Abstract

Adaptive Optics Scanning Laser Ophthalmoscopy was used to noninvasively acquire videos of single-file flow through live human retinal parafoveal capillaries. Videos were analyzed offline to investigate capillary flow dynamics. Certain capillaries accounted for a clear majority of leukocyte traffic (Leukocyte-Preferred-Paths, LPPs), while other capillaries primarily featured plasma gap flow (Plasma-Gap-Capillaries, PGCs). LPPs may serve as a protective mechanism to prevent inactivated leukocytes from entering exchange capillaries, and PGCs may serve as relief valves to minimize flow disruption due to the presence of a leukocyte in a neighboring LPP.

© 2011 OSA

Full Article  |  PDF Article

References

  • View by:
  • |
  • |
  • |

  1. B. W. Zweifach, Functional Behavior of the Microcirculation (Charles C Thomas, Springfield, Illinois, 1961).
  2. J. C. Hogg and C. M. Doerschuk, “Leukocyte traffic in the lung,” Annu. Rev. Physiol. 57(1), 97–114 (1995).
    [CrossRef] [PubMed]
  3. G. W. Schmid-Schönbein, R. Skalak, S. Usami, and S. Chien, “Cell distribution in capillary networks,” Microvasc. Res. 19(1), 18–44 (1980).
    [CrossRef] [PubMed]
  4. B. W. Zweifach, “Quantitative studies of microcirculatory structure and function. I. Analysis of pressure distribution in the terminal vascular bed in cat mesentery,” Circ. Res. 34(6), 843–857 (1974).
    [PubMed]
  5. J. A. Martin and A. Roorda, “Pulsatility of parafoveal capillary leukocytes,” Exp. Eye Res. 88(3), 356–360 (2009).
    [CrossRef] [PubMed]
  6. B. W. Zweifach, “Quantitative studies of microcirculatory structure and function. II. Direct measurement of capillary pressure in splanchnic mesenteric vessels,” Circ. Res. 34(6), 858–866 (1974).
    [PubMed]
  7. A. S. Popel and P. C. Johnson, “Microcirculation and Hemorheology,” Annu. Rev. Fluid Mech. 37(1), 43–69 (2005).
    [CrossRef] [PubMed]
  8. H. H. Lipowsky, “Microvascular rheology and hemodynamics,” Microcirculation 12(1), 5–15 (2005).
    [CrossRef] [PubMed]
  9. G. W. Schmid-Schönbein, Y. Y. Shih, and S. Chien, “Morphometry of human leukocytes,” Blood 56(5), 866–875 (1980).
    [PubMed]
  10. J. Ben-nun, “Comparative flow velocity of erythrocytes and leukocytes in feline retinal capillaries,” Invest. Ophthalmol. Vis. Sci. 37(9), 1854–1859 (1996).
    [PubMed]
  11. W. M. Kuebler, G. E. H. Kuhnle, J. Groh, and A. E. Goetz, “Leukocyte kinetics in pulmonary microcirculation: intravital fluorescence microscopic study,” J. Appl. Physiol. 76(1), 65–71 (1994).
    [PubMed]
  12. E. R. Damiano and T. M. Stace, “Flow and deformation of the capillary glycocalyx in the wake of a leukocyte,” Phys. Fluids 17(3), 031509 (2005).
    [CrossRef]
  13. J. M. Fitz-Gerald, “Plasma motions in narrow capillary flow,” J. Fluid Mech. 51(03), 463–476 (1972).
    [CrossRef]
  14. 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).
    [PubMed]
  15. G. W. Schmid-Schönbein, S. Usami, R. Skalak, and S. Chien, “The interaction of leukocytes and erythrocytes in capillary and postcapillary vessels,” Microvasc. Res. 19(1), 45–70 (1980).
    [CrossRef] [PubMed]
  16. D. W. Sutton and G. W. Schmid-Schönbein, “Elevation of organ resistance due to leukocyte perfusion,” Am. J. Physiol. 262(6 Pt 2), H1646–H1650 (1992).
    [PubMed]
  17. J. A. Martin and A. Roorda, “Direct and noninvasive assessment of parafoveal capillary leukocyte velocity,” Ophthalmology 112(12), 2219–2224 (2005).
    [CrossRef] [PubMed]
  18. Y. Zhang, S. Poonja, and A. Roorda, “MEMS-based adaptive optics scanning laser ophthalmoscopy,” Opt. Lett. 31(9), 1268–1270 (2006).
    [CrossRef] [PubMed]
  19. A. Roorda, F. Romero-Borja, W. Donnelly Iii, H. Queener, T. J. Hebert, and M. C. W. Campbell, “Adaptive optics scanning laser ophthalmoscopy,” Opt. Express 10(9), 405–412 (2002).
    [PubMed]
  20. 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]
  21. L. Laatikainen and J. Larinkari, “Capillary-free area of the fovea with advancing age,” Invest. Ophthalmol. Vis. Sci. 16(12), 1154–1157 (1977).
    [PubMed]
  22. D. M. Snodderly, R. S. Weinhaus, and J. C. Choi, “Neural-vascular relationships in central retina of macaque monkeys (Macaca fascicularis),” J. Neurosci. 12(4), 1169–1193 (1992).
    [PubMed]
  23. E. Evans and Y. C. Fung, “Improved measurements of the erythrocyte geometry,” Microvasc. Res. 4(4), 335–347 (1972).
    [CrossRef] [PubMed]
  24. G. A. Lutty, J. Cao, and D. S. McLeod, “Relationship of polymorphonuclear leukocytes to capillary dropout in the human diabetic choroid,” Am. J. Pathol. 151(3), 707–714 (1997).
    [PubMed]
  25. P. K. Yu, C. Balaratnasingam, S. J. Cringle, I. L. McAllister, J. Provis, and D. Y. Yu, “Microstructure and network organization of the microvasculature in the human macula,” Invest. Ophthalmol. Vis. Sci. 51(12), 6735–6743 (2010).
    [CrossRef] [PubMed]
  26. I. C. Michaelson, Retinal Circulation in Man and Animals (Charles C Thomas, Springfield, Illinois, USA, 1954).
  27. 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]
  28. B. W. Zweifach, D. B. Metz, and E. R. Clark, “Selective distribution of blood through the terminal vascular bed of mesenteric structures and skeletal muscle,” Angiology 6(4), 282–290 (1955).
    [CrossRef] [PubMed]
  29. A. G. Hudetz, “Blood flow in the cerebral capillary network: a review emphasizing observations with intravital microscopy,” Microcirculation 4(2), 233–252 (1997).
    [CrossRef] [PubMed]
  30. E. Friedman, T. R. Smith, and T. Kuwabara, “Retinal Microcirculation in vivo,” Invest. Ophthalmol. 3, 217–226 (1964).
    [PubMed]
  31. R. Flower, E. Peiretti, M. Magnani, L. Rossi, S. Serafini, Z. Gryczynski, and I. Gryczynski, “Observation of erythrocyte dynamics in the retinal capillaries and choriocapillaris using ICG-loaded erythrocyte ghost cells,” Invest. Ophthalmol. Vis. Sci. 49(12), 5510–5516 (2008).
    [CrossRef] [PubMed]
  32. P. S. Jensen and M. R. Glucksberg, “Regional variation in capillary hemodynamics in the cat retina,” Invest. Ophthalmol. Vis. Sci. 39(2), 407–415 (1998).
    [PubMed]
  33. H. Nishiwaki, Y. Ogura, H. Kimura, J. Kiryu, K. Miyamoto, and N. Matsuda, “Visualization and quantitative analysis of leukocyte dynamics in retinal microcirculation of rats,” Invest. Ophthalmol. Vis. Sci. 37(7), 1341–1347 (1996).
    [PubMed]
  34. D. A. Nelson, S. Krupsky, A. Pollack, E. Aloni, M. Belkin, I. Vanzetta, M. Rosner, and A. Grinvald, “Special report: Noninvasive multi-parameter functional optical imaging of the eye,” Ophthalmic Surg. Lasers Imaging 36(1), 57–66 (2005).
    [PubMed]
  35. M. Paques, B. Boval, S. Richard, R. Tadayoni, P. Massin, O. Mundler, A. Gaudric, and E. Vicaut, “Evaluation of fluorescein-labeled autologous leukocytes for examination of retinal circulation in humans,” Curr. Eye Res. 21(1), 560–565 (2000).
    [PubMed]
  36. H. M. Becker, M. Chen, J. B. Hay, and M. I. Cybulsky, “Tracking of leukocyte recruitment into tissues of mice by in situ labeling of blood cells with the fluorescent dye CFDA SE,” J. Immunol. Methods 286(1-2), 69–78 (2004).
    [CrossRef] [PubMed]
  37. G. W. Schmid-Schönbein, K. L. Sung, H. Tözeren, R. Skalak, and S. Chien, “Passive mechanical properties of human leukocytes,” Biophys. J. 36(1), 243–256 (1981).
    [CrossRef] [PubMed]
  38. American National Standard for the Safe Use of Lasers, ANSI Z136.1–2007 (American National Standard Institute, New York, 2007).
  39. K. Y. Li, P. Tiruveedhula, and A. Roorda, “Intersubject variability of foveal cone photoreceptor density in relation to eye length,” Invest. Ophthalmol. Vis. Sci. 51(12), 6858–6867 (2010).
    [CrossRef] [PubMed]
  40. D. W. Arathorn, Q. Yang, C. R. Vogel, Y. Zhang, P. Tiruveedhula, and A. Roorda, “Retinally stabilized cone-targeted stimulus delivery,” Opt. Express 15(21), 13731–13744 (2007).
    [CrossRef] [PubMed]
  41. C. R. Vogel, D. W. Arathorn, A. Roorda, and A. Parker, “Retinal motion estimation in adaptive optics scanning laser ophthalmoscopy,” Opt. Express 14(2), 487–497 (2006).
    [CrossRef] [PubMed]
  42. J. Tam, and A. Roorda, “Enhanced detection of cell paths in spatiotemporal plots for noninvasive microscopy of the human retina,” in 2010 IEEE International Symposium on Biomedical Imaging: From Nano to Macro (IEEE, 2010) , pp. 584–587.
  43. J. Tam and A. Roorda, “Speed quantification and tracking of moving objects in adaptive optics scanning laser ophthalmoscopy,” J. Biomed. Opt. (to be published).
  44. C. E. Riva and B. Petrig, “Blue field entoptic phenomenon and blood velocity in the retinal capillaries,” J. Opt. Soc. Am. 70(10), 1234–1238 (1980).
    [CrossRef] [PubMed]
  45. M. Meinke, G. Müller, J. Helfmann, and M. Friebel, “Optical properties of platelets and blood plasma and their influence on the optical behavior of whole blood in the visible to near infrared wavelength range,” J. Biomed. Opt. 12(1), 014024 (2007).
    [CrossRef] [PubMed]
  46. T. Nagaoka and A. Yoshida, “Noninvasive evaluation of wall shear stress on retinal microcirculation in humans,” Invest. Ophthalmol. Vis. Sci. 47(3), 1113–1119 (2006).
    [CrossRef] [PubMed]

