Visible light optical coherence tomography measures retinal oxygen metabolic response to systemic oxygenation

Ji Yi; Wenzhong Liu; Siyu Chen; Vadim Backman; Nader Sheibani; Christine M. Sorenson; Amani A. Fawzi; Robert A. Linsenmeier; Hao F. Zhang

doi:10.1038/lsa.2015.107

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Visible light optical coherence tomography measures retinal oxygen metabolic response to systemic oxygenation

Original Articles

- Visible light optical coherence tomography measures retinal oxygen metabolic response to systemic oxygenation
- Light: Science & Applications Vol. 4, Issue 4, (2015)
- Affiliations：
  
  1.Department of Biomedical Engineering, Northwestern University, Evanston, IL 60208, USA
  2.McPherson Eye Research Institute, University of Wisconsin, Madison, WI 53705, USA
  3.Department of Ophthalmology, Northwestern University, Chicago Illinois 60611, USA
  4.Department of Neurobiology, Northwestern University, Evanston, IL 60208, USA
- Author bio：
  
  HF Zhang, Email: hfzhang@northwestern.edu
- Funds：
- DOI：10.1038/lsa.2015.107
  CLC：
- Published：2015-12，
  
  Published Online：10 June 2015，
  
  Received：11 March 2015，
  
  Revised：01 June 2015，
  
  Accepted：07 June 2015
- Accepted：
Scan QR Code
Yi, J. et al. Visible light optical coherence tomography measures retinal oxygen metabolic response to systemic oxygenation. Light: Science & Applications, 4, e334 (2015).
DOI：

Yi, J. et al. Visible light optical coherence tomography measures retinal oxygen metabolic response to systemic oxygenation. Light: Science & Applications, 4, e334 (2015). DOI： 10.1038/lsa.2015.107.

摘要

Abstract

The lack of capability to quantify oxygen metabolism noninvasively impedes both fundamental investigation and clinical diagnosis of a wide spectrum of diseases including all the major blinding diseases such as age-related macular degeneration

diabetic retinopathy

and glaucoma. Using visible light optical coherence tomography (vis-OCT)

we demonstrated accurate and robust measurement of retinal oxygen metabolic rate (rMRO

) noninvasively in rat eyes. We continuously monitored the regulatory response of oxygen consumption to a progressive hypoxic challenge. We found that both oxygen delivery

and rMRO

increased from the highly regulated retinal circulation (RC) under hypoxia

by 0.28 ± 0.08 µL min

−1

(

0.001)

and 0.20 ± 0.04 µL min

−1

(

0.001) per 100 mmHg

systemic pO

reduction

respectively. The increased oxygen extraction compensated for the deficient oxygen supply from the poorly regulated choroidal circulation. Results from an oxygen diffusion model based on previous oxygen electrode measurements corroborated our

in vivo

observations. We believe that vis-OCT has the potential to reveal the fundamental role of oxygen metabolism in various retinal diseases.

关键词

Keywords

oxygen metabolismretinal circulationvisible light optical coherence tomography

references

Hammes HP. Pericytes and the pathogenesis of diabetic retinopathy.Horm Metab Res2005;37: 39–43..

Mozaffarieh M, Grieshaber MC, Flammer J. Oxygen and blood flow: players in the pathogenesis of glaucoma.Mol Vis2008;14: 224–233..

Nowak JZ. Age-related macular degeneration (AMD): pathogenesis and therapy.Pharmacol Rep2006;58: 353–363..

Caprara C, Grimm C. From oxygen to erythropoietin: relevance of hypoxia for retinal development, health and disease.Prog Retin Eye Res2012;31: 89–119..

Lange CA, Bainbridge JW. Oxygen sensing in retinal health and disease.Ophthalmologica2012;227: 115–131..

Crosson LA, Kroes RA, Moskal JR, Linsenmeier RA. Gene expression patterns in hypoxic and post-hypoxic adult rat retina with special reference to the NMDA receptor and its interactome.Mol Vis2009;15: 296–311..

Kaur C, Sivakumar V, Foulds WS. Early response of neurons and glial cells to hypoxia in the retina.Invest Ophthalmol Vis Sci2006;47: 1126–1141..

Arjamaa O, Nikinmaa M. Oxygen-dependent diseases in the retina: role of hypoxia-inducible factors.Exp Eye Res2006;83: 473–483..

Linsenmeier RA, Braun RD, McRipley MA, Padnick LB, Ahmed Jet al. Retinal hypoxia in long-term diabetic cats.Invest Ophthalmol Vis Sci1998;39: 1647–1657..

