthalmol. Vis. Sci. 52(3), 1325–1335 (2011).
    [Crossref] [PubMed]
  31. Z. Zhong, G. Huang, T. Y. P. Chui, B. L. Petrig, and S. A. Burns, “Local flicker stimulation evokes local retinal blood velocity changes,” J. Vis. 12(6), 3 (2012).
    [Crossref] [PubMed]
  32. M. J. Dumskyj, J. E. Eriksen, C. J. Doré, and E. M. Kohner, “Autoregulation in the Human Retinal Circulation: Assessment Using Isometric Exercise, Laser Doppler Velocimetry, and Computer-Assisted Image Analysis,” Microvasc. Res. 51(3), 378–392 (1996).
    [Crossref] [PubMed]
  33. Y. Zhang, O. San Emeterio Nateras, Q. Peng, C. A. Rosende, and T. Q. Duong, “Blood Flow MRI of the Human Retina/Choroid During Rest and Isometric Exercise,” Invest. Ophthalmol. Vis. Sci. 53(7), 4299–4305 (2012).
    [Crossref] [PubMed]
  34. T. J. H. Essex and P. O. Byrne, “A laser Doppler scanner for imaging blood flow in skin,” J. Biomed. Eng. 13(3), 189–194 (1991).
    [Crossref] [PubMed]
  35. B. R. Berg and I. H. Sarelius, “Erythrocyte flux in capillary networks during maturation: implications for oxygen delivery,” Am. J. Physiol. 271(6 Pt 2), H2263–H2273 (1996).
    [PubMed]
  36. ANSI, “American National Standard for Safe Use of Lasers,” ANSI Z136.1 (2014).
  37. G. Wyszecki and W. S. Stiles, Color Science: Concepts and Methods, Quantitative Data E Formulae (Wiley, 2000).
  38. G. Wald, “Human Vision and the Spectrum,” Science 101(2635), 653–658 (1945).
    [Crossref] [PubMed]
  39. Y. Geng, A. Dubra, L. Yin, W. H. Merigan, R. Sharma, R. T. Libby, and D. R. Williams, “Adaptive optics retinal imaging in the living mouse eye,” Biomed. Opt. Express 3(4), 715–734 (2012).
    [Crossref] [PubMed]
  40. A. Guevara-Torres, D. R. Williams, and J. B. Schallek, “Imaging translucent cell bodies in the living mouse retina without contrast agents,” Biomed. Opt. Express 6(6), 2106–2119 (2015).
    [Crossref] [PubMed]
  41. D. Scoles, Y. N. Sulai, C. S. Langlo, G. A. Fishman, C. A. Curcio, J. Carroll, and A. Dubra, “In Vivo Imaging of Human Cone Photoreceptor Inner Segments,” Invest. Ophthalmol. Vis. Sci. 55(7), 4244–4251 (2014).
    [Crossref] [PubMed]
  42. T. Y. P. Chui, D. A. Vannasdale, and S. A. Burns, “The use of forward scatter to improve retinal vascular imaging with an adaptive optics scanning laser ophthalmoscope,” Biomed. Opt. Express 3(10), 2537–2549 (2012).
    [Crossref] [PubMed]
  43. A. Dubra and Z. Harvey, “Registration of 2D Images from Fast Scanning Ophthalmic Instruments,” in Biomedical Image Registration, Lecture Notes in Computer Science (Springer Berlin / Heidelberg, 2010), Vol. 6204, pp. 60–71–71.
  44. J. Tam, J. A. Martin, and A. Roorda, “Noninvasive Visualization and Analysis of Parafoveal Capillaries in Humans,” Invest. Ophthalmol. Vis. Sci. 51(3), 1691–1698 (2010).
    [Crossref] [PubMed]
  45. S. Remtulla and P. E. Hallett, “A schematic eye for the mouse, and comparisons with the rat,” Vision Res. 25(1), 21–31 (1985).
    [Crossref] [PubMed]
  46. C. Schmucker and F. Schaeffel, “A paraxial schematic eye model for the growing C57BL/6 mouse,” Vision Res. 44(16), 1857–1867 (2004).
    [Crossref] [PubMed]
  47. The Jackson Laboratory: Mouse phenome database at the Jackson Laboratory, “Physiological Data Summary – C57BL/6J (000664),” (2007).
  48. R. M. Hochmuth, R. N. Marple, and S. P. Sutera, “Capillary blood flow. I. Erythrocyte deformation in glass capillaries,” Microvasc. Res. 2(4), 409–419 (1970).
    [Crossref] [PubMed]
  49. J. Schallek, Y. Geng, H. Nguyen, and D. R. Williams, “Morphology and Topography of Retinal Pericytes in the Living Mouse Retina Using In Vivo Adaptive Optics Imaging and Ex Vivo Characterization,” Invest. Ophthalmol. Vis. Sci. 54(13), 8237–8250 (2013).
    [Crossref] [PubMed]
  50. H. Vink and B. R. Duling, “Identification of Distinct Luminal Domains for Macromolecules, Erythrocytes, and Leukocytes Within Mammalian Capillaries,” Circ. Res. 79(3), 581–589 (1996).
    [Crossref] [PubMed]
  51. R. Skalak and P. I. Branemark, “Deformation of Red Blood Cells in Capillaries,” Science 164(3880), 717–719 (1969).
    [Crossref] [PubMed]
  52. J. H. Jeong, Y. Sugii, M. Minamiyama, and K. Okamoto, “Measurement of RBC deformation and velocity in capillaries in vivo,” Microvasc. Res. 71(3), 212–217 (2006).
    [Crossref] [PubMed]
  53. K. Y. Li and A. Roorda, “Automated identification of cone photoreceptors in adaptive optics retinal images,” J. Opt. Soc. Am. A 24(5), 1358–1363 (2007).
    [Crossref] [PubMed]
  54. J. L. McWhirter, H. Noguchi, and G. Gompper, “Flow-induced clustering and alignment of vesicles and red blood cells in microcapillaries,” Proc. Natl. Acad. Sci. U.S.A. 106(15), 6039–6043 (2009).
    [Crossref] [PubMed]
  55. M. Paques, R. Tadayoni, R. Sercombe, P. Laurent, O. Genevois, A. Gaudric, and E. Vicaut, “Structural and Hemodynamic Analysis of the Mouse Retinal Microcirculation,” Invest. Ophthalmol. Vis. Sci. 44(11), 4960–4967 (2003).
    [Crossref] [PubMed]
  56. N. E. Everds, “Chapter 5 - Hematology of the Laboratory Mouse A2,” in The Mouse in Biomedical Research, 2nd ed., M. T. Davisson, F. W. Quimby, S. W. Barthold, C. E. Newcomer, and A. L. Smith, eds. (Academic Press, 2007), pp. 133–153.
  57. T. E. Kornfield and E. A. Newman, “Regulation of Blood Flow in the Retinal Trilaminar Vascular Network,” J. Neurosci. 34(34), 11504–11513 (2014).
    [Crossref] [PubMed]
  58. L. Sargento, H. Sobral do Rosário, C. Saldanha, and J. Martins-Silva, “Hemorheological effects of sodium fluorescein in rats,” Clin. Hemorheol. Microcirc. 24(3), 175–181 (2001).
    [PubMed]
  59. S. P. Sutera, V. Seshadri, P. A. Croce, and R. M. Hochmuth, “Capillary blood flow. II. Deformable model cells in tube flow,” Microvasc. Res. 2(4), 420–433 (1970).
    [Crossref] [PubMed]
  60. A. R. Pries, T. W. Secomb, P. Gaehtgens, and J. F. Gross, “Blood flow in microvascular networks. Experiments and simulation,” Circ. Res. 67(4), 826–834 (1990).
    [Crossref] [PubMed]
  61. A. Parpaleix, Y. Goulam Houssen, and S. Charpak, “Imaging local neuronal activity by monitoring PO2 transients in capillaries,” Nat. Med. 19(2), 241–246 (2013).
    [Crossref] [PubMed]
  62. J. Lecoq, A. Parpaleix, E. Roussakis, M. Ducros, Y. Goulam Houssen, S. A. Vinogradov, and S. Charpak, “Simultaneous two-photon imaging of oxygen and blood flow in deep cerebral vessels,” Nat. Med. 17(7), 893–898 (2011).
    [Crossref] [PubMed]
  63. J. Perkkiö and R. Keskinen, “Hematocrit reduction in bifurcations due to plasma skimming,” Bull. Math. Biol. 45(1), 41–50 (1983).
    [Crossref] [PubMed]
  64. K. H. Albrecht, P. Gaehtgens, A. Pries, and M. Heuser, “The Fahraeus effect in narrow capillaries (i.d. 3.3 to 11.0 µm),” Microvasc. Res. 18(1), 33–47 (1979).
    [Crossref] [PubMed]
  65. F. Felberer, M. Rechenmacher, R. Haindl, B. Baumann, C. K. Hitzenberger, and M. Pircher, “Imaging of retinal vasculature using adaptive optics SLO/OCT,” Biomed. Opt. Express 6(4), 1407–1418 (2015).
    [Crossref] [PubMed]
  66. R. J. Zawadzki, P. Zhang, A. Zam, E. B. Miller, M. Goswami, X. Wang, R. S. Jonnal, S.-H. Lee, D. Y. Kim, J. G. Flannery, J. S. Werner, M. E. Burns, and E. N. Pugh., “Adaptive-optics SLO imaging combined with widefield OCT and SLO enables precise 3D localization of fluorescent cells in the mouse retina,” Biomed. Opt. Express 6(6), 2191–2210 (2015).
    [Crossref] [PubMed]
  67. T. E. de Carlo, A. Romano, N. K. Waheed, and J. S. Duker, “A review of optical coherence tomography angiography (OCTA),” International Journal of Retina and Vitreous 1(1), 5 (2015).
    [Crossref]
  68. C. Riva, B. Ross, and G. B. Benedek, “Laser Doppler Measurements of Blood Flow in Capillary Tubes and Retinal Arteries,” Invest. Ophthalmol. 11(11), 936–944 (1972).
    [PubMed]
  69. R. A. Leitgeb, R. M. Werkmeister, C. Blatter, and L. Schmetterer, “Doppler Optical Coherence Tomography,” Prog. Retin. Eye Res. 41, 26–43 (2014).
    [Crossref] [PubMed]
  70. D. A. Boas and A. K. Dunn, “Laser speckle contrast imaging in biomedical optics,” J. Biomed. Opt. 15, 11109 (2010).
  71. T. Sugiyama, M. Araie, C. E. Riva, L. Schmetterer, and S. Orgul, “Use of laser speckle flowgraphy in ocular blood flow research,” Acta Ophthalmol. 88(7), 723–729 (2010).
    [Crossref] [PubMed]
  72. B. Li, J. Lee, D. A. Boas, and F. Lesage, “Contribution of low- and high-flux capillaries to slow hemodynamic fluctuations in the cerebral cortex of mice,” J. Cereb. Blood Flow Metab. 36(8), 1351–1356 (2016).
    [Crossref] [PubMed]
  73. Y. Jia, J. C. Morrison, J. Tokayer, O. Tan, L. Lombardi, B. Baumann, C. D. Lu, W. Choi, J. G. Fujimoto, and D. Huang, “Quantitative OCT angiography of optic nerve head blood flow,” Biomed. Opt. Express 3(12), 3127–3137 (2012).
    [Crossref] [PubMed]
  74. C.-L. Chen, A. Zhang, K. D. Bojikian, J. C. Wen, Q. Zhang, C. Xin, R. C. Mudumbai, M. A. Johnstone, P. P. Chen, and R. K. Wang, “Peripapillary Retinal Nerve Fiber Layer Vascular Microcirculation in Glaucoma Using Optical Coherence Tomography-Based Microangiography,” Invest. Ophthalmol. Vis. Sci. 57(9), OCT475 (2016).
    [Crossref] [PubMed]
  75. Y. N. Sulai, D. Scoles, Z. Harvey, and A. Dubra, “Visualization of retinal vascular structure and perfusion with a nonconfocal adaptive optics scanning light ophthalmoscope,” J. Opt. Soc. Am. A 31(3), 569–579 (2014).
    [Crossref] [PubMed]
  76. Q. Yang, J. Zhang, K. Nozato, K. Saito, D. R. Williams, A. Roorda, and E. A. Rossi, “Closed-loop optical stabilization and digital image registration in adaptive optics scanning light ophthalmoscopy,” Biomed. Opt. Express 5(9), 3174–3191 (2014).
    [Crossref] [PubMed]
  77. J. Zhang, Q. Yang, K. Saito, K. Nozato, D. R. Williams, and E. A. Rossi, “An adaptive optics imaging system designed for clinical use,” Biomed. Opt. Express 6(6), 2120–2137 (2015).
    [Crossref] [PubMed]

2016 (4)

D. G. Lyons, A. Parpaleix, M. Roche, and S. Charpak, “Mapping oxygen concentration in the awake mouse brain,” eLife 5, e12024 (2016).
[Crossref] [PubMed]

B. Li, J. Lee, D. A. Boas, and F. Lesage, “Contribution of low- and high-flux capillaries to slow hemodynamic fluctuations in the cerebral cortex of mice,” J. Cereb. Blood Flow Metab. 36(8), 1351–1356 (2016).
[Crossref] [PubMed]

C.-L. Chen, A. Zhang, K. D. Bojikian, J. C. Wen, Q. Zhang, C. Xin, R. C. Mudumbai, M. A. Johnstone, P. P. Chen, and R. K. Wang, “Peripapillary Retinal Nerve Fiber Layer Vascular Microcirculation in Glaucoma Using Optical Coherence Tomography-Based Microangiography,” Invest. Ophthalmol. Vis. Sci. 57(9), OCT475 (2016).
[Crossref] [PubMed]

A. de Castro, G. Huang, L. Sawides, T. Luo, and S. A. Burns, “Rapid high resolution imaging with a dual-channel scanning technique,” Opt. Lett. 41(8), 1881–1884 (2016).
[Crossref] [PubMed]

2015 (5)

2014 (6)

R. A. Leitgeb, R. M. Werkmeister, C. Blatter, and L. Schmetterer, “Doppler Optical Coherence Tomography,” Prog. Retin. Eye Res. 41, 26–43 (2014).
[Crossref] [PubMed]

T. E. Kornfield and E. A. Newman, “Regulation of Blood Flow in the Retinal Trilaminar Vascular Network,” J. Neurosci. 34(34), 11504–11513 (2014).
[Crossref] [PubMed]

