Abstract

Optic nerve head (ONH) blood flow may be associated with glaucoma development. A reliable method to quantify ONH blood flow could provide insight into the vascular component of glaucoma pathophysiology. Using ultrahigh-speed optical coherence tomography (OCT), we developed a new 3D angiography algorithm called split-spectrum amplitude-decorrelation angiography (SSADA) for imaging ONH microcirculation. In this study, a method to quantify SSADA results was developed and used to detect ONH perfusion changes in early glaucoma. En face maximum projection was used to obtain 2D disc angiograms, from which the average decorrelation values (flow index) and the percentage area occupied by vessels (vessel density) were computed from the optic disc and a selected region within it. Preperimetric glaucoma patients had significant reductions of ONH perfusion compared to normals. This pilot study indicates OCT angiography can detect the abnormalities of ONH perfusion and has the potential to reveal the ONH blood flow mechanism related to glaucoma.

© 2012 OSA

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2012 (2)

Y. Jia, O. Tan, J. Tokayer, B. Potsaid, Y. Wang, J. J. Liu, M. F. Kraus, H. Subhash, J. G. Fujimoto, J. Hornegger, and D. Huang, “Split-spectrum amplitude-decorrelation angiography with optical coherence tomography,” Opt. Express20(4), 4710–4725 (2012).
[CrossRef] [PubMed]

J. C. Hwang, R. Konduru, X. Zhang, O. Tan, B. A. Francis, R. Varma, M. Sehi, D. S. Greenfield, S. R. Sadda, and D. Huang, “Relationship among visual field, blood flow, and neural structure measurements in glaucoma,” Invest. Ophthalmol. Vis. Sci.53(6), 3020–3026 (2012).
[CrossRef] [PubMed]

2010 (4)

A. Mariampillai, M. K. Leung, M. Jarvi, B. A. Standish, K. Lee, B. C. Wilson, A. Vitkin, and V. X. Yang, “Optimized speckle variance OCT imaging of microvasculature,” Opt. Lett.35(8), 1257–1259 (2010).
[CrossRef] [PubMed]

B. Potsaid, B. Baumann, D. Huang, S. Barry, A. E. Cable, J. S. Schuman, J. S. Duker, and J. G. Fujimoto, “Ultrahigh speed 1050nm swept source/Fourier domain OCT retinal and anterior segment imaging at 100,000 to 400,000 axial scans per second,” Opt. Express18(19), 20029–20048 (2010).
[CrossRef] [PubMed]

Z. Hu, M. D. Abràmoff, Y. H. Kwon, K. Lee, and M. K. Garvin, “Automated segmentation of neural canal opening and optic cup in 3D spectral optical coherence tomography volumes of the optic nerve head,” Invest. Ophthalmol. Vis. Sci.51(11), 5708–5717 (2010).
[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. (Copenh.)88(7), 723–729 (2010).
[CrossRef] [PubMed]

2009 (3)

N. G. Strouthidis, H. Yang, J. F. Reynaud, J. L. Grimm, S. K. Gardiner, B. Fortune, and C. F. Burgoyne, “Comparison of clinical and spectral domain optical coherence tomography optic disc margin anatomy,” Invest. Ophthalmol. Vis. Sci.50(10), 4709–4718 (2009).
[CrossRef] [PubMed]

N. Strouthidis, H. Yang, B. Fortune, J. Crawford Downs, and C. Burgoyne, “Detection of optic nerve head neural canal opening within histomorphometric and spectral domain optical coherence tomography data sets,” Invest. Ophthalmol. Vis. Sci.50(1), 214–223 (2009).
[CrossRef] [PubMed]

Y. Wang, A. Fawzi, O. Tan, J. Gil-Flamer, and D. Huang, “Retinal blood flow detection in diabetic patients by Doppler Fourier domain optical coherence tomography,” Opt. Express17(5), 4061–4073 (2009).
[CrossRef] [PubMed]

2008 (2)

2004 (1)

S. S. Hayreh, “Posterior ciliary artery circulation in health and disease: the Weisenfeld lecture,” Invest. Ophthalmol. Vis. Sci.45(3), 749–757, 748 (2004).
[CrossRef] [PubMed]

2003 (3)

2002 (1)

G. H. Garcia, K. M. Donahue, J. L. Ulmer, and G. J. Harris, “Qualitative perfusion imaging of the human optic nerve,” Ophthal. Plast. Reconstr. Surg.18(2), 107–113 (2002).
[CrossRef] [PubMed]

2001 (4)

J. R. Piltz-seymour, J. E. Grunwald, S. M. Hariprasad, and J. Dupont, “Optic nerve blood flow is diminished in eyes of primary open-angle glaucoma suspects,” Am. J. Ophthalmol.132(1), 63–69 (2001).
[CrossRef] [PubMed]

C. E. Riva, “Basic principles of laser Doppler flowmetry and application to the ocular circulation,” Int. Ophthalmol.23(4/6), 183–189 (2001).
[CrossRef] [PubMed]

C. P. Jonescu-Cuypers, H. S. Chung, L. Kagemann, Y. Ishii, D. Zarfati, and A. Harris, “New neuroretinal rim blood flow evaluation method combining Heidelberg retina flowmetry and tomography,” Br. J. Ophthalmol.85(3), 304–309 (2001).
[CrossRef] [PubMed]

L. Hyman, S. Y. Wu, A. M. Connell, A. Schachat, B. Nemesure, A. Hennis, and M. C. Leske, “Prevalence and causes of visual impairment in The Barbados Eye Study,” Ophthalmology108(10), 1751–1756 (2001).
[CrossRef] [PubMed]