2010

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]

P. K. Yu, C. Balaratnasingam, S. J. Cringle, I. L. McAllister, J. Provis, and D. Y. Yu, “Microstructure and network organization of the microvasculature in the human macula,” Invest. Ophthalmol. Vis. Sci. 51(12), 6735–6743 (2010).
[CrossRef] [PubMed]

K. Y. Li, P. Tiruveedhula, and A. Roorda, “Intersubject variability of foveal cone photoreceptor density in relation to eye length,” Invest. Ophthalmol. Vis. Sci. 51(12), 6858–6867 (2010).
[CrossRef] [PubMed]

2009

J. A. Martin and A. Roorda, “Pulsatility of parafoveal capillary leukocytes,” Exp. Eye Res. 88(3), 356–360 (2009).
[CrossRef] [PubMed]

2008

R. Flower, E. Peiretti, M. Magnani, L. Rossi, S. Serafini, Z. Gryczynski, and I. Gryczynski, “Observation of erythrocyte dynamics in the retinal capillaries and choriocapillaris using ICG-loaded erythrocyte ghost cells,” Invest. Ophthalmol. Vis. Sci. 49(12), 5510–5516 (2008).
[CrossRef] [PubMed]

2007

D. W. Arathorn, Q. Yang, C. R. Vogel, Y. Zhang, P. Tiruveedhula, and A. Roorda, “Retinally stabilized cone-targeted stimulus delivery,” Opt. Express 15(21), 13731–13744 (2007).
[CrossRef] [PubMed]

M. Meinke, G. Müller, J. Helfmann, and M. Friebel, “Optical properties of platelets and blood plasma and their influence on the optical behavior of whole blood in the visible to near infrared wavelength range,” J. Biomed. Opt. 12(1), 014024 (2007).
[CrossRef] [PubMed]

2006

2005

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

E. R. Damiano and T. M. Stace, “Flow and deformation of the capillary glycocalyx in the wake of a leukocyte,” Phys. Fluids 17(3), 031509 (2005).
[CrossRef]

A. S. Popel and P. C. Johnson, “Microcirculation and Hemorheology,” Annu. Rev. Fluid Mech. 37(1), 43–69 (2005).
[CrossRef] [PubMed]

H. H. Lipowsky, “Microvascular rheology and hemodynamics,” Microcirculation 12(1), 5–15 (2005).
[CrossRef] [PubMed]

D. A. Nelson, S. Krupsky, A. Pollack, E. Aloni, M. Belkin, I. Vanzetta, M. Rosner, and A. Grinvald, “Special report: Noninvasive multi-parameter functional optical imaging of the eye,” Ophthalmic Surg. Lasers Imaging 36(1), 57–66 (2005).
[PubMed]

2004

H. M. Becker, M. Chen, J. B. Hay, and M. I. Cybulsky, “Tracking of leukocyte recruitment into tissues of mice by in situ labeling of blood cells with the fluorescent dye CFDA SE,” J. Immunol. Methods 286(1-2), 69–78 (2004).
[CrossRef] [PubMed]

2002

2000

M. Paques, B. Boval, S. Richard, R. Tadayoni, P. Massin, O. Mundler, A. Gaudric, and E. Vicaut, “Evaluation of fluorescein-labeled autologous leukocytes for examination of retinal circulation in humans,” Curr. Eye Res. 21(1), 560–565 (2000).
[PubMed]

1998

P. S. Jensen and M. R. Glucksberg, “Regional variation in capillary hemodynamics in the cat retina,” Invest. Ophthalmol. Vis. Sci. 39(2), 407–415 (1998).
[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]

1997

A. G. Hudetz, “Blood flow in the cerebral capillary network: a review emphasizing observations with intravital microscopy,” Microcirculation 4(2), 233–252 (1997).
[CrossRef] [PubMed]

G. A. Lutty, J. Cao, and D. S. McLeod, “Relationship of polymorphonuclear leukocytes to capillary dropout in the human diabetic choroid,” Am. J. Pathol. 151(3), 707–714 (1997).
[PubMed]

1996

H. Nishiwaki, Y. Ogura, H. Kimura, J. Kiryu, K. Miyamoto, and N. Matsuda, “Visualization and quantitative analysis of leukocyte dynamics in retinal microcirculation of rats,” Invest. Ophthalmol. Vis. Sci. 37(7), 1341–1347 (1996).
[PubMed]

J. Ben-nun, “Comparative flow velocity of erythrocytes and leukocytes in feline retinal capillaries,” Invest. Ophthalmol. Vis. Sci. 37(9), 1854–1859 (1996).
[PubMed]