Y. N. Sulai, D. Scoles, Z. Harvey, and A. Dubra, “Visualization of retinal vascular structure and perfusion with a nonconfocal adaptive optics scanning light ophthalmoscope,” J. Opt. Soc. Am. A 31(3), 569–579 (2014).
[Crossref] [PubMed]

Q. Yang, J. Zhang, K. Nozato, K. Saito, D. R. Williams, A. Roorda, and E. A. Rossi, “Closed-loop optical stabilization and digital image registration in adaptive optics scanning light ophthalmoscopy,” Biomed. Opt. Express 5(9), 3174–3191 (2014).
[Crossref] [PubMed]

Y. Akagi-Kurashige, A. Tsujikawa, S. Ooto, Y. Makiyama, Y. Muraoka, K. Kumagai, A. Uji, S. Arichika, T. Murakami, K. Miyamoto, and N. Yoshimura, “Retinal Microstructural Changes in Eyes With Resolved Branch Retinal Vein Occlusion: An Adaptive Optics Scanning Laser Ophthalmoscopy Study,” Am. J. Ophthalmol. 157(6), 1239–1249 (2014).
[Crossref] [PubMed]

D. Scoles, Y. N. Sulai, C. S. Langlo, G. A. Fishman, C. A. Curcio, J. Carroll, and A. Dubra, “In Vivo Imaging of Human Cone Photoreceptor Inner Segments,” Invest. Ophthalmol. Vis. Sci. 55(7), 4244–4251 (2014).
[Crossref] [PubMed]

2013 (3)

J. Schallek, Y. Geng, H. Nguyen, and D. R. Williams, “Morphology and Topography of Retinal Pericytes in the Living Mouse Retina Using In Vivo Adaptive Optics Imaging and Ex Vivo Characterization,” Invest. Ophthalmol. Vis. Sci. 54(13), 8237–8250 (2013).
[Crossref] [PubMed]

J. Lee, W. Wu, F. Lesage, and D. A. Boas, “Multiple-capillary measurement of RBC speed, flux, and density with optical coherence tomography,” J. Cereb. Blood Flow Metab. 33(11), 1707–1710 (2013).
[Crossref] [PubMed]

A. Parpaleix, Y. Goulam Houssen, and S. Charpak, “Imaging local neuronal activity by monitoring PO2 transients in capillaries,” Nat. Med. 19(2), 241–246 (2013).
[Crossref] [PubMed]

2012 (8)

Y. Geng, A. Dubra, L. Yin, W. H. Merigan, R. Sharma, R. T. Libby, and D. R. Williams, “Adaptive optics retinal imaging in the living mouse eye,” Biomed. Opt. Express 3(4), 715–734 (2012).
[Crossref] [PubMed]

T. Y. P. Chui, D. A. Vannasdale, and S. A. Burns, “The use of forward scatter to improve retinal vascular imaging with an adaptive optics scanning laser ophthalmoscope,” Biomed. Opt. Express 3(10), 2537–2549 (2012).
[Crossref] [PubMed]

Y. Jia, J. C. Morrison, J. Tokayer, O. Tan, L. Lombardi, B. Baumann, C. D. Lu, W. Choi, J. G. Fujimoto, and D. Huang, “Quantitative OCT angiography of optic nerve head blood flow,” Biomed. Opt. Express 3(12), 3127–3137 (2012).
[Crossref] [PubMed]

P. Bedggood and A. Metha, “Direct visualization and characterization of erythrocyte flow in human retinal capillaries,” Biomed. Opt. Express 3(12), 3264–3277 (2012).
[Crossref] [PubMed]

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).
[Crossref] [PubMed]

D. A. Antonetti, R. Klein, and T. W. Gardner, “Diabetic Retinopathy,” N. Engl. J. Med. 366(13), 1227–1239 (2012).
[Crossref] [PubMed]

Z. Zhong, G. Huang, T. Y. P. Chui, B. L. Petrig, and S. A. Burns, “Local flicker stimulation evokes local retinal blood velocity changes,” J. Vis. 12(6), 3 (2012).
[Crossref] [PubMed]

Y. Zhang, O. San Emeterio Nateras, Q. Peng, C. A. Rosende, and T. Q. Duong, “Blood Flow MRI of the Human Retina/Choroid During Rest and Isometric Exercise,” Invest. Ophthalmol. Vis. Sci. 53(7), 4299–4305 (2012).
[Crossref] [PubMed]

2011 (5)

J. Schallek and D. Ts’o, “Blood Contrast Agents Enhance Intrinsic Signals in the Retina: Evidence for an Underlying Blood Volume Component,” Invest. Ophthalmol. Vis. Sci. 52(3), 1325–1335 (2011).
[Crossref] [PubMed]

Z. Zhong, H. Song, T. Y. P. Chui, B. L. Petrig, and S. A. Burns, “Noninvasive measurements and analysis of blood velocity profiles in human retinal vessels,” Invest. Ophthalmol. Vis. Sci. 52(7), 4151–4157 (2011).
[Crossref] [PubMed]

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).
[Crossref] [PubMed]

J. Tam, P. Tiruveedhula, and A. Roorda, “Characterization of single-file flow through human retinal parafoveal capillaries using an adaptive optics scanning laser ophthalmoscope,” Biomed. Opt. Express 2(4), 781–793 (2011).
[Crossref] [PubMed]

J. Lecoq, A. Parpaleix, E. Roussakis, M. Ducros, Y. Goulam Houssen, S. A. Vinogradov, and S. Charpak, “Simultaneous two-photon imaging of oxygen and blood flow in deep cerebral vessels,” Nat. Med. 17(7), 893–898 (2011).
[Crossref] [PubMed]

2010 (4)

D. A. Boas and A. K. Dunn, “Laser speckle contrast imaging in biomedical optics,” J. Biomed. Opt. 15, 11109 (2010).

T. Sugiyama, M. Araie, C. E. Riva, L. Schmetterer, and S. Orgul, “Use of laser speckle flowgraphy in ocular blood flow research,” Acta Ophthalmol. 88(7), 723–729 (2010).
[Crossref] [PubMed]

M. T. T. Wong-Riley, “Energy metabolism of the visual system,” Eye Brain 2, 99–116 (2010).
[Crossref] [PubMed]

J. Tam, J. A. Martin, and A. Roorda, “Noninvasive Visualization and Analysis of Parafoveal Capillaries in Humans,” Invest. Ophthalmol. Vis. Sci. 51(3), 1691–1698 (2010).
[Crossref] [PubMed]

2009 (4)

J. L. McWhirter, H. Noguchi, and G. Gompper, “Flow-induced clustering and alignment of vesicles and red blood cells in microcapillaries,” Proc. Natl. Acad. Sci. U.S.A. 106(15), 6039–6043 (2009).
[Crossref] [PubMed]

J. Schallek, H. Li, R. Kardon, Y. Kwon, M. Abramoff, P. Soliz, and D. Ts’o, “Stimulus-Evoked Intrinsic Optical Signals in the Retina: Spatial and Temporal Characteristics,” Invest. Ophthalmol. Vis. Sci. 50(10), 4865–4872 (2009).
[Crossref] [PubMed]

J. A. Martin and A. Roorda, “Pulsatility of Parafoveal Capillary Leukocytes,” Exp. Eye Res. 88(3), 356–360 (2009).
[Crossref] [PubMed]

J. L. McWhirter, H. Noguchi, and G. Gompper, “Flow-induced clustering and alignment of vesicles and red blood cells in microcapillaries,” Proc. Natl. Acad. Sci. U.S.A. 106(15), 6039–6043 (2009).
[Crossref] [PubMed]

2008 (1)

2007 (1)

2006 (1)

J. H. Jeong, Y. Sugii, M. Minamiyama, and K. Okamoto, “Measurement of RBC deformation and velocity in capillaries in vivo,” Microvasc. Res. 71(3), 212–217 (2006).
[Crossref] [PubMed]

2005 (2)

C. E. Riva, E. Logean, and B. Falsini, “Visually evoked hemodynamical response and assessment of neurovascular coupling in the optic nerve and retina,” Prog. Retin. Eye Res. 24(2), 183–215 (2005).
[Crossref] [PubMed]

J. A. Martin and A. Roorda, “Direct and noninvasive assessment of parafoveal capillary leukocyte velocity,” Ophthalmology 112(12), 2219–2224 (2005).
[Crossref] [PubMed]

2004 (2)

C. Schmucker and F. Schaeffel, “A paraxial schematic eye model for the growing C57BL/6 mouse,” Vision Res. 44(16), 1857–1867 (2004).
[Crossref] [PubMed]

D. S. Fong, L. P. Aiello, F. L. Ferris, and R. Klein, “Diabetic Retinopathy,” Diabetes Care 27(10), 2540–2553 (2004).
[Crossref] [PubMed]

2003 (2)

P. Lennie, “The Cost of Cortical Computation,” Curr. Biol. 13(6), 493–497 (2003).
[Crossref] [PubMed]

M. Paques, R. Tadayoni, R. Sercombe, P. Laurent, O. Genevois, A. Gaudric, and E. Vicaut, “Structural and Hemodynamic Analysis of the Mouse Retinal Microcirculation,” Invest. Ophthalmol. Vis. Sci. 44(11), 4960–4967 (2003).
[Crossref] [PubMed]

2001 (1)

L. Sargento, H. Sobral do Rosário, C. Saldanha, and J. Martins-Silva, “Hemorheological effects of sodium fluorescein in rats,” Clin. Hemorheol. Microcirc. 24(3), 175–181 (2001).
[PubMed]

1998 (1)

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

1997 (1)

1996 (3)

H. Vink and B. R. Duling, “Identification of Distinct Luminal Domains for Macromolecules, Erythrocytes, and Leukocytes Within Mammalian Capillaries,” Circ. Res. 79(3), 581–589 (1996).
[Crossref] [PubMed]

M. J. Dumskyj, J. E. Eriksen, C. J. Doré, and E. M. Kohner, “Autoregulation in the Human Retinal Circulation: Assessment Using Isometric Exercise, Laser Doppler Velocimetry, and Computer-Assisted Image Analysis,” Microvasc. Res. 51(3), 378–392 (1996).
[Crossref] [PubMed]

B. R. Berg and I. H. Sarelius, “Erythrocyte flux in capillary networks during maturation: implications for oxygen delivery,” Am. J. Physiol. 271(6 Pt 2), H2263–H2273 (1996).
[PubMed]

1991 (2)

T. J. H. Essex and P. O. Byrne, “A laser Doppler scanner for imaging blood flow in skin,” J. Biomed. Eng. 13(3), 189–194 (1991).
[Crossref] [PubMed]

C. E. Riva, S. Harino, R. D. Shonat, and B. L. Petrig, “Flicker evoked increase in optic nerve head blood flow in anesthetized cats,” Neurosci. Lett. 128(2), 291–296 (1991).
[Crossref] [PubMed]

1990 (1)

A. R. Pries, T. W. Secomb, P. Gaehtgens, and J. F. Gross, “Blood flow in microvascular networks. Experiments and simulation,” Circ. Res. 67(4), 826–834 (1990).
[Crossref] [PubMed]

1985 (1)

S. Remtulla and P. E. Hallett, “A schematic eye for the mouse, and comparisons with the rat,” Vision Res. 25(1), 21–31 (1985).
[Crossref] [PubMed]

1984 (2)

R. Klein, B. E. K. Klein, S. E. Moss, M. D. Davis, and D. L. DeMets, “The Wisconsin Epidemiologic Study of Diabetic Retinopathy. III. Prevalence and Risk of Diabetic Retinopathy When Age at Diagnosis Is 30 or More Years,” Arch. Ophthalmol. 102(4), 527–532 (1984).
[Crossref] [PubMed]

R. Klein, B. E. Klein, S. E. Moss, M. D. Davis, and D. L. DeMets, “The Wisconsin epidemiologic study of diabetic retinopathy. IV. Diabetic macular edema,” Ophthalmology 91(12), 1464–1474 (1984).
[Crossref] [PubMed]

1983 (1)

J. Perkkiö and R. Keskinen, “Hematocrit reduction in bifurcations due to plasma skimming,” Bull. Math. Biol. 45(1), 41–50 (1983).
[Crossref] [PubMed]

1982 (1)

I. H. Sarelius and B. R. Duling, “Direct measurement of microvessel hematocrit, red cell flux, velocity, and transit time,” Am. J. Physiol. 243(6), H1018–H1026 (1982).
[PubMed]

1979 (1)

K. H. Albrecht, P. Gaehtgens, A. Pries, and M. Heuser, “The Fahraeus effect in narrow capillaries (i.d. 3.3 to 11.0 µm),” Microvasc. Res. 18(1), 33–47 (1979).
[Crossref] [PubMed]

1972 (1)

C. Riva, B. Ross, and G. B. Benedek, “Laser Doppler Measurements of Blood Flow in Capillary Tubes and Retinal Arteries,” Invest. Ophthalmol. 11(11), 936–944 (1972).
[PubMed]

1970 (2)

S. P. Sutera, V. Seshadri, P. A. Croce, and R. M. Hochmuth, “Capillary blood flow. II. Deformable model cells in tube flow,” Microvasc. Res. 2(4), 420–433 (1970).
[Crossref] [PubMed]

R. M. Hochmuth, R. N. Marple, and S. P. Sutera, “Capillary blood flow. I. Erythrocyte deformation in glass capillaries,” Microvasc. Res. 2(4), 409–419 (1970).
[Crossref] [PubMed]

1969 (1)

R. Skalak and P. I. Branemark, “Deformation of Red Blood Cells in Capillaries,” Science 164(3880), 717–719 (1969).
[Crossref] [PubMed]

1961 (1)

D. G. Cogan, D. Toussaint, and T. Kuwabara, “Retinal vascular patterns. IV. Diabetic retinopathy,” Arch. Ophthalmol. 66(3), 366–378 (1961).
[Crossref] [PubMed]

1945 (1)

G. Wald, “Human Vision and the Spectrum,” Science 101(2635), 653–658 (1945).
[Crossref] [PubMed]

Abramoff, M.

J. Schallek, H. Li, R. Kardon, Y. Kwon, M. Abramoff, P. Soliz, and D. Ts’o, “Stimulus-Evoked Intrinsic Optical Signals in the Retina: Spatial and Temporal Characteristics,” Invest. Ophthalmol. Vis. Sci. 50(10), 4865–4872 (2009).
[Crossref] [PubMed]

Aiello, L. P.