1999 (1)

B. L. Petrig, C. E. Riva, and S. S. Hayreh, “Laser Doppler flowmetry and optic nerve head blood flow,” Am. J. Ophthalmol.127(4), 413–425 (1999).
[CrossRef] [PubMed]

1998 (1)

J. Kerr, P. Nelson, and C. O’Brien, “A comparison of ocular blood flow in untreated primary open-angle glaucoma and ocular hypertension,” Am. J. Ophthalmol.126(1), 42–51 (1998).
[CrossRef] [PubMed]

1997 (3)

K. M. Joos, L. E. Pillunat, R. W. Knighton, D. R. Anderson, and W. J. Feuer, “Reproducibility of laser Doppler flowmetry in the human optic nerve head,” J. Glaucoma6(4), 212–216 (1997).
[CrossRef] [PubMed]

Z. Chen, T. E. Milner, S. Srinivas, X. Wang, A. Malekafzali, M. J. C. van Gemert, and J. S. Nelson, “Noninvasive imaging of in vivo blood flow velocity using optical Doppler tomography,” Opt. Lett.22(14), 1119–1121 (1997).
[CrossRef] [PubMed]

H. A. Quigley and S. Vitale, “Models of open-angle glaucoma prevalence and incidence in the United States,” Invest. Ophthalmol. Vis. Sci.38(1), 83–91 (1997).
[PubMed]

1996 (1)

G. Michelson, M. J. Langhans, and M. J. Groh, “Perfusion of the juxtapapillary retina and the neuroretinal rim area in primary open angle glaucoma,” J. Glaucoma5(2), 91–98 (1996).
[CrossRef] [PubMed]

1995 (1)

C. Prünte, J. Flammer, R. Markstein, and M. Rudin, “Quantification of optic nerve blood flow changes using magnetic resonance imaging,” Invest. Ophthalmol. Vis. Sci.36(1), 247–251 (1995).
[PubMed]

1994 (2)

S. S. Hayreh, “Progress in the understanding of the vascular etiology of glaucoma,” Curr. Opin. Ophthalmol.5(2), 26–35 (1994).
[CrossRef]

P. Hamard, H. Hamard, J. Dufaux, and S. Quesnot, “Optic nerve head blood flow using a laser Doppler velocimeter and haemorheology in primary open angle glaucoma and normal pressure glaucoma,” Br. J. Ophthalmol.78(6), 449–453 (1994).
[CrossRef] [PubMed]

1993 (1)

S. Wolf, O. Arend, W. E. Sponsel, K. Schulte, L. B. Cantor, and M. Reim, “Retinal hemodynamics using scanning laser ophthalmoscopy and hemorheology in chronic open-angle glaucoma,” Ophthalmology100(10), 1561–1566 (1993).
[PubMed]

1991 (1)

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

1974 (1)

J. François and J. J. de Laey, “Fluorescein angiography of the glaucomatous disc,” Ophthalmologica168(4), 288–298 (1974).
[CrossRef] [PubMed]

1972 (1)

S. S. Hayreh, “Colour and fluorescence of the optic disc,” Ophthalmologica165(2), 100–108 (1972).
[CrossRef] [PubMed]

1971 (1)

M. R. Stein and C. W. Parker, “Reactions following intravenous fluorescein,” Am. J. Ophthalmol.72(5), 861–868 (1971).
[PubMed]

1969 (1)

S. S. Hayreh, “Blood supply of the optic nerve head and its role in optic atrophy, glaucoma, and oedema of the optic disc,” Br. J. Ophthalmol.53(11), 721–748 (1969).
[CrossRef] [PubMed]

Abràmoff, M. D.

Z. Hu, M. D. Abràmoff, Y. H. Kwon, K. Lee, and M. K. Garvin, “Automated segmentation of neural canal opening and optic cup in 3D spectral optical coherence tomography volumes of the optic nerve head,” Invest. Ophthalmol. Vis. Sci.51(11), 5708–5717 (2010).
[CrossRef] [PubMed]

Anderson, D. R.

K. M. Joos, L. E. Pillunat, R. W. Knighton, D. R. Anderson, and W. J. Feuer, “Reproducibility of laser Doppler flowmetry in the human optic nerve head,” J. Glaucoma6(4), 212–216 (1997).
[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. (Copenh.)88(7), 723–729 (2010).
[CrossRef] [PubMed]

Arend, O.

S. Wolf, O. Arend, W. E. Sponsel, K. Schulte, L. B. Cantor, and M. Reim, “Retinal hemodynamics using scanning laser ophthalmoscopy and hemorheology in chronic open-angle glaucoma,” Ophthalmology100(10), 1561–1566 (1993).
[PubMed]

Bajraszewski, T.

Barry, S.

Baumann, B.

Bizzarro, R. L. G.

A. S. Hafez, R. L. G. Bizzarro, and M. R. Lesk, “Evaluation of optic nerve head and peripapillary retinal blood flow in glaucoma patients, ocular hypertensives, and normal subjects,” Am. J. Ophthalmol.136(6), 1022–1031 (2003).
[CrossRef] [PubMed]

Bouma, B.

Bower, B. A.

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]

Burgoyne, C.

N. Strouthidis, H. Yang, B. Fortune, J. Crawford Downs, and C. Burgoyne, “Detection of optic nerve head neural canal opening within histomorphometric and spectral domain optical coherence tomography data sets,” Invest. Ophthalmol. Vis. Sci.50(1), 214–223 (2009).
[CrossRef] [PubMed]

Burgoyne, C. F.

