OSA's Digital Library

Biomedical Optics Express

Biomedical Optics Express

  • Editor: Joseph A. Izatt
  • Vol. 3, Iss. 12 — Dec. 1, 2012
  • pp: 3264–3277

Direct visualization and characterization of erythrocyte flow in human retinal capillaries

Phillip Bedggood and Andrew Metha  »View Author Affiliations


Biomedical Optics Express, Vol. 3, Issue 12, pp. 3264-3277 (2012)
http://dx.doi.org/10.1364/BOE.3.003264


View Full Text Article

Enhanced HTML    Acrobat PDF (3047 KB)





Browse Journals / Lookup Meetings

Browse by Journal and Year


   


Lookup Conference Papers

Close Browse Journals / Lookup Meetings

Article Tools

Share
Citations

Abstract

Imaging the retinal vasculature offers a surrogate view of systemic vascular health, allowing noninvasive and longitudinal assessment of vascular pathology. The earliest anomalies in vascular disease arise in the microvasculature, however current imaging methods lack the spatiotemporal resolution to track blood flow at the capillary level. We report here on novel imaging technology that allows direct, noninvasive optical imaging of erythrocyte flow in human retinal capillaries. This was made possible using adaptive optics for high spatial resolution (1.5 μm), sCMOS camera technology for high temporal resolution (460 fps), and tunable wavebands from a broadband laser for maximal erythrocyte contrast. Particle image velocimetry on our data sequences was used to quantify flow. We observed marked spatiotemporal variability in velocity, which ranged from 0.3 to 3.3 mm/s, and changed by up to a factor of 4 in a given capillary during the 130 ms imaging period. Both mean and standard deviation across the imaged capillary network varied markedly with time, yet their ratio remained a relatively constant parameter (0.50 ± 0.056). Our observations concur with previous work using less direct methods, validating this as an investigative tool for the study of microvascular disease in humans.

© 2012 OSA

OCIS Codes
(120.7250) Instrumentation, measurement, and metrology : Velocimetry
(170.1470) Medical optics and biotechnology : Blood or tissue constituent monitoring
(170.4470) Medical optics and biotechnology : Ophthalmology
(170.2655) Medical optics and biotechnology : Functional monitoring and imaging
(110.1080) Imaging systems : Active or adaptive optics

ToC Category:
Cardiovascular Applications

History
Original Manuscript: August 31, 2012
Revised Manuscript: October 8, 2012
Manuscript Accepted: November 13, 2012
Published: November 15, 2012

Citation
Phillip Bedggood and Andrew Metha, "Direct visualization and characterization of erythrocyte flow in human retinal capillaries," Biomed. Opt. Express 3, 3264-3277 (2012)
http://www.opticsinfobase.org/boe/abstract.cfm?URI=boe-3-12-3264