D. S. Fong, L. P. Aiello, F. L. Ferris, and R. Klein, “Diabetic Retinopathy,” Diabetes Care 27(10), 2540–2553 (2004).
[Crossref] [PubMed]

Akagi-Kurashige, Y.

Y. Akagi-Kurashige, A. Tsujikawa, S. Ooto, Y. Makiyama, Y. Muraoka, K. Kumagai, A. Uji, S. Arichika, T. Murakami, K. Miyamoto, and N. Yoshimura, “Retinal Microstructural Changes in Eyes With Resolved Branch Retinal Vein Occlusion: An Adaptive Optics Scanning Laser Ophthalmoscopy Study,” Am. J. Ophthalmol. 157(6), 1239–1249 (2014).
[Crossref] [PubMed]

Albrecht, K. H.

K. H. Albrecht, P. Gaehtgens, A. Pries, and M. Heuser, “The Fahraeus effect in narrow capillaries (i.d. 3.3 to 11.0 µm),” Microvasc. Res. 18(1), 33–47 (1979).
[Crossref] [PubMed]

Antonetti, D. A.

D. A. Antonetti, R. Klein, and T. W. Gardner, “Diabetic Retinopathy,” N. Engl. J. Med. 366(13), 1227–1239 (2012).
[Crossref] [PubMed]

Araie, M.

T. Sugiyama, M. Araie, C. E. Riva, L. Schmetterer, and S. Orgul, “Use of laser speckle flowgraphy in ocular blood flow research,” Acta Ophthalmol. 88(7), 723–729 (2010).
[Crossref] [PubMed]

Arichika, S.

Y. Akagi-Kurashige, A. Tsujikawa, S. Ooto, Y. Makiyama, Y. Muraoka, K. Kumagai, A. Uji, S. Arichika, T. Murakami, K. Miyamoto, and N. Yoshimura, “Retinal Microstructural Changes in Eyes With Resolved Branch Retinal Vein Occlusion: An Adaptive Optics Scanning Laser Ophthalmoscopy Study,” Am. J. Ophthalmol. 157(6), 1239–1249 (2014).
[Crossref] [PubMed]

Baumann, B.

Bedggood, P.

Benedek, G. B.

C. Riva, B. Ross, and G. B. Benedek, “Laser Doppler Measurements of Blood Flow in Capillary Tubes and Retinal Arteries,” Invest. Ophthalmol. 11(11), 936–944 (1972).
[PubMed]

Berg, B. R.

B. R. Berg and I. H. Sarelius, “Erythrocyte flux in capillary networks during maturation: implications for oxygen delivery,” Am. J. Physiol. 271(6 Pt 2), H2263–H2273 (1996).
[PubMed]

Blatter, C.

R. A. Leitgeb, R. M. Werkmeister, C. Blatter, and L. Schmetterer, “Doppler Optical Coherence Tomography,” Prog. Retin. Eye Res. 41, 26–43 (2014).
[Crossref] [PubMed]

Boas, D. A.

B. Li, J. Lee, D. A. Boas, and F. Lesage, “Contribution of low- and high-flux capillaries to slow hemodynamic fluctuations in the cerebral cortex of mice,” J. Cereb. Blood Flow Metab. 36(8), 1351–1356 (2016).
[Crossref] [PubMed]

J. Lee, W. Wu, F. Lesage, and D. A. Boas, “Multiple-capillary measurement of RBC speed, flux, and density with optical coherence tomography,” J. Cereb. Blood Flow Metab. 33(11), 1707–1710 (2013).
[Crossref] [PubMed]

D. A. Boas and A. K. Dunn, “Laser speckle contrast imaging in biomedical optics,” J. Biomed. Opt. 15, 11109 (2010).

Bojikian, K. D.

C.-L. Chen, A. Zhang, K. D. Bojikian, J. C. Wen, Q. Zhang, C. Xin, R. C. Mudumbai, M. A. Johnstone, P. P. Chen, and R. K. Wang, “Peripapillary Retinal Nerve Fiber Layer Vascular Microcirculation in Glaucoma Using Optical Coherence Tomography-Based Microangiography,” Invest. Ophthalmol. Vis. Sci. 57(9), OCT475 (2016).
[Crossref] [PubMed]

Branemark, P. I.

R. Skalak and P. I. Branemark, “Deformation of Red Blood Cells in Capillaries,” Science 164(3880), 717–719 (1969).
[Crossref] [PubMed]

Burns, M. E.

Burns, S. A.

Byrne, P. O.

T. J. H. Essex and P. O. Byrne, “A laser Doppler scanner for imaging blood flow in skin,” J. Biomed. Eng. 13(3), 189–194 (1991).
[Crossref] [PubMed]

Carroll, J.

D. Scoles, Y. N. Sulai, C. S. Langlo, G. A. Fishman, C. A. Curcio, J. Carroll, and A. Dubra, “In Vivo Imaging of Human Cone Photoreceptor Inner Segments,” Invest. Ophthalmol. Vis. Sci. 55(7), 4244–4251 (2014).
[Crossref] [PubMed]

Charpak, S.

D. G. Lyons, A. Parpaleix, M. Roche, and S. Charpak, “Mapping oxygen concentration in the awake mouse brain,” eLife 5, e12024 (2016).
[Crossref] [PubMed]

A. Parpaleix, Y. Goulam Houssen, and S. Charpak, “Imaging local neuronal activity by monitoring PO2 transients in capillaries,” Nat. Med. 19(2), 241–246 (2013).
[Crossref] [PubMed]

J. Lecoq, A. Parpaleix, E. Roussakis, M. Ducros, Y. Goulam Houssen, S. A. Vinogradov, and S. Charpak, “Simultaneous two-photon imaging of oxygen and blood flow in deep cerebral vessels,” Nat. Med. 17(7), 893–898 (2011).
[Crossref] [PubMed]

Chen, C.-L.

C.-L. Chen, A. Zhang, K. D. Bojikian, J. C. Wen, Q. Zhang, C. Xin, R. C. Mudumbai, M. A. Johnstone, P. P. Chen, and R. K. Wang, “Peripapillary Retinal Nerve Fiber Layer Vascular Microcirculation in Glaucoma Using Optical Coherence Tomography-Based Microangiography,” Invest. Ophthalmol. Vis. Sci. 57(9), OCT475 (2016).
[Crossref] [PubMed]

Chen, P. P.

C.-L. Chen, A. Zhang, K. D. Bojikian, J. C. Wen, Q. Zhang, C. Xin, R. C. Mudumbai, M. A. Johnstone, P. P. Chen, and R. K. Wang, “Peripapillary Retinal Nerve Fiber Layer Vascular Microcirculation in Glaucoma Using Optical Coherence Tomography-Based Microangiography,” Invest. Ophthalmol. Vis. Sci. 57(9), OCT475 (2016).
[Crossref] [PubMed]

Choi, W.

Chui, T. Y. P.

T. Y. P. Chui, D. A. Vannasdale, and S. A. Burns, “The use of forward scatter to improve retinal vascular imaging with an adaptive optics scanning laser ophthalmoscope,” Biomed. Opt. Express 3(10), 2537–2549 (2012).
[Crossref] [PubMed]

Z. Zhong, G. Huang, T. Y. P. Chui, B. L. Petrig, and S. A. Burns, “Local flicker stimulation evokes local retinal blood velocity changes,” J. Vis. 12(6), 3 (2012).
[Crossref] [PubMed]

Z. Zhong, H. Song, T. Y. P. Chui, B. L. Petrig, and S. A. Burns, “Noninvasive measurements and analysis of blood velocity profiles in human retinal vessels,” Invest. Ophthalmol. Vis. Sci. 52(7), 4151–4157 (2011).
[Crossref] [PubMed]

Cogan, D. G.

D. G. Cogan, D. Toussaint, and T. Kuwabara, “Retinal vascular patterns. IV. Diabetic retinopathy,” Arch. Ophthalmol. 66(3), 366–378 (1961).
[Crossref] [PubMed]

Croce, P. A.

S. P. Sutera, V. Seshadri, P. A. Croce, and R. M. Hochmuth, “Capillary blood flow. II. Deformable model cells in tube flow,” Microvasc. Res. 2(4), 420–433 (1970).
[Crossref] [PubMed]

Curcio, C. A.

D. Scoles, Y. N. Sulai, C. S. Langlo, G. A. Fishman, C. A. Curcio, J. Carroll, and A. Dubra, “In Vivo Imaging of Human Cone Photoreceptor Inner Segments,” Invest. Ophthalmol. Vis. Sci. 55(7), 4244–4251 (2014).
[Crossref] [PubMed]

Davis, M. D.

R. Klein, B. E. K. Klein, S. E. Moss, M. D. Davis, and D. L. DeMets, “The Wisconsin Epidemiologic Study of Diabetic Retinopathy. III. Prevalence and Risk of Diabetic Retinopathy When Age at Diagnosis Is 30 or More Years,” Arch. Ophthalmol. 102(4), 527–532 (1984).
[Crossref] [PubMed]

R. Klein, B. E. Klein, S. E. Moss, M. D. Davis, and D. L. DeMets, “The Wisconsin epidemiologic study of diabetic retinopathy. IV. Diabetic macular edema,” Ophthalmology 91(12), 1464–1474 (1984).
[Crossref] [PubMed]

de Carlo, T. E.

T. E. de Carlo, A. Romano, N. K. Waheed, and J. S. Duker, “A review of optical coherence tomography angiography (OCTA),” International Journal of Retina and Vitreous 1(1), 5 (2015).
[Crossref]

de Castro, A.

DeMets, D. L.

R. Klein, B. E. Klein, S. E. Moss, M. D. Davis, and D. L. DeMets, “The Wisconsin epidemiologic study of diabetic retinopathy. IV. Diabetic macular edema,” Ophthalmology 91(12), 1464–1474 (1984).
[Crossref] [PubMed]

R. Klein, B. E. K. Klein, S. E. Moss, M. D. Davis, and D. L. DeMets, “The Wisconsin Epidemiologic Study of Diabetic Retinopathy. III. Prevalence and Risk of Diabetic Retinopathy When Age at Diagnosis Is 30 or More Years,” Arch. Ophthalmol. 102(4), 527–532 (1984).
[Crossref] [PubMed]

Denk, W.

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

Doré, C. J.

M. J. Dumskyj, J. E. Eriksen, C. J. Doré, and E. M. Kohner, “Autoregulation in the Human Retinal Circulation: Assessment Using Isometric Exercise, Laser Doppler Velocimetry, and Computer-Assisted Image Analysis,” Microvasc. Res. 51(3), 378–392 (1996).
[Crossref] [PubMed]

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).
[Crossref] [PubMed]

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).
[Crossref] [PubMed]

Dubra, A.

Ducros, M.

J. Lecoq, A. Parpaleix, E. Roussakis, M. Ducros, Y. Goulam Houssen, S. A. Vinogradov, and S. Charpak, “Simultaneous two-photon imaging of oxygen and blood flow in deep cerebral vessels,” Nat. Med. 17(7), 893–898 (2011).
[Crossref] [PubMed]

Duker, J. S.

T. E. de Carlo, A. Romano, N. K. Waheed, and J. S. Duker, “A review of optical coherence tomography angiography (OCTA),” International Journal of Retina and Vitreous 1(1), 5 (2015).
[Crossref]

Duling, B. R.

H. Vink and B. R. Duling, “Identification of Distinct Luminal Domains for Macromolecules, Erythrocytes, and Leukocytes Within Mammalian Capillaries,” Circ. Res. 79(3), 581–589 (1996).
[Crossref] [PubMed]

I. H. Sarelius and B. R. Duling, “Direct measurement of microvessel hematocrit, red cell flux, velocity, and transit time,” Am. J. Physiol. 243(6), H1018–H1026 (1982).
[PubMed]

Dumskyj, M. J.

M. J. Dumskyj, J. E. Eriksen, C. J. Doré, and E. M. Kohner, “Autoregulation in the Human Retinal Circulation: Assessment Using Isometric Exercise, Laser Doppler Velocimetry, and Computer-Assisted Image Analysis,” Microvasc. Res. 51(3), 378–392 (1996).
[Crossref] [PubMed]

Dunn, A. K.

D. A. Boas and A. K. Dunn, “Laser speckle contrast imaging in biomedical optics,” J. Biomed. Opt. 15, 11109 (2010).

Duong, T. Q.

Y. Zhang, O. San Emeterio Nateras, Q. Peng, C. A. Rosende, and T. Q. Duong, “Blood Flow MRI of the Human Retina/Choroid During Rest and Isometric Exercise,” Invest. Ophthalmol. Vis. Sci. 53(7), 4299–4305 (2012).
[Crossref] [PubMed]

Eriksen, J. E.

M. J. Dumskyj, J. E. Eriksen, C. J. Doré, and E. M. Kohner, “Autoregulation in the Human Retinal Circulation: Assessment Using Isometric Exercise, Laser Doppler Velocimetry, and Computer-Assisted Image Analysis,” Microvasc. Res. 51(3), 378–392 (1996).
[Crossref] [PubMed]

Essex, T. J. H.

T. J. H. Essex and P. O. Byrne, “A laser Doppler scanner for imaging blood flow in skin,” J. Biomed. Eng. 13(3), 189–194 (1991).
[Crossref] [PubMed]

Falsini, B.

C. E. Riva, E. Logean, and B. Falsini, “Visually evoked hemodynamical response and assessment of neurovascular coupling in the optic nerve and retina,” Prog. Retin. Eye Res. 24(2), 183–215 (2005).
[Crossref] [PubMed]

Felberer, F.

Ferris, F. L.

D. S. Fong, L. P. Aiello, F. L. Ferris, and R. Klein, “Diabetic Retinopathy,” Diabetes Care 27(10), 2540–2553 (2004).
[Crossref] [PubMed]

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).
[Crossref] [PubMed]

Fishman, G. A.

D. Scoles, Y. N. Sulai, C. S. Langlo, G. A. Fishman, C. A. Curcio, J. Carroll, and A. Dubra, “In Vivo Imaging of Human Cone Photoreceptor Inner Segments,” Invest. Ophthalmol. Vis. Sci. 55(7), 4244–4251 (2014).
[Crossref] [PubMed]

Flannery, J. G.