N. G. Strouthidis, H. Yang, J. F. Reynaud, J. L. Grimm, S. K. Gardiner, B. Fortune, and C. F. Burgoyne, “Comparison of clinical and spectral domain optical coherence tomography optic disc margin anatomy,” Invest. Ophthalmol. Vis. Sci.50(10), 4709–4718 (2009).
[CrossRef] [PubMed]

Cable, A.

Cable, A. E.

Cantor, L. B.

S. Wolf, O. Arend, W. E. Sponsel, K. Schulte, L. B. Cantor, and M. Reim, “Retinal hemodynamics using scanning laser ophthalmoscopy and hemorheology in chronic open-angle glaucoma,” Ophthalmology100(10), 1561–1566 (1993).
[PubMed]

Cense, B.

Chang, W.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Chen, T.

Chen, Z.

Chung, H. S.

C. P. Jonescu-Cuypers, H. S. Chung, L. Kagemann, Y. Ishii, D. Zarfati, and A. Harris, “New neuroretinal rim blood flow evaluation method combining Heidelberg retina flowmetry and tomography,” Br. J. Ophthalmol.85(3), 304–309 (2001).
[CrossRef] [PubMed]

Connell, A. M.

L. Hyman, S. Y. Wu, A. M. Connell, A. Schachat, B. Nemesure, A. Hennis, and M. C. Leske, “Prevalence and causes of visual impairment in The Barbados Eye Study,” Ophthalmology108(10), 1751–1756 (2001).
[CrossRef] [PubMed]

Crawford Downs, J.

N. Strouthidis, H. Yang, B. Fortune, J. Crawford Downs, and C. Burgoyne, “Detection of optic nerve head neural canal opening within histomorphometric and spectral domain optical coherence tomography data sets,” Invest. Ophthalmol. Vis. Sci.50(1), 214–223 (2009).
[CrossRef] [PubMed]

de Boer, J.

de Laey, J. J.

J. François and J. J. de Laey, “Fluorescein angiography of the glaucomatous disc,” Ophthalmologica168(4), 288–298 (1974).
[CrossRef] [PubMed]

Donahue, K. M.

G. H. Garcia, K. M. Donahue, J. L. Ulmer, and G. J. Harris, “Qualitative perfusion imaging of the human optic nerve,” Ophthal. Plast. Reconstr. Surg.18(2), 107–113 (2002).
[CrossRef] [PubMed]

Drexler, W.

Dufaux, J.

P. Hamard, H. Hamard, J. Dufaux, and S. Quesnot, “Optic nerve head blood flow using a laser Doppler velocimeter and haemorheology in primary open angle glaucoma and normal pressure glaucoma,” Br. J. Ophthalmol.78(6), 449–453 (1994).
[CrossRef] [PubMed]

Duker, J. S.

Dupont, J.

J. R. Piltz-seymour, J. E. Grunwald, S. M. Hariprasad, and J. Dupont, “Optic nerve blood flow is diminished in eyes of primary open-angle glaucoma suspects,” Am. J. Ophthalmol.132(1), 63–69 (2001).
[CrossRef] [PubMed]

Fawzi, A.

Fercher, A.

Feuer, W. J.

K. M. Joos, L. E. Pillunat, R. W. Knighton, D. R. Anderson, and W. J. Feuer, “Reproducibility of laser Doppler flowmetry in the human optic nerve head,” J. Glaucoma6(4), 212–216 (1997).
[CrossRef] [PubMed]

Flammer, J.

C. Prünte, J. Flammer, R. Markstein, and M. Rudin, “Quantification of optic nerve blood flow changes using magnetic resonance imaging,” Invest. Ophthalmol. Vis. Sci.36(1), 247–251 (1995).
[PubMed]

Flotte, T.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Fortune, B.

N. Strouthidis, H. Yang, B. Fortune, J. Crawford Downs, and C. Burgoyne, “Detection of optic nerve head neural canal opening within histomorphometric and spectral domain optical coherence tomography data sets,” Invest. Ophthalmol. Vis. Sci.50(1), 214–223 (2009).
[CrossRef] [PubMed]

N. G. Strouthidis, H. Yang, J. F. Reynaud, J. L. Grimm, S. K. Gardiner, B. Fortune, and C. F. Burgoyne, “Comparison of clinical and spectral domain optical coherence tomography optic disc margin anatomy,” Invest. Ophthalmol. Vis. Sci.50(10), 4709–4718 (2009).
[CrossRef] [PubMed]

Francis, B. A.

J. C. Hwang, R. Konduru, X. Zhang, O. Tan, B. A. Francis, R. Varma, M. Sehi, D. S. Greenfield, S. R. Sadda, and D. Huang, “Relationship among visual field, blood flow, and neural structure measurements in glaucoma,” Invest. Ophthalmol. Vis. Sci.53(6), 3020–3026 (2012).
[CrossRef] [PubMed]

François, J.

J. François and J. J. de Laey, “Fluorescein angiography of the glaucomatous disc,” Ophthalmologica168(4), 288–298 (1974).
[CrossRef] [PubMed]

Fujimoto, J. G.

Garcia, G. H.

G. H. Garcia, K. M. Donahue, J. L. Ulmer, and G. J. Harris, “Qualitative perfusion imaging of the human optic nerve,” Ophthal. Plast. Reconstr. Surg.18(2), 107–113 (2002).
[CrossRef] [PubMed]

Gardiner, S. K.

N. G. Strouthidis, H. Yang, J. F. Reynaud, J. L. Grimm, S. K. Gardiner, B. Fortune, and C. F. Burgoyne, “Comparison of clinical and spectral domain optical coherence tomography optic disc margin anatomy,” Invest. Ophthalmol. Vis. Sci.50(10), 4709–4718 (2009).
[CrossRef] [PubMed]

Garvin, M. K.

