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Functional Imaging of Cerebral Oxygenation with Intrinsic Optical Contrast and Phosphorescent Probes

Part of the Neuromethods book series (NM,volume 85)

Abstract

Microscopic in vivo measurements of cerebral oxygenation are of key importance for understanding normal cerebral energy metabolism and its dysregulation in a wide range of clinical conditions. Relevant cerebral pathologies include compromised blood perfusion following stroke and a decrease in efficiency of single-cell respiratory processes that occurs in neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. In this chapter we review a number of quantitative optical approaches to measuring oxygenation of blood and cerebral tissue. These methods can be applied to map the hemodynamic response and study neurovascular and neurometabolic coupling, and can provide microscopic imaging of biomarkers in animal models of human disease, which would be useful for screening potential therapeutic approaches.

Key words

  • O2 sensing
  • Phosphorescence quenching
  • Intrinsic optical signals
  • Energy metabolism
  • In vivo imaging
  • Hemoglobin
  • Two-photon microscopy
  • CCD

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References

  1. Grinvald A, Lieke E, Frostig RD, Gilbert CD, Wiesel TN (1986) Functional architecture of cortex revealed by optical imaging of intrinsic signals. Nature 324:361–364

    CAS  PubMed  Google Scholar 

  2. Berwick J, Martin C, Martindale J, Jones M, Johnston D, Zheng Y, Redgrave P, Mayhew J (2002) Hemodynamic response in the unanesthetized rat: intrinsic optical imaging and spectroscopy of the barrel cortex. J Cereb Blood Flow Metab 22:670–679

    PubMed  Google Scholar 

  3. Jones M, Berwick J, Mayhew J (2002) Changes in blood flow, oxygenation, and volume following extended stimulation of rodent barrel cortex. Neuroimage 15:474–487

    PubMed  Google Scholar 

  4. Frostig RD, Lieke EE, Ts’o DY, Grinvald A (1990) 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 USA 87: 6082–6086

    CAS  PubMed  Google Scholar 

  5. Malonek D, Dirnagl U, Lindauer U, Yamada K, Kanno I, Grinvald A (1997) Vascular imprints of neuronal activity: relationships between the dynamics of cortical blood flow, oxygenation, and volume changes following sensory stimulation. Proc Natl Acad Sci USA 94:14826–14831

    CAS  PubMed  Google Scholar 

  6. Malonek D, Grinvald A (1996) Interactions between electrical activity and cortical microcirculation revealed by imaging spectroscopy: implications for functional brain mapping. Science 272:551–554

    CAS  PubMed  Google Scholar 

  7. Martindale J, Mayhew J, Berwick J, Jones M, Martin C, Johnston D, Redgrave P, Zheng Y (2003) The hemodynamic impulse response to a single neural event. J Cereb Blood Flow Metab 23:546–555

    PubMed  Google Scholar 

  8. Mayhew J, Johnston D, Berwick J, Jones M, Coffey P, Zheng Y (2000) Spectroscopic analysis of neural activity in brain: increased oxygen consumption following activation of barrel cortex. Neuroimage 12:664–675

    CAS  PubMed  Google Scholar 

  9. Nemoto M, Sheth S, Guiou M, Pouratian N, Chen JW, Toga AW (2004) Functional signal- and paradigm-dependent linear relationships between synaptic activity and hemodynamic responses in rat somatosensory cortex. J Neurosci 24:3850–3861

    CAS  PubMed  Google Scholar 

  10. Sheth S, Nemoto M, Guiou M, Walker M, Pouratian N, Toga AW (2003) Evaluation of coupling between optical intrinsic signals and neuronal activity in rat somatosensory cortex. Neuroimage 19:884–894

    PubMed  Google Scholar 

  11. Vanzetta I, Hildesheim R, Grinvald A (2005) Compartment-resolved imaging of activity-dependent dynamics of cortical blood volume and oximetry. J Neurosci 25:2233–2244

    CAS  PubMed  Google Scholar 

  12. Chen G, Lu HD, Roe AW (2008) A map for horizontal disparity in monkey V2. Neuron 58:442–450

    CAS  PubMed Central  PubMed  Google Scholar 

  13. Erinjeri JP, Woolsey TA (2002) Spatial integration of vascular changes with neural activity in mouse cortex. J Cereb Blood Flow Metab 22:353–360

    PubMed  Google Scholar 

  14. Shtoyerman E, Arieli A, Slovin H, Vanzetta I, Grinvald A (2000) Long-term optical imaging and spectroscopy reveal mechanisms underlying the intrinsic signal and stability of cortical maps in V1 of behaving monkeys. J Neurosci 20:8111–8121

    CAS  PubMed  Google Scholar 

  15. Sirotin YB, Das A (2009) Anticipatory haemodynamic signals in sensory cortex not predicted by local neuronal activity. Nature 457:475–479

    CAS  PubMed Central  PubMed  Google Scholar 

  16. Roy CS, Sherrington CS (1890) On the regulation of the blood-supply of the brain. J Physiol 11:85–158

    CAS  PubMed  Google Scholar 

  17. Fox PT, Raichle ME (1984) Stimulus rate dependence of regional cerebral blood flow in human striate cortex, demonstrated by positron emission tomography. J Neurophysiol 51:1109–1120