Fong, D. S.

D. S. Fong, L. P. Aiello, F. L. Ferris, and R. Klein, “Diabetic Retinopathy,” Diabetes Care 27(10), 2540–2553 (2004).
[Crossref] [PubMed]

Fujimoto, J. G.

Gaehtgens, P.

A. R. Pries, T. W. Secomb, P. Gaehtgens, and J. F. Gross, “Blood flow in microvascular networks. Experiments and simulation,” Circ. Res. 67(4), 826–834 (1990).
[Crossref] [PubMed]

K. H. Albrecht, P. Gaehtgens, A. Pries, and M. Heuser, “The Fahraeus effect in narrow capillaries (i.d. 3.3 to 11.0 µm),” Microvasc. Res. 18(1), 33–47 (1979).
[Crossref] [PubMed]

Gardner, T. W.

D. A. Antonetti, R. Klein, and T. W. Gardner, “Diabetic Retinopathy,” N. Engl. J. Med. 366(13), 1227–1239 (2012).
[Crossref] [PubMed]

Gaudric, A.

M. Paques, R. Tadayoni, R. Sercombe, P. Laurent, O. Genevois, A. Gaudric, and E. Vicaut, “Structural and Hemodynamic Analysis of the Mouse Retinal Microcirculation,” Invest. Ophthalmol. Vis. Sci. 44(11), 4960–4967 (2003).
[Crossref] [PubMed]

Genevois, O.

M. Paques, R. Tadayoni, R. Sercombe, P. Laurent, O. Genevois, A. Gaudric, and E. Vicaut, “Structural and Hemodynamic Analysis of the Mouse Retinal Microcirculation,” Invest. Ophthalmol. Vis. Sci. 44(11), 4960–4967 (2003).
[Crossref] [PubMed]

Geng, Y.

J. Schallek, Y. Geng, H. Nguyen, and D. R. Williams, “Morphology and Topography of Retinal Pericytes in the Living Mouse Retina Using In Vivo Adaptive Optics Imaging and Ex Vivo Characterization,” Invest. Ophthalmol. Vis. Sci. 54(13), 8237–8250 (2013).
[Crossref] [PubMed]

Y. Geng, A. Dubra, L. Yin, W. H. Merigan, R. Sharma, R. T. Libby, and D. R. Williams, “Adaptive optics retinal imaging in the living mouse eye,” Biomed. Opt. Express 3(4), 715–734 (2012).
[Crossref] [PubMed]

Gompper, G.

J. L. McWhirter, H. Noguchi, and G. Gompper, “Flow-induced clustering and alignment of vesicles and red blood cells in microcapillaries,” Proc. Natl. Acad. Sci. U.S.A. 106(15), 6039–6043 (2009).
[Crossref] [PubMed]

J. L. McWhirter, H. Noguchi, and G. Gompper, “Flow-induced clustering and alignment of vesicles and red blood cells in microcapillaries,” Proc. Natl. Acad. Sci. U.S.A. 106(15), 6039–6043 (2009).
[Crossref] [PubMed]

Goswami, M.

Goulam Houssen, Y.

A. Parpaleix, Y. Goulam Houssen, and S. Charpak, “Imaging local neuronal activity by monitoring PO2 transients in capillaries,” Nat. Med. 19(2), 241–246 (2013).
[Crossref] [PubMed]

J. Lecoq, A. Parpaleix, E. Roussakis, M. Ducros, Y. Goulam Houssen, S. A. Vinogradov, and S. Charpak, “Simultaneous two-photon imaging of oxygen and blood flow in deep cerebral vessels,” Nat. Med. 17(7), 893–898 (2011).
[Crossref] [PubMed]

Gross, J. F.

A. R. Pries, T. W. Secomb, P. Gaehtgens, and J. F. Gross, “Blood flow in microvascular networks. Experiments and simulation,” Circ. Res. 67(4), 826–834 (1990).
[Crossref] [PubMed]

Guevara-Torres, A.

Haindl, R.

Hallett, P. E.

S. Remtulla and P. E. Hallett, “A schematic eye for the mouse, and comparisons with the rat,” Vision Res. 25(1), 21–31 (1985).
[Crossref] [PubMed]

Harino, S.

C. E. Riva, S. Harino, R. D. Shonat, and B. L. Petrig, “Flicker evoked increase in optic nerve head blood flow in anesthetized cats,” Neurosci. Lett. 128(2), 291–296 (1991).
[Crossref] [PubMed]

Harvey, Z.

Helmchen, F.

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

Heuser, M.

K. H. Albrecht, P. Gaehtgens, A. Pries, and M. Heuser, “The Fahraeus effect in narrow capillaries (i.d. 3.3 to 11.0 µm),” Microvasc. Res. 18(1), 33–47 (1979).
[Crossref] [PubMed]

Hitzenberger, C. K.

Hochmuth, R. M.

S. P. Sutera, V. Seshadri, P. A. Croce, and R. M. Hochmuth, “Capillary blood flow. II. Deformable model cells in tube flow,” Microvasc. Res. 2(4), 420–433 (1970).
[Crossref] [PubMed]

R. M. Hochmuth, R. N. Marple, and S. P. Sutera, “Capillary blood flow. I. Erythrocyte deformation in glass capillaries,” Microvasc. Res. 2(4), 409–419 (1970).
[Crossref] [PubMed]

Huang, D.

Huang, G.

A. de Castro, G. Huang, L. Sawides, T. Luo, and S. A. Burns, “Rapid high resolution imaging with a dual-channel scanning technique,” Opt. Lett. 41(8), 1881–1884 (2016).
[Crossref] [PubMed]

Z. Zhong, G. Huang, T. Y. P. Chui, B. L. Petrig, and S. A. Burns, “Local flicker stimulation evokes local retinal blood velocity changes,” J. Vis. 12(6), 3 (2012).
[Crossref] [PubMed]

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).
[Crossref] [PubMed]

Jeong, J. H.

J. H. Jeong, Y. Sugii, M. Minamiyama, and K. Okamoto, “Measurement of RBC deformation and velocity in capillaries in vivo,” Microvasc. Res. 71(3), 212–217 (2006).
[Crossref] [PubMed]

Jia, Y.

Johnstone, M. A.

C.-L. Chen, A. Zhang, K. D. Bojikian, J. C. Wen, Q. Zhang, C. Xin, R. C. Mudumbai, M. A. Johnstone, P. P. Chen, and R. K. Wang, “Peripapillary Retinal Nerve Fiber Layer Vascular Microcirculation in Glaucoma Using Optical Coherence Tomography-Based Microangiography,” Invest. Ophthalmol. Vis. Sci. 57(9), OCT475 (2016).
[Crossref] [PubMed]

Jonnal, R. S.

Kardon, R.

J. Schallek, H. Li, R. Kardon, Y. Kwon, M. Abramoff, P. Soliz, and D. Ts’o, “Stimulus-Evoked Intrinsic Optical Signals in the Retina: Spatial and Temporal Characteristics,” Invest. Ophthalmol. Vis. Sci. 50(10), 4865–4872 (2009).
[Crossref] [PubMed]

Keskinen, R.

J. Perkkiö and R. Keskinen, “Hematocrit reduction in bifurcations due to plasma skimming,” Bull. Math. Biol. 45(1), 41–50 (1983).
[Crossref] [PubMed]

Kim, D. Y.

Klein, B. E.

R. Klein, B. E. Klein, S. E. Moss, M. D. Davis, and D. L. DeMets, “The Wisconsin epidemiologic study of diabetic retinopathy. IV. Diabetic macular edema,” Ophthalmology 91(12), 1464–1474 (1984).
[Crossref] [PubMed]

Klein, B. E. K.

R. Klein, B. E. K. Klein, S. E. Moss, M. D. Davis, and D. L. DeMets, “The Wisconsin Epidemiologic Study of Diabetic Retinopathy. III. Prevalence and Risk of Diabetic Retinopathy When Age at Diagnosis Is 30 or More Years,” Arch. Ophthalmol. 102(4), 527–532 (1984).
[Crossref] [PubMed]

Klein, R.

D. A. Antonetti, R. Klein, and T. W. Gardner, “Diabetic Retinopathy,” N. Engl. J. Med. 366(13), 1227–1239 (2012).
[Crossref] [PubMed]

D. S. Fong, L. P. Aiello, F. L. Ferris, and R. Klein, “Diabetic Retinopathy,” Diabetes Care 27(10), 2540–2553 (2004).
[Crossref] [PubMed]

R. Klein, B. E. K. Klein, S. E. Moss, M. D. Davis, and D. L. DeMets, “The Wisconsin Epidemiologic Study of Diabetic Retinopathy. III. Prevalence and Risk of Diabetic Retinopathy When Age at Diagnosis Is 30 or More Years,” Arch. Ophthalmol. 102(4), 527–532 (1984).
[Crossref] [PubMed]

R. Klein, B. E. Klein, S. E. Moss, M. D. Davis, and D. L. DeMets, “The Wisconsin epidemiologic study of diabetic retinopathy. IV. Diabetic macular edema,” Ophthalmology 91(12), 1464–1474 (1984).
[Crossref] [PubMed]

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).
[Crossref] [PubMed]

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

Kohner, E. M.

M. J. Dumskyj, J. E. Eriksen, C. J. Doré, and E. M. Kohner, “Autoregulation in the Human Retinal Circulation: Assessment Using Isometric Exercise, Laser Doppler Velocimetry, and Computer-Assisted Image Analysis,” Microvasc. Res. 51(3), 378–392 (1996).
[Crossref] [PubMed]

Kornfield, T. E.

T. E. Kornfield and E. A. Newman, “Regulation of Blood Flow in the Retinal Trilaminar Vascular Network,” J. Neurosci. 34(34), 11504–11513 (2014).
[Crossref] [PubMed]

Kumagai, K.

Y. Akagi-Kurashige, A. Tsujikawa, S. Ooto, Y. Makiyama, Y. Muraoka, K. Kumagai, A. Uji, S. Arichika, T. Murakami, K. Miyamoto, and N. Yoshimura, “Retinal Microstructural Changes in Eyes With Resolved Branch Retinal Vein Occlusion: An Adaptive Optics Scanning Laser Ophthalmoscopy Study,” Am. J. Ophthalmol. 157(6), 1239–1249 (2014).
[Crossref] [PubMed]

Kuwabara, T.

D. G. Cogan, D. Toussaint, and T. Kuwabara, “Retinal vascular patterns. IV. Diabetic retinopathy,” Arch. Ophthalmol. 66(3), 366–378 (1961).
[Crossref] [PubMed]

Kwon, Y.

J. Schallek, H. Li, R. Kardon, Y. Kwon, M. Abramoff, P. Soliz, and D. Ts’o, “Stimulus-Evoked Intrinsic Optical Signals in the Retina: Spatial and Temporal Characteristics,” Invest. Ophthalmol. Vis. Sci. 50(10), 4865–4872 (2009).
[Crossref] [PubMed]

Langlo, C. S.

D. Scoles, Y. N. Sulai, C. S. Langlo, G. A. Fishman, C. A. Curcio, J. Carroll, and A. Dubra, “In Vivo Imaging of Human Cone Photoreceptor Inner Segments,” Invest. Ophthalmol. Vis. Sci. 55(7), 4244–4251 (2014).
[Crossref] [PubMed]

Laurent, P.

M. Paques, R. Tadayoni, R. Sercombe, P. Laurent, O. Genevois, A. Gaudric, and E. Vicaut, “Structural and Hemodynamic Analysis of the Mouse Retinal Microcirculation,” Invest. Ophthalmol. Vis. Sci. 44(11), 4960–4967 (2003).
[Crossref] [PubMed]

Lecoq, J.

J. Lecoq, A. Parpaleix, E. Roussakis, M. Ducros, Y. Goulam Houssen, S. A. Vinogradov, and S. Charpak, “Simultaneous two-photon imaging of oxygen and blood flow in deep cerebral vessels,” Nat. Med. 17(7), 893–898 (2011).
[Crossref] [PubMed]

Lee, J.

B. Li, J. Lee, D. A. Boas, and F. Lesage, “Contribution of low- and high-flux capillaries to slow hemodynamic fluctuations in the cerebral cortex of mice,” J. Cereb. Blood Flow Metab. 36(8), 1351–1356 (2016).
[Crossref] [PubMed]

J. Lee, W. Wu, F. Lesage, and D. A. Boas, “Multiple-capillary measurement of RBC speed, flux, and density with optical coherence tomography,” J. Cereb. Blood Flow Metab. 33(11), 1707–1710 (2013).
[Crossref] [PubMed]

Lee, S.-H.

Leitgeb, R. A.

R. A. Leitgeb, R. M. Werkmeister, C. Blatter, and L. Schmetterer, “Doppler Optical Coherence Tomography,” Prog. Retin. Eye Res. 41, 26–43 (2014).
[Crossref] [PubMed]

Lennie, P.

P. Lennie, “The Cost of Cortical Computation,” Curr. Biol. 13(6), 493–497 (2003).
[Crossref] [PubMed]

Lesage, F.

B. Li, J. Lee, D. A. Boas, and F. Lesage, “Contribution of low- and high-flux capillaries to slow hemodynamic fluctuations in the cerebral cortex of mice,” J. Cereb. Blood Flow Metab. 36(8), 1351–1356 (2016).
[Crossref] [PubMed]

J. Lee, W. Wu, F. Lesage, and D. A. Boas, “Multiple-capillary measurement of RBC speed, flux, and density with optical coherence tomography,” J. Cereb. Blood Flow Metab. 33(11), 1707–1710 (2013).
[Crossref] [PubMed]

Li, B.

B. Li, J. Lee, D. A. Boas, and F. Lesage, “Contribution of low- and high-flux capillaries to slow hemodynamic fluctuations in the cerebral cortex of mice,” J. Cereb. Blood Flow Metab. 36(8), 1351–1356 (2016).
[Crossref] [PubMed]

Li, H.

J. Schallek, H. Li, R. Kardon, Y. Kwon, M. Abramoff, P. Soliz, and D. Ts’o, “Stimulus-Evoked Intrinsic Optical Signals in the Retina: Spatial and Temporal Characteristics,” Invest. Ophthalmol. Vis. Sci. 50(10), 4865–4872 (2009).
[Crossref] [PubMed]

Li, K. Y.

Liang, J.

Libby, R. T.

Logean, E.