Z. Hu, M. D. Abràmoff, Y. H. Kwon, K. Lee, and M. K. Garvin, “Automated segmentation of neural canal opening and optic cup in 3D spectral optical coherence tomography volumes of the optic nerve head,” Invest. Ophthalmol. Vis. Sci.51(11), 5708–5717 (2010).
[CrossRef] [PubMed]

Gil-Flamer, J.

Greenfield, D. S.

J. C. Hwang, R. Konduru, X. Zhang, O. Tan, B. A. Francis, R. Varma, M. Sehi, D. S. Greenfield, S. R. Sadda, and D. Huang, “Relationship among visual field, blood flow, and neural structure measurements in glaucoma,” Invest. Ophthalmol. Vis. Sci.53(6), 3020–3026 (2012).
[CrossRef] [PubMed]

Gregory, K.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Greve, E. L.

G. Holló, T. J. van den Berg, and E. L. Greve, “Scanning laser Doppler flowmetry in glaucoma,” Int. Ophthalmol.20(1-3), 63–70 (1996-1997).
[PubMed]

Grimm, J. L.

N. G. Strouthidis, H. Yang, J. F. Reynaud, J. L. Grimm, S. K. Gardiner, B. Fortune, and C. F. Burgoyne, “Comparison of clinical and spectral domain optical coherence tomography optic disc margin anatomy,” Invest. Ophthalmol. Vis. Sci.50(10), 4709–4718 (2009).
[CrossRef] [PubMed]

Groh, M. J.

G. Michelson, M. J. Langhans, and M. J. Groh, “Perfusion of the juxtapapillary retina and the neuroretinal rim area in primary open angle glaucoma,” J. Glaucoma5(2), 91–98 (1996).
[CrossRef] [PubMed]

Grunwald, J. E.

J. R. Piltz-seymour, J. E. Grunwald, S. M. Hariprasad, and J. Dupont, “Optic nerve blood flow is diminished in eyes of primary open-angle glaucoma suspects,” Am. J. Ophthalmol.132(1), 63–69 (2001).
[CrossRef] [PubMed]

Hafez, A. S.

A. S. Hafez, R. L. G. Bizzarro, and M. R. Lesk, “Evaluation of optic nerve head and peripapillary retinal blood flow in glaucoma patients, ocular hypertensives, and normal subjects,” Am. J. Ophthalmol.136(6), 1022–1031 (2003).
[CrossRef] [PubMed]

Hamard, H.

P. Hamard, H. Hamard, J. Dufaux, and S. Quesnot, “Optic nerve head blood flow using a laser Doppler velocimeter and haemorheology in primary open angle glaucoma and normal pressure glaucoma,” Br. J. Ophthalmol.78(6), 449–453 (1994).
[CrossRef] [PubMed]

Hamard, P.

P. Hamard, H. Hamard, J. Dufaux, and S. Quesnot, “Optic nerve head blood flow using a laser Doppler velocimeter and haemorheology in primary open angle glaucoma and normal pressure glaucoma,” Br. J. Ophthalmol.78(6), 449–453 (1994).
[CrossRef] [PubMed]

Hariprasad, S. M.

J. R. Piltz-seymour, J. E. Grunwald, S. M. Hariprasad, and J. Dupont, “Optic nerve blood flow is diminished in eyes of primary open-angle glaucoma suspects,” Am. J. Ophthalmol.132(1), 63–69 (2001).
[CrossRef] [PubMed]

Harris, A.

C. P. Jonescu-Cuypers, H. S. Chung, L. Kagemann, Y. Ishii, D. Zarfati, and A. Harris, “New neuroretinal rim blood flow evaluation method combining Heidelberg retina flowmetry and tomography,” Br. J. Ophthalmol.85(3), 304–309 (2001).
[CrossRef] [PubMed]

Harris, G. J.

G. H. Garcia, K. M. Donahue, J. L. Ulmer, and G. J. Harris, “Qualitative perfusion imaging of the human optic nerve,” Ophthal. Plast. Reconstr. Surg.18(2), 107–113 (2002).
[CrossRef] [PubMed]

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S. S. Hayreh, “Posterior ciliary artery circulation in health and disease: the Weisenfeld lecture,” Invest. Ophthalmol. Vis. Sci.45(3), 749–757, 748 (2004).
[CrossRef] [PubMed]

B. L. Petrig, C. E. Riva, and S. S. Hayreh, “Laser Doppler flowmetry and optic nerve head blood flow,” Am. J. Ophthalmol.127(4), 413–425 (1999).
[CrossRef] [PubMed]

S. S. Hayreh, “Progress in the understanding of the vascular etiology of glaucoma,” Curr. Opin. Ophthalmol.5(2), 26–35 (1994).
[CrossRef]

S. S. Hayreh, “Colour and fluorescence of the optic disc,” Ophthalmologica165(2), 100–108 (1972).
[CrossRef] [PubMed]

S. S. Hayreh, “Blood supply of the optic nerve head and its role in optic atrophy, glaucoma, and oedema of the optic disc,” Br. J. Ophthalmol.53(11), 721–748 (1969).
[CrossRef] [PubMed]

Hee, M. R.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Hennis, A.

L. Hyman, S. Y. Wu, A. M. Connell, A. Schachat, B. Nemesure, A. Hennis, and M. C. Leske, “Prevalence and causes of visual impairment in The Barbados Eye Study,” Ophthalmology108(10), 1751–1756 (2001).
[CrossRef] [PubMed]

Holló, G.