1995

J. C. Hogg and C. M. Doerschuk, “Leukocyte traffic in the lung,” Annu. Rev. Physiol. 57(1), 97–114 (1995).
[CrossRef] [PubMed]

1994

W. M. Kuebler, G. E. H. Kuhnle, J. Groh, and A. E. Goetz, “Leukocyte kinetics in pulmonary microcirculation: intravital fluorescence microscopic study,” J. Appl. Physiol. 76(1), 65–71 (1994).
[PubMed]

1992

D. W. Sutton and G. W. Schmid-Schönbein, “Elevation of organ resistance due to leukocyte perfusion,” Am. J. Physiol. 262(6 Pt 2), H1646–H1650 (1992).
[PubMed]

D. M. Snodderly, R. S. Weinhaus, and J. C. Choi, “Neural-vascular relationships in central retina of macaque monkeys (Macaca fascicularis),” J. Neurosci. 12(4), 1169–1193 (1992).
[PubMed]

1990

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).
[PubMed]

1981

G. W. Schmid-Schönbein, K. L. Sung, H. Tözeren, R. Skalak, and S. Chien, “Passive mechanical properties of human leukocytes,” Biophys. J. 36(1), 243–256 (1981).
[CrossRef] [PubMed]

1980

G. W. Schmid-Schönbein, S. Usami, R. Skalak, and S. Chien, “The interaction of leukocytes and erythrocytes in capillary and postcapillary vessels,” Microvasc. Res. 19(1), 45–70 (1980).
[CrossRef] [PubMed]

G. W. Schmid-Schönbein, Y. Y. Shih, and S. Chien, “Morphometry of human leukocytes,” Blood 56(5), 866–875 (1980).
[PubMed]

G. W. Schmid-Schönbein, R. Skalak, S. Usami, and S. Chien, “Cell distribution in capillary networks,” Microvasc. Res. 19(1), 18–44 (1980).
[CrossRef] [PubMed]

C. E. Riva and B. Petrig, “Blue field entoptic phenomenon and blood velocity in the retinal capillaries,” J. Opt. Soc. Am. 70(10), 1234–1238 (1980).
[CrossRef] [PubMed]

1977

L. Laatikainen and J. Larinkari, “Capillary-free area of the fovea with advancing age,” Invest. Ophthalmol. Vis. Sci. 16(12), 1154–1157 (1977).
[PubMed]

1974

B. W. Zweifach, “Quantitative studies of microcirculatory structure and function. I. Analysis of pressure distribution in the terminal vascular bed in cat mesentery,” Circ. Res. 34(6), 843–857 (1974).
[PubMed]

B. W. Zweifach, “Quantitative studies of microcirculatory structure and function. II. Direct measurement of capillary pressure in splanchnic mesenteric vessels,” Circ. Res. 34(6), 858–866 (1974).
[PubMed]

1972

J. M. Fitz-Gerald, “Plasma motions in narrow capillary flow,” J. Fluid Mech. 51(03), 463–476 (1972).
[CrossRef]

E. Evans and Y. C. Fung, “Improved measurements of the erythrocyte geometry,” Microvasc. Res. 4(4), 335–347 (1972).
[CrossRef] [PubMed]

1964

E. Friedman, T. R. Smith, and T. Kuwabara, “Retinal Microcirculation in vivo,” Invest. Ophthalmol. 3, 217–226 (1964).
[PubMed]

1955

B. W. Zweifach, D. B. Metz, and E. R. Clark, “Selective distribution of blood through the terminal vascular bed of mesenteric structures and skeletal muscle,” Angiology 6(4), 282–290 (1955).
[CrossRef] [PubMed]

Aloni, E.

D. A. Nelson, S. Krupsky, A. Pollack, E. Aloni, M. Belkin, I. Vanzetta, M. Rosner, and A. Grinvald, “Special report: Noninvasive multi-parameter functional optical imaging of the eye,” Ophthalmic Surg. Lasers Imaging 36(1), 57–66 (2005).
[PubMed]

Arathorn, D. W.

Balaratnasingam, C.

P. K. Yu, C. Balaratnasingam, S. J. Cringle, I. L. McAllister, J. Provis, and D. Y. Yu, “Microstructure and network organization of the microvasculature in the human macula,” Invest. Ophthalmol. Vis. Sci. 51(12), 6735–6743 (2010).
[CrossRef] [PubMed]

Becker, H. M.

H. M. Becker, M. Chen, J. B. Hay, and M. I. Cybulsky, “Tracking of leukocyte recruitment into tissues of mice by in situ labeling of blood cells with the fluorescent dye CFDA SE,” J. Immunol. Methods 286(1-2), 69–78 (2004).
[CrossRef] [PubMed]

Belkin, M.

D. A. Nelson, S. Krupsky, A. Pollack, E. Aloni, M. Belkin, I. Vanzetta, M. Rosner, and A. Grinvald, “Special report: Noninvasive multi-parameter functional optical imaging of the eye,” Ophthalmic Surg. Lasers Imaging 36(1), 57–66 (2005).
[PubMed]

Ben-nun, J.

J. Ben-nun, “Comparative flow velocity of erythrocytes and leukocytes in feline retinal capillaries,” Invest. Ophthalmol. Vis. Sci. 37(9), 1854–1859 (1996).
[PubMed]

Boval, B.

M. Paques, B. Boval, S. Richard, R. Tadayoni, P. Massin, O. Mundler, A. Gaudric, and E. Vicaut, “Evaluation of fluorescein-labeled autologous leukocytes for examination of retinal circulation in humans,” Curr. Eye Res. 21(1), 560–565 (2000).
[PubMed]

Campbell, M. C. W.

Cao, J.

G. A. Lutty, J. Cao, and D. S. McLeod, “Relationship of polymorphonuclear leukocytes to capillary dropout in the human diabetic choroid,” Am. J. Pathol. 151(3), 707–714 (1997).
[PubMed]

Chen, M.

H. M. Becker, M. Chen, J. B. Hay, and M. I. Cybulsky, “Tracking of leukocyte recruitment into tissues of mice by in situ labeling of blood cells with the fluorescent dye CFDA SE,” J. Immunol. Methods 286(1-2), 69–78 (2004).
[CrossRef] [PubMed]

Chien, S.

G. W. Schmid-Schönbein, K. L. Sung, H. Tözeren, R. Skalak, and S. Chien, “Passive mechanical properties of human leukocytes,” Biophys. J. 36(1), 243–256 (1981).
[CrossRef] [PubMed]

G. W. Schmid-Schönbein, R. Skalak, S. Usami, and S. Chien, “Cell distribution in capillary networks,” Microvasc. Res. 19(1), 18–44 (1980).
[CrossRef] [PubMed]

G. W. Schmid-Schönbein, Y. Y. Shih, and S. Chien, “Morphometry of human leukocytes,” Blood 56(5), 866–875 (1980).
[PubMed]

G. W. Schmid-Schönbein, S. Usami, R. Skalak, and S. Chien, “The interaction of leukocytes and erythrocytes in capillary and postcapillary vessels,” Microvasc. Res. 19(1), 45–70 (1980).
[CrossRef] [PubMed]

Choi, J. C.

D. M. Snodderly, R. S. Weinhaus, and J. C. Choi, “Neural-vascular relationships in central retina of macaque monkeys (Macaca fascicularis),” J. Neurosci. 12(4), 1169–1193 (1992).
[PubMed]

Clark, E. R.

B. W. Zweifach, D. B. Metz, and E. R. Clark, “Selective distribution of blood through the terminal vascular bed of mesenteric structures and skeletal muscle,” Angiology 6(4), 282–290 (1955).
[CrossRef] [PubMed]

Cringle, S. J.

P. K. Yu, C. Balaratnasingam, S. J. Cringle, I. L. McAllister, J. Provis, and D. Y. Yu, “Microstructure and network organization of the microvasculature in the human macula,” Invest. Ophthalmol. Vis. Sci. 51(12), 6735–6743 (2010).
[CrossRef] [PubMed]

Cybulsky, M. I.