C. E. Riva, E. Logean, and B. Falsini, “Visually evoked hemodynamical response and assessment of neurovascular coupling in the optic nerve and retina,” Prog. Retin. Eye Res. 24(2), 183–215 (2005).
[Crossref] [PubMed]

Lombardi, L.

Lu, C. D.

Luo, T.

Lyons, D. G.

D. G. Lyons, A. Parpaleix, M. Roche, and S. Charpak, “Mapping oxygen concentration in the awake mouse brain,” eLife 5, e12024 (2016).
[Crossref] [PubMed]

Makiyama, Y.

Y. Akagi-Kurashige, A. Tsujikawa, S. Ooto, Y. Makiyama, Y. Muraoka, K. Kumagai, A. Uji, S. Arichika, T. Murakami, K. Miyamoto, and N. Yoshimura, “Retinal Microstructural Changes in Eyes With Resolved Branch Retinal Vein Occlusion: An Adaptive Optics Scanning Laser Ophthalmoscopy Study,” Am. J. Ophthalmol. 157(6), 1239–1249 (2014).
[Crossref] [PubMed]

Marple, R. N.

R. M. Hochmuth, R. N. Marple, and S. P. Sutera, “Capillary blood flow. I. Erythrocyte deformation in glass capillaries,” Microvasc. Res. 2(4), 409–419 (1970).
[Crossref] [PubMed]

Martin, J. A.

J. Tam, J. A. Martin, and A. Roorda, “Noninvasive Visualization and Analysis of Parafoveal Capillaries in Humans,” Invest. Ophthalmol. Vis. Sci. 51(3), 1691–1698 (2010).
[Crossref] [PubMed]

J. A. Martin and A. Roorda, “Pulsatility of Parafoveal Capillary Leukocytes,” Exp. Eye Res. 88(3), 356–360 (2009).
[Crossref] [PubMed]

J. A. Martin and A. Roorda, “Direct and noninvasive assessment of parafoveal capillary leukocyte velocity,” Ophthalmology 112(12), 2219–2224 (2005).
[Crossref] [PubMed]

Martins-Silva, J.

L. Sargento, H. Sobral do Rosário, C. Saldanha, and J. Martins-Silva, “Hemorheological effects of sodium fluorescein in rats,” Clin. Hemorheol. Microcirc. 24(3), 175–181 (2001).
[PubMed]

McWhirter, J. L.

J. L. McWhirter, H. Noguchi, and G. Gompper, “Flow-induced clustering and alignment of vesicles and red blood cells in microcapillaries,” Proc. Natl. Acad. Sci. U.S.A. 106(15), 6039–6043 (2009).
[Crossref] [PubMed]

J. L. McWhirter, H. Noguchi, and G. Gompper, “Flow-induced clustering and alignment of vesicles and red blood cells in microcapillaries,” Proc. Natl. Acad. Sci. U.S.A. 106(15), 6039–6043 (2009).
[Crossref] [PubMed]

Merigan, W. H.

Metha, A.

Miller, D. T.

Miller, E. B.

Minamiyama, M.

J. H. Jeong, Y. Sugii, M. Minamiyama, and K. Okamoto, “Measurement of RBC deformation and velocity in capillaries in vivo,” Microvasc. Res. 71(3), 212–217 (2006).
[Crossref] [PubMed]

Mitra, P. P.

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

Miyamoto, K.

Y. Akagi-Kurashige, A. Tsujikawa, S. Ooto, Y. Makiyama, Y. Muraoka, K. Kumagai, A. Uji, S. Arichika, T. Murakami, K. Miyamoto, and N. Yoshimura, “Retinal Microstructural Changes in Eyes With Resolved Branch Retinal Vein Occlusion: An Adaptive Optics Scanning Laser Ophthalmoscopy Study,” Am. J. Ophthalmol. 157(6), 1239–1249 (2014).
[Crossref] [PubMed]

Morrison, J. C.

Moss, S. E.

R. Klein, B. E. K. Klein, S. E. Moss, M. D. Davis, and D. L. DeMets, “The Wisconsin Epidemiologic Study of Diabetic Retinopathy. III. Prevalence and Risk of Diabetic Retinopathy When Age at Diagnosis Is 30 or More Years,” Arch. Ophthalmol. 102(4), 527–532 (1984).
[Crossref] [PubMed]

R. Klein, B. E. Klein, S. E. Moss, M. D. Davis, and D. L. DeMets, “The Wisconsin epidemiologic study of diabetic retinopathy. IV. Diabetic macular edema,” Ophthalmology 91(12), 1464–1474 (1984).
[Crossref] [PubMed]

Mudumbai, R. C.

C.-L. Chen, A. Zhang, K. D. Bojikian, J. C. Wen, Q. Zhang, C. Xin, R. C. Mudumbai, M. A. Johnstone, P. P. Chen, and R. K. Wang, “Peripapillary Retinal Nerve Fiber Layer Vascular Microcirculation in Glaucoma Using Optical Coherence Tomography-Based Microangiography,” Invest. Ophthalmol. Vis. Sci. 57(9), OCT475 (2016).
[Crossref] [PubMed]

Murakami, T.

Y. Akagi-Kurashige, A. Tsujikawa, S. Ooto, Y. Makiyama, Y. Muraoka, K. Kumagai, A. Uji, S. Arichika, T. Murakami, K. Miyamoto, and N. Yoshimura, “Retinal Microstructural Changes in Eyes With Resolved Branch Retinal Vein Occlusion: An Adaptive Optics Scanning Laser Ophthalmoscopy Study,” Am. J. Ophthalmol. 157(6), 1239–1249 (2014).
[Crossref] [PubMed]

Muraoka, Y.

Y. Akagi-Kurashige, A. Tsujikawa, S. Ooto, Y. Makiyama, Y. Muraoka, K. Kumagai, A. Uji, S. Arichika, T. Murakami, K. Miyamoto, and N. Yoshimura, “Retinal Microstructural Changes in Eyes With Resolved Branch Retinal Vein Occlusion: An Adaptive Optics Scanning Laser Ophthalmoscopy Study,” Am. J. Ophthalmol. 157(6), 1239–1249 (2014).
[Crossref] [PubMed]

Newman, E. A.

T. E. Kornfield and E. A. Newman, “Regulation of Blood Flow in the Retinal Trilaminar Vascular Network,” J. Neurosci. 34(34), 11504–11513 (2014).
[Crossref] [PubMed]

Nguyen, H.

J. Schallek, Y. Geng, H. Nguyen, and D. R. Williams, “Morphology and Topography of Retinal Pericytes in the Living Mouse Retina Using In Vivo Adaptive Optics Imaging and Ex Vivo Characterization,” Invest. Ophthalmol. Vis. Sci. 54(13), 8237–8250 (2013).
[Crossref] [PubMed]

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).
[Crossref] [PubMed]

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).
[Crossref] [PubMed]

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).
[Crossref] [PubMed]

Noguchi, H.

J. L. McWhirter, H. Noguchi, and G. Gompper, “Flow-induced clustering and alignment of vesicles and red blood cells in microcapillaries,” Proc. Natl. Acad. Sci. U.S.A. 106(15), 6039–6043 (2009).
[Crossref] [PubMed]

J. L. McWhirter, H. Noguchi, and G. Gompper, “Flow-induced clustering and alignment of vesicles and red blood cells in microcapillaries,” Proc. Natl. Acad. Sci. U.S.A. 106(15), 6039–6043 (2009).
[Crossref] [PubMed]

Nozato, K.

Okamoto, K.

J. H. Jeong, Y. Sugii, M. Minamiyama, and K. Okamoto, “Measurement of RBC deformation and velocity in capillaries in vivo,” Microvasc. Res. 71(3), 212–217 (2006).
[Crossref] [PubMed]

Ooto, S.

Y. Akagi-Kurashige, A. Tsujikawa, S. Ooto, Y. Makiyama, Y. Muraoka, K. Kumagai, A. Uji, S. Arichika, T. Murakami, K. Miyamoto, and N. Yoshimura, “Retinal Microstructural Changes in Eyes With Resolved Branch Retinal Vein Occlusion: An Adaptive Optics Scanning Laser Ophthalmoscopy Study,” Am. J. Ophthalmol. 157(6), 1239–1249 (2014).
[Crossref] [PubMed]

Orgul, S.

T. Sugiyama, M. Araie, C. E. Riva, L. Schmetterer, and S. Orgul, “Use of laser speckle flowgraphy in ocular blood flow research,” Acta Ophthalmol. 88(7), 723–729 (2010).
[Crossref] [PubMed]

Paques, M.

M. Paques, R. Tadayoni, R. Sercombe, P. Laurent, O. Genevois, A. Gaudric, and E. Vicaut, “Structural and Hemodynamic Analysis of the Mouse Retinal Microcirculation,” Invest. Ophthalmol. Vis. Sci. 44(11), 4960–4967 (2003).
[Crossref] [PubMed]

Parpaleix, A.

D. G. Lyons, A. Parpaleix, M. Roche, and S. Charpak, “Mapping oxygen concentration in the awake mouse brain,” eLife 5, e12024 (2016).
[Crossref] [PubMed]

A. Parpaleix, Y. Goulam Houssen, and S. Charpak, “Imaging local neuronal activity by monitoring PO2 transients in capillaries,” Nat. Med. 19(2), 241–246 (2013).
[Crossref] [PubMed]

J. Lecoq, A. Parpaleix, E. Roussakis, M. Ducros, Y. Goulam Houssen, S. A. Vinogradov, and S. Charpak, “Simultaneous two-photon imaging of oxygen and blood flow in deep cerebral vessels,” Nat. Med. 17(7), 893–898 (2011).
[Crossref] [PubMed]

Peng, Q.

Y. Zhang, O. San Emeterio Nateras, Q. Peng, C. A. Rosende, and T. Q. Duong, “Blood Flow MRI of the Human Retina/Choroid During Rest and Isometric Exercise,” Invest. Ophthalmol. Vis. Sci. 53(7), 4299–4305 (2012).
[Crossref] [PubMed]

Perkkiö, J.

J. Perkkiö and R. Keskinen, “Hematocrit reduction in bifurcations due to plasma skimming,” Bull. Math. Biol. 45(1), 41–50 (1983).
[Crossref] [PubMed]

Petrig, B. L.

Z. Zhong, G. Huang, T. Y. P. Chui, B. L. Petrig, and S. A. Burns, “Local flicker stimulation evokes local retinal blood velocity changes,” J. Vis. 12(6), 3 (2012).
[Crossref] [PubMed]

Z. Zhong, H. Song, T. Y. P. Chui, B. L. Petrig, and S. A. Burns, “Noninvasive measurements and analysis of blood velocity profiles in human retinal vessels,” Invest. Ophthalmol. Vis. Sci. 52(7), 4151–4157 (2011).
[Crossref] [PubMed]

Z. Zhong, B. L. Petrig, X. Qi, and S. A. Burns, “In vivo measurement of erythrocyte velocity and retinal blood flow using adaptive optics scanning laser ophthalmoscopy,” Opt. Express 16(17), 12746–12756 (2008).
[Crossref] [PubMed]

C. E. Riva, S. Harino, R. D. Shonat, and B. L. Petrig, “Flicker evoked increase in optic nerve head blood flow in anesthetized cats,” Neurosci. Lett. 128(2), 291–296 (1991).
[Crossref] [PubMed]

Pircher, M.

Pries, A.

K. H. Albrecht, P. Gaehtgens, A. Pries, and M. Heuser, “The Fahraeus effect in narrow capillaries (i.d. 3.3 to 11.0 µm),” Microvasc. Res. 18(1), 33–47 (1979).
[Crossref] [PubMed]

Pries, A. R.

A. R. Pries, T. W. Secomb, P. Gaehtgens, and J. F. Gross, “Blood flow in microvascular networks. Experiments and simulation,” Circ. Res. 67(4), 826–834 (1990).
[Crossref] [PubMed]

Pugh, E. N.

Qi, X.

Rechenmacher, M.

Remtulla, S.

S. Remtulla and P. E. Hallett, “A schematic eye for the mouse, and comparisons with the rat,” Vision Res. 25(1), 21–31 (1985).
[Crossref] [PubMed]

Riva, C.

C. Riva, B. Ross, and G. B. Benedek, “Laser Doppler Measurements of Blood Flow in Capillary Tubes and Retinal Arteries,” Invest. Ophthalmol. 11(11), 936–944 (1972).
[PubMed]

Riva, C. E.

T. Sugiyama, M. Araie, C. E. Riva, L. Schmetterer, and S. Orgul, “Use of laser speckle flowgraphy in ocular blood flow research,” Acta Ophthalmol. 88(7), 723–729 (2010).
[Crossref] [PubMed]

C. E. Riva, E. Logean, and B. Falsini, “Visually evoked hemodynamical response and assessment of neurovascular coupling in the optic nerve and retina,” Prog. Retin. Eye Res. 24(2), 183–215 (2005).
[Crossref] [PubMed]

C. E. Riva, S. Harino, R. D. Shonat, and B. L. Petrig, “Flicker evoked increase in optic nerve head blood flow in anesthetized cats,” Neurosci. Lett. 128(2), 291–296 (1991).
[Crossref] [PubMed]

Roche, M.

D. G. Lyons, A. Parpaleix, M. Roche, and S. Charpak, “Mapping oxygen concentration in the awake mouse brain,” eLife 5, e12024 (2016).
[Crossref] [PubMed]

Romano, A.

T. E. de Carlo, A. Romano, N. K. Waheed, and J. S. Duker, “A review of optical coherence tomography angiography (OCTA),” International Journal of Retina and Vitreous 1(1), 5 (2015).
[Crossref]

Roorda, A.

Rosende, C. A.

Y. Zhang, O. San Emeterio Nateras, Q. Peng, C. A. Rosende, and T. Q. Duong, “Blood Flow MRI of the Human Retina/Choroid During Rest and Isometric Exercise,” Invest. Ophthalmol. Vis. Sci. 53(7), 4299–4305 (2012).
[Crossref] [PubMed]

Ross, B.

C. Riva, B. Ross, and G. B. Benedek, “Laser Doppler Measurements of Blood Flow in Capillary Tubes and Retinal Arteries,” Invest. Ophthalmol. 11(11), 936–944 (1972).
[PubMed]

Rossi, E. A.

Roussakis, E.