G. Holló, T. J. van den Berg, and E. L. Greve, “Scanning laser Doppler flowmetry in glaucoma,” Int. Ophthalmol.20(1-3), 63–70 (1996-1997).
[PubMed]

Hornegger, J.

Hu, Z.

Z. Hu, M. D. Abràmoff, Y. H. Kwon, K. Lee, and M. K. Garvin, “Automated segmentation of neural canal opening and optic cup in 3D spectral optical coherence tomography volumes of the optic nerve head,” Invest. Ophthalmol. Vis. Sci.51(11), 5708–5717 (2010).
[CrossRef] [PubMed]

Huang, D.

Y. Jia, O. Tan, J. Tokayer, B. Potsaid, Y. Wang, J. J. Liu, M. F. Kraus, H. Subhash, J. G. Fujimoto, J. Hornegger, and D. Huang, “Split-spectrum amplitude-decorrelation angiography with optical coherence tomography,” Opt. Express20(4), 4710–4725 (2012).
[CrossRef] [PubMed]

J. C. Hwang, R. Konduru, X. Zhang, O. Tan, B. A. Francis, R. Varma, M. Sehi, D. S. Greenfield, S. R. Sadda, and D. Huang, “Relationship among visual field, blood flow, and neural structure measurements in glaucoma,” Invest. Ophthalmol. Vis. Sci.53(6), 3020–3026 (2012).
[CrossRef] [PubMed]

B. Potsaid, B. Baumann, D. Huang, S. Barry, A. E. Cable, J. S. Schuman, J. S. Duker, and J. G. Fujimoto, “Ultrahigh speed 1050nm swept source/Fourier domain OCT retinal and anterior segment imaging at 100,000 to 400,000 axial scans per second,” Opt. Express18(19), 20029–20048 (2010).
[CrossRef] [PubMed]

Y. Wang, A. Fawzi, O. Tan, J. Gil-Flamer, and D. Huang, “Retinal blood flow detection in diabetic patients by Doppler Fourier domain optical coherence tomography,” Opt. Express17(5), 4061–4073 (2009).
[CrossRef] [PubMed]

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]

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Hwang, J. C.

J. C. Hwang, R. Konduru, X. Zhang, O. Tan, B. A. Francis, R. Varma, M. Sehi, D. S. Greenfield, S. R. Sadda, and D. Huang, “Relationship among visual field, blood flow, and neural structure measurements in glaucoma,” Invest. Ophthalmol. Vis. Sci.53(6), 3020–3026 (2012).
[CrossRef] [PubMed]

Hyman, L.

L. Hyman, S. Y. Wu, A. M. Connell, A. Schachat, B. Nemesure, A. Hennis, and M. C. Leske, “Prevalence and causes of visual impairment in The Barbados Eye Study,” Ophthalmology108(10), 1751–1756 (2001).
[CrossRef] [PubMed]

Ishii, Y.

C. P. Jonescu-Cuypers, H. S. Chung, L. Kagemann, Y. Ishii, D. Zarfati, and A. Harris, “New neuroretinal rim blood flow evaluation method combining Heidelberg retina flowmetry and tomography,” Br. J. Ophthalmol.85(3), 304–309 (2001).
[CrossRef] [PubMed]

Izatt, J. A.

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]

Jarvi, M.

Jia, Y.

Jiang, J.

Jonescu-Cuypers, C. P.

C. P. Jonescu-Cuypers, H. S. Chung, L. Kagemann, Y. Ishii, D. Zarfati, and A. Harris, “New neuroretinal rim blood flow evaluation method combining Heidelberg retina flowmetry and tomography,” Br. J. Ophthalmol.85(3), 304–309 (2001).
[CrossRef] [PubMed]

Joos, K. M.

K. M. Joos, L. E. Pillunat, R. W. Knighton, D. R. Anderson, and W. J. Feuer, “Reproducibility of laser Doppler flowmetry in the human optic nerve head,” J. Glaucoma6(4), 212–216 (1997).
[CrossRef] [PubMed]

Kagemann, L.

C. P. Jonescu-Cuypers, H. S. Chung, L. Kagemann, Y. Ishii, D. Zarfati, and A. Harris, “New neuroretinal rim blood flow evaluation method combining Heidelberg retina flowmetry and tomography,” Br. J. Ophthalmol.85(3), 304–309 (2001).
[CrossRef] [PubMed]

Kerr, J.

J. Kerr, P. Nelson, and C. O’Brien, “A comparison of ocular blood flow in untreated primary open-angle glaucoma and ocular hypertension,” Am. J. Ophthalmol.126(1), 42–51 (1998).
[CrossRef] [PubMed]

Khurana, M.

Knighton, R. W.

K. M. Joos, L. E. Pillunat, R. W. Knighton, D. R. Anderson, and W. J. Feuer, “Reproducibility of laser Doppler flowmetry in the human optic nerve head,” J. Glaucoma6(4), 212–216 (1997).
[CrossRef] [PubMed]

Konduru, R.

J. C. Hwang, R. Konduru, X. Zhang, O. Tan, B. A. Francis, R. Varma, M. Sehi, D. S. Greenfield, S. R. Sadda, and D. Huang, “Relationship among visual field, blood flow, and neural structure measurements in glaucoma,” Invest. Ophthalmol. Vis. Sci.53(6), 3020–3026 (2012).
[CrossRef] [PubMed]

Kraus, M. F.

Kwon, Y. H.

Z. Hu, M. D. Abràmoff, Y. H. Kwon, K. Lee, and M. K. Garvin, “Automated segmentation of neural canal opening and optic cup in 3D spectral optical coherence tomography volumes of the optic nerve head,” Invest. Ophthalmol. Vis. Sci.51(11), 5708–5717 (2010).
[CrossRef] [PubMed]

Langhans, M. J.