H. M. Becker, M. Chen, J. B. Hay, and M. I. Cybulsky, “Tracking of leukocyte recruitment into tissues of mice by in situ labeling of blood cells with the fluorescent dye CFDA SE,” J. Immunol. Methods 286(1-2), 69–78 (2004).
[CrossRef] [PubMed]

Damiano, E. R.

E. R. Damiano and T. M. Stace, “Flow and deformation of the capillary glycocalyx in the wake of a leukocyte,” Phys. Fluids 17(3), 031509 (2005).
[CrossRef]

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]

Doerschuk, C. M.

J. C. Hogg and C. M. Doerschuk, “Leukocyte traffic in the lung,” Annu. Rev. Physiol. 57(1), 97–114 (1995).
[CrossRef] [PubMed]

Donnelly Iii, W.

Evans, E.

E. Evans and Y. C. Fung, “Improved measurements of the erythrocyte geometry,” Microvasc. Res. 4(4), 335–347 (1972).
[CrossRef] [PubMed]

Fitz-Gerald, J. M.

J. M. Fitz-Gerald, “Plasma motions in narrow capillary flow,” J. Fluid Mech. 51(03), 463–476 (1972).
[CrossRef]

Flower, R.

R. Flower, E. Peiretti, M. Magnani, L. Rossi, S. Serafini, Z. Gryczynski, and I. Gryczynski, “Observation of erythrocyte dynamics in the retinal capillaries and choriocapillaris using ICG-loaded erythrocyte ghost cells,” Invest. Ophthalmol. Vis. Sci. 49(12), 5510–5516 (2008).
[CrossRef] [PubMed]

Friebel, M.

M. Meinke, G. Müller, J. Helfmann, and M. Friebel, “Optical properties of platelets and blood plasma and their influence on the optical behavior of whole blood in the visible to near infrared wavelength range,” J. Biomed. Opt. 12(1), 014024 (2007).
[CrossRef] [PubMed]

Friedman, E.

E. Friedman, T. R. Smith, and T. Kuwabara, “Retinal Microcirculation in vivo,” Invest. Ophthalmol. 3, 217–226 (1964).
[PubMed]

Fung, Y. C.

E. Evans and Y. C. Fung, “Improved measurements of the erythrocyte geometry,” Microvasc. Res. 4(4), 335–347 (1972).
[CrossRef] [PubMed]

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).
[PubMed]

Gaudric, A.

M. Paques, B. Boval, S. Richard, R. Tadayoni, P. Massin, O. Mundler, A. Gaudric, and E. Vicaut, “Evaluation of fluorescein-labeled autologous leukocytes for examination of retinal circulation in humans,” Curr. Eye Res. 21(1), 560–565 (2000).
[PubMed]

Glucksberg, M. R.

P. S. Jensen and M. R. Glucksberg, “Regional variation in capillary hemodynamics in the cat retina,” Invest. Ophthalmol. Vis. Sci. 39(2), 407–415 (1998).
[PubMed]

Goetz, A. E.

W. M. Kuebler, G. E. H. Kuhnle, J. Groh, and A. E. Goetz, “Leukocyte kinetics in pulmonary microcirculation: intravital fluorescence microscopic study,” J. Appl. Physiol. 76(1), 65–71 (1994).
[PubMed]

Grinvald, A.

D. A. Nelson, S. Krupsky, A. Pollack, E. Aloni, M. Belkin, I. Vanzetta, M. Rosner, and A. Grinvald, “Special report: Noninvasive multi-parameter functional optical imaging of the eye,” Ophthalmic Surg. Lasers Imaging 36(1), 57–66 (2005).
[PubMed]

Groh, J.

W. M. Kuebler, G. E. H. Kuhnle, J. Groh, and A. E. Goetz, “Leukocyte kinetics in pulmonary microcirculation: intravital fluorescence microscopic study,” J. Appl. Physiol. 76(1), 65–71 (1994).
[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).
[PubMed]

Gryczynski, I.

R. Flower, E. Peiretti, M. Magnani, L. Rossi, S. Serafini, Z. Gryczynski, and I. Gryczynski, “Observation of erythrocyte dynamics in the retinal capillaries and choriocapillaris using ICG-loaded erythrocyte ghost cells,” Invest. Ophthalmol. Vis. Sci. 49(12), 5510–5516 (2008).
[CrossRef] [PubMed]

Gryczynski, Z.

R. Flower, E. Peiretti, M. Magnani, L. Rossi, S. Serafini, Z. Gryczynski, and I. Gryczynski, “Observation of erythrocyte dynamics in the retinal capillaries and choriocapillaris using ICG-loaded erythrocyte ghost cells,” Invest. Ophthalmol. Vis. Sci. 49(12), 5510–5516 (2008).
[CrossRef] [PubMed]

Hay, J. B.

H. M. Becker, M. Chen, J. B. Hay, and M. I. Cybulsky, “Tracking of leukocyte recruitment into tissues of mice by in situ labeling of blood cells with the fluorescent dye CFDA SE,” J. Immunol. Methods 286(1-2), 69–78 (2004).
[CrossRef] [PubMed]

Hebert, T. J.

Helfmann, J.

M. Meinke, G. Müller, J. Helfmann, and M. Friebel, “Optical properties of platelets and blood plasma and their influence on the optical behavior of whole blood in the visible to near infrared wavelength range,” J. Biomed. Opt. 12(1), 014024 (2007).
[CrossRef] [PubMed]

Helmchen, F.

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

Hogg, J. C.

J. C. Hogg and C. M. Doerschuk, “Leukocyte traffic in the lung,” Annu. Rev. Physiol. 57(1), 97–114 (1995).
[CrossRef] [PubMed]

Hudetz, A. G.

A. G. Hudetz, “Blood flow in the cerebral capillary network: a review emphasizing observations with intravital microscopy,” Microcirculation 4(2), 233–252 (1997).
[CrossRef] [PubMed]

Jensen, P. S.

P. S. Jensen and M. R. Glucksberg, “Regional variation in capillary hemodynamics in the cat retina,” Invest. Ophthalmol. Vis. Sci. 39(2), 407–415 (1998).
[PubMed]

Johnson, P. C.

A. S. Popel and P. C. Johnson, “Microcirculation and Hemorheology,” Annu. Rev. Fluid Mech. 37(1), 43–69 (2005).
[CrossRef] [PubMed]

Kimura, H.

H. Nishiwaki, Y. Ogura, H. Kimura, J. Kiryu, K. Miyamoto, and N. Matsuda, “Visualization and quantitative analysis of leukocyte dynamics in retinal microcirculation of rats,” Invest. Ophthalmol. Vis. Sci. 37(7), 1341–1347 (1996).
[PubMed]

Kiryu, J.

H. Nishiwaki, Y. Ogura, H. Kimura, J. Kiryu, K. Miyamoto, and N. Matsuda, “Visualization and quantitative analysis of leukocyte dynamics in retinal microcirculation of rats,” Invest. Ophthalmol. Vis. Sci. 37(7), 1341–1347 (1996).
[PubMed]

Kleinfeld, D.

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]

Krupsky, S.

D. A. Nelson, S. Krupsky, A. Pollack, E. Aloni, M. Belkin, I. Vanzetta, M. Rosner, and A. Grinvald, “Special report: Noninvasive multi-parameter functional optical imaging of the eye,” Ophthalmic Surg. Lasers Imaging 36(1), 57–66 (2005).
[PubMed]

Kuebler, W. M.

W. M. Kuebler, G. E. H. Kuhnle, J. Groh, and A. E. Goetz, “Leukocyte kinetics in pulmonary microcirculation: intravital fluorescence microscopic study,” J. Appl. Physiol. 76(1), 65–71 (1994).
[PubMed]

Kuhnle, G. E. H.

W. M. Kuebler, G. E. H. Kuhnle, J. Groh, and A. E. Goetz, “Leukocyte kinetics in pulmonary microcirculation: intravital fluorescence microscopic study,” J. Appl. Physiol. 76(1), 65–71 (1994).
[PubMed]

Kuwabara, T.