J. Lecoq, A. Parpaleix, E. Roussakis, M. Ducros, Y. Goulam Houssen, S. A. Vinogradov, and S. Charpak, “Simultaneous two-photon imaging of oxygen and blood flow in deep cerebral vessels,” Nat. Med. 17(7), 893–898 (2011).
[Crossref] [PubMed]

Saito, K.

Saldanha, C.

L. Sargento, H. Sobral do Rosário, C. Saldanha, and J. Martins-Silva, “Hemorheological effects of sodium fluorescein in rats,” Clin. Hemorheol. Microcirc. 24(3), 175–181 (2001).
[PubMed]

San Emeterio Nateras, O.

Y. Zhang, O. San Emeterio Nateras, Q. Peng, C. A. Rosende, and T. Q. Duong, “Blood Flow MRI of the Human Retina/Choroid During Rest and Isometric Exercise,” Invest. Ophthalmol. Vis. Sci. 53(7), 4299–4305 (2012).
[Crossref] [PubMed]

Sarelius, I. H.

B. R. Berg and I. H. Sarelius, “Erythrocyte flux in capillary networks during maturation: implications for oxygen delivery,” Am. J. Physiol. 271(6 Pt 2), H2263–H2273 (1996).
[PubMed]

I. H. Sarelius and B. R. Duling, “Direct measurement of microvessel hematocrit, red cell flux, velocity, and transit time,” Am. J. Physiol. 243(6), H1018–H1026 (1982).
[PubMed]

Sargento, L.

L. Sargento, H. Sobral do Rosário, C. Saldanha, and J. Martins-Silva, “Hemorheological effects of sodium fluorescein in rats,” Clin. Hemorheol. Microcirc. 24(3), 175–181 (2001).
[PubMed]

Sawides, L.

Schaeffel, F.

C. Schmucker and F. Schaeffel, “A paraxial schematic eye model for the growing C57BL/6 mouse,” Vision Res. 44(16), 1857–1867 (2004).
[Crossref] [PubMed]

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).
[Crossref] [PubMed]

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).
[Crossref] [PubMed]

Schallek, J.

J. Schallek, Y. Geng, H. Nguyen, and D. R. Williams, “Morphology and Topography of Retinal Pericytes in the Living Mouse Retina Using In Vivo Adaptive Optics Imaging and Ex Vivo Characterization,” Invest. Ophthalmol. Vis. Sci. 54(13), 8237–8250 (2013).
[Crossref] [PubMed]

J. Schallek and D. Ts’o, “Blood Contrast Agents Enhance Intrinsic Signals in the Retina: Evidence for an Underlying Blood Volume Component,” Invest. Ophthalmol. Vis. Sci. 52(3), 1325–1335 (2011).
[Crossref] [PubMed]

J. Schallek, H. Li, R. Kardon, Y. Kwon, M. Abramoff, P. Soliz, and D. Ts’o, “Stimulus-Evoked Intrinsic Optical Signals in the Retina: Spatial and Temporal Characteristics,” Invest. Ophthalmol. Vis. Sci. 50(10), 4865–4872 (2009).
[Crossref] [PubMed]

Schallek, J. B.

Schmetterer, L.

R. A. Leitgeb, R. M. Werkmeister, C. Blatter, and L. Schmetterer, “Doppler Optical Coherence Tomography,” Prog. Retin. Eye Res. 41, 26–43 (2014).
[Crossref] [PubMed]

T. Sugiyama, M. Araie, C. E. Riva, L. Schmetterer, and S. Orgul, “Use of laser speckle flowgraphy in ocular blood flow research,” Acta Ophthalmol. 88(7), 723–729 (2010).
[Crossref] [PubMed]

Schmucker, C.

C. Schmucker and F. Schaeffel, “A paraxial schematic eye model for the growing C57BL/6 mouse,” Vision Res. 44(16), 1857–1867 (2004).
[Crossref] [PubMed]

Scoles, D.

Y. N. Sulai, D. Scoles, Z. Harvey, and A. Dubra, “Visualization of retinal vascular structure and perfusion with a nonconfocal adaptive optics scanning light ophthalmoscope,” J. Opt. Soc. Am. A 31(3), 569–579 (2014).
[Crossref] [PubMed]

D. Scoles, Y. N. Sulai, C. S. Langlo, G. A. Fishman, C. A. Curcio, J. Carroll, and A. Dubra, “In Vivo Imaging of Human Cone Photoreceptor Inner Segments,” Invest. Ophthalmol. Vis. Sci. 55(7), 4244–4251 (2014).
[Crossref] [PubMed]

Secomb, T. W.

A. R. Pries, T. W. Secomb, P. Gaehtgens, and J. F. Gross, “Blood flow in microvascular networks. Experiments and simulation,” Circ. Res. 67(4), 826–834 (1990).
[Crossref] [PubMed]

Sercombe, R.

M. Paques, R. Tadayoni, R. Sercombe, P. Laurent, O. Genevois, A. Gaudric, and E. Vicaut, “Structural and Hemodynamic Analysis of the Mouse Retinal Microcirculation,” Invest. Ophthalmol. Vis. Sci. 44(11), 4960–4967 (2003).
[Crossref] [PubMed]

Seshadri, V.

S. P. Sutera, V. Seshadri, P. A. Croce, and R. M. Hochmuth, “Capillary blood flow. II. Deformable model cells in tube flow,” Microvasc. Res. 2(4), 420–433 (1970).
[Crossref] [PubMed]

Sharma, R.

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).
[Crossref] [PubMed]

Shonat, R. D.

C. E. Riva, S. Harino, R. D. Shonat, and B. L. Petrig, “Flicker evoked increase in optic nerve head blood flow in anesthetized cats,” Neurosci. Lett. 128(2), 291–296 (1991).
[Crossref] [PubMed]

Skalak, R.

R. Skalak and P. I. Branemark, “Deformation of Red Blood Cells in Capillaries,” Science 164(3880), 717–719 (1969).
[Crossref] [PubMed]

Sobral do Rosário, H.

L. Sargento, H. Sobral do Rosário, C. Saldanha, and J. Martins-Silva, “Hemorheological effects of sodium fluorescein in rats,” Clin. Hemorheol. Microcirc. 24(3), 175–181 (2001).
[PubMed]

Soliz, P.

J. Schallek, H. Li, R. Kardon, Y. Kwon, M. Abramoff, P. Soliz, and D. Ts’o, “Stimulus-Evoked Intrinsic Optical Signals in the Retina: Spatial and Temporal Characteristics,” Invest. Ophthalmol. Vis. Sci. 50(10), 4865–4872 (2009).
[Crossref] [PubMed]

Song, H.

Z. Zhong, H. Song, T. Y. P. Chui, B. L. Petrig, and S. A. Burns, “Noninvasive measurements and analysis of blood velocity profiles in human retinal vessels,” Invest. Ophthalmol. Vis. Sci. 52(7), 4151–4157 (2011).
[Crossref] [PubMed]

Sugii, Y.

J. H. Jeong, Y. Sugii, M. Minamiyama, and K. Okamoto, “Measurement of RBC deformation and velocity in capillaries in vivo,” Microvasc. Res. 71(3), 212–217 (2006).
[Crossref] [PubMed]

Sugiyama, T.

T. Sugiyama, M. Araie, C. E. Riva, L. Schmetterer, and S. Orgul, “Use of laser speckle flowgraphy in ocular blood flow research,” Acta Ophthalmol. 88(7), 723–729 (2010).
[Crossref] [PubMed]

Sulai, Y. N.

Y. N. Sulai, D. Scoles, Z. Harvey, and A. Dubra, “Visualization of retinal vascular structure and perfusion with a nonconfocal adaptive optics scanning light ophthalmoscope,” J. Opt. Soc. Am. A 31(3), 569–579 (2014).
[Crossref] [PubMed]

D. Scoles, Y. N. Sulai, C. S. Langlo, G. A. Fishman, C. A. Curcio, J. Carroll, and A. Dubra, “In Vivo Imaging of Human Cone Photoreceptor Inner Segments,” Invest. Ophthalmol. Vis. Sci. 55(7), 4244–4251 (2014).
[Crossref] [PubMed]

Sutera, S. P.

R. M. Hochmuth, R. N. Marple, and S. P. Sutera, “Capillary blood flow. I. Erythrocyte deformation in glass capillaries,” Microvasc. Res. 2(4), 409–419 (1970).
[Crossref] [PubMed]

S. P. Sutera, V. Seshadri, P. A. Croce, and R. M. Hochmuth, “Capillary blood flow. II. Deformable model cells in tube flow,” Microvasc. Res. 2(4), 420–433 (1970).
[Crossref] [PubMed]

Tadayoni, R.

M. Paques, R. Tadayoni, R. Sercombe, P. Laurent, O. Genevois, A. Gaudric, and E. Vicaut, “Structural and Hemodynamic Analysis of the Mouse Retinal Microcirculation,” Invest. Ophthalmol. Vis. Sci. 44(11), 4960–4967 (2003).
[Crossref] [PubMed]

Tam, J.

Tan, O.

Tiruveedhula, P.

Tokayer, J.

Toussaint, D.

D. G. Cogan, D. Toussaint, and T. Kuwabara, “Retinal vascular patterns. IV. Diabetic retinopathy,” Arch. Ophthalmol. 66(3), 366–378 (1961).
[Crossref] [PubMed]

Ts’o, D.

J. Schallek and D. Ts’o, “Blood Contrast Agents Enhance Intrinsic Signals in the Retina: Evidence for an Underlying Blood Volume Component,” Invest. Ophthalmol. Vis. Sci. 52(3), 1325–1335 (2011).
[Crossref] [PubMed]

J. Schallek, H. Li, R. Kardon, Y. Kwon, M. Abramoff, P. Soliz, and D. Ts’o, “Stimulus-Evoked Intrinsic Optical Signals in the Retina: Spatial and Temporal Characteristics,” Invest. Ophthalmol. Vis. Sci. 50(10), 4865–4872 (2009).
[Crossref] [PubMed]

Tsujikawa, A.

Y. Akagi-Kurashige, A. Tsujikawa, S. Ooto, Y. Makiyama, Y. Muraoka, K. Kumagai, A. Uji, S. Arichika, T. Murakami, K. Miyamoto, and N. Yoshimura, “Retinal Microstructural Changes in Eyes With Resolved Branch Retinal Vein Occlusion: An Adaptive Optics Scanning Laser Ophthalmoscopy Study,” Am. J. Ophthalmol. 157(6), 1239–1249 (2014).
[Crossref] [PubMed]

Uji, A.

Y. Akagi-Kurashige, A. Tsujikawa, S. Ooto, Y. Makiyama, Y. Muraoka, K. Kumagai, A. Uji, S. Arichika, T. Murakami, K. Miyamoto, and N. Yoshimura, “Retinal Microstructural Changes in Eyes With Resolved Branch Retinal Vein Occlusion: An Adaptive Optics Scanning Laser Ophthalmoscopy Study,” Am. J. Ophthalmol. 157(6), 1239–1249 (2014).
[Crossref] [PubMed]

Vannasdale, D. A.

Vicaut, E.

M. Paques, R. Tadayoni, R. Sercombe, P. Laurent, O. Genevois, A. Gaudric, and E. Vicaut, “Structural and Hemodynamic Analysis of the Mouse Retinal Microcirculation,” Invest. Ophthalmol. Vis. Sci. 44(11), 4960–4967 (2003).
[Crossref] [PubMed]

Vink, H.

H. Vink and B. R. Duling, “Identification of Distinct Luminal Domains for Macromolecules, Erythrocytes, and Leukocytes Within Mammalian Capillaries,” Circ. Res. 79(3), 581–589 (1996).
[Crossref] [PubMed]

Vinogradov, S. A.

J. Lecoq, A. Parpaleix, E. Roussakis, M. Ducros, Y. Goulam Houssen, S. A. Vinogradov, and S. Charpak, “Simultaneous two-photon imaging of oxygen and blood flow in deep cerebral vessels,” Nat. Med. 17(7), 893–898 (2011).
[Crossref] [PubMed]

Waheed, N. K.

T. E. de Carlo, A. Romano, N. K. Waheed, and J. S. Duker, “A review of optical coherence tomography angiography (OCTA),” International Journal of Retina and Vitreous 1(1), 5 (2015).
[Crossref]

Wald, G.

G. Wald, “Human Vision and the Spectrum,” Science 101(2635), 653–658 (1945).
[Crossref] [PubMed]

Wang, R. K.

C.-L. Chen, A. Zhang, K. D. Bojikian, J. C. Wen, Q. Zhang, C. Xin, R. C. Mudumbai, M. A. Johnstone, P. P. Chen, and R. K. Wang, “Peripapillary Retinal Nerve Fiber Layer Vascular Microcirculation in Glaucoma Using Optical Coherence Tomography-Based Microangiography,” Invest. Ophthalmol. Vis. Sci. 57(9), OCT475 (2016).
[Crossref] [PubMed]

Wang, X.

Wen, J. C.

C.-L. Chen, A. Zhang, K. D. Bojikian, J. C. Wen, Q. Zhang, C. Xin, R. C. Mudumbai, M. A. Johnstone, P. P. Chen, and R. K. Wang, “Peripapillary Retinal Nerve Fiber Layer Vascular Microcirculation in Glaucoma Using Optical Coherence Tomography-Based Microangiography,” Invest. Ophthalmol. Vis. Sci. 57(9), OCT475 (2016).
[Crossref] [PubMed]

Werkmeister, R. M.

R. A. Leitgeb, R. M. Werkmeister, C. Blatter, and L. Schmetterer, “Doppler Optical Coherence Tomography,” Prog. Retin. Eye Res. 41, 26–43 (2014).
[Crossref] [PubMed]

Werner, J. S.

Williams, D. R.

Wong-Riley, M. T. T.

M. T. T. Wong-Riley, “Energy metabolism of the visual system,” Eye Brain 2, 99–116 (2010).
[Crossref] [PubMed]

Wu, W.

J. Lee, W. Wu, F. Lesage, and D. A. Boas, “Multiple-capillary measurement of RBC speed, flux, and density with optical coherence tomography,” J. Cereb. Blood Flow Metab. 33(11), 1707–1710 (2013).
[Crossref] [PubMed]

Xin, C.