    CAS  PubMed  Google Scholar 

  18. Lassen NA, Ingvar DH (1961) The blood flow of the cerebral cortex determined by radioactive krypton. Experientia 17:42–43

    CAS  PubMed  Google Scholar 

  19. Sokoloff L, Reivich M, Kennedy C, Des Rosiers MH, Patlak CS, Pettigrew KD, Sakurada O, Shinohara M (1977) The [14C]deoxyglucose method for the measurement of local cerebral glucose utilization: theory, procedure, and normal values in the conscious and anesthetized albino rat. J Neurochem 28:897–916

    CAS  PubMed  Google Scholar 

  20. Sokoloff L (1981) Localization of functional activity in the central nervous system by measurement of glucose utilization with radioactive deoxyglucose. J Cereb Blood Flow Metab 1:7–36

    CAS  PubMed  Google Scholar 

  21. Penfield W (1933) The evidence for a cerebral vascular mechanism in epilepsy. Ann Intern Med 7:303–310

    Google Scholar 

  22. Jobsis FF (1977) Noninvasive, infrared monitoring of cerebral and myocardial oxygen sufficiency and circulatory parameters. Science 198:1264–1267

    CAS  PubMed  Google Scholar 

  23. Chance B, Cohen P, Jobsis F, Schoener B (1962) Intracellular oxidation-reduction states in vivo. Science 137:499–508

    CAS  PubMed  Google Scholar 

  24. Vanzetta I, Slovin H, Omer DB, Grinvald A (2004) Columnar resolution of blood volume and oximetry functional maps in the behaving monkey; implications for FMRI. Neuron 42:843–854

    CAS  PubMed  Google Scholar 

  25. Vanzetta I, Grinvald A (1999) Increased cortical oxidative metabolism due to sensory stimulation: implications for functional brain imaging. Science 286:1555–1558

    CAS  PubMed  Google Scholar 

  26. Sheth SA, Nemoto M, Guiou MW, Walker MA, Toga AW (2005) Spatiotemporal evolution of functional hemodynamic changes and their relationship to neuronal activity. J Cereb Blood Flow Metab 25:830–841

    PubMed  Google Scholar 

  27. Sheth SA, Nemoto M, Guiou M, Walker M, Pouratian N, Toga AW (2004) Linear and nonlinear relationships between neuronal activity, oxygen metabolism, and hemodynamic responses. Neuron 42:347–355

    CAS  PubMed  Google Scholar 

  28. Buxton RB (2001) The elusive initial dip. Neuroimage 13:953–958

    CAS  PubMed  Google Scholar 

  29. Lindauer U, Royl G, Leithner C, Kuhl M, Gold L, Gethmann J, Kohl-Bareis M, Villringer A, Dirnagl U (2001) No evidence for early decrease in blood oxygenation in rat whisker cortex in response to functional activation. Neuroimage 13:988–1001

    CAS  PubMed  Google Scholar 

  30. Sirotin YB, Hillman EM, Bordier C, Das A (2009) Spatiotemporal precision and hemodynamic mechanism of optical point spreads in alert primates. Proc Natl Acad Sci USA 106:18390–18395

    CAS  PubMed  Google Scholar 

  31. Vanzetta I, Grinvald A (2001) Evidence and lack of evidence for the initial dip in the anesthetized rat: implications for human functional brain imaging. Neuroimage 13:959–967

    CAS  PubMed  Google Scholar 

  32. Harel N, Mori N, Sawada S, Mount RJ, Harrison RV (2000) Three distinct auditory areas of cortex (AI, AII, and AAF) defined by optical imaging of intrinsic signals. Neuroimage 11:302–312

    CAS  PubMed  Google Scholar 

  33. Spitzer MW, Calford MB, Clarey JC, Pettigrew JD, Roe AW (2001) Spontaneous and stimulus-evoked intrinsic optical signals in primary auditory cortex of the cat. J Neurophysiol 85:1283–1298

    CAS  PubMed  Google Scholar 

  34. Versnel H, Mossop JE, Mrsic-Flogel TD, Ahmed B, Moore DR (2002) Optical imaging of intrinsic signals in ferret auditory cortex: responses to narrowband sound stimuli. J Neurophysiol 88:1545–1558

    PubMed  Google Scholar 

  35. Chen-Bee CH, Agoncillo T, Xiong Y, Frostig RD (2007) The triphasic intrinsic signal: implications for functional imaging. J Neurosci 27:4572–4586

    CAS  PubMed  Google Scholar 

  36. Sheth SA, Nemoto M, Guiou M, Walker M, Pouratian N, Hageman N, Toga AW (2004) Columnar specificity of microvascular oxygenation and volume responses: implications for functional brain mapping. J Neurosci 24: 634–641

    CAS  PubMed  Google Scholar 

  37. Mc Loughlin NP, Blasdel GG (1998) Wavelength-dependent differences between optically determined functional maps from macaque striate cortex. Neuroimage 7:326–336

    CAS  PubMed  Google Scholar 

  38. Kohl M, Lindauer U, Royl G, Kuhl M, Gold L, Villringer A, Dirnagl U (2000) Physical model for the spectroscopic analysis of cortical intrinsic optical signals. Phys Med Biol 45: 3749–3764