Sort:  Author  |  Year  |  Journal  |  Reset  

References

  1. J. Hirschberg, “Ueber diabetische Netzhautentzündung,” Dtsch. Med. Wochenschr.16(51), 1181–1185 (1890). [CrossRef]
  2. R. Gunn, “Ophthalmoscopic evidence of (1) arterial changes associated with chronic renal diseases and (2) of increased arterial tension,” Trans. Ophthalmol. Soc. U. K.12, 124–125 (1892).
  3. N. Patton, T. Aslam, T. Macgillivray, A. Pattie, I. J. Deary, and B. Dhillon, “Retinal vascular image analysis as a potential screening tool for cerebrovascular disease: a rationale based on homology between cerebral and retinal microvasculatures,” J. Anat.206(4), 319–348 (2005). [CrossRef] [PubMed]
  4. M. L. Baker, P. J. Hand, J. J. Wang, and T. Y. Wong, “Retinal signs and stroke: revisiting the link between the eye and brain,” Stroke39(4), 1371–1379 (2008). [CrossRef] [PubMed]
  5. M. K. Ikram, C. Y. Cheung, T. Y. Wong, and C. P. Chen, “Retinal pathology as biomarker for cognitive impairment and Alzheimer’s disease,” J. Neurol. Neurosurg. Psychiatry83(9), 917–922 (2012). [CrossRef] [PubMed]
  6. K. M. Rose, T. Y. Wong, A. P. Carson, D. J. Couper, R. Klein, and A. R. Sharrett, “Migraine and retinal microvascular abnormalities: the Atherosclerosis Risk in Communities Study,” Neurology68(20), 1694–1700 (2007). [CrossRef] [PubMed]
  7. P. Gasser and J. Flammer, “Blood-cell velocity in the nailfold capillaries of patients with normal-tension and high-tension glaucoma,” Am. J. Ophthalmol.111(5), 585–588 (1991). [PubMed]
  8. H. H. Parving, G. C. Viberti, H. Keen, J. S. Christiansen, and N. A. Lassen, “Hemodynamic factors in the genesis of diabetic microangiopathy,” Metabolism32(9), 943–949 (1983). [CrossRef] [PubMed]
  9. G. G. Pietra, F. Capron, S. Stewart, O. Leone, M. Humbert, I. M. Robbins, L. M. Reid, and R. M. Tuder, “Pathologic assessment of vasculopathies in pulmonary hypertension,” J. Am. Coll. Cardiol.43(12Suppl S), S25–S32 (2004). [CrossRef] [PubMed]
  10. J. C. de la Torre, “Is Alzheimer’s disease a neurodegenerative or a vascular disorder? Data, dogma, and dialectics,” Lancet Neurol.3(3), 184–190 (2004). [CrossRef] [PubMed]
  11. G. J. del Zoppo, G. W. Schmid-Schönbein, E. Mori, B. R. Copeland, and C. M. Chang, “Polymorphonuclear leukocytes occlude capillaries following middle cerebral artery occlusion and reperfusion in baboons,” Stroke22(10), 1276–1283 (1991). [CrossRef] [PubMed]
  12. P. Gasser and O. Meienberg, “Finger microcirculation in classical migraine. A video-microscopic study of nailfold capillaries,” Eur. Neurol.31(3), 168–171 (1991). [CrossRef] [PubMed]
  13. H. A. Quigley, “Neuronal death in glaucoma,” Prog. Retin. Eye Res.18(1), 39–57 (1999). [CrossRef] [PubMed]
  14. T. Tanaka, C. Riva, and B. Ben-Sira, “Blood velocity measurements in human retinal vessels,” Science186(4166), 830–831 (1974). [CrossRef] [PubMed]
  15. K. Yaoeda, M. Shirakashi, S. Funaki, H. Funaki, T. Nakatsue, and H. Abe, “Measurement of microcirculation in the optic nerve head by laser speckle flowgraphy and scanning laser Doppler flowmetry,” Am. J. Ophthalmol.129(6), 734–739 (2000). [CrossRef] [PubMed]
  16. B. White, M. Pierce, N. Nassif, B. Cense, B. Park, G. Tearney, B. Bouma, T. Chen, and J. de Boer, “In vivo dynamic human retinal blood flow imaging using ultra-high-speed spectral domain optical coherence tomography,” Opt. Express11(25), 3490–3497 (2003). [CrossRef] [PubMed]
  17. J. Briers, “Laser Doppler and time-varying speckle: a reconciliation,” J. Opt. Soc. Am. A13(2), 345–350 (1996). [CrossRef]
  18. V. J. Srinivasan, H. Radhakrishnan, E. H. Lo, E. T. Mandeville, J. Y. Jiang, S. Barry, and A. E. Cable, “OCT methods for capillary velocimetry,” Biomed. Opt. Express3(3), 612–629 (2012). [CrossRef] [PubMed]
