Functional Neuroimaging

Optical Approaches
  • Arno Villringer
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 413)


Optical methods assess different types of light tissue interactions such as light absorption, fluorescence, phosphoresence, scattering, and Doppler shift. In this article, it is reviewed how these different types of light-tissue interactions can be measured and how these measurements can be related to brain function. Based on these considerations, a new classification scheme of functional optical methods is proposed.


Cerebral Blood Flow Laser Doppler Flowmetry Cereb Blood Flow Optical Intrinsic Signal Functional Brain Activation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. Adams S.R., Harootunian A.T., Buechler Y.J., Taylor S.S., Tsien R.Y. (1991) Fluorescence ratio imaging of cyclic AMP in single cells. Nature, 349, 694–697.ADSCrossRefGoogle Scholar
  2. Albowitz B., Kuhnt U. (1995) Epileptiform activity in the guinea pig neocortical slice spreads preferentially along supragranular layers: recordings with voltage sensitive dyes European Journal of Neuroscience, 7, 1273–1284.CrossRefGoogle Scholar
  3. Bandettini P.A., Wong E.C., Hinks R.S., Tikofsky R.S., Hyde J.S. (1992). Time course EPI of human brain function during task activation. Magn Reson Med 25:390–7.CrossRefGoogle Scholar
  4. Bandettini et al. (1995). Proc. 3rd SMR-meeting 453.Google Scholar
  5. Bird G.S., Rossier M.F., Hughes A.R., Shears S.B., Armstrong D.L., Putney J.W.J. (1991) Activation of Ca2+ entry into acinar cells by a non-phosphorylatable inositol trisphosphate [see comments]. Nature, 352, 162–165.ADSCrossRefGoogle Scholar
  6. Bonner R., Nossal R. (1981) A model for laser Doppler measurements of blood flow in tissue. Applied Optics, 20, 2097–2107.ADSCrossRefGoogle Scholar
  7. Brocard J.B., Rajdev S., Reynolds I.J. (1993) Glutamate-induced increases in intracellular free Mg2+ in cultured cortical neurons. Neuron, 11, 751–757.CrossRefGoogle Scholar
  8. Chance B., Graham N., Mayer D. (1971). A time sharing fluorometer for the readout of intracellular oxidation-reduction states of NADH and flavoprotein. Rev Sci Instrum 42:951–7.ADSCrossRefGoogle Scholar
  9. Chance B., Cohen P., Jobsis F., Schoener B. (1962) Intracellular oxidation-reduction states in vivo. Science, 137, 499–508.ADSCrossRefGoogle Scholar
  10. Chance B., Zhuang Z., Unah C, Alter C, Lipton L. (1993) Cognition-activated low-frequency modulation of light absorption in human brain. Proc Natl Acad Sci USA, 90, 3770–3774.ADSCrossRefGoogle Scholar
  11. Cohen L.B., Keynes R.D. (1971). Changes in light scattering associated with the action potential in crab nerves. J Physiol 212:259–275.Google Scholar
  12. Cooper C.E., Matcher S.J., Wyatt J.S., Cope M., Brown G.C. (1994). Near-infrared spectroscopy of the brain: relevance to cytochrome oxidase bioenergetics. Biochem Soc Trans 22:974–980.Google Scholar
  13. Cooper C.E., Elwell C.E, Meek J.H., Matcher S.J., Wyatt J.S., Cope M., et al. (1996) The noninvasive measurement of absolute cerebral deoxyhemoglobin concentration and mean optical path length in the neonatal brain by second derivative near infrared spectroscopy. Pediatr Res, 39, 32–38.CrossRefGoogle Scholar
  14. Cooper R., Crow H.J., Walter W.G., Winter A.L.(1965). Variations of occipital blood flow, oxygen availability and the EEG during reading and flicker in man. Electroencephalogr Clin Neurophysiol. 19:315.Google Scholar
  15. Cope M., Delpy D.T. (1988) System for long-term measurement of cerebral blood and tissue oxygenation on newborn infants by near infra-red transillumination. Med Biol Eng Comput, 26, 289–294.CrossRefGoogle Scholar