E. Friedman, T. R. Smith, and T. Kuwabara, “Retinal Microcirculation in vivo,” Invest. Ophthalmol. 3, 217–226 (1964).
[PubMed]

Laatikainen, L.

L. Laatikainen and J. Larinkari, “Capillary-free area of the fovea with advancing age,” Invest. Ophthalmol. Vis. Sci. 16(12), 1154–1157 (1977).
[PubMed]

Larinkari, J.

L. Laatikainen and J. Larinkari, “Capillary-free area of the fovea with advancing age,” Invest. Ophthalmol. Vis. Sci. 16(12), 1154–1157 (1977).
[PubMed]

Li, K. Y.

K. Y. Li, P. Tiruveedhula, and A. Roorda, “Intersubject variability of foveal cone photoreceptor density in relation to eye length,” Invest. Ophthalmol. Vis. Sci. 51(12), 6858–6867 (2010).
[CrossRef] [PubMed]

Lipowsky, H. H.

H. H. Lipowsky, “Microvascular rheology and hemodynamics,” Microcirculation 12(1), 5–15 (2005).
[CrossRef] [PubMed]

Lutty, G. A.

G. A. Lutty, J. Cao, and D. S. McLeod, “Relationship of polymorphonuclear leukocytes to capillary dropout in the human diabetic choroid,” Am. J. Pathol. 151(3), 707–714 (1997).
[PubMed]

Magnani, M.

R. Flower, E. Peiretti, M. Magnani, L. Rossi, S. Serafini, Z. Gryczynski, and I. Gryczynski, “Observation of erythrocyte dynamics in the retinal capillaries and choriocapillaris using ICG-loaded erythrocyte ghost cells,” Invest. Ophthalmol. Vis. Sci. 49(12), 5510–5516 (2008).
[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]

Massin, P.

M. Paques, B. Boval, S. Richard, R. Tadayoni, P. Massin, O. Mundler, A. Gaudric, and E. Vicaut, “Evaluation of fluorescein-labeled autologous leukocytes for examination of retinal circulation in humans,” Curr. Eye Res. 21(1), 560–565 (2000).
[PubMed]

Matsuda, N.

H. Nishiwaki, Y. Ogura, H. Kimura, J. Kiryu, K. Miyamoto, and N. Matsuda, “Visualization and quantitative analysis of leukocyte dynamics in retinal microcirculation of rats,” Invest. Ophthalmol. Vis. Sci. 37(7), 1341–1347 (1996).
[PubMed]

McAllister, I. L.

P. K. Yu, C. Balaratnasingam, S. J. Cringle, I. L. McAllister, J. Provis, and D. Y. Yu, “Microstructure and network organization of the microvasculature in the human macula,” Invest. Ophthalmol. Vis. Sci. 51(12), 6735–6743 (2010).
[CrossRef] [PubMed]

McLeod, D. S.

G. A. Lutty, J. Cao, and D. S. McLeod, “Relationship of polymorphonuclear leukocytes to capillary dropout in the human diabetic choroid,” Am. J. Pathol. 151(3), 707–714 (1997).
[PubMed]

Meinke, M.

M. Meinke, G. Müller, J. Helfmann, and M. Friebel, “Optical properties of platelets and blood plasma and their influence on the optical behavior of whole blood in the visible to near infrared wavelength range,” J. Biomed. Opt. 12(1), 014024 (2007).
[CrossRef] [PubMed]

Metz, D. B.

B. W. Zweifach, D. B. Metz, and E. R. Clark, “Selective distribution of blood through the terminal vascular bed of mesenteric structures and skeletal muscle,” Angiology 6(4), 282–290 (1955).
[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.

H. Nishiwaki, Y. Ogura, H. Kimura, J. Kiryu, K. Miyamoto, and N. Matsuda, “Visualization and quantitative analysis of leukocyte dynamics in retinal microcirculation of rats,” Invest. Ophthalmol. Vis. Sci. 37(7), 1341–1347 (1996).
[PubMed]

Müller, G.

M. Meinke, G. Müller, J. Helfmann, and M. Friebel, “Optical properties of platelets and blood plasma and their influence on the optical behavior of whole blood in the visible to near infrared wavelength range,” J. Biomed. Opt. 12(1), 014024 (2007).
[CrossRef] [PubMed]

Mundler, O.

M. Paques, B. Boval, S. Richard, R. Tadayoni, P. Massin, O. Mundler, A. Gaudric, and E. Vicaut, “Evaluation of fluorescein-labeled autologous leukocytes for examination of retinal circulation in humans,” Curr. Eye Res. 21(1), 560–565 (2000).
[PubMed]

Nagaoka, T.

T. Nagaoka and A. Yoshida, “Noninvasive evaluation of wall shear stress on retinal microcirculation in humans,” Invest. Ophthalmol. Vis. Sci. 47(3), 1113–1119 (2006).
[CrossRef] [PubMed]

Nelson, D. A.

D. A. Nelson, S. Krupsky, A. Pollack, E. Aloni, M. Belkin, I. Vanzetta, M. Rosner, and A. Grinvald, “Special report: Noninvasive multi-parameter functional optical imaging of the eye,” Ophthalmic Surg. Lasers Imaging 36(1), 57–66 (2005).
[PubMed]

Nishiwaki, H.

H. Nishiwaki, Y. Ogura, H. Kimura, J. Kiryu, K. Miyamoto, and N. Matsuda, “Visualization and quantitative analysis of leukocyte dynamics in retinal microcirculation of rats,” Invest. Ophthalmol. Vis. Sci. 37(7), 1341–1347 (1996).
[PubMed]

Ogura, Y.

H. Nishiwaki, Y. Ogura, H. Kimura, J. Kiryu, K. Miyamoto, and N. Matsuda, “Visualization and quantitative analysis of leukocyte dynamics in retinal microcirculation of rats,” Invest. Ophthalmol. Vis. Sci. 37(7), 1341–1347 (1996).
[PubMed]

Paques, M.

M. Paques, B. Boval, S. Richard, R. Tadayoni, P. Massin, O. Mundler, A. Gaudric, and E. Vicaut, “Evaluation of fluorescein-labeled autologous leukocytes for examination of retinal circulation in humans,” Curr. Eye Res. 21(1), 560–565 (2000).
[PubMed]

Parker, A.

Peiretti, E.

R. Flower, E. Peiretti, M. Magnani, L. Rossi, S. Serafini, Z. Gryczynski, and I. Gryczynski, “Observation of erythrocyte dynamics in the retinal capillaries and choriocapillaris using ICG-loaded erythrocyte ghost cells,” Invest. Ophthalmol. Vis. Sci. 49(12), 5510–5516 (2008).
[CrossRef] [PubMed]

Petrig, B.

Pollack, A.

D. A. Nelson, S. Krupsky, A. Pollack, E. Aloni, M. Belkin, I. Vanzetta, M. Rosner, and A. Grinvald, “Special report: Noninvasive multi-parameter functional optical imaging of the eye,” Ophthalmic Surg. Lasers Imaging 36(1), 57–66 (2005).
[PubMed]

Poonja, S.

Popel, A. S.

A. S. Popel and P. C. Johnson, “Microcirculation and Hemorheology,” Annu. Rev. Fluid Mech. 37(1), 43–69 (2005).
[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).
[PubMed]

Provis, J.

P. K. Yu, C. Balaratnasingam, S. J. Cringle, I. L. McAllister, J. Provis, and D. Y. Yu, “Microstructure and network organization of the microvasculature in the human macula,” Invest. Ophthalmol. Vis. Sci. 51(12), 6735–6743 (2010).
[CrossRef] [PubMed]

Queener, H.

Richard, S.