G. Michelson, M. J. Langhans, and M. J. Groh, “Perfusion of the juxtapapillary retina and the neuroretinal rim area in primary open angle glaucoma,” J. Glaucoma5(2), 91–98 (1996).
[CrossRef] [PubMed]

Lee, K.

Z. Hu, M. D. Abràmoff, Y. H. Kwon, K. Lee, and M. K. Garvin, “Automated segmentation of neural canal opening and optic cup in 3D spectral optical coherence tomography volumes of the optic nerve head,” Invest. Ophthalmol. Vis. Sci.51(11), 5708–5717 (2010).
[CrossRef] [PubMed]

A. Mariampillai, M. K. Leung, M. Jarvi, B. A. Standish, K. Lee, B. C. Wilson, A. Vitkin, and V. X. Yang, “Optimized speckle variance OCT imaging of microvasculature,” Opt. Lett.35(8), 1257–1259 (2010).
[CrossRef] [PubMed]

Leitgeb, R.

Lesk, M. R.

A. S. Hafez, R. L. G. Bizzarro, and M. R. Lesk, “Evaluation of optic nerve head and peripapillary retinal blood flow in glaucoma patients, ocular hypertensives, and normal subjects,” Am. J. Ophthalmol.136(6), 1022–1031 (2003).
[CrossRef] [PubMed]

Leske, M. C.

L. Hyman, S. Y. Wu, A. M. Connell, A. Schachat, B. Nemesure, A. Hennis, and M. C. Leske, “Prevalence and causes of visual impairment in The Barbados Eye Study,” Ophthalmology108(10), 1751–1756 (2001).
[CrossRef] [PubMed]

Leung, M. K.

Leung, M. K. K.

Lin, C. P.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Liu, J. J.

Malekafzali, A.

Mariampillai, A.

Markstein, R.

C. Prünte, J. Flammer, R. Markstein, and M. Rudin, “Quantification of optic nerve blood flow changes using magnetic resonance imaging,” Invest. Ophthalmol. Vis. Sci.36(1), 247–251 (1995).
[PubMed]

Michelson, G.

G. Michelson, M. J. Langhans, and M. J. Groh, “Perfusion of the juxtapapillary retina and the neuroretinal rim area in primary open angle glaucoma,” J. Glaucoma5(2), 91–98 (1996).
[CrossRef] [PubMed]

Milner, T. E.

Moriyama, E. H.

Munce, N. R.

Nassif, N.

Nelson, J. S.

Nelson, P.

J. Kerr, P. Nelson, and C. O’Brien, “A comparison of ocular blood flow in untreated primary open-angle glaucoma and ocular hypertension,” Am. J. Ophthalmol.126(1), 42–51 (1998).
[CrossRef] [PubMed]

Nemesure, B.

L. Hyman, S. Y. Wu, A. M. Connell, A. Schachat, B. Nemesure, A. Hennis, and M. C. Leske, “Prevalence and causes of visual impairment in The Barbados Eye Study,” Ophthalmology108(10), 1751–1756 (2001).
[CrossRef] [PubMed]

O’Brien, C.

J. Kerr, P. Nelson, and C. O’Brien, “A comparison of ocular blood flow in untreated primary open-angle glaucoma and ocular hypertension,” Am. J. Ophthalmol.126(1), 42–51 (1998).
[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. (Copenh.)88(7), 723–729 (2010).
[CrossRef] [PubMed]

Park, B.

Parker, C. W.

M. R. Stein and C. W. Parker, “Reactions following intravenous fluorescein,” Am. J. Ophthalmol.72(5), 861–868 (1971).
[PubMed]

Petrig, B. L.

B. L. Petrig, C. E. Riva, and S. S. Hayreh, “Laser Doppler flowmetry and optic nerve head blood flow,” Am. J. Ophthalmol.127(4), 413–425 (1999).
[CrossRef] [PubMed]

Pierce, M.

Pillunat, L. E.

K. M. Joos, L. E. Pillunat, R. W. Knighton, D. R. Anderson, and W. J. Feuer, “Reproducibility of laser Doppler flowmetry in the human optic nerve head,” J. Glaucoma6(4), 212–216 (1997).
[CrossRef] [PubMed]

Piltz-seymour, J. R.

J. R. Piltz-seymour, J. E. Grunwald, S. M. Hariprasad, and J. Dupont, “Optic nerve blood flow is diminished in eyes of primary open-angle glaucoma suspects,” Am. J. Ophthalmol.132(1), 63–69 (2001).
[CrossRef] [PubMed]

Potsaid, B.

Prünte, C.

C. Prünte, J. Flammer, R. Markstein, and M. Rudin, “Quantification of optic nerve blood flow changes using magnetic resonance imaging,” Invest. Ophthalmol. Vis. Sci.36(1), 247–251 (1995).
[PubMed]

Puliafito, C. A.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Quesnot, S.

P. Hamard, H. Hamard, J. Dufaux, and S. Quesnot, “Optic nerve head blood flow using a laser Doppler velocimeter and haemorheology in primary open angle glaucoma and normal pressure glaucoma,” Br. J. Ophthalmol.78(6), 449–453 (1994).
[CrossRef] [PubMed]

Quigley, H. A.

H. A. Quigley and S. Vitale, “Models of open-angle glaucoma prevalence and incidence in the United States,” Invest. Ophthalmol. Vis. Sci.38(1), 83–91 (1997).
[PubMed]

Reim, M.