    CAS  PubMed  Google Scholar 

  39. Bosking WH, Zhang Y, Schofield B, Fitzpatrick D (1997) Orientation selectivity and the arrangement of horizontal connections in tree shrew striate cortex. J Neurosci 17:2112–2127

    CAS  PubMed  Google Scholar 

  40. Lu HD, Chen G, Tanigawa H, Roe AW (2010) A motion direction map in macaque V2. Neuron 68:1002–1013

    CAS  PubMed Central  PubMed  Google Scholar 

  41. Ts’o DY, Frostig RD, Lieke EE, Grinvald A (1990) Functional organization of primate visual cortex revealed by high resolution optical imaging. Science 249:417–420

    PubMed  Google Scholar 

  42. Ts’o DY, Roe AW, Gilbert CD (2001) A hierarchy of the functional organization for color, form and disparity in primate visual area V2. Vision Res 41:1333–1349

    PubMed  Google Scholar 

  43. Malonek D, Tootell RB, Grinvald A (1994) Optical imaging reveals the functional architecture of neurons processing shape and motion in owl monkey area MT. Proc Biol Sci 258:109–119

    CAS  PubMed  Google Scholar 

  44. Tanigawa H, Lu HD, Roe AW (2010) Functional organization for color and orientation in macaque V4. Nat Neurosci 13: 1542–1548

    CAS  PubMed Central  PubMed  Google Scholar 

  45. Wang G, Tanaka K, Tanifuji M (1996) Optical imaging of functional organization in the monkey inferotemporal cortex. Science 272: 1665–1668

    CAS  PubMed  Google Scholar 

  46. Kalatsky VA, Polley DB, Merzenich MM, Schreiner CE, Stryker MP (2005) Fine functional organization of auditory cortex revealed by Fourier optical imaging. Proc Natl Acad Sci USA 102:13325–13330

    CAS  PubMed  Google Scholar 

  47. Bakin JS, Kwon MC, Masino SA, Weinberger NM, Frostig RD (1996) Suprathreshold auditory cortex activation visualized by intrinsic signal optical imaging. Cereb Cortex 6: 120–130

    CAS  PubMed  Google Scholar 

  48. Masino SA, Kwon MC, Dory Y, Frostig RD (1993) Characterization of functional organization within rat barrel cortex using intrinsic signal optical imaging through a thinned skull. Proc Natl Acad Sci USA 90: 9998–10002

    CAS  PubMed  Google Scholar 

  49. Chen LM, Friedman RM, Ramsden BM, LaMotte RH, Roe AW (2001) Fine-scale organization of SI (area 3b) in the squirrel monkey revealed with intrinsic optical imaging. J Neurophysiol 86:3011–3029

    CAS  PubMed  Google Scholar 

  50. Chen LM, Friedman RM, Roe AW (2003) Optical imaging of a tactile illusion in area 3b of the primary somatosensory cortex. Science 302:881–885

    CAS  PubMed  Google Scholar 

  51. Shoham D, Grinvald A (2001) The cortical representation of the hand in macaque and human area S-I: high resolution optical imaging. J Neurosci 21:6820–6835

    CAS  PubMed  Google Scholar 

  52. Chen LM, Friedman RM, Roe AW (2009) Area-specific representation of mechanical nociceptive stimuli within SI cortex of squirrel monkeys. Pain 141:258–268

    PubMed Central  PubMed  Google Scholar 

  53. Grinvald A, Frostig RD, Siegel RM, Bartfeld E (1991) High-resolution optical imaging of functional brain architecture in the awake monkey. Proc Natl Acad Sci USA 88: 11559–11563

    CAS  PubMed  Google Scholar 

  54. Vnek N, Ramsden BM, Hung CP, Goldman-Rakic PS, Roe AW (1999) Optical imaging of functional domains in the cortex of the awake and behaving monkey. Proc Natl Acad Sci USA 96:4057–4060

    CAS  PubMed  Google Scholar 

  55. Arieli A, Grinvald A, Slovin H (2002) Dural substitute for long-term imaging of cortical activity in behaving monkeys and its clinical implications. J Neurosci Methods 114:119–133

    PubMed  Google Scholar 

  56. Chen LM, Heider B, Williams GV, Healy FL, Ramsden BM, Roe AW (2002) A chamber and artificial dura method for long-term optical imaging in the monkey. J Neurosci Methods 113:41–49

    PubMed  Google Scholar 

  57. Chapman B, Stryker MP, Bonhoeffer T (1996) Development of orientation preference maps in ferret primary visual cortex. J Neurosci 16:6443–6453

    CAS  PubMed Central  PubMed  Google Scholar 

  58. Godecke I, Kim DS, Bonhoeffer T, Singer W (1997) Development of orientation preference maps in area 18 of kitten visual cortex. Eur J Neurosci 9:1754–1762

    CAS  PubMed  Google Scholar 

  59. Lowel S, Schmidt KE, Kim DS, Wolf F, Hoffsummer F, Singer W, Bonhoeffer T (1998) The layout of orientation and ocular dominance domains in area 17 of strabismic cats. Eur J Neurosci 10:2629–2643