  16. Cope M., Delpy D.T., Wray S., Wyatt J.S., Reynolds E.O. (1989) A CCD spectrophotometer to quantitate the concentration of chromophores in living tissue utilising the absorption peak of water at 975 nm. Adv Exp Med Biol, 248, 33–40.CrossRefGoogle Scholar
  17. Dalkara T., Irikura K., Huang Z., Panahian N., Moskowitz M.A. (1995). Cerebrovascular responses under controlled and monitored physiological conditions in the anesthetized mouse. J Cereb Blood Flow Metab. 15:631–8.CrossRefGoogle Scholar
  18. Dirnagl U., Kaplan B., Jacewicz M., Pulsinelll W. (1989) Continuous measurement of cerebral cortical blood flow by laser-Dopplerflowmetry in a rat stroke model. J Cereb Blood Flow Metab, 9, 589–596.CrossRefGoogle Scholar
  19. Duncan A., Meek J.H., Clemence M., Elwell C.E., Tyszczuk L, Cope M., et al. (1995) Optical pathlength measurements on adult head, calf and forearm and the head of the newborn infant using phase resolved optical spectroscopy. Phys Med Biol, 40, 295–304.CrossRefGoogle Scholar
  20. Eke A. (1982) Reflectometric mapping of microregional blood flow and blood volume in the brain cortex. J Cereb Blood Flow Metab, 2, 41–53.CrossRefGoogle Scholar
  21. Elwell C.E., Cope M., Edwards A.D., Wyatt J.S., Delpy D.T., Reynolds E.O. (1994) Quantification of adult cerebral hemodynamics by near-infrared spectroscopy. J Appl Physiol, 77, 2753–2760.Google Scholar
  22. Fast V.G., Kleber A.G. (1994) Anisotropie conduction in monolayers of neonatal rat heart cells cultured on collagen substrate. Circ Res, 75, 591–595.CrossRefGoogle Scholar
  23. Fast V.G., Kleber A.G. (1995) Cardiac tissue geometry as a determinant of unidirectional conduction block: assessment of microscopic excitation spread by optical mapping in patterned cell cultures and in a computer model. Cardiovasc Res, 29, 697–707.Google Scholar
  24. Fox P.T., Raichle M.E. (1986) Focal physiological uncoupling of cerebral blood flow and oxidative metabolism during somatosensory stimulation in human subjects. Proc Natl Acad Sci 83:1140–1144.ADSCrossRefGoogle Scholar
  25. Fox P.T., Raichle M.E., Mintun M.A., Dence C. (1988). Nonoxidative glucose consumption during focal physiologic neural activity. Science 1988:241:462–4.ADSCrossRefGoogle Scholar
  26. Frahm J., Bruhn H., Merboldt K.D., Hänicke W. (1992). Dynamic MRI of human brain oxygenation. J Magn Res Imag 2:501–50.CrossRefGoogle Scholar
  27. Gratton G., Fabiani M., Friedman D., Franceschini M.A., Fantini S., Corballis P., et al. (1995) Rapid changes of optical parameters in the human brain during a tapping task. J Cogn Neurosci, 7, 446–456.CrossRefGoogle Scholar
  28. Grinvald A., Anglister L., Freeman J.A., Hildesheim R., Manker A. (1984). Real-time optical imaging of naturally evoked electrical activity in intact frog brain. Nature 308:848–50.ADSCrossRefGoogle Scholar
  29. Grinvald A., Frostig R.D., Siegel R.M., Bartfei D.E. (1991) High-resolution optical imaging of functional brain architecture in the awake monkey. Proc Natl Acad Sci USA, 88, 11559–11563.ADSCrossRefGoogle Scholar
  30. Grinvald A., Lieke E., Frostig R.D., Gilbert CD., Wiesel T.N. (1986) Functional architecture of cortex revealed by optical imaging of intrinsic signals. Nature, 324, 361–364.ADSCrossRefGoogle Scholar
  31. Haberl R.L., Heizer M.L., Marmarou A., Ellis E.F. (1989) Laser-Doppler assessment of brain microcirculation: effect of systemic alterations. AmJ Physiol, 256, H1247–H1254.Google Scholar
  32. Haglund M.M., Ojemann G.A., Hochman D.W. (1992). Optical imaging of epileptiform and functional activity in human cerebral cortex. Nature 358:668–71.ADSCrossRefGoogle Scholar
  33. Hampson N.B.; Piantadosi C.A. (1990). Near-infrared optical responses in feline brain and skeletal muscle tissues during respiratory acid-base imbalance. Brain-Res. 519:249–54.CrossRefGoogle Scholar