M. Paques, B. Boval, S. Richard, R. Tadayoni, P. Massin, O. Mundler, A. Gaudric, and E. Vicaut, “Evaluation of fluorescein-labeled autologous leukocytes for examination of retinal circulation in humans,” Curr. Eye Res. 21(1), 560–565 (2000).
[PubMed]

Riva, C. E.

Romero-Borja, F.

Roorda, 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]

K. Y. Li, P. Tiruveedhula, and A. Roorda, “Intersubject variability of foveal cone photoreceptor density in relation to eye length,” Invest. Ophthalmol. Vis. Sci. 51(12), 6858–6867 (2010).
[CrossRef] [PubMed]

J. A. Martin and A. Roorda, “Pulsatility of parafoveal capillary leukocytes,” Exp. Eye Res. 88(3), 356–360 (2009).
[CrossRef] [PubMed]

D. W. Arathorn, Q. Yang, C. R. Vogel, Y. Zhang, P. Tiruveedhula, and A. Roorda, “Retinally stabilized cone-targeted stimulus delivery,” Opt. Express 15(21), 13731–13744 (2007).
[CrossRef] [PubMed]

C. R. Vogel, D. W. Arathorn, A. Roorda, and A. Parker, “Retinal motion estimation in adaptive optics scanning laser ophthalmoscopy,” Opt. Express 14(2), 487–497 (2006).
[CrossRef] [PubMed]

Y. Zhang, S. Poonja, and A. Roorda, “MEMS-based adaptive optics scanning laser ophthalmoscopy,” Opt. Lett. 31(9), 1268–1270 (2006).
[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]

A. Roorda, F. Romero-Borja, W. Donnelly Iii, H. Queener, T. J. Hebert, and M. C. W. Campbell, “Adaptive optics scanning laser ophthalmoscopy,” Opt. Express 10(9), 405–412 (2002).
[PubMed]

J. Tam and A. Roorda, “Speed quantification and tracking of moving objects in adaptive optics scanning laser ophthalmoscopy,” J. Biomed. Opt. (to be published).

Rosner, M.

D. A. Nelson, S. Krupsky, A. Pollack, E. Aloni, M. Belkin, I. Vanzetta, M. Rosner, and A. Grinvald, “Special report: Noninvasive multi-parameter functional optical imaging of the eye,” Ophthalmic Surg. Lasers Imaging 36(1), 57–66 (2005).
[PubMed]

Rossi, L.

R. Flower, E. Peiretti, M. Magnani, L. Rossi, S. Serafini, Z. Gryczynski, and I. Gryczynski, “Observation of erythrocyte dynamics in the retinal capillaries and choriocapillaris using ICG-loaded erythrocyte ghost cells,” Invest. Ophthalmol. Vis. Sci. 49(12), 5510–5516 (2008).
[CrossRef] [PubMed]

Schmid-Schönbein, G. W.

D. W. Sutton and G. W. Schmid-Schönbein, “Elevation of organ resistance due to leukocyte perfusion,” Am. J. Physiol. 262(6 Pt 2), H1646–H1650 (1992).
[PubMed]

G. W. Schmid-Schönbein, K. L. Sung, H. Tözeren, R. Skalak, and S. Chien, “Passive mechanical properties of human leukocytes,” Biophys. J. 36(1), 243–256 (1981).
[CrossRef] [PubMed]

G. W. Schmid-Schönbein, S. Usami, R. Skalak, and S. Chien, “The interaction of leukocytes and erythrocytes in capillary and postcapillary vessels,” Microvasc. Res. 19(1), 45–70 (1980).
[CrossRef] [PubMed]

G. W. Schmid-Schönbein, R. Skalak, S. Usami, and S. Chien, “Cell distribution in capillary networks,” Microvasc. Res. 19(1), 18–44 (1980).
[CrossRef] [PubMed]

G. W. Schmid-Schönbein, Y. Y. Shih, and S. Chien, “Morphometry of human leukocytes,” Blood 56(5), 866–875 (1980).
[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).
[PubMed]

Serafini, S.

R. Flower, E. Peiretti, M. Magnani, L. Rossi, S. Serafini, Z. Gryczynski, and I. Gryczynski, “Observation of erythrocyte dynamics in the retinal capillaries and choriocapillaris using ICG-loaded erythrocyte ghost cells,” Invest. Ophthalmol. Vis. Sci. 49(12), 5510–5516 (2008).
[CrossRef] [PubMed]

Shih, Y. Y.

G. W. Schmid-Schönbein, Y. Y. Shih, and S. Chien, “Morphometry of human leukocytes,” Blood 56(5), 866–875 (1980).
[PubMed]

Skalak, R.

G. W. Schmid-Schönbein, K. L. Sung, H. Tözeren, R. Skalak, and S. Chien, “Passive mechanical properties of human leukocytes,” Biophys. J. 36(1), 243–256 (1981).
[CrossRef] [PubMed]

G. W. Schmid-Schönbein, R. Skalak, S. Usami, and S. Chien, “Cell distribution in capillary networks,” Microvasc. Res. 19(1), 18–44 (1980).
[CrossRef] [PubMed]

G. W. Schmid-Schönbein, S. Usami, R. Skalak, and S. Chien, “The interaction of leukocytes and erythrocytes in capillary and postcapillary vessels,” Microvasc. Res. 19(1), 45–70 (1980).
[CrossRef] [PubMed]

Smith, T. R.

E. Friedman, T. R. Smith, and T. Kuwabara, “Retinal Microcirculation in vivo,” Invest. Ophthalmol. 3, 217–226 (1964).
[PubMed]

Snodderly, D. M.

D. M. Snodderly, R. S. Weinhaus, and J. C. Choi, “Neural-vascular relationships in central retina of macaque monkeys (Macaca fascicularis),” J. Neurosci. 12(4), 1169–1193 (1992).
[PubMed]

Stace, T. M.

E. R. Damiano and T. M. Stace, “Flow and deformation of the capillary glycocalyx in the wake of a leukocyte,” Phys. Fluids 17(3), 031509 (2005).
[CrossRef]

Sung, K. L.

G. W. Schmid-Schönbein, K. L. Sung, H. Tözeren, R. Skalak, and S. Chien, “Passive mechanical properties of human leukocytes,” Biophys. J. 36(1), 243–256 (1981).
[CrossRef] [PubMed]

Sutton, D. W.

D. W. Sutton and G. W. Schmid-Schönbein, “Elevation of organ resistance due to leukocyte perfusion,” Am. J. Physiol. 262(6 Pt 2), H1646–H1650 (1992).
[PubMed]

Tadayoni, R.

M. Paques, B. Boval, S. Richard, R. Tadayoni, P. Massin, O. Mundler, A. Gaudric, and E. Vicaut, “Evaluation of fluorescein-labeled autologous leukocytes for examination of retinal circulation in humans,” Curr. Eye Res. 21(1), 560–565 (2000).
[PubMed]

Tam, J.

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. Tam and A. Roorda, “Speed quantification and tracking of moving objects in adaptive optics scanning laser ophthalmoscopy,” J. Biomed. Opt. (to be published).

Tiruveedhula, P.

K. Y. Li, P. Tiruveedhula, and A. Roorda, “Intersubject variability of foveal cone photoreceptor density in relation to eye length,” Invest. Ophthalmol. Vis. Sci. 51(12), 6858–6867 (2010).
[CrossRef] [PubMed]

D. W. Arathorn, Q. Yang, C. R. Vogel, Y. Zhang, P. Tiruveedhula, and A. Roorda, “Retinally stabilized cone-targeted stimulus delivery,” Opt. Express 15(21), 13731–13744 (2007).
[CrossRef] [PubMed]

Tözeren, H.

G. W. Schmid-Schönbein, K. L. Sung, H. Tözeren, R. Skalak, and S. Chien, “Passive mechanical properties of human leukocytes,” Biophys. J. 36(1), 243–256 (1981).
[CrossRef] [PubMed]

Usami, S.

