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Multi-Spectral Imaging of Blood Volume, Metabolism, Oximetry, and Light Scattering

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Neurovascular Coupling Methods

Part of the book series: Neuromethods ((NM,volume 88))

Abstract

Advances in functional imaging techniques including fMRI, PET, and SPECT have improved our understanding of the relationship between brain activity and brain energy supply. Neurovascular and neurometabolic coupling are critical to supply the energy demands of brain tissue during both normal physiological function and pathological conditions. With the use of multi-spectral imaging techniques, one can simultaneously measure changes in cerebral blood volume, oxyhemoglobin, deoxyhemoglobin, light scattering, and local metabolism during epilepsy.

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References

  1. Logothetis NK, Wandell BA (2004) Interpreting the BOLD signal. Annu Rev Physiol 66:735–769

    Article  CAS  PubMed  Google Scholar 

  2. Raichle ME, Mintun MA (2006) Brain work and brain imaging. Annu Rev Neurosci 29:449–476. doi:10.1146/annurev.neuro.29.051605.112819

    Article  CAS  PubMed  Google Scholar 

  3. Girouard H, Iadecola C (2006) Neurovascular coupling in the normal brain and in hypertension, stroke, and Alzheimer disease. J Appl Physiol 100(1):328–335. doi:10.1152/japplphysiol.00966.2005

    Article  CAS  PubMed  Google Scholar 

  4. Frostig RD, Lieke EE, Ts’o DY et al (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 87:6082–6086

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. 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

    Article  CAS  PubMed  Google Scholar 

  6. Sheth SA, Nemoto M, Guiou M et al (2004) Columnar specificity of microvascular oxygenation and volume responses: implications for functional brain mapping. J Neurosci 24(3): 634–641

    Article  CAS  PubMed  Google Scholar 

  7. Salzberg BM, Obaid AL, Gainer H (1985) Large and rapid changes in light scattering accompany secretion by nerve terminals in the mammalian neurohypophysis. J Gen Physiol 86(3):395–411

    Article  CAS  PubMed  Google Scholar 

  8. Obaid AL, Flores R, Salzberg BM (1989) Calcium channels that are required for secretion from intact nerve terminals of vertebrates are sensitive to omega-conotoxin and relatively insensitive to dihydropyridines. Optical studies with and without voltage-sensitive dyes. J Gen Physiol 93(4):715–729

    Article  CAS  PubMed  Google Scholar 

  9. MacVicar BA, Hochman D (1991) Imaging of synaptically evoked intrinsic optical signals in hippocampal slices. J Neurosci 11(5):1458–1469

    CAS  PubMed  Google Scholar 

  10. Alivisatos AP, Chun M, Church George M et al (2012) The brain activity map project and the challenge of functional connectomics. Neuron 74(6):970–974

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Hill DK, Keynes RD (1949) Opacity changes in stimulated nerve. J Physiol 108(3): 278–281

    PubMed Central  Google Scholar 

  12. Jobsis F (1977) Noninvasive, infrared monitoring of cerebral and myocardial oxygen sufficiency and circulatory parameters. Science 198(4323):1264–1267. doi:10.1126/science.929199

    Article  CAS  PubMed  Google Scholar 

  13. Chance B, Cohen P, Jobsis F et al (1962) Intracellular oxidation-reduction states in vivo: the microfluorometry of pyridine nucleotide gives a continuous measurement of the oxidation state. Science 137(3529):499–508. doi:10.1126/science.137.3529.499

    Article  CAS  PubMed  Google Scholar 

  14. Grinvald A (1985) Real-time optical mapping of neuronal activity: from single growth cones to the intact mammalian brain. Annu Rev Neurosci 8(1):263–305. doi:10.1146/annurev.ne.08.030185.001403

    Article  CAS  PubMed  Google Scholar 

  15. Grinvald A, Lieke E, Frostig RD et al (1986) Functional architecture of cortex revealed by optical imaging of intrinsic signals. Nature 324(6095):361–364