  34. Hill D.K. and Keynes R.D. (1949). Opacity changes in stimulated nerve. J. Physiol 108:278–281.Google Scholar
  35. Hoshi Y., Tamura M. (1993a). Detection of dynamic changes in cerebral oxygenation coupled to neuronal function during mental work in man. Neurosci Lett 150:5–8.CrossRefGoogle Scholar
  36. Hoshi Y., Tamura M. (1993b). Dynamic changes in cerebral oxygenation in chemically induced seizures in rats: study by near-infrared spectrophotometry. Brain Res 603:215–21.CrossRefGoogle Scholar
  37. Jobsis F.F. (1977) Noninvasive, infrared monitoring of cerebral and myocardial oxygen sufficiency and circulatory parameters. Science, 198, 1264–1267.ADSCrossRefGoogle Scholar
  38. Kato T., Kamei A., Takashima S., Ozaki T. (1993). Human visual cortical function during photic stimulation monitoring by means of near-infrared spectroscopy. J Cereb Blood Flow Metab 13:516–20.CrossRefGoogle Scholar
  39. Kauer J.S. (1988). Real-time imaging of evoked activity in local circuits of the salamander olfactory bulb. Nature 331:166–8.ADSCrossRefGoogle Scholar
  40. Kruger G., Kleinschmidt A., Frahm J. (1996). Dynamic MRI sensitized to cerebral blood oxygenation and flow during sustained activation of human visual cortex. Magn Reson Med. 35:797–800.CrossRefGoogle Scholar
  41. Kwong K.K., Belliveau J.W., Chesler D.A., Goldberg I.E., Weisskoff R.M., Poncelet B.P., Kennedy D.N., Hoppel B.E., Cohen M.S., Turner R., Hong-Ming C, Brady T.J., Rosen B.R. (1992). Dynamic magnetic resonance imaging of human brain activity during primary sensory stimulation. Proc Natl Acad Sci 89:5675–5679.ADSCrossRefGoogle Scholar
  42. Lauritzen M., Fabricius M. (1995). Real time laser-Doppler perfusion imaging of cortical spreading depression in rat neocortex. Neuroreport 6:1271–3.CrossRefGoogle Scholar
  43. Lindauer U., Villringer A., Dirnagl U. (1993). Characterization of the cerebral blood flow response to somatosensory stimulation: the model and the influence of anesthetics. Am J Physiol 264:H1223–1228.Google Scholar
  44. Lipton P. (1973). Effects of membrane depolarization on light scattering by cerebral cortical slices. J Physiol 231:365–383.Google Scholar
  45. Macvicar B. A., Hochman D. (1991) Imaging of synaptically evoked intrinsic optical signals in hippocampal slices. J Neurosci, 11, 1458–1469.Google Scholar
  46. Malonek D., Grinvald A. (1996) Interactions between electrical acitivity and cortical microcirculation revealed by imaging spectroscopy: implications for functional brain mapping. Science 272:551–554.ADSCrossRefGoogle Scholar
  47. Masino S.A., Kwon M.C., Dory Y, Frostig R.D. (1993). Characterization of functional organization within rat barrel cortex using intrinsic signal optical imaging through a thinned skull. Proc Natl Acad Sei: 90:9998–10002.ADSCrossRefGoogle Scholar
  48. Masters B.R., Falk S., Chance B. (1981) In vivo flavoprotein redox measurements of rabbit corneal normoxic-anoxic transitions. Curr Eye Res, 1, 623–627.CrossRefGoogle Scholar
  49. Matcher S.J., Cooper C.E. (1994) Absolute Quantification of Deoxyhaemoglobin Concentration in Tissue Near Infrared Spectroscopy. Phys Med Biol, 39, 1295–1312.CrossRefGoogle Scholar
  50. Matcher S.J., Cope M., Delpy D.T. (1994) Use of the Water Absorption Spectrum to Quantify Tissue Chromophore Concentration Changes in Near-Infrared Spectroscopy. Phys Med Biol, 39, 177–196.CrossRefGoogle Scholar
  51. Mayevsky A., Chance B. (1982) Intracellular oxidation-reduction state measured in situ by a multichannel fiberoptic surface fluorometer. Science, 217, 537–540.ADSCrossRefGoogle Scholar
  52. Meglinsky I.V., Boas D.A., Yodh G., Chance B. (1996). In vivo measurements of blood flow changes using diffusing wave correlation techniques. In OS A Proceedings 1996.Google Scholar