C.-L. Chen, A. Zhang, K. D. Bojikian, J. C. Wen, Q. Zhang, C. Xin, R. C. Mudumbai, M. A. Johnstone, P. P. Chen, and R. K. Wang, “Peripapillary Retinal Nerve Fiber Layer Vascular Microcirculation in Glaucoma Using Optical Coherence Tomography-Based Microangiography,” Invest. Ophthalmol. Vis. Sci. 57(9), OCT475 (2016).
[Crossref] [PubMed]

Yang, Q.

Yin, L.

Yoshimura, N.

Y. Akagi-Kurashige, A. Tsujikawa, S. Ooto, Y. Makiyama, Y. Muraoka, K. Kumagai, A. Uji, S. Arichika, T. Murakami, K. Miyamoto, and N. Yoshimura, “Retinal Microstructural Changes in Eyes With Resolved Branch Retinal Vein Occlusion: An Adaptive Optics Scanning Laser Ophthalmoscopy Study,” Am. J. Ophthalmol. 157(6), 1239–1249 (2014).
[Crossref] [PubMed]

Zam, A.

Zawadzki, R. J.

Zhang, A.

C.-L. Chen, A. Zhang, K. D. Bojikian, J. C. Wen, Q. Zhang, C. Xin, R. C. Mudumbai, M. A. Johnstone, P. P. Chen, and R. K. Wang, “Peripapillary Retinal Nerve Fiber Layer Vascular Microcirculation in Glaucoma Using Optical Coherence Tomography-Based Microangiography,” Invest. Ophthalmol. Vis. Sci. 57(9), OCT475 (2016).
[Crossref] [PubMed]

Zhang, J.

Zhang, P.

Zhang, Q.

C.-L. Chen, A. Zhang, K. D. Bojikian, J. C. Wen, Q. Zhang, C. Xin, R. C. Mudumbai, M. A. Johnstone, P. P. Chen, and R. K. Wang, “Peripapillary Retinal Nerve Fiber Layer Vascular Microcirculation in Glaucoma Using Optical Coherence Tomography-Based Microangiography,” Invest. Ophthalmol. Vis. Sci. 57(9), OCT475 (2016).
[Crossref] [PubMed]

Zhang, Y.

Y. Zhang, O. San Emeterio Nateras, Q. Peng, C. A. Rosende, and T. Q. Duong, “Blood Flow MRI of the Human Retina/Choroid During Rest and Isometric Exercise,” Invest. Ophthalmol. Vis. Sci. 53(7), 4299–4305 (2012).
[Crossref] [PubMed]

Zhong, Z.

Z. Zhong, G. Huang, T. Y. P. Chui, B. L. Petrig, and S. A. Burns, “Local flicker stimulation evokes local retinal blood velocity changes,” J. Vis. 12(6), 3 (2012).
[Crossref] [PubMed]

Z. Zhong, H. Song, T. Y. P. Chui, B. L. Petrig, and S. A. Burns, “Noninvasive measurements and analysis of blood velocity profiles in human retinal vessels,” Invest. Ophthalmol. Vis. Sci. 52(7), 4151–4157 (2011).
[Crossref] [PubMed]

Z. Zhong, B. L. Petrig, X. Qi, and S. A. Burns, “In vivo measurement of erythrocyte velocity and retinal blood flow using adaptive optics scanning laser ophthalmoscopy,” Opt. Express 16(17), 12746–12756 (2008).
[Crossref] [PubMed]

Acta Ophthalmol. (1)

T. Sugiyama, M. Araie, C. E. Riva, L. Schmetterer, and S. Orgul, “Use of laser speckle flowgraphy in ocular blood flow research,” Acta Ophthalmol. 88(7), 723–729 (2010).
[Crossref] [PubMed]

Am. J. Ophthalmol. (1)

Y. Akagi-Kurashige, A. Tsujikawa, S. Ooto, Y. Makiyama, Y. Muraoka, K. Kumagai, A. Uji, S. Arichika, T. Murakami, K. Miyamoto, and N. Yoshimura, “Retinal Microstructural Changes in Eyes With Resolved Branch Retinal Vein Occlusion: An Adaptive Optics Scanning Laser Ophthalmoscopy Study,” Am. J. Ophthalmol. 157(6), 1239–1249 (2014).
[Crossref] [PubMed]

Am. J. Physiol. (2)

I. H. Sarelius and B. R. Duling, “Direct measurement of microvessel hematocrit, red cell flux, velocity, and transit time,” Am. J. Physiol. 243(6), H1018–H1026 (1982).
[PubMed]

B. R. Berg and I. H. Sarelius, “Erythrocyte flux in capillary networks during maturation: implications for oxygen delivery,” Am. J. Physiol. 271(6 Pt 2), H2263–H2273 (1996).
[PubMed]

Arch. Ophthalmol. (2)

D. G. Cogan, D. Toussaint, and T. Kuwabara, “Retinal vascular patterns. IV. Diabetic retinopathy,” Arch. Ophthalmol. 66(3), 366–378 (1961).
[Crossref] [PubMed]

R. Klein, B. E. K. Klein, S. E. Moss, M. D. Davis, and D. L. DeMets, “The Wisconsin Epidemiologic Study of Diabetic Retinopathy. III. Prevalence and Risk of Diabetic Retinopathy When Age at Diagnosis Is 30 or More Years,” Arch. Ophthalmol. 102(4), 527–532 (1984).
[Crossref] [PubMed]

Biomed. Opt. Express (10)

J. Tam, P. Tiruveedhula, and A. Roorda, “Characterization of single-file flow through human retinal parafoveal capillaries using an adaptive optics scanning laser ophthalmoscope,” Biomed. Opt. Express 2(4), 781–793 (2011).
[Crossref] [PubMed]

P. Bedggood and A. Metha, “Direct visualization and characterization of erythrocyte flow in human retinal capillaries,” Biomed. Opt. Express 3(12), 3264–3277 (2012).
[Crossref] [PubMed]

Y. Geng, A. Dubra, L. Yin, W. H. Merigan, R. Sharma, R. T. Libby, and D. R. Williams, “Adaptive optics retinal imaging in the living mouse eye,” Biomed. Opt. Express 3(4), 715–734 (2012).
[Crossref] [PubMed]

A. Guevara-Torres, D. R. Williams, and J. B. Schallek, “Imaging translucent cell bodies in the living mouse retina without contrast agents,” Biomed. Opt. Express 6(6), 2106–2119 (2015).
[Crossref] [PubMed]

T. Y. P. Chui, D. A. Vannasdale, and S. A. Burns, “The use of forward scatter to improve retinal vascular imaging with an adaptive optics scanning laser ophthalmoscope,” Biomed. Opt. Express 3(10), 2537–2549 (2012).
[Crossref] [PubMed]

F. Felberer, M. Rechenmacher, R. Haindl, B. Baumann, C. K. Hitzenberger, and M. Pircher, “Imaging of retinal vasculature using adaptive optics SLO/OCT,” Biomed. Opt. Express 6(4), 1407–1418 (2015).
[Crossref] [PubMed]

R. J. Zawadzki, P. Zhang, A. Zam, E. B. Miller, M. Goswami, X. Wang, R. S. Jonnal, S.-H. Lee, D. Y. Kim, J. G. Flannery, J. S. Werner, M. E. Burns, and E. N. Pugh., “Adaptive-optics SLO imaging combined with widefield OCT and SLO enables precise 3D localization of fluorescent cells in the mouse retina,” Biomed. Opt. Express 6(6), 2191–2210 (2015).
[Crossref] [PubMed]

Y. Jia, J. C. Morrison, J. Tokayer, O. Tan, L. Lombardi, B. Baumann, C. D. Lu, W. Choi, J. G. Fujimoto, and D. Huang, “Quantitative OCT angiography of optic nerve head blood flow,” Biomed. Opt. Express 3(12), 3127–3137 (2012).
[Crossref] [PubMed]

Q. Yang, J. Zhang, K. Nozato, K. Saito, D. R. Williams, A. Roorda, and E. A. Rossi, “Closed-loop optical stabilization and digital image registration in adaptive optics scanning light ophthalmoscopy,” Biomed. Opt. Express 5(9), 3174–3191 (2014).
[Crossref] [PubMed]

J. Zhang, Q. Yang, K. Saito, K. Nozato, D. R. Williams, and E. A. Rossi, “An adaptive optics imaging system designed for clinical use,” Biomed. Opt. Express 6(6), 2120–2137 (2015).
[Crossref] [PubMed]

Bull. Math. Biol. (1)

J. Perkkiö and R. Keskinen, “Hematocrit reduction in bifurcations due to plasma skimming,” Bull. Math. Biol. 45(1), 41–50 (1983).
[Crossref] [PubMed]

Circ. Res. (2)

A. R. Pries, T. W. Secomb, P. Gaehtgens, and J. F. Gross, “Blood flow in microvascular networks. Experiments and simulation,” Circ. Res. 67(4), 826–834 (1990).
[Crossref] [PubMed]

H. Vink and B. R. Duling, “Identification of Distinct Luminal Domains for Macromolecules, Erythrocytes, and Leukocytes Within Mammalian Capillaries,” Circ. Res. 79(3), 581–589 (1996).
[Crossref] [PubMed]

Clin. Hemorheol. Microcirc. (1)

L. Sargento, H. Sobral do Rosário, C. Saldanha, and J. Martins-Silva, “Hemorheological effects of sodium fluorescein in rats,” Clin. Hemorheol. Microcirc. 24(3), 175–181 (2001).
[PubMed]

Curr. Biol. (1)

P. Lennie, “The Cost of Cortical Computation,” Curr. Biol. 13(6), 493–497 (2003).
[Crossref] [PubMed]

Diabetes Care (1)

D. S. Fong, L. P. Aiello, F. L. Ferris, and R. Klein, “Diabetic Retinopathy,” Diabetes Care 27(10), 2540–2553 (2004).
[Crossref] [PubMed]

eLife (1)

D. G. Lyons, A. Parpaleix, M. Roche, and S. Charpak, “Mapping oxygen concentration in the awake mouse brain,” eLife 5, e12024 (2016).
[Crossref] [PubMed]

Exp. Eye Res. (1)

J. A. Martin and A. Roorda, “Pulsatility of Parafoveal Capillary Leukocytes,” Exp. Eye Res. 88(3), 356–360 (2009).
[Crossref] [PubMed]

Eye Brain (1)

M. T. T. Wong-Riley, “Energy metabolism of the visual system,” Eye Brain 2, 99–116 (2010).
[Crossref] [PubMed]

International Journal of Retina and Vitreous (1)

T. E. de Carlo, A. Romano, N. K. Waheed, and J. S. Duker, “A review of optical coherence tomography angiography (OCTA),” International Journal of Retina and Vitreous 1(1), 5 (2015).
[Crossref]

Invest. Ophthalmol. (1)

C. Riva, B. Ross, and G. B. Benedek, “Laser Doppler Measurements of Blood Flow in Capillary Tubes and Retinal Arteries,” Invest. Ophthalmol. 11(11), 936–944 (1972).
[PubMed]

Invest. Ophthalmol. Vis. Sci. (9)

M. Paques, R. Tadayoni, R. Sercombe, P. Laurent, O. Genevois, A. Gaudric, and E. Vicaut, “Structural and Hemodynamic Analysis of the Mouse Retinal Microcirculation,” Invest. Ophthalmol. Vis. Sci. 44(11), 4960–4967 (2003).
[Crossref] [PubMed]

J. Schallek, Y. Geng, H. Nguyen, and D. R. Williams, “Morphology and Topography of Retinal Pericytes in the Living Mouse Retina Using In Vivo Adaptive Optics Imaging and Ex Vivo Characterization,” Invest. Ophthalmol. Vis. Sci. 54(13), 8237–8250 (2013).
[Crossref] [PubMed]

D. Scoles, Y. N. Sulai, C. S. Langlo, G. A. Fishman, C. A. Curcio, J. Carroll, and A. Dubra, “In Vivo Imaging of Human Cone Photoreceptor Inner Segments,” Invest. Ophthalmol. Vis. Sci. 55(7), 4244–4251 (2014).
[Crossref] [PubMed]

J. Tam, J. A. Martin, and A. Roorda, “Noninvasive Visualization and Analysis of Parafoveal Capillaries in Humans,” Invest. Ophthalmol. Vis. Sci. 51(3), 1691–1698 (2010).
[Crossref] [PubMed]

Y. Zhang, O. San Emeterio Nateras, Q. Peng, C. A. Rosende, and T. Q. Duong, “Blood Flow MRI of the Human Retina/Choroid During Rest and Isometric Exercise,” Invest. Ophthalmol. Vis. Sci. 53(7), 4299–4305 (2012).
[Crossref] [PubMed]

J. Schallek, H. Li, R. Kardon, Y. Kwon, M. Abramoff, P. Soliz, and D. Ts’o, “Stimulus-Evoked Intrinsic Optical Signals in the Retina: Spatial and Temporal Characteristics,” Invest. Ophthalmol. Vis. Sci. 50(10), 4865–4872 (2009).
[Crossref] [PubMed]

J. Schallek and D. Ts’o, “Blood Contrast Agents Enhance Intrinsic Signals in the Retina: Evidence for an Underlying Blood Volume Component,” Invest. Ophthalmol. Vis. Sci. 52(3), 1325–1335 (2011).
[Crossref] [PubMed]

Z. Zhong, H. Song, T. Y. P. Chui, B. L. Petrig, and S. A. Burns, “Noninvasive measurements and analysis of blood velocity profiles in human retinal vessels,” Invest. Ophthalmol. Vis. Sci. 52(7), 4151–4157 (2011).
[Crossref] [PubMed]

C.-L. Chen, A. Zhang, K. D. Bojikian, J. C. Wen, Q. Zhang, C. Xin, R. C. Mudumbai, M. A. Johnstone, P. P. Chen, and R. K. Wang, “Peripapillary Retinal Nerve Fiber Layer Vascular Microcirculation in Glaucoma Using Optical Coherence Tomography-Based Microangiography,” Invest. Ophthalmol. Vis. Sci. 57(9), OCT475 (2016).
[Crossref] [PubMed]

J. Biomed. Eng. (1)

T. J. H. Essex and P. O. Byrne, “A laser Doppler scanner for imaging blood flow in skin,” J. Biomed. Eng. 13(3), 189–194 (1991).
[Crossref] [PubMed]