S. Wolf, O. Arend, W. E. Sponsel, K. Schulte, L. B. Cantor, and M. Reim, “Retinal hemodynamics using scanning laser ophthalmoscopy and hemorheology in chronic open-angle glaucoma,” Ophthalmology100(10), 1561–1566 (1993).
[PubMed]

Reynaud, J. F.

N. G. Strouthidis, H. Yang, J. F. Reynaud, J. L. Grimm, S. K. Gardiner, B. Fortune, and C. F. Burgoyne, “Comparison of clinical and spectral domain optical coherence tomography optic disc margin anatomy,” Invest. Ophthalmol. Vis. Sci.50(10), 4709–4718 (2009).
[CrossRef] [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. (Copenh.)88(7), 723–729 (2010).
[CrossRef] [PubMed]

C. E. Riva, “Basic principles of laser Doppler flowmetry and application to the ocular circulation,” Int. Ophthalmol.23(4/6), 183–189 (2001).
[CrossRef] [PubMed]

B. L. Petrig, C. E. Riva, and S. S. Hayreh, “Laser Doppler flowmetry and optic nerve head blood flow,” Am. J. Ophthalmol.127(4), 413–425 (1999).
[CrossRef] [PubMed]

Rudin, M.

C. Prünte, J. Flammer, R. Markstein, and M. Rudin, “Quantification of optic nerve blood flow changes using magnetic resonance imaging,” Invest. Ophthalmol. Vis. Sci.36(1), 247–251 (1995).
[PubMed]

Sadda, S. R.

J. C. Hwang, R. Konduru, X. Zhang, O. Tan, B. A. Francis, R. Varma, M. Sehi, D. S. Greenfield, S. R. Sadda, and D. Huang, “Relationship among visual field, blood flow, and neural structure measurements in glaucoma,” Invest. Ophthalmol. Vis. Sci.53(6), 3020–3026 (2012).
[CrossRef] [PubMed]

Schachat, A.

L. Hyman, S. Y. Wu, A. M. Connell, A. Schachat, B. Nemesure, A. Hennis, and M. C. Leske, “Prevalence and causes of visual impairment in The Barbados Eye Study,” Ophthalmology108(10), 1751–1756 (2001).
[CrossRef] [PubMed]

Schmetterer, L.

Schulte, K.

S. Wolf, O. Arend, W. E. Sponsel, K. Schulte, L. B. Cantor, and M. Reim, “Retinal hemodynamics using scanning laser ophthalmoscopy and hemorheology in chronic open-angle glaucoma,” Ophthalmology100(10), 1561–1566 (1993).
[PubMed]

Schuman, J. S.

B. Potsaid, B. Baumann, D. Huang, S. Barry, A. E. Cable, J. S. Schuman, J. S. Duker, and J. G. Fujimoto, “Ultrahigh speed 1050nm swept source/Fourier domain OCT retinal and anterior segment imaging at 100,000 to 400,000 axial scans per second,” Opt. Express18(19), 20029–20048 (2010).
[CrossRef] [PubMed]

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Sehi, M.

J. C. Hwang, R. Konduru, X. Zhang, O. Tan, B. A. Francis, R. Varma, M. Sehi, D. S. Greenfield, S. R. Sadda, and D. Huang, “Relationship among visual field, blood flow, and neural structure measurements in glaucoma,” Invest. Ophthalmol. Vis. Sci.53(6), 3020–3026 (2012).
[CrossRef] [PubMed]

Sponsel, W. E.

S. Wolf, O. Arend, W. E. Sponsel, K. Schulte, L. B. Cantor, and M. Reim, “Retinal hemodynamics using scanning laser ophthalmoscopy and hemorheology in chronic open-angle glaucoma,” Ophthalmology100(10), 1561–1566 (1993).
[PubMed]

Srinivas, S.

Standish, B. A.

Stein, M. R.

M. R. Stein and C. W. Parker, “Reactions following intravenous fluorescein,” Am. J. Ophthalmol.72(5), 861–868 (1971).
[PubMed]

Stinson, W. G.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Strouthidis, N.

N. Strouthidis, H. Yang, B. Fortune, J. Crawford Downs, and C. Burgoyne, “Detection of optic nerve head neural canal opening within histomorphometric and spectral domain optical coherence tomography data sets,” Invest. Ophthalmol. Vis. Sci.50(1), 214–223 (2009).
[CrossRef] [PubMed]

Strouthidis, N. G.

N. G. Strouthidis, H. Yang, J. F. Reynaud, J. L. Grimm, S. K. Gardiner, B. Fortune, and C. F. Burgoyne, “Comparison of clinical and spectral domain optical coherence tomography optic disc margin anatomy,” Invest. Ophthalmol. Vis. Sci.50(10), 4709–4718 (2009).
[CrossRef] [PubMed]

Subhash, H.

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. (Copenh.)88(7), 723–729 (2010).
[CrossRef] [PubMed]

Swanson, E. A.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science254(5035), 1178–1181 (1991).
[CrossRef] [PubMed]

Tan, O.

Y. Jia, O. Tan, J. Tokayer, B. Potsaid, Y. Wang, J. J. Liu, M. F. Kraus, H. Subhash, J. G. Fujimoto, J. Hornegger, and D. Huang, “Split-spectrum amplitude-decorrelation angiography with optical coherence tomography,” Opt. Express20(4), 4710–4725 (2012).
[CrossRef] [PubMed]

J. C. Hwang, R. Konduru, X. Zhang, O. Tan, B. A. Francis, R. Varma, M. Sehi, D. S. Greenfield, S. R. Sadda, and D. Huang, “Relationship among visual field, blood flow, and neural structure measurements in glaucoma,” Invest. Ophthalmol. Vis. Sci.53(6), 3020–3026 (2012).
[CrossRef] [PubMed]

Y. Wang, A. Fawzi, O. Tan, J. Gil-Flamer, and D. Huang, “Retinal blood flow detection in diabetic patients by Doppler Fourier domain optical coherence tomography,” Opt. Express17(5), 4061–4073 (2009).
[CrossRef] [PubMed]

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]

Tearney, G.