  53. Menon R.S., Ogawa S., Hu X., Strupp J.P., Anderson R, UgurbiL K. (1995). BOLD based functional MRI at 4 Tesla includes a capillary bed contribution: echo-planar imaging correlates with previous optical imaging using intrinsic signals. Magn Reson Med 33:453–9.CrossRefGoogle Scholar
  54. Narayan S.M., Santori E.M., Toga A.W. (1994) Mapping functional activity in rodent cortex using optical intrin-sicsignals. Cereb Cortex, 4, 195–204.CrossRefGoogle Scholar
  55. Nelson D.A., Katz L.C. (1995) Emergence of functional circuits in ferret visual cortex visualized by optical imaging. Neuron, 15, 23–34.CrossRefGoogle Scholar
  56. Ngai AC, Meno JR, Winn HR (1995). Simultaneous measurements of pial arteriolar diameter and laser-Doppler flow during somatosensory stimulation. J Cereb Blood Flow Metab 15:124–127.CrossRefGoogle Scholar
  57. Obaid A.L., Flores R., Salzberg B.M. (1989). Calcium channels that are required for secretion from intact nerve terminals of vertebrates are sensitive to w-conotoxoin and relatively insensitive to dihydropyridines. J Gen Physiol 93:715–729.CrossRefGoogle Scholar
  58. Obrig H., Villringer A. (1996) What is the typical NIRS-response to functional brain activation?. Adv Exp Med Biol, in press.Google Scholar
  59. Oeberg P.A., Tenland T., Nilsson G.E. (1984) Laser-Doppler flowmetry — a noninvasive and continuous method for blood flow evaluation in microvascular studies. Acta Med Scand, 687 suppl., 17-24.Google Scholar
  60. Ogawa S., Tank D.W., Menon R., Eilermann J.M., Kim S.G., Merkle H., Ugurbil K. (1992). Intrinsic signal changes accompanying sensory stimulation: functional brain mapping with magnetic resonance imaging. Proc-Natl-Acad-Sci (1992) 89:5951–5.ADSCrossRefGoogle Scholar
  61. Olano M., Song D., Murphy S., Wilson D.F., Pastuszko A. (1995) Relationships of dopamine, cortical oxygen pressure, and hydroxyl radicals in brain of newborn piglets during hypoxia and posthypoxic recovery. J Neurochem, 65, 1205–1212.CrossRefGoogle Scholar
  62. Paradiso A.M., Tsien R.Y., Machen T.E. (1987) Digital image processing of intracellular pH in gastric oxyntic and chief cells. Nature, 325, 447–450.ADSCrossRefGoogle Scholar
  63. Renault G., Raynal E., Sinet M., Muffat-Joly M., Berthier J-P, Cornillault J., et al. (1984) In situ double-beam NADH laser fluorimetry: choice of a reference wavelength. Am J Physiol, 246, H491–H499.Google Scholar
  64. Rumsey Wl., Vanderkooi J.M., Wilson D.F. (1988) Imaging of phosphorescence: a novel method for measuring oxygen distribution in perfused tissue. Science, 241, 1649–1651.ADSCrossRefGoogle Scholar
  65. Salzberg B.M., Obaid A.L., Gainer H. (1985). Large and rapid changes in light scattering accompany secretion by nerve terminals in the mammalian neurohypophysis. J Gen Physiol 86:887–908.CrossRefGoogle Scholar
  66. Seitz R.J., Roland P.E. (1992). Vibratory stimulation increases and decreases the regional cerebral blood flow and oxidative metabolism: a positron emission tomography (PET) study. Acta Neurol Scand 1992; 86:60–67.CrossRefGoogle Scholar
  67. Senseman D.M. (1996) High speed optical imaging of afferent flow through olfactory bulb slices: voltag sensitive dye signals reveal periglomerula cell activity. Journal of Neuroscience 16, 313–324.Google Scholar
  68. Sevick E.M., Chance B., Leigh J., Nioka S., Maris M. (1991) Quantitation of time-and frequency-resolved optical spectra for the determination of tissue oxygenation. Anal Biochem, 195, 330–351.CrossRefGoogle Scholar
  69. Shockley R.R, LaManna J.C. (1988). Determination of rat cerebral cortical blood volume changes by capillary mean transit time analysis during hypoxia, hypercapnia and hyperventilation. Brain Res 454:170–8.CrossRefGoogle Scholar