J. Biomed. Opt. (1)

D. A. Boas and A. K. Dunn, “Laser speckle contrast imaging in biomedical optics,” J. Biomed. Opt. 15, 11109 (2010).

J. Cereb. Blood Flow Metab. (4)

J. Lee, W. Wu, F. Lesage, and D. A. Boas, “Multiple-capillary measurement of RBC speed, flux, and density with optical coherence tomography,” J. Cereb. Blood Flow Metab. 33(11), 1707–1710 (2013).
[Crossref] [PubMed]

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).
[Crossref] [PubMed]

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).
[Crossref] [PubMed]

B. Li, J. Lee, D. A. Boas, and F. Lesage, “Contribution of low- and high-flux capillaries to slow hemodynamic fluctuations in the cerebral cortex of mice,” J. Cereb. Blood Flow Metab. 36(8), 1351–1356 (2016).
[Crossref] [PubMed]

J. Neurosci. (1)

T. E. Kornfield and E. A. Newman, “Regulation of Blood Flow in the Retinal Trilaminar Vascular Network,” J. Neurosci. 34(34), 11504–11513 (2014).
[Crossref] [PubMed]

J. Opt. Soc. Am. A (3)

J. Vis. (1)

Z. Zhong, G. Huang, T. Y. P. Chui, B. L. Petrig, and S. A. Burns, “Local flicker stimulation evokes local retinal blood velocity changes,” J. Vis. 12(6), 3 (2012).
[Crossref] [PubMed]

Microvasc. Res. (5)

M. J. Dumskyj, J. E. Eriksen, C. J. Doré, and E. M. Kohner, “Autoregulation in the Human Retinal Circulation: Assessment Using Isometric Exercise, Laser Doppler Velocimetry, and Computer-Assisted Image Analysis,” Microvasc. Res. 51(3), 378–392 (1996).
[Crossref] [PubMed]

S. P. Sutera, V. Seshadri, P. A. Croce, and R. M. Hochmuth, “Capillary blood flow. II. Deformable model cells in tube flow,” Microvasc. Res. 2(4), 420–433 (1970).
[Crossref] [PubMed]

K. H. Albrecht, P. Gaehtgens, A. Pries, and M. Heuser, “The Fahraeus effect in narrow capillaries (i.d. 3.3 to 11.0 µm),” Microvasc. Res. 18(1), 33–47 (1979).
[Crossref] [PubMed]

J. H. Jeong, Y. Sugii, M. Minamiyama, and K. Okamoto, “Measurement of RBC deformation and velocity in capillaries in vivo,” Microvasc. Res. 71(3), 212–217 (2006).
[Crossref] [PubMed]

R. M. Hochmuth, R. N. Marple, and S. P. Sutera, “Capillary blood flow. I. Erythrocyte deformation in glass capillaries,” Microvasc. Res. 2(4), 409–419 (1970).
[Crossref] [PubMed]

N. Engl. J. Med. (1)

D. A. Antonetti, R. Klein, and T. W. Gardner, “Diabetic Retinopathy,” N. Engl. J. Med. 366(13), 1227–1239 (2012).
[Crossref] [PubMed]

Nat. Med. (2)

A. Parpaleix, Y. Goulam Houssen, and S. Charpak, “Imaging local neuronal activity by monitoring PO2 transients in capillaries,” Nat. Med. 19(2), 241–246 (2013).
[Crossref] [PubMed]

J. Lecoq, A. Parpaleix, E. Roussakis, M. Ducros, Y. Goulam Houssen, S. A. Vinogradov, and S. Charpak, “Simultaneous two-photon imaging of oxygen and blood flow in deep cerebral vessels,” Nat. Med. 17(7), 893–898 (2011).
[Crossref] [PubMed]

Neurosci. Lett. (1)

C. E. Riva, S. Harino, R. D. Shonat, and B. L. Petrig, “Flicker evoked increase in optic nerve head blood flow in anesthetized cats,” Neurosci. Lett. 128(2), 291–296 (1991).
[Crossref] [PubMed]

Ophthalmology (2)

J. A. Martin and A. Roorda, “Direct and noninvasive assessment of parafoveal capillary leukocyte velocity,” Ophthalmology 112(12), 2219–2224 (2005).
[Crossref] [PubMed]

R. Klein, B. E. Klein, S. E. Moss, M. D. Davis, and D. L. DeMets, “The Wisconsin epidemiologic study of diabetic retinopathy. IV. Diabetic macular edema,” Ophthalmology 91(12), 1464–1474 (1984).
[Crossref] [PubMed]

Opt. Express (1)

Opt. Lett. (1)

Proc. Natl. Acad. Sci. U.S.A. (3)

J. L. McWhirter, H. Noguchi, and G. Gompper, “Flow-induced clustering and alignment of vesicles and red blood cells in microcapillaries,” Proc. Natl. Acad. Sci. U.S.A. 106(15), 6039–6043 (2009).
[Crossref] [PubMed]

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

J. L. McWhirter, H. Noguchi, and G. Gompper, “Flow-induced clustering and alignment of vesicles and red blood cells in microcapillaries,” Proc. Natl. Acad. Sci. U.S.A. 106(15), 6039–6043 (2009).
[Crossref] [PubMed]

Prog. Retin. Eye Res. (2)

R. A. Leitgeb, R. M. Werkmeister, C. Blatter, and L. Schmetterer, “Doppler Optical Coherence Tomography,” Prog. Retin. Eye Res. 41, 26–43 (2014).
[Crossref] [PubMed]

C. E. Riva, E. Logean, and B. Falsini, “Visually evoked hemodynamical response and assessment of neurovascular coupling in the optic nerve and retina,” Prog. Retin. Eye Res. 24(2), 183–215 (2005).
[Crossref] [PubMed]

Science (2)

G. Wald, “Human Vision and the Spectrum,” Science 101(2635), 653–658 (1945).
[Crossref] [PubMed]

R. Skalak and P. I. Branemark, “Deformation of Red Blood Cells in Capillaries,” Science 164(3880), 717–719 (1969).
[Crossref] [PubMed]

Vision Res. (2)

S. Remtulla and P. E. Hallett, “A schematic eye for the mouse, and comparisons with the rat,” Vision Res. 25(1), 21–31 (1985).
[Crossref] [PubMed]

C. Schmucker and F. Schaeffel, “A paraxial schematic eye model for the growing C57BL/6 mouse,” Vision Res. 44(16), 1857–1867 (2004).
[Crossref] [PubMed]

Other (8)

The Jackson Laboratory: Mouse phenome database at the Jackson Laboratory, “Physiological Data Summary – C57BL/6J (000664),” (2007).

ANSI, “American National Standard for Safe Use of Lasers,” ANSI Z136.1 (2014).

G. Wyszecki and W. S. Stiles, Color Science: Concepts and Methods, Quantitative Data E Formulae (Wiley, 2000).

A. Dubra and Z. Harvey, “Registration of 2D Images from Fast Scanning Ophthalmic Instruments,” in Biomedical Image Registration, Lecture Notes in Computer Science (Springer Berlin / Heidelberg, 2010), Vol. 6204, pp. 60–71–71.

N. E. Everds, “Chapter 5 - Hematology of the Laboratory Mouse A2,” in The Mouse in Biomedical Research, 2nd ed., M. T. Davisson, F. W. Quimby, S. W. Barthold, C. E. Newcomer, and A. L. Smith, eds. (Academic Press, 2007), pp. 133–153.

A. Dubra, Z. Harvey, B. Fischer, B. M. Dawant, and C. Lorenz, “Registration of 2D Images from Fast Scanning Ophthalmic Instruments,” in Biomedical Image Registration, Lecture Notes in Computer Science No. 6204 (Springer Berlin Heidelberg, 1), pp. 60–71.

J. Porter, Adaptive Optics for Vision Science: Principles, Practices, Design, and Applications (John Wiley and Sons, 2006).

W. H. Organization, Prevention of Blindness from Diabetes Mellitus: Report of a WHO Consultation in Geneva, Switzerland, 9–11 November 2005 (World Health Organization, 2006).

Supplementary Material (1)

NameDescription
» Visualization 1: AVI (5862 KB)      Video sequence where capillary flow is initially arrested and is later reperfused.

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) Optical setup of the non-confocal AOSLO. This system uses a 796nm superluminescent diode for imaging and a 847nm (or 904nm) laser as the wavefront sensing beacon (WFSB). In place of a typical confocal pinhole, a knife edge beamsplitter splits light into two detectors with synchronized acquisition. B) The two scanning modes. The 2D raster scan captured en-face images of the retina. The other scanning pattern was “line scan”, where the 15.45 kHz resonance scanner scanned a point orthogonally to the capillary of interest. RBCs were imaged as they moved across the stationary imaging beam. This imaging scheme yields images where the ordinate axis is space and the abscissa represents time. A third visible light source and synchronized detector (not shown) were used for sodium fluorescein excitation/imaging.

Fig. 2
Fig. 2

A) Capillary lumen diameter measurement line scan image showing the 10 best correlated target images with respect to a user-selected reference image of RBC surrounded by plasma. B) Spatial intensity profile averaged over time. C) Standard deviation (St. Dev.) of pixel intensity across time. Dotted line in C shows mean standard deviation in regions clearly outside the lumen of the vessel.

Fig. 3
Fig. 3

A) Deformed RBCs observed in the living mouse eye imaged with split-detector configuration over 34 seconds of stopped flow (Visualization 1). B) Deformed RBCs as observed in the ex vivo retina of a different mouse using a 40x bright field microscope. The biconcavity of RBCs can be observed in both cases.

Fig. 4
Fig. 4

A) 2D motion contrast image of a capillary in confocal configuration B) The corresponding confocal 1D line scan sequence revealing blood cell glints. C) 2D raster image of a capillary in a different animal captured in split configuration D) Corresponding line scan sequence. Split-detector reveals shape, deformation and arrangement of red blood cells. E) Simultaneously acquired line scan fluorescence from blood plasma labeled with sodium fluorescein. F) 2D raster image of a second blood vessel in the same animal containing high flux and G) corresponding split-detector line scan sequence. H) Simultaneously acquired plasma fluorescence. RBC flux is considerably higher in capillary F compared to C. In cases of high RBC flux and high capillary hematocrit, it is more challenging to distinguish individual RBCs in the fluorescence image compared to the contrast provided by split-detector. Scale bar for A, C and F: 4μm. Fluorescence images have been corrected for small lateral offsets in the time dimension (relative to split-detector images) due to transverse chromatic aberration.

Fig. 5
Fig. 5

RBCs arranged in different configurations as observed in four different retinal capillaries A) RBCs arranged in parachute configuration. B) Manual segmentation of the RBC boundaries in A are shown in red and capillary boundaries in gray. C) Capillary with similar blood velocity and diameter, but with higher volume fraction of RBCs (local hematocrit) D) RBCs arranged in a zigzag configuration where blood cells closely interdigitate with minimal plasma gaps. E) Capillary with disordered flow shows RBCs without consistent arrangement or orientation.

Fig. 6
Fig. 6

A) Line scan image where a moving average window centered on each cell was used to generate its average cell. B) Average cell image corresponding to A where the average target cell is highly visible and because of the regularity in the flow, the average neighboring cells too have appreciable contrast. C) Plot of the pixel intensity of the two lines of the darkest and brightest pixels in the image also marked by the arrows on the right of B and E. The orange plot has a prominent central peak, where the width of the central peak is used to determine cell velocity. There are also slightly less prominent peaks on each side of the central one corresponding to the surrounding cells. D) Line scan image of another capillary with irregular spacing between cells E) Average cell plot corresponding to D where the average target cell is highly visible but because of the lack of regularity in flow, the average neighboring cells have washed out contrast due to temporal variability. F) Linear profile corresponding to the arrows on the right of E. The orange plot has very faint peaks on either side of the central peak.

Fig. 7
Fig. 7

A) Pulsatility of blood cell flux due to cardiac cycle is demonstrated in capillary with lumen diameter of 3.6 µm. Instantaneous flux is plotted over 78.7 seconds of continuous data capture. Only the first and last 5 seconds of measurements are shown for better visualization. The Fourier transform of measured flux showed a strong peak at 176.9 cycles/min (FFT not shown). For visualization, a moving average of 33 ms was applied to the raw data corresponding to an oversampling of 5.1x Nyquist limit of cell velocity. B) A zoomed region of instantaneous flux measured for 1 second of data (shaded region in A). Flux variability over time shows ~3 putative cardiac cycles. The arrangement of blood cells at the maximum and minimum of one cycle is shown inset (66 ms time windows, scale bar = 5 ms). Two representative RBCs in these time windows are magnified on the right. Using velocity estimation described in section 2.8, the representative RBC in the putative diastolic phase is ~41% slower as compared to that in the putative systolic epoch.

Fig. 8
Fig. 8

A) Motion contrast image shows enhanced contrast of multiple converging capillaries in the living mouse retina. Line scans at positions indicated by arrows are compared in B-E. The convergence of vessels B and E containing parachute RBC flow become interdigitated at point of confluence (C) and remain in zigzag configuration 15 micrometers downstream.

Fig. 9
Fig. 9

Capillaries showing the conservation of flux. In both bifurcations we observe how the sum of the lower flux vessels is approximately equal to the one of the high flux vessel. There is a small difference in RBC flux of the different vessels, this is likely due to the sequential nature of capture and the variability contained therein.

Fig. 10
Fig. 10

A) Scatter plot of lumen diameters and RBC flux in 99 retinal capillaries across 10 animals, along with histograms of the distribution of flux and diameter. B) Sample line scan images from four capillaries. The colored boundary of each image corresponds to the same colored data point in the normal data set (A). Vertical scale bar is 4 µm and horizontal scale bar is 10 ms.

Fig. 11
Fig. 11

Changing plane of focus provides independent imaging of the three vascular stratifications of the mouse retina. Split detector intensity images (left) and corresponding motion contrast images (right). Despite lack of a confocal pinhole, stratifications are independently imaged. Vessels parallel to the knife edge are most visible in the split–detector images (red arrow), whereas contrast from orthogonal vessels are less visible (white arrow). Motion contrast images show a double line profile in vessels parallel to the knife edge (red arrowhead) while a single line can be observed in orthogonal vessels (white arrowhead).

Fig. 12
Fig. 12

A) Images of platelets visualized with line scan split-detector B) Enlarged image where an RBC, platelets and vessel wall can be clearly seen and the intensity profile of each of the vascular constituents is plotted to the right. The RBC and platelet have the same polarity of contrast (bright on top) while the vessel wall has the opposite polarity.

Equations (1)

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

v= d Δt

Metrics