  19. A. Harris, L. Kagemann, and G. A. Cioffi, “Assessment of human ocular hemodynamics,” Surv. Ophthalmol.42(6), 509–533 (1998). [CrossRef] [PubMed]
  20. Y. Wang, B. A. Bower, J. A. Izatt, O. Tan, and D. Huang, “Retinal blood flow measurement by circumpapillary Fourier domain Doppler optical coherence tomography,” J. Biomed. Opt.13(6), 064003 (2008). [CrossRef] [PubMed]
  21. C. E. Riva, J. E. Grunwald, and S. H. Sinclair, “Laser Doppler measurement of relative blood velocity in the human optic nerve head,” Invest. Ophthalmol. Vis. Sci.22(2), 241–248 (1982). [PubMed]
  22. J. Liang, D. R. Williams, and D. T. Miller, “Supernormal vision and high-resolution retinal imaging through adaptive optics,” J. Opt. Soc. Am. A14(11), 2884–2892 (1997). [CrossRef] [PubMed]
  23. J. A. Martin and A. Roorda, “Direct and noninvasive assessment of parafoveal capillary leukocyte velocity,” Ophthalmology112(12), 2219–2224 (2005). [CrossRef] [PubMed]
  24. J. A. Martin and A. Roorda, “Pulsatility of parafoveal capillary leukocytes,” Exp. Eye Res.88(3), 356–360 (2009). [CrossRef] [PubMed]
  25. 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. Express2(4), 781–793 (2011). [CrossRef] [PubMed]
  26. J. Tam, K. P. Dhamdhere, P. Tiruveedhula, S. Manzanera, S. Barez, M. A. Bearse, A. J. Adams, and A. Roorda, “Disruption of the retinal parafoveal capillary network in type 2 diabetes before the onset of diabetic retinopathy,” Invest. Ophthalmol. Vis. Sci.52(12), 9257–9266 (2011). [CrossRef] [PubMed]
  27. R. Chibber, B. M. Ben-Mahmud, S. Chibber, and E. M. Kohner, “Leukocytes in diabetic retinopathy,” Curr. Diabetes Rev.3(1), 3–14 (2007). [CrossRef] [PubMed]
  28. K. Miyamoto and Y. Ogura, “Pathogenetic potential of leukocytes in diabetic retinopathy,” Semin. Ophthalmol.14(4), 233–239 (1999). [CrossRef] [PubMed]
  29. G. W. Schmid-Schönbein, Y. Y. Shih, and S. Chien, “Morphometry of human leukocytes,” Blood56(5), 866–875 (1980). [PubMed]
  30. B. P. Helmke, S. N. Bremner, B. W. Zweifach, R. Skalak, and G. W. Schmid-Schönbein, “Mechanisms for increased blood flow resistance due to leukocytes,” Am. J. Physiol.273(6 Pt 2), H2884–H2890 (1997). [PubMed]
  31. 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. Express16(17), 12746–12756 (2008). [CrossRef] [PubMed]
  32. Z. Zhong, H. Song, T. Y. 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]
  33. Z. Zhong, G. Huang, T. Y. 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]
  34. P. Bedggood and A. Metha, “Variability in bleach kinetics and amount of photopigment between individual foveal cones,” Invest. Ophthalmol. Vis. Sci.53(7), 3673–3681 (2012). [CrossRef] [PubMed]
  35. F. C. Delori, R. H. Webb, D. H. Sliney, and American National Standards Institute, “Maximum permissible exposures for ocular safety (ANSI 2000), with emphasis on ophthalmic devices,” J. Opt. Soc. Am. A24(5), 1250–1265 (2007). [CrossRef] [PubMed]
  36. R. D. Frostig, E. E. Lieke, D. Y. Ts’o, and A. Grinvald, “Cortical functional architecture and local coupling between neuronal activity and the microcirculation revealed by in vivo high-resolution optical imaging of intrinsic signals,” Proc. Natl. Acad. Sci. U.S.A.87(16), 6082–6086 (1990). [CrossRef] [PubMed]
  37. B. Falsini, C. E. Riva, and E. Logean, “Flicker-evoked changes in human optic nerve blood flow: relationship with retinal neural activity,” Invest. Ophthalmol. Vis. Sci.43(7), 2309–2316 (2002). [PubMed]
  38. 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]
  39. P. Bedggood and A. Metha, “Oximetry imaging of the retinal microvasculature using adaptive optics,” in Association for Research in Vision and Ophthalmology Annual Meeting (Fort Lauderdale, FL, 2012).
  40. R. Keane and R. Adrian, “Theory of cross-correlation analysis of PIV images,” Appl. Sci. Res.49(3), 191–215 (1992). [CrossRef]