  70. Skarphedinsson J.O., Harding H., Thoren P. (1988) Repeated measurements of cerebral blood flow in rats. Comparisons between the hydrogen clearance method and laser Doppler flowmetry. Acta Physiol Scand, 134, 133–142.CrossRefGoogle Scholar
  71. Snow R.W., Taylor C.P., Dudek F.E. (1983). Electrophysiological and optical changes in slices or rat hippocampus during spreading depression. J Neurophysiol 50:561–672.Google Scholar
  72. Song D., Olano M., Wilson D.F., Pastuszko A., Tammela O., Nho K., et al. (1995) Comparison of the efficacy of blood and polyethylene glycol-hemoglobin in recovery of newborn piglets from hemorrhagic hypotension: effect on blood pressure, cortical oxygen, and extracellular dopamine in the brain. Transfusion, 35, 552–558.CrossRefGoogle Scholar
  73. Stern M.D. (1975) In vivo evaluation of microcirculation by coherent light scattering. Nature, 254, 56–58.ADSCrossRefGoogle Scholar
  74. Stone H.B., Brown J.M., Phillips T.L., Sutherland R.M. (1993) Oxygen in human tumors: correlations between methods of measurement and response to therapy. Summary of a workshop held November 19–20, 1992, at the National Cancer Institute, Bethesda, Maryland. Radiat Res, 136, 422–434.CrossRefGoogle Scholar
  75. Them A. (1993) Intracellular ion concentrations in the brain: approaches towards in situ confocal imaging. Adv Exp Med Biol, 333, 145–175.CrossRefGoogle Scholar
  76. Tsubota K., Laing R.A., Kenyon K.R. (1987) Noninvasive measurements of pyridine nucleotide and flavoprotein in the lens. Invest Ophthalmol Vis Sci, 28, 785–789.Google Scholar
  77. Uematsu D., Greenberg J.H., Reivich M., Karp A. (1989). Cytosolic free calcium and NAD/NADH redox state in the cat cortex during in vivo activation of NMD A receptors. Brain Res 482:129–35.CrossRefGoogle Scholar
  78. Uematsu D., Araki N., Greenberg J.H., Reivich M. (1990). Alterations in cytosolic free calcium in the cat cortex during bicuculline-induced epilepsy. Brain Res Bull 1990 24:285–8.CrossRefGoogle Scholar
  79. Vanderkooi J.M., Maniara G., Green T.J., Wilson D.F. (1987) An optical method for measurement of dioxygen concentration based upon quenching of phosphorescence. J Biol Chem, 262, 5476–5482.Google Scholar
  80. Villringer A., Planck J., Hock C, Schleinkofer L., Dirnagl U. (1993) Near infrared spectroscopy (NIRS): a new tool to study hemodynamic changes during activation of brain function in human adults. Neurosci Lett, 154, 101–104.CrossRefGoogle Scholar
  81. Villringer A., Them A., Lindauer U., Einhaupl K., Dirnagl U. (1994) Capillary perfusion of the rat brain cortex. An in vivo confocal microscopy study. Circ Res, 75, 55–62.CrossRefGoogle Scholar
  82. Villringer A., Dirnagl U. (1995) Coupling of brain activity and cerebral blood flow: basis of functional neuroimaging. Cerebrovasc Brain Metab Rev, 7, 240–276.Google Scholar
  83. Wardell K., Jakobsson A., Nilsson G.E. (1993) Laser Doppler perfusion imaging by dynamic light scattering. IEEE Trans Biomed Eng, 40, 309–316.CrossRefGoogle Scholar
  84. Weisskoff R.M., Chesler D., Boxerman J.L., Rosen B.R. (1993) Pitfalls in MR measurement of tissue blood flow with intravascular tracers: which mean transit time?. Magn Reson Med, 29, 553–558.CrossRefGoogle Scholar
  85. Wilson D.F., Gomi S., Pastuszko A., Greenberg J.H. (1993). Microvascular damage in the cortex of cat brain from middle cerebral artery occlusion and reperfusion. J Appl Physiol 74:580–9.Google Scholar

Copyright information

© Springer Science+Business Media New York 1997

Authors and Affiliations

  • Arno Villringer
    • 1
  1. 1.Neurologische Klinik und Poliklinik, Medizinische Fakultät (Charité)Humboldt-Universität zu BerlinBerlinGermany

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