G. W. Schmid-Schönbein, S. Usami, R. Skalak, and S. Chien, “The interaction of leukocytes and erythrocytes in capillary and postcapillary vessels,” Microvasc. Res. 19(1), 45–70 (1980).
[CrossRef] [PubMed]

G. W. Schmid-Schönbein, R. Skalak, S. Usami, and S. Chien, “Cell distribution in capillary networks,” Microvasc. Res. 19(1), 18–44 (1980).
[CrossRef] [PubMed]

Vanzetta, I.

D. A. Nelson, S. Krupsky, A. Pollack, E. Aloni, M. Belkin, I. Vanzetta, M. Rosner, and A. Grinvald, “Special report: Noninvasive multi-parameter functional optical imaging of the eye,” Ophthalmic Surg. Lasers Imaging 36(1), 57–66 (2005).
[PubMed]

Vicaut, E.

M. Paques, B. Boval, S. Richard, R. Tadayoni, P. Massin, O. Mundler, A. Gaudric, and E. Vicaut, “Evaluation of fluorescein-labeled autologous leukocytes for examination of retinal circulation in humans,” Curr. Eye Res. 21(1), 560–565 (2000).
[PubMed]

Vogel, C. R.

Weinhaus, R. S.

D. M. Snodderly, R. S. Weinhaus, and J. C. Choi, “Neural-vascular relationships in central retina of macaque monkeys (Macaca fascicularis),” J. Neurosci. 12(4), 1169–1193 (1992).
[PubMed]

Yang, Q.

Yoshida, A.

T. Nagaoka and A. Yoshida, “Noninvasive evaluation of wall shear stress on retinal microcirculation in humans,” Invest. Ophthalmol. Vis. Sci. 47(3), 1113–1119 (2006).
[CrossRef] [PubMed]

Yu, D. Y.

P. K. Yu, C. Balaratnasingam, S. J. Cringle, I. L. McAllister, J. Provis, and D. Y. Yu, “Microstructure and network organization of the microvasculature in the human macula,” Invest. Ophthalmol. Vis. Sci. 51(12), 6735–6743 (2010).
[CrossRef] [PubMed]

Yu, P. K.

P. K. Yu, C. Balaratnasingam, S. J. Cringle, I. L. McAllister, J. Provis, and D. Y. Yu, “Microstructure and network organization of the microvasculature in the human macula,” Invest. Ophthalmol. Vis. Sci. 51(12), 6735–6743 (2010).
[CrossRef] [PubMed]

Zhang, Y.

Zweifach, B. W.

B. W. Zweifach, “Quantitative studies of microcirculatory structure and function. II. Direct measurement of capillary pressure in splanchnic mesenteric vessels,” Circ. Res. 34(6), 858–866 (1974).
[PubMed]

B. W. Zweifach, “Quantitative studies of microcirculatory structure and function. I. Analysis of pressure distribution in the terminal vascular bed in cat mesentery,” Circ. Res. 34(6), 843–857 (1974).
[PubMed]

B. W. Zweifach, D. B. Metz, and E. R. Clark, “Selective distribution of blood through the terminal vascular bed of mesenteric structures and skeletal muscle,” Angiology 6(4), 282–290 (1955).
[CrossRef] [PubMed]

Am. J. Pathol.

G. A. Lutty, J. Cao, and D. S. McLeod, “Relationship of polymorphonuclear leukocytes to capillary dropout in the human diabetic choroid,” Am. J. Pathol. 151(3), 707–714 (1997).
[PubMed]

Am. J. Physiol.

D. W. Sutton and G. W. Schmid-Schönbein, “Elevation of organ resistance due to leukocyte perfusion,” Am. J. Physiol. 262(6 Pt 2), H1646–H1650 (1992).
[PubMed]

Angiology

B. W. Zweifach, D. B. Metz, and E. R. Clark, “Selective distribution of blood through the terminal vascular bed of mesenteric structures and skeletal muscle,” Angiology 6(4), 282–290 (1955).
[CrossRef] [PubMed]

Annu. Rev. Fluid Mech.

A. S. Popel and P. C. Johnson, “Microcirculation and Hemorheology,” Annu. Rev. Fluid Mech. 37(1), 43–69 (2005).
[CrossRef] [PubMed]

Annu. Rev. Physiol.

J. C. Hogg and C. M. Doerschuk, “Leukocyte traffic in the lung,” Annu. Rev. Physiol. 57(1), 97–114 (1995).
[CrossRef] [PubMed]

Biophys. J.

G. W. Schmid-Schönbein, K. L. Sung, H. Tözeren, R. Skalak, and S. Chien, “Passive mechanical properties of human leukocytes,” Biophys. J. 36(1), 243–256 (1981).
[CrossRef] [PubMed]

Blood

G. W. Schmid-Schönbein, Y. Y. Shih, and S. Chien, “Morphometry of human leukocytes,” Blood 56(5), 866–875 (1980).
[PubMed]

Circ. Res.

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).
[PubMed]

B. W. Zweifach, “Quantitative studies of microcirculatory structure and function. I. Analysis of pressure distribution in the terminal vascular bed in cat mesentery,” Circ. Res. 34(6), 843–857 (1974).
[PubMed]

B. W. Zweifach, “Quantitative studies of microcirculatory structure and function. II. Direct measurement of capillary pressure in splanchnic mesenteric vessels,” Circ. Res. 34(6), 858–866 (1974).
[PubMed]

Curr. Eye Res.

M. Paques, B. Boval, S. Richard, R. Tadayoni, P. Massin, O. Mundler, A. Gaudric, and E. Vicaut, “Evaluation of fluorescein-labeled autologous leukocytes for examination of retinal circulation in humans,” Curr. Eye Res. 21(1), 560–565 (2000).
[PubMed]

Exp. Eye Res.

J. A. Martin and A. Roorda, “Pulsatility of parafoveal capillary leukocytes,” Exp. Eye Res. 88(3), 356–360 (2009).
[CrossRef] [PubMed]

Invest. Ophthalmol.

E. Friedman, T. R. Smith, and T. Kuwabara, “Retinal Microcirculation in vivo,” Invest. Ophthalmol. 3, 217–226 (1964).
[PubMed]

Invest. Ophthalmol. Vis. Sci.

R. Flower, E. Peiretti, M. Magnani, L. Rossi, S. Serafini, Z. Gryczynski, and I. Gryczynski, “Observation of erythrocyte dynamics in the retinal capillaries and choriocapillaris using ICG-loaded erythrocyte ghost cells,” Invest. Ophthalmol. Vis. Sci. 49(12), 5510–5516 (2008).
[CrossRef] [PubMed]

P. S. Jensen and M. R. Glucksberg, “Regional variation in capillary hemodynamics in the cat retina,” Invest. Ophthalmol. Vis. Sci. 39(2), 407–415 (1998).
[PubMed]

H. Nishiwaki, Y. Ogura, H. Kimura, J. Kiryu, K. Miyamoto, and N. Matsuda, “Visualization and quantitative analysis of leukocyte dynamics in retinal microcirculation of rats,” Invest. Ophthalmol. Vis. Sci. 37(7), 1341–1347 (1996).
[PubMed]

P. K. Yu, C. Balaratnasingam, S. J. Cringle, I. L. McAllister, J. Provis, and D. Y. Yu, “Microstructure and network organization of the microvasculature in the human macula,” Invest. Ophthalmol. Vis. Sci. 51(12), 6735–6743 (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]

L. Laatikainen and J. Larinkari, “Capillary-free area of the fovea with advancing age,” Invest. Ophthalmol. Vis. Sci. 16(12), 1154–1157 (1977).
[PubMed]

J. Ben-nun, “Comparative flow velocity of erythrocytes and leukocytes in feline retinal capillaries,” Invest. Ophthalmol. Vis. Sci. 37(9), 1854–1859 (1996).
[PubMed]

K. Y. Li, P. Tiruveedhula, and A. Roorda, “Intersubject variability of foveal cone photoreceptor density in relation to eye length,” Invest. Ophthalmol. Vis. Sci. 51(12), 6858–6867 (2010).
[CrossRef] [PubMed]

T. Nagaoka and A. Yoshida, “Noninvasive evaluation of wall shear stress on retinal microcirculation in humans,” Invest. Ophthalmol. Vis. Sci. 47(3), 1113–1119 (2006).
[CrossRef] [PubMed]

J. Appl. Physiol.

W. M. Kuebler, G. E. H. Kuhnle, J. Groh, and A. E. Goetz, “Leukocyte kinetics in pulmonary microcirculation: intravital fluorescence microscopic study,” J. Appl. Physiol. 76(1), 65–71 (1994).
[PubMed]

J. Biomed. Opt.

M. Meinke, G. Müller, J. Helfmann, and M. Friebel, “Optical properties of platelets and blood plasma and their influence on the optical behavior of whole blood in the visible to near infrared wavelength range,” J. Biomed. Opt. 12(1), 014024 (2007).
[CrossRef] [PubMed]

J. Tam and A. Roorda, “Speed quantification and tracking of moving objects in adaptive optics scanning laser ophthalmoscopy,” J. Biomed. Opt. (to be published).