    CAS  PubMed  Google Scholar 

  60. Schmidt KE, Singer W, Galuske RA (2004) Processing deficits in primary visual cortex of amblyopic cats. J Neurophysiol 91:1661–1671

    PubMed  Google Scholar 

  61. Schwartz TH, Bonhoeffer T (2001) In vivo optical mapping of epileptic foci and surround inhibition in ferret cerebral cortex. Nat Med 7:1063–1067

    CAS  PubMed  Google Scholar 

  62. Zhao M, Suh M, Ma H, Perry C, Geneslaw A, Schwartz TH (2007) Focal increases in perfusion and decreases in hemoglobin oxygenation precede seizure onset in spontaneous human epilepsy. Epilepsia 48:2059–2067

    PubMed  Google Scholar 

  63. Pouratian N, Cannestra AF, Martin NA, Toga AW (2002) Intraoperative optical intrinsic signal imaging: a clinical tool for functional brain mapping. Neurosurg Focus 13:e1

    PubMed  Google Scholar 

  64. Toga AW, Cannestra AF, Black KL (1995) The temporal/spatial evolution of optical signals in human cortex. Cereb Cortex 5: 561–565

    CAS  PubMed  Google Scholar 

  65. Eaton WA, Henry ER, Hofrichter J, Mozzarelli A (1999) Is cooperative oxygen binding by hemoglobin really understood? Nat Struct Biol 6:351–358

    CAS  PubMed  Google Scholar 

  66. Dunn AK, Devor A, Dale AM, Boas DA (2005) Spatial extent of oxygen metabolism and hemodynamic changes during functional activation of the rat somatosensory cortex. Neuroimage 27:279–290

    PubMed  Google Scholar 

  67. Devor A, Dunn AK, Andermann ML, Ulbert I, Boas DA, Dale AM (2003) Coupling of total hemoglobin concentration, oxygenation, and neural activity in rat somatosensory cortex. Neuron 39:353–359

    CAS  PubMed  Google Scholar 

  68. Dunn AK, Devor A, Bolay H, Andermann ML, Moskowitz MA, Dale AM, Boas DA (2003) Simultaneous imaging of total cerebral hemoglobin concentration, oxygenation, and blood flow during functional activation. Opt Lett 28:28–30

    CAS  PubMed  Google Scholar 

  69. Wilson DF, Pastuszko A, DiGiacomo JE, Pawlowski M, Schneiderman R, Delivoria-Papadopoulos M (1991) Effect of hyperventilation on oxygenation of the brain cortex of newborn piglets. J Appl Physiol 70:2691–2696

    CAS  PubMed  Google Scholar 

  70. Wilson DF, Gomi S, Pastuszko A, Greenberg JH (1993) Microvascular damage in the cortex of cat brain from middle cerebral artery occlusion and reperfusion. J Appl Physiol 74: 580–589

    CAS  PubMed  Google Scholar 

  71. Estrada AD, Ponticorvo A, Ford TN, Dunn AK (2008) Microvascular oxygen quantification using two-photon microscopy. Opt Lett 33:1038–1040

    CAS  PubMed  Google Scholar 

  72. Rumsey WL, Vanderkooi JM, Wilson DF (1988) Imaging of phosphorescence: a novel method for measuring oxygen distribution in perfused tissue. Science 241:1649–1651

    CAS  PubMed  Google Scholar 

  73. Vanderkooi JM, Maniara G, Green TJ, Wilson DF (1987) An optical method for measurement of dioxygen concentration based upon quenching of phosphorescence. J Biol Chem 262:5476–5482

    CAS  PubMed  Google Scholar 

  74. Lebedev AY, Cheprakov AV, Sakadzic S, Boas DA, Wilson DF, Vinogradov SA (2009) Dendritic phosphorescent probes for oxygen imaging in biological systems. ACS Appl Mater Interfaces 1:1292–1304

    CAS  PubMed Central  PubMed  Google Scholar 

  75. Vinogradov SA, Wilson DF (2011) Porphyrin-dendrimers as biological oxygen sensors. In: Campagna S, Ceroni P, Puntoriero F (eds) Designing dendrimers. Wiley, New York

    Google Scholar 

  76. Vinogradov SA, Wilson DF (1995) Metallotetrabenzoporphyrins. New phosphorescent probes for oxygen measurements. J Chem Soc Perkin Trans 2:103–111

    Google Scholar 

  77. Vinogradov SA, Lo LW, Wilson DF (1999) Dendritic polyglutamic porphyrins: probing porphyrin protection by oxygen-dependent quenching of phosphorescence. Chem Eur J 5:1338–1347

    CAS  Google Scholar 

  78. Rietveld IB, Kim E, Vinogradov SA (2003) Dendrimers with tetrabenzoporphyrin cores: near infrared phosphors for in vivo oxygen imaging. Tetrahedron 59:3821–3831

    CAS  Google Scholar 

  79. Dunphy I, Vinogradov SA, Wilson DF (2002) Oxyphor R2 and G2: phosphors for measuring oxygen by oxygen-dependent quenching of phosphorescence. Anal Biochem 310: 191–198

    CAS  PubMed  Google Scholar 

  80. Lebedev AY, Troxler T, Vinogradov SA (2008) Design of metalloporphyrin-based dendritic nanoprobes for two-photon microscopy of oxygen. J Porphyr Phthalocyanines 12:1261–1269