Shahidi M, Wanek J, Blair NP, Little DM, Wu T. Retinal tissue oxygen tension imaging in the rat.Invest Ophthalmol Vis Sci2010;51: 4766–4770..

Berkowitz BA, Kowluru RA, Frank RN, Kern TS, Hohman TCet al. Subnormal retinal oxygenation response precedes diabetic-like retinopathy.Invest Ophthalmol Vis Sci1999;40: 2100–2105..

Riva CE, Grunwald JE, Petrig BL. Autoregulation of human retinal blood flow. An investigation with laser Doppler velocimetry.Invest Ophthalmol Vis Sci1986;27: 1706–1712..

Palkovits S, Told R, Schmidl D, Boltz A, Napora KJet al. Regulation of retinal oxygen metabolism in humans during graded hypoxia.Am J Physiol Heart Circ Physiol2014;307: H1412–H1418..

Palkovits S,Lasta M, Told R, Schmidl D, Boltz Aet al. Retinal oxygen metabolism during normoxia and hyperoxia in healthy subjects.Invest Ophthalmol Vis Sci2014;55: 4707–4713..

Harris A, Dinn RB, Kagemann L, Rechtman E. A review of methods for human retinal oximetry.Ophthalmic Surg Lasers Imaging2003;34: 152..

Hardarson SH, Harris A, Karlsson RA, Halldorsson GH, Kagemann Let al. Automatic retinal oximetry.Invest Ophthalmol Vis Sci2006;47: 5011–5016..

Palsson O, Geirsdottir A, Hardarson SH, Olafsdottir OB, Kristjansdottir JVet al. Retinal oximetry images must be standardized: a methodological analysis.Invest Ophthalmol Vis Sci2012;53: 1729–1733..

Kristjansdottir JV, Hardarson SH, Halldorsson GH, Karlsson RA, Eliasdottir TSet al. Retinal oximetry with a scanning laser ophthalmoscope.Invest Ophthalmol Vis Sci2014;55: 3120–3126..

Jiao S, Jiang M, Hu J, Fawzi A, Zhou Qet al. Photoacoustic ophthalmoscopy forin vivoretinal imaging.Opt Express2010;18: 3967–3972..

Song W, Wei Q, Liu W, Liu T, Yi Jet al. A combined method to quantify the retinal metabolic rate of oxygen using photoacoustic ophthalmoscopy and optical coherence tomography.Sci Rep2014;4: 6525..

Yazdanfar S, Rollins AM, Izatt JA. Imaging and velocimetry of the human retinal circulation with color Doppler optical coherence tomography.Opt Lett2000;25: 1448–1450..

Zhao Y, Chen Z, Saxer C, Xiang S, de Boer JFet al. Phase-resolved optical coherence tomography and optical Doppler tomography for imaging blood flow in human skin with fast scanning speed and high velocity sensitivity.Opt Lett2000;25: 114–116..

Wang Y, Bower BA, Izatt JA, Tan O, Huang D. Retinal blood flow measurement by circumpapillary Fourier domain Doppler optical coherence tomography.J Biomed Opt2008;13: 064003..

Zhi Z, Cepurna W, Johnson E, Shen T, Morrison Jet al. Volumetric and quantitative imaging of retinal blood flow in rats with optical microangiography.Biomed Opt Express2011;2: 579–591..

Yi J, Wei Q, Liu W, Backman V, Zhang HF. Visible-light optical coherence tomography for retinal oximetry.Opt Lett2013;38: 1796–1798..

Yi J, Li X. Estimation of oxygen saturation from erythrocytes by high-resolution spectroscopic optical coherence tomography.Opt Lett2010;35: 2094–2096..

Robles FE, Wilson C, Grant G, Wax A. Molecular imaging true-colour spectroscopic optical coherence tomography.Nat Photonics2011;5: 744–747..

de Villota ED, Carmona MT, Rubio JJ, de Andrés SR. Equality of the in vivo and in vitro oxygen-binding capacity of haemoglobin in patients with severe respiratorydisease.Br J Anaesth1981;53: 1325–1328..

Wang Y, Bower BA, Izatt JA, Tan O, Huang D.In vivototal retinal blood flow measurement by Fourier domain Doppler optical coherence tomography.J Biomed Opt2007;12: 041215..

Suzuki H, Watkins DN, Jair KW, Schuebel KE, Markowitz SDet al. Epigenetic inactivation of SFRP genes allows constitutive WNT signaling in colorectal cancer.Nat Genet2004;36: 417–422..

Wang Y, Fawzi AA, Varma R, Sadun AA, Zhang Xet al. Pilot study of optical coherence tomography measurement of retinal blood flow in retinal and optic nerve diseases.Invest Ophthalmol Vis Sci2011;52(2): 840–845..