Tokayer, J.

Ulmer, J. L.

G. H. Garcia, K. M. Donahue, J. L. Ulmer, and G. J. Harris, “Qualitative perfusion imaging of the human optic nerve,” Ophthal. Plast. Reconstr. Surg.18(2), 107–113 (2002).
[CrossRef] [PubMed]

van den Berg, T. J.

G. Holló, T. J. van den Berg, and E. L. Greve, “Scanning laser Doppler flowmetry in glaucoma,” Int. Ophthalmol.20(1-3), 63–70 (1996-1997).
[PubMed]

van Gemert, M. J. C.

Varma, R.

J. C. Hwang, R. Konduru, X. Zhang, O. Tan, B. A. Francis, R. Varma, M. Sehi, D. S. Greenfield, S. R. Sadda, and D. Huang, “Relationship among visual field, blood flow, and neural structure measurements in glaucoma,” Invest. Ophthalmol. Vis. Sci.53(6), 3020–3026 (2012).
[CrossRef] [PubMed]

Vitale, S.

H. A. Quigley and S. Vitale, “Models of open-angle glaucoma prevalence and incidence in the United States,” Invest. Ophthalmol. Vis. Sci.38(1), 83–91 (1997).
[PubMed]

Vitkin, A.

Vitkin, I. A.

Wang, X.

Wang, Y.

White, B.

Wilson, B. C.

Wolf, S.

S. Wolf, O. Arend, W. E. Sponsel, K. Schulte, L. B. Cantor, and M. Reim, “Retinal hemodynamics using scanning laser ophthalmoscopy and hemorheology in chronic open-angle glaucoma,” Ophthalmology100(10), 1561–1566 (1993).
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Figures (5)

Fig. 1
Fig. 1

Flow chart detailing the basic steps of the SSADA algorithm. Eight OCT M-B frames were scanned consecutively at the same spatial location to produce 8 spectral interferograms and 8 standard-resolution cross-sectional images. In conventional decorrelation angiography, decorrelation is calculated between these standard resolution images, but this produces a low-quality angiogram. In SSADA, each full spectral interferogram was split into 4 spectral bands. There were 8 OCT image frames at each spectral band, from which 7 decorrelation frames were calculated. The 28 decorrelation frames were averaged to produce one final decorrelation-based flow cross-section of much higher quality [26].

Fig. 2
Fig. 2

In vivo 3D volumetric [3.0 (x) × 3.0 (y) × 2.9 (z) mm] OCT images of the ONH in the right eye of a normal subject. The images in (E) and (F) were cropped from 2.9 mm to 1.8 mm axially. (A) Rendering of a scanned disc volume reflectance intensity image . (B) 3D rendering of flow image. (C) An en face maximum reflectance intensity projection showed branches of the central retinal vessels. (D) En face maximum decorrelation projection angiogram. (E) OCT cross-section at the plane marked by red dashed line in (C). The boundary of the neural canal opening (NCO), indicated by two green dashed lines, was determined by the termination of the RPE/BM complex, shown by two green arrows that corresponded to the two margin points in (C) & (D). (F) Cross-sectional gray scale reflectance intensity image overlaid by the color scale flow (decorrelation) image shows that the abundant ONH circulation resides mainly in the lamina cribosa region. The ONH blood flow was obviously lower than that of the major retinal vessels and choroidal vessels, but it was clearly shown in the maximum projection map (see the temporal section of (D)).

Fig. 3
Fig. 3

Flow chart displaying extraction of the flow regions for quantification. (A) The en face maximum decorrelation projection angiogram. The color scale (decorrelation) was related to the localized blood flow magnitude. (B1) The whole disc mask with known value of VD and HD, created by the method described in section 2.4.2. (B2) The temporal elliptical area, derived from the primary whole disc ellipse. The arrow indicates the tilted angle based on the disc-fovea axis. (C1) and (C2) Final segmented flow maps, achieved by multiplying the original disc flow map (A) with two different disc masks (B1 and B2). Further processing could be applied for quantification.

Fig. 4
Fig. 4

Relationship between reflectance intensity and decorrelation used for quality control of 3D decorrelation values. The median values of log intensity and median values of decorrelation were acquired through two 3D outputs (reflectance intensity/decorrelation). All of the values were collected from 4 normal subjects (16 scans). This plot indicates 4.1 (log intensity) can be considered as the cutoff point to remove the scans with lower intensity values that would bias the resulting decorrelation/flow values.

Fig. 5
Fig. 5

Disc photographs (A, C) and en face OCT angiograms (B, D) of the ONH in representative normal (A, B) and preperimetric glaucoma (PPG) subjects (C, D). Both examples are from left eyes. In (B) and (D) the solid circles indicate the whole discs, and the dash circles indicate the temporal ellipses. A dense microvascular network was visible on the OCT angiography of the normal disc (B). This network was greatly attenuated in the glaucomatous disc (D).

Tables (2)

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Table 1 OCT disc perfusion measurements on the whole disc regiona

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Table 2 OCT disc perfusion measurements on the temporal ellipse of the disca

Equations (2)

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A DVdA A dA (V=1, if vessel; V=0, if not),
A VdA A dA (V=1, if vessel; V=0, if not),

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