    CAS  PubMed Central  PubMed  Google Scholar 

  81. Finikova OS, Lebedev AY, Aprelev A, Troxler T, Gao F, Garnacho C, Muro S, Hochstrasser RM, Vinogradov SA (2008) Oxygen microscopy by two-photon-excited phosphorescence. Chemphyschem 9:1673–1679

    CAS  PubMed Central  PubMed  Google Scholar 

  82. Sakadzic S, Roussakis E, Yaseen MA, Srinivasan VJ, Mandeville ET, Devor A, Lo EH, Vinogradov SA, Boas DA (2010) Two-photon high-resolution 3D imaging of partial pressure of oxygen in cerebral vasculature and tissue. Nat Methods 7:755–759

    CAS  PubMed Central  PubMed  Google Scholar 

  83. Lecoq J, Parpaleix A, Roussakis E, Ducros M, Houssen YG, Vinogradov SA, Charpak S (2011) Simultaneous two-photon imaging of oxygen and blood flow in deep cerebral vessels. Nat Med 17:893–898

    CAS  PubMed Central  PubMed  Google Scholar 

  84. Devor A, Sakadzic S, Saisan PA, Yaseen MA, Roussakis E, Srinivasan VJ, Vinogradov SA, Rosen BR, Buxton RB, Dale AM, Boas DA (2011) “Overshoot” of O2 is required to maintain baseline tissue oxygenation at locations distal to blood vessels. J Neurosci 31: 13676–13681

    CAS  PubMed Central  PubMed  Google Scholar 

  85. Tootell RB, Silverman MS, De Valois RL, Jacobs GH (1983) Functional organization of the second cortical visual area in primates. Science 220:737–739

    CAS  PubMed  Google Scholar 

  86. Weber B, Keller AL, Reichold J, Logothetis NK (2008) The microvascular system of the striate and extrastriate visual cortex of the macaque. Cereb Cortex 18:2318–2330

    PubMed  Google Scholar 

  87. Keller AL, Schuz A, Logothetis NK, Weber B (2011) Vascularization of cytochrome oxidase-rich blobs in the primary visual cortex of squirrel and macaque monkeys. J Neurosci 31: 1246–1253

    CAS  PubMed  Google Scholar 

  88. Fatt I (1976) Polarographic oxygen sensors. CRC Press, Cleveland

    Google Scholar 

  89. Thompson JK, Peterson MR, Freeman RD (2003) Single-neuron activity and tissue oxygenation in the cerebral cortex. Science 299: 1070–1072

    CAS  PubMed  Google Scholar 

  90. Viswanathan A, Freeman RD (2007) Neurometabolic coupling in cerebral cortex reflects synaptic more than spiking activity. Nat Neurosci 10:1308–1312

    CAS  PubMed  Google Scholar 

  91. Offenhauser N, Thomsen K, Caesar K, Lauritzen M (2005) Activity-induced tissue oxygenation changes in rat cerebellar cortex: interplay of postsynaptic activation and blood flow. J Physiol 565:279–294

    CAS  PubMed  Google Scholar 

  92. Erecinska M, Silver IA (2001) Tissue oxygen tension and brain sensitivity to hypoxia. Respir Physiol 128:263–276

    CAS  PubMed  Google Scholar 

  93. Masamoto K, Takizawa N, Kobayashi H, Oka K, Tanishita K (2003) Dual responses of tissue partial pressure of oxygen after functional stimulation in rat somatosensory cortex. Brain Res 979:104–113

    CAS  PubMed  Google Scholar 

  94. Sharan M, Vovenko EP, Vadapalli A, Popel AS, Pittman RN (2008) Experimental and theoretical studies of oxygen gradients in rat pial microvessels. J Cereb Blood Flow Metab 28:1597–1604

    PubMed Central  PubMed  Google Scholar 

  95. Vazquez AL, Fukuda M, Tasker ML, Masamoto K, Kim SG (2010) Changes in cerebral arterial, tissue and venous oxygenation with evoked neural stimulation: implications for hemoglobin-based functional neuroimaging. J Cereb Blood Flow Metab 30: 428–439

    CAS  PubMed  Google Scholar 

  96. Vovenko E (1999) Distribution of oxygen tension on the surface of arterioles, capillaries and venules of brain cortex and in tissue in normoxia: an experimental study on rats. Pflugers Arch 437:617–623

    CAS  PubMed  Google Scholar 

  97. Koch CJ (2002) Measurement of absolute oxygen levels in cells and tissues using oxygen sensors and 2-nitroimidazole EF5. Methods Enzymol 352:3–31

    CAS  PubMed  Google Scholar 

  98. Swartz HM, Clarkson RB (1998) The measurement of oxygen in vivo using EPR techniques. Phys Med Biol 43:1957–1975

    CAS  PubMed  Google Scholar 

  99. Ahmad R, Kuppusamy P (2010) Theory, instrumentation, and applications of electron paramagnetic resonance oximetry. Chem Rev 110:3212–3236