  41. S. Wolf, O. Arend, H. Toonen, B. Bertram, F. Jung, and M. Reim, “Retinal capillary blood flow measurement with a scanning laser ophthalmoscope. Preliminary results,” Ophthalmology98(6), 996–1000 (1991). [PubMed]
  42. A. G. Hudetz, “Blood flow in the cerebral capillary network: a review emphasizing observations with intravital microscopy,” Microcirculation4(2), 233–252 (1997). [CrossRef] [PubMed]
  43. M. Iwasaki and H. Inomata, “Relation between superficial capillaries and foveal structures in the human retina,” Invest. Ophthalmol. Vis. Sci.27(12), 1698–1705 (1986). [PubMed]
  44. Y. C. Fung, “Stochastic flow in capillary blood vessels,” Microvasc. Res.5(1), 34–48 (1973). [CrossRef] [PubMed]
  45. P. C. Johnson and H. Wayland, “Regulation of blood flow in single capillaries,” Am. J. Physiol.212(6), 1405–1415 (1967). [PubMed]
  46. G. Pawlik, A. Rackl, and R. J. Bing, “Quantitative capillary topography and blood flow in the cerebral cortex of cats: an in vivo microscopic study,” Brain Res.208(1), 35–58 (1981). [CrossRef] [PubMed]
  47. A. Villringer, A. Them, U. Lindauer, K. Einhäupl, and U. Dirnagl, “Capillary perfusion of the rat brain cortex. An in vivo confocal microscopy study,” Circ. Res.75(1), 55–62 (1994). [CrossRef] [PubMed]
  48. Y. C. Fung, “Blood flow in the capillary bed,” J. Biomech.2(4), 353–372 (1969). [CrossRef] [PubMed]
  49. D. Cousineau, C. P. Rose, D. Lamoureux, and C. A. Goresky, “Changes in cardiac transcapillary exchange with metabolic coronary vasodilation in the intact dog,” Circ. Res.53(6), 719–730 (1983). [CrossRef] [PubMed]
  50. I. Krolo and A. G. Hudetz, “Hypoxemia alters erythrocyte perfusion pattern in the cerebral capillary network,” Microvasc. Res.59(1), 72–79 (2000). [CrossRef] [PubMed]
  51. M. L. Schulte, J. D. Wood, and A. G. Hudetz, “Cortical electrical stimulation alters erythrocyte perfusion pattern in the cerebral capillary network of the rat,” Brain Res.963(1-2), 81–92 (2003). [CrossRef] [PubMed]
  52. J. Vogel and W. Kuschinsky, “Decreased heterogeneity of capillary plasma flow in the rat whisker-barrel cortex during functional hyperemia,” J. Cereb. Blood Flow Metab.16(6), 1300–1306 (1996). [CrossRef] [PubMed]
  53. S. N. Jespersen and L. Østergaard, “The roles of cerebral blood flow, capillary transit time heterogeneity, and oxygen tension in brain oxygenation and metabolism,” J. Cereb. Blood Flow Metab.32(2), 264–277 (2012). [CrossRef] [PubMed]
  54. H. K. Rucker, H. J. Wynder, and W. E. Thomas, “Cellular mechanisms of CNS pericytes,” Brain Res. Bull.51(5), 363–369 (2000). [CrossRef] [PubMed]
  55. S. S. Segal, “Regulation of blood flow in the microcirculation,” Microcirculation12(1), 33–45 (2005). [CrossRef] [PubMed]
  56. M. M. Guest, T. P. Bond, R. G. Cooper, and J. R. Derrick, “Red Blood Cells: Change in Shape in Capillaries,” Science142(3597), 1319–1321 (1963). [CrossRef] [PubMed]
  57. F. Grubbs, “Procedures for detecting outlying observations in samples,” Technometrics11(1), 1–21 (1969). [CrossRef]
  58. D. Cook, “Detection of influential observations in linear regression,” Technometrics19(1), 15–18 (1977). [CrossRef]

Cited By

Alert me when this paper is cited

OSA is able to provide readers links to articles that cite this paper by participating in CrossRef's Cited-By Linking service. CrossRef includes content from more than 3000 publishers and societies. In addition to listing OSA journal articles that cite this paper, citing articles from other participating publishers will also be listed.

Multimedia

Multimedia FilesRecommended Software
» Media 1: MOV (1686 KB)      QuickTime
» Media 2: MOV (1682 KB)      QuickTime

« Previous Article  |  Next Article »

OSA is a member of CrossRef.

CrossCheck Deposited