    Article  CAS  PubMed  Google Scholar 

  16. Bonhoeffer T, Grinvald A (1991) Iso-orientation domains in cat visual cortex are arranged in pinwheel-like patterns. Nature 353(6343):429–431

    Article  CAS  PubMed  Google Scholar 

  17. Schwartz TH, Bonhoeffer T (2001) In vivo optical mapping of epileptic foci and surround inhibition in ferret cerebral cortex. Nat Med 7(9):1063–1067

    Article  CAS  PubMed  Google Scholar 

  18. Schwartz TH, Chen LM, Friedman RM et al (2004) Intraoperative optical imaging of human face cortical topography: a case study. Neuroreport 15(9):1527–1531

    Article  PubMed  Google Scholar 

  19. Zepeda A, Arias C, Sengpiel F (2004) Optical imaging of intrinsic signals: recent developments in the methodology and its applications. J Neurosci Methods 136(1):1–21

    Article  PubMed  Google Scholar 

  20. Cohen LB (1973) Changes in neuron structure during action potential propagation and synaptic transmission. Physiol Rev 53(2):373–418

    CAS  PubMed  Google Scholar 

  21. Sheth SA, Nemoto M, Guiou G et al (2004) Linear and nonlinear relationships between neuronal activity, oxygen metabolism, and hemodynamic response. Neuron 42:347–355

    Article  CAS  PubMed  Google Scholar 

  22. Georgakoudi I, Quinn KP (2012) Optical imaging using endogenous contrast to assess metabolic state. Annu Rev Biomed Eng 14(1):351–367. doi:10.1146/annurev-bioeng-071811-150108

    Article  CAS  PubMed  Google Scholar 

  23. Chance B, Ernster L, Garland PB et al (1967) Flavoproteins of the mitochondrial respiratory chain. Proc Natl Acad Sci U S A 57(5): 1498–1505

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Reinert KC, Dunbar RL, Gao W et al (2004) Flavoprotein autofluorescence imaging of neuronal activation in the cerebellar cortex in vivo. J Neurophysiol 92(1):199–211. doi:10.1152/jn.01275.2003, pii: 01275.2003

    Article  CAS  PubMed  Google Scholar 

  25. Reinert KC, Gao W, Chen G et al (2007) Flavoprotein autofluorescence imaging in the cerebellar cortex in vivo. J Neurosci Res 85(15):3221–3232. doi:10.1002/jnr.21348

    Article  CAS  PubMed  Google Scholar 

  26. Llano DA, Theyel BB, Mallik AK et al (2009) Rapid and sensitive mapping of long-range connections in vitro using flavoprotein autofluorescence imaging combined with laser photostimulation. J Neurophysiol 101(6):3325–3340. doi:10.1152/jn.91291.2008, pii: 91291.2008

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Sirotin YB, Das A (2010) Spatial relationship between flavoprotein fluorescence and the hemodynamic response in the primary visual cortex of alert macaque monkeys. Front Neuroenergetics 2:6. doi:10.3389/fnene.2010.00006

    CAS  PubMed Central  PubMed  Google Scholar 

  28. Chance B, Sager R (1957) Oxygen and light induced oxidations of cytochrome, flavoprotein, and pyridine nucleotide in a chlamydomonas mutant. Plant Physiol 32(6):548–561

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Chance B, Schoener B, Oshino R et al (1979) Oxidation-reduction ratio studies of mitochondria in freeze-trapped samples. NADH and flavoprotein fluorescence signals. J Biol Chem 254(11):4764–4771

    CAS  PubMed  Google Scholar 

  30. Gao W, Chen G, Reinert KC et al (2006) Cerebellar cortical molecular layer inhibition is organized in parasagittal zones. J Neurosci 26(32):8377–8387. doi:10.1523/JNEUROSCI.2434-06.2006, pii: 26/32/8377

    Article  CAS  PubMed  Google Scholar 

  31. Theyel BB, Llano DA, Sherman SM (