    CAS  PubMed Central  PubMed  Google Scholar 

  100. Wang LV (2009) Multiscale photoacoustic microscopy and computed tomography. Nat Photonics 3:503–509

    CAS  PubMed Central  PubMed  Google Scholar 

  101. Fu D, Matthews TE, Ye T, Piletic IR, Warren WS (2008) Label-free in vivo optical imaging of microvasculature and oxygenation level. J Biomed Opt 13:040503

    PubMed  Google Scholar 

  102. Ashkenazi S, Huang SW, Horvath T, Koo YE, Kopelman R (2008) Photoacoustic probing of fluorophore excited state lifetime with application to oxygen sensing. J Biomed Opt 13:034023

    PubMed  Google Scholar 

  103. Geissbuehler M, Spielmann T, Formey A, Marki I, Leutenegger M, Hinz B, Johnsson K, Van De Ville D, Lasser T (2010) Triplet imaging of oxygen consumption during the contraction of a single smooth muscle cell (A7r5). Biophys J 98:339–349

    CAS  PubMed Central  PubMed  Google Scholar 

  104. Spielmann T, Blom H, Geissbuehler M, Lasser T, Widengren J (2010) Transient state monitoring by total internal reflection fluorescence microscopy. J Phys Chem B 114: 4035–4046

    CAS  PubMed  Google Scholar 

  105. Mik EG, van Leeuwen TG, Raat NJ, Ince C (2004) Quantitative determination of localized tissue oxygen concentration in vivo by two-photon excitation phosphorescence lifetime measurements. J Appl Physiol 97: 1962–1969

    PubMed  Google Scholar 

  106. Brinas RP, Troxler T, Hochstrasser RM, Vinogradov SA (2005) Phosphorescent oxygen sensor with dendritic protection and two-photon absorbing antenna. J Am Chem Soc 127:11851–11862

    CAS  PubMed Central  PubMed  Google Scholar 

  107. Srinivasan VJ, Sakadzic S, Gorczynska I, Ruvinskaya L, Wu W, Fujimoto JG, Boas DA (2010) Quantitative cerebral blood flow with optical coherence tomography. Opt Express 18:2477–2494

    CAS  PubMed  Google Scholar 

  108. Srinivasan VJ, Sakadzic S, Gorczynska I, Ruvinskaya S, Wu W, Fujimoto JG, Boas DA (2009) Depth-resolved microscopy of cortical hemodynamics with optical coherence tomography. Opt Lett 34:3086–3088

    PubMed Central  PubMed  Google Scholar 

  109. Deneux T, Faugeras O, Takerkart S, Masson G, Vanzetta I (2011) A new variational method for erythrocyte velocity estimation in wide-field imaging in-vivo. IEEE Trans Med Imaging 30:1527–1545

    PubMed  Google Scholar 

  110. Turner DA, Foster KA, Galeffi F, Somjen GG (2007) Differences in O2 availability resolve the apparent discrepancies in metabolic intrinsic optical signals in vivo and in vitro. Trends Neurosci 30:390–398

    CAS  PubMed Central  PubMed  Google Scholar 

  111. Nemoto M, Nomura Y, Sato C, Tamura M, Houkin K, Koyanagi I, Abe H (1999) Analysis of optical signals evoked by peripheral nerve stimulation in rat somatosensory cortex: dynamic changes in hemoglobin concentration and oxygenation. J Cereb Blood Flow Metab 19:246–259

    CAS  PubMed  Google Scholar 

  112. Narayan SM, Esfahani P, Blood AJ, Sikkens L, Toga AW (1995) Functional increases in cerebral blood volume over somatosensory cortex. J Cereb Blood Flow Metab 15: 754–765

    CAS  PubMed  Google Scholar 

  113. Narayan SM, Santori EM, Blood AJ, Burton JS, Toga AW (1994) Imaging optical reflectance in rodent barrel and forelimb sensory cortex. Neuroimage 1:181–190

    CAS  PubMed  Google Scholar 

  114. Grinvald A (1992) Optical imaging of architecture and function in the living brain sheds new light on cortical mechanisms underlying visual perception. Brain Topogr 5: 71–75

    CAS  PubMed  Google Scholar 

  115. Huang D, Swanson EA, Lin CP, Schuman JS, Stinson WG, Chang W, Hee MR, Flotte T, Gregory K, Puliafito CA et al (1991) Optical coherence tomography. Science 254: 1178–1181

    CAS  PubMed  Google Scholar 

  116. Wojtkowski M, Bajraszewski T, Targowski P, Kowalczyk A (2003) Real-time in vivo imaging by high-speed spectral optical coherence tomography. Opt Lett 28:1745–1747

    CAS  PubMed  Google Scholar 

  117. Harbig K, Chance B, Kovach AG, Reivich M (1976) In vivo measurement of pyridine nucleotide fluorescence from cat brain cortex. J Appl Physiol 41:480–488

    CAS  PubMed  Google Scholar 

  118. Lothman E, Lamanna J, Cordingley G, Rosenthal M, Somjen G (1975) Responses of electrical potential, potassium levels, and oxidative metabolic activity of the cerebral neocortex of cats. Brain Res 88:15–36