J. Fluid Mech.

J. M. Fitz-Gerald, “Plasma motions in narrow capillary flow,” J. Fluid Mech. 51(03), 463–476 (1972).
[CrossRef]

J. Immunol. Methods

H. M. Becker, M. Chen, J. B. Hay, and M. I. Cybulsky, “Tracking of leukocyte recruitment into tissues of mice by in situ labeling of blood cells with the fluorescent dye CFDA SE,” J. Immunol. Methods 286(1-2), 69–78 (2004).
[CrossRef] [PubMed]

J. Neurosci.

D. M. Snodderly, R. S. Weinhaus, and J. C. Choi, “Neural-vascular relationships in central retina of macaque monkeys (Macaca fascicularis),” J. Neurosci. 12(4), 1169–1193 (1992).
[PubMed]

J. Opt. Soc. Am.

Microcirculation

A. G. Hudetz, “Blood flow in the cerebral capillary network: a review emphasizing observations with intravital microscopy,” Microcirculation 4(2), 233–252 (1997).
[CrossRef] [PubMed]

H. H. Lipowsky, “Microvascular rheology and hemodynamics,” Microcirculation 12(1), 5–15 (2005).
[CrossRef] [PubMed]

Microvasc. Res.

G. W. Schmid-Schönbein, R. Skalak, S. Usami, and S. Chien, “Cell distribution in capillary networks,” Microvasc. Res. 19(1), 18–44 (1980).
[CrossRef] [PubMed]

G. W. Schmid-Schönbein, S. Usami, R. Skalak, and S. Chien, “The interaction of leukocytes and erythrocytes in capillary and postcapillary vessels,” Microvasc. Res. 19(1), 45–70 (1980).
[CrossRef] [PubMed]

E. Evans and Y. C. Fung, “Improved measurements of the erythrocyte geometry,” Microvasc. Res. 4(4), 335–347 (1972).
[CrossRef] [PubMed]

Ophthalmic Surg. Lasers Imaging

D. A. Nelson, S. Krupsky, A. Pollack, E. Aloni, M. Belkin, I. Vanzetta, M. Rosner, and A. Grinvald, “Special report: Noninvasive multi-parameter functional optical imaging of the eye,” Ophthalmic Surg. Lasers Imaging 36(1), 57–66 (2005).
[PubMed]

Ophthalmology

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

Opt. Express

Opt. Lett.

Phys. Fluids

E. R. Damiano and T. M. Stace, “Flow and deformation of the capillary glycocalyx in the wake of a leukocyte,” Phys. Fluids 17(3), 031509 (2005).
[CrossRef]

Proc. Natl. Acad. Sci. U.S.A.

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]

Other

J. Tam, and A. Roorda, “Enhanced detection of cell paths in spatiotemporal plots for noninvasive microscopy of the human retina,” in 2010 IEEE International Symposium on Biomedical Imaging: From Nano to Macro (IEEE, 2010) , pp. 584–587.

American National Standard for the Safe Use of Lasers, ANSI Z136.1–2007 (American National Standard Institute, New York, 2007).

B. W. Zweifach, Functional Behavior of the Microcirculation (Charles C Thomas, Springfield, Illinois, 1961).

I. C. Michaelson, Retinal Circulation in Man and Animals (Charles C Thomas, Springfield, Illinois, USA, 1954).

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 (9)

Fig. 1
Fig. 1

Three consecutive frames showing a low contrast leukocyte (circled) moving through a human parafoveal capillary. The spatial contrast is very low, since no contrast agents are used; however, by examining consecutive frames, the motion of individual leukocytes can be detected. Small circular dots are photoreceptors. Frames have been corrected for scanning distortion and eye motion. Scale bar, 100 µm.

Fig. 2
Fig. 2

Two different images generated from the same AOSLO video. (A) Photoreceptor image generated by calculating the average of all frames. (B) Capillary perfusion image generated by applying motion contrast enhancement.

Fig. 3
Fig. 3

Generation and analysis of a spatiotemporal plot from the AOSLO video shown in Fig. 1. A vessel centerline is identified on the image of perfused capillaries. Vessel coordinates are converted from (x,y) coordinates to (s) coordinates to reduce data by one spatial dimension. To generate the spatiotemporal plot, intensities along s are plotted for each frame of the division video. A 120-frame segment of the spatiotemporal plot for the selected vessel is shown. Sloped traces, which correspond to motion of fluid parcels, are manually extracted. Purely vertical traces are due to artifacts – one example, due to a blink, is shown (arrow). Two example traces that were extracted are shown. The extracted traces were analyzed to give information about flow direction, frequency, speed, and pulsatility as described in the text. FT1 and FT2 are the frames at which traces were extracted; FB’, FB”, and FB”’ are the frames at which pulse blips occurred.

Fig. 4
Fig. 4

Montage showing parafoveal capillaries generated by applying motion contrast enhancement to 76 overlapping AOSLO videos acquired noninvasively without contrast agent. Arrows denote arterioles. Scale bar, 500 µm.

Fig. 5
Fig. 5

Comparison of AOSLO with red free fundus photography. (A) AOSLO overlay on fundus photograph. The black box is magnified in panels (B) and (C).

Fig. 6
Fig. 6

Interpretation of spatiotemporal plots, showing representative traces due to (A) plasma gaps and (B) leukocytes. These traces were isolated from full spatiotemporal plots to illustrate the two categories of traces that were identified for analysis. Plasma gap traces are thin and dense, while leukocyte traces are thick, high contrast, sparse, and unidirectional. 200-frame segments of spatiotemporal plots are shown from capillary segments that were identified as a (C) PGC, (D) LPP, and (E) neither a PGC nor a LPP. Note the areas of apparent bidirectionality in the PGC (arrow in C), and artifacts due to poor stabilization when correcting for eye motion (arrows in D) and a blink (arrow in E). Vertical scale bar, 0.5 mm; Horizontal scale bar, 0.5 seconds.

Fig. 7
Fig. 7

Identification of leukocyte-preferred paths (LPPs) and plasma gap capillaries (PGCs). The distribution of leukocyte and plasma gap frequencies [#/min] are shown across all analyzed capillary segments. Vertical lines are inserted at breaks in the histograms to define LPPs and PGCs.

Fig. 8
Fig. 8

Spatial distribution of LPPs (green), PGCs (yellow), and all others capillaries that were selected for analysis (gray). Terminal arterioles (red) and collecting venules (blue) are shown for reference.

Fig. 9
Fig. 9

Examples of averaged velocity waveforms for leukocytes in a single representative LPP segment (top) and plasma gaps in a single representative PGC (bottom), demonstrating the existence of pulsatility in capillaries with single-file flow. Data from extracted leukocytes and plasma gaps are averaged for five equal segments of the cardiac cycle to generate an averaged waveform.

Metrics