Boettner EA, Wolter JR. Transmission of the ocular media.Invest Ophthalmol Vis Sci1962;1: 776–783..

Schwinn DA, McIntyre RW, Reves JG. Isoflurane-induced vasodilation: role of the [α]-adrenergic nervous system.Anesth Analg1990;71: 451–459..

Lau JC, Linsenmeier RA. Oxygen consumption and distribution in the Long-Evans rat retina.Exp Eye Res2012;102: 50–58..

Linsenmeier RA, Braun RD. Oxygen distribution and consumption in the cat retina during normoxia and hypoxemia.J Gen Physiol1992;99: 177–197..

Ahmed J, Braun RD, Dunn R, Linsenmeier RA. Oxygen distribution in the macaque retina.Invest Ophthalmol Vis Sci1993;34: 516–521..

Faber DJ, Aalders MC, Mik EG, Hooper BA, van Gemert MJet al. Oxygen saturation-dependent absorption and scattering of blood.Phys Rev Lett2004;93: 028102..

Bosschaart N, Edelman GJ, Aalders MC, van Leeuwen TG, Faber DJ. A literature review and novel theoretical approach on the optical properties of whole blood.Lasers Med Sci2014;29: 453–479..

Srinivasan VJ, Radhakrishnan H. Total average blood flow and angiography in the rat retina.J Biomed Opt2013;18: 076025..

Choi W, Baumann B, Liu JJ, Clermont AC, Feener EPet al. Measurement of pulsatile total blood flow in the human and rat retina with ultrahigh speed spectral/Fourier domain OCT.Biomed Opt Express2012;3: 1047–1061..

Nagaoka T, Sakamoto T, Mori F, Sato E, Yoshida A. The effect of nitric oxide on retinal blood flow during hypoxia in cats.Invest Ophthalmol Vis Sci2002;43: 3037–3044..

Hill AV. The combinations of haemoglobin with oxygen and with carbon monoxide. Ⅰ.Biochem J1913;7: 471–480..

Pournaras CJ, Rungger-Brändle E, Riva CE, Hardarson SH, Stefansson E. Regulation of retinal blood flow in health and disease.Prog Retin Eye Res2008;27: 284–330..

Wanek J, Teng PY, Blair NP, Shahidi M. Inner retinal oxygen delivery and metabolism under normoxia and hypoxia in rat.Invest Ophthalmol Vis Sci2013;54: 5012–5019..

Kur J, Newman EA, Chan-Ling T. Cellular and physiological mechanisms underlying blood flow regulation in the retina choroid in health disease.Prog Retin Eye Res2012;31: 377–406..

Newman EA. Functional hyperemia and mechanisms of neurovascular coupling in the retinal vasculature.J Cereb Blood Flow Metab2013;33: 1685–1695..

Teng PY, Wanek J, Blair NP, Shahidi M. Response of inner retinal oxygen extraction fraction to light flicker under normoxia and hypoxia in rat.Invest Ophthalmol Vis Sci2014;55: 6055–6058..

Riva CE, Logean E, Petrig BL, Falsini B. Effectof dark adaptation on retinal blood flow.Klin Monbl Augenheilkd2000;216: 309–310..

Braun RD, Linsenmeier RA, Goldstick TK. Oxygen consumption in the inner and outer retina of the cat.Invest Ophthalmol Vis Sci1995;36: 542–554..

Kohner EM, Hamilton AM, Saunders SJ, Sutcliffe BA, Bulpitt CJ. The retinal blood flow in diabetes.Diabetologia1975;11: 27–33..

Kohner EM, Patel V, Rassam SM. Role of blood flow and impaired autoregulation in the pathogenesis of diabetic retinopathy.Diabetes1995;44: 603–607..

Feke GT, Buzney SM, Ogasawara H, Fujio N, Goger DGet al. Retinal circulatory abnormalities in type 1 diabetes.Invest Ophthalmol Vis Sci1994;35: 2968–2975..

Bursell SE, Clermont AC, Kinsley BT, Simonson DC, Aiello LMet al. Retinal blood flow changes in patients with insulin-dependent diabetes mellitus and no diabetic retinopathy.Invest Ophthalmol Vis Sci1996;37: 886–897..

Wright WS, McElhatten RM, Harris NR. Increase in retinal hypoxia-inducible factor-2α, but not hypoxia, early in the progression of diabetes in the rat.Exp Eye Res2011;93: 437–441..

Flammer J, Orgül S, Costa VP, Orzalesi N, Krieglstein GKet al. The impact of ocular blood flow in glaucoma.Prog Retin Eye Res2002;21: 359–393..

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