    CAS  PubMed  Google Scholar 

  119. Mayevsky A (1984) Brain NADH redox state monitored in vivo by fiber optic surface fluorometry. Brain Res 319:49–68

    CAS  PubMed  Google Scholar 

  120. Baraghis E, Devor A, Fang Q, Srinivasan VJ, Yaseen MA, Wu W, Lesage F, Ayata C, Kasischke KA, Boas DA, Sakadzic S (2011) Two-photon microscopy of cortical NADH fluorescence intensity changes: correcting contamination from the hemodynamic response. J Biomed Opt 16:106003

    PubMed  Google Scholar 

  121. Kramer RS, Pearlstein RD (1979) Cerebral cortical microfluorometry at isosbestic wavelengths for correction of vascular artifact. Science 205:693–696

    CAS  PubMed  Google Scholar 

  122. Boas DA, Jones SR, Devor A, Huppert TJ, Dale AM (2008) A vascular anatomical network model of the spatio-temporal response to brain activation. Neuroimage 40:1116–1129

    PubMed Central  PubMed  Google Scholar 

  123. Devor A, Ulbert I, Dunn AK, Narayanan SN, Jones SR, Andermann ML, Boas DA, Dale AM (2005) Coupling of the cortical hemodynamic response to cortical and thalamic neuronal activity. Proc Natl Acad Sci USA 102: 3822–3827

    CAS  PubMed  Google Scholar 

  124. Hillman EM (2007) Optical brain imaging in vivo: techniques and applications from animal to man. J Biomed Opt 12:051402

    PubMed Central  PubMed  Google Scholar 

  125. Berwick J, Johnston D, Jones M, Martindale J, Martin C, Kennerley AJ, Redgrave P, Mayhew JE (2008) Fine detail of neurovascular coupling revealed by spatiotemporal analysis of the hemodynamic response to single whisker stimulation in rat barrel cortex. J Neurophysiol 99:787–798

    CAS  PubMed  Google Scholar 

  126. Devor A, Hillman EM, Tian P, Waeber C, Teng IC, Ruvinskaya L, Shalinsky MH, Zhu H, Haslinger RH, Narayanan SN, Ulbert I, Dunn AK, Lo EH, Rosen BR, Dale AM, Kleinfeld D, Boas DA (2008) Stimulus-induced changes in blood flow and 2-deoxyglucose uptake dissociate in ipsilateral somatosensory cortex. J Neurosci 28:14347–14357

    CAS  PubMed Central  PubMed  Google Scholar 

  127. Devor A, Tian P, Nishimura N, Teng IC, Hillman EM, Narayanan SN, Ulbert I, Boas DA, Kleinfeld D, Dale AM (2007) Suppressed neuronal activity and concurrent arteriolar vasoconstriction may explain negative blood oxygenation level-dependent signal. J Neurosci 27:4452–4459

    CAS  PubMed Central  PubMed  Google Scholar 

  128. Bouchard MB, Chen BR, Burgess SA, Hillman EM (2009) Ultra-fast multispectral optical imaging of cortical oxygenation, blood flow, and intracellular calcium dynamics. Opt Express 17:15670–15678

    CAS  PubMed Central  PubMed  Google Scholar 

  129. Calcinaghi N, Jolivet R, Wyss MT, Ametamey SM, Gasparini F, Buck A, Weber B (2011) Metabotropic glutamate receptor mGluR5 is not involved in the early hemodynamic response. J Cereb Blood Flow Metab 31: e1–e10

    CAS  PubMed  Google Scholar 

  130. Jones PB, Shin HK, Boas DA, Hyman BT, Moskowitz MA, Ayata C, Dunn AK (2008) Simultaneous multispectral reflectance imaging and laser speckle flowmetry of cerebral blood flow and oxygen metabolism in focal cerebral ischemia. J Biomed Opt 13:044007

    PubMed Central  PubMed  Google Scholar 

  131. Polimeni JR, Granquist-Fraser D, Wood RJ, Schwartz EL (2005) Physical limits to spatial resolution of optical recording: clarifying the spatial structure of cortical hypercolumns. Proc Natl Acad Sci USA 102:4158–4163

    CAS  PubMed  Google Scholar 

  132. Tian P, Teng IC, May LD, Kurz R, Lu K, Scadeng M, Hillman EM, De Crespigny AJ, D’Arceuil HE, Mandeville JB, Marota JJ, Rosen BR, Liu TT, Boas DA, Buxton RB, Dale AM, Devor A (2010) Cortical depth-specific microvascular dilation underlies laminar differences in blood oxygenation level-dependent functional MRI signal. Proc Natl Acad Sci USA 107:15246–15251

    CAS  PubMed  Google Scholar 

  133. Boas D, Culver J, Stott J, Dunn A (2002) Three dimensional Monte Carlo code for photon migration through complex heterogeneous media including the adult human head. Opt Express 10:159–170

    PubMed  Google Scholar 

  134. Tian P, Devor A, Sakadzic S, Dale AM, Boas DA (2010) Monte Carlo simulation of the spatial resolution and depth sensitivity of two-dimensional optical imaging of the brain. J Biomed Opt 16:016006

    Google Scholar 

  135. Wilson BC, Adam G (1983) A Monte Carlo model for the absorption and flux distributions of light in tissue. Med Phys 10:24–830

    Google Scholar 

  136. Chen BR, Bouchard MB, McCaslin AF, Burgess SA, Hillman EM (2011) High-speed vascular dynamics of the hemodynamic response. Neuroimage 54:1021–1030

    PubMed Central  PubMed  Google Scholar 

  137. Tian P, Teng IC, Dunn AK, Boas DA, Dale AM, Devor A (2007) Hemodynamic augmentation in response to a paired whisker stimulus as a function of cortical distance. In: Program No. 87.6. Neuroscience 2007 abstracts, Society for Neuroscience, San Diego. Online

    Google Scholar 

  138. Vinogradov SA, Lo LW, Jenkins WT, Evans SM, Koch C, Wilson DF (1996) Noninvasive imaging of the distribution in oxygen in tissue in vivo using near-infrared phosphors. Biophys J 70:1609–1617

    CAS  PubMed Central  PubMed  Google Scholar 

  139. Sakadzic S, Yuan S, Dilekoz E, Ruvinskaya S, Vinogradov SA, Ayata C, Boas DA (2009) Simultaneous imaging of cerebral partial pressure of oxygen and blood flow during functional activation and cortical spreading depression. Appl Opt 48:D169–D177

    CAS  PubMed Central  PubMed  Google Scholar 

  140. Apreleva SV, Wilson DF, Vinogradov SA (2006) Tomographic imaging of oxygen by phosphorescence lifetime. Appl Opt 45:8547–8559

    CAS  PubMed Central  PubMed  Google Scholar 

  141. Golub AS, Barker MC, Pittman RN (2007) PO2 profiles near arterioles and tissue oxygen consumption in rat mesentery. Am J Physiol Heart Circ Physiol 293:H1097–H1106

    CAS  PubMed  Google Scholar 

  142. Golub AS, Pittman RN (2008) PO2 measurements in the microcirculation using phosphorescence quenching microscopy at high magnification. Am J Physiol Heart Circ Physiol 294:H2905–H2916

    CAS  PubMed  Google Scholar 

  143. Yaseen MA, Srinivasan VJ, Sakadzic S, Wu W, Ruvinskaya S, Vinogradov SA, Boas DA (2009) Optical monitoring of oxygen tension in cortical microvessels with confocal microscopy. Opt Express 17:22341–22350

    CAS  PubMed Central  PubMed  Google Scholar 

  144. Wilson DF, Vinogradov SA, Grosul P, Vaccarezza MN, Kuroki A, Bennett J (2005) Oxygen distribution and vascular injury in the mouse eye measured by phosphorescence-lifetime imaging. Appl Opt 44:5239–5248

    CAS  PubMed Central  PubMed  Google Scholar 

  145. Shonat RD, Kight AC (2003) Oxygen tension imaging in the mouse retina. Ann Biomed Eng 31:1084–1096

    PubMed  Google Scholar 

  146. Shonat RD, Wilson DF, Riva CE, Pawlowski M (1992) Oxygen distribution in the retinal and choroidal vessels of the cat as measured by a new phosphorescence imaging method. Appl Opt 31:3711–3718

    CAS  PubMed  Google Scholar 

  147. Ponticorvo A, Dunn AK (2010) Simultaneous imaging of oxygen tension and blood flow in animals using a digital micromirror device. Opt Express 18:8160–8170

    CAS  PubMed  Google Scholar 

  148. Sinks LE, Robbins GP, Roussakis E, Troxler T, Hammer DA, Vinogradov SA (2010) Two-photon microscopy of oxygen: polymersomes as probe carrier vehicles. J Phys Chem B 114:14373–14382

    CAS  PubMed Central  PubMed  Google Scholar 

  149. Garaschuk O, Milos RI, Konnerth A (2006) Targeted bulk-loading of fluorescent indicators for two-photon brain imaging in vivo. Nat Protoc 1:380–386

    CAS  PubMed  Google Scholar 

  150. Boorman L, Kennerley AJ, Johnston D, Jones M, Zheng Y, Redgrave P, Berwick J (2010) Negative blood oxygen level dependence in the rat: a model for investigating the role of suppression in neurovascular coupling. J Neurosci 30:4285–4294

    CAS  PubMed  Google Scholar 

  151. Kennerley AJ, Berwick J, Martindale J, Johnston D, Papadakis N, Mayhew JE (2005) Concurrent fMRI and optical measures for the investigation of the hemodynamic response function. Magn Reson Med 54:354–365

    PubMed  Google Scholar 

  152. Stosiek C, Garaschuk O, Holthoff K, Konnerth A (2003) In vivo two-photon calcium imaging of neuronal networks. Proc Natl Acad Sci USA 100:7319–7324

    CAS  PubMed  Google Scholar 

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Acknowledgements

We gratefully acknowledge support from the NINDS (NS051188 and NS057198 to A.D., NS057476 and NS055104 to D.A.B.), NIBIB (EB00790 to A.M.D., EB009118 to A.D., EB2066 to B.R.R., EB007279 to S.A.V.), American Heart Association Grant No. 11SDG7600037 to S.S., and NIH SIG S10-RR022428 to D.A.B.

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Devor, A. et al. (2014). Functional Imaging of Cerebral Oxygenation with Intrinsic Optical Contrast and Phosphorescent Probes. In: Weber, B., Helmchen, F. (eds) Optical Imaging of Neocortical Dynamics. Neuromethods, vol 85. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-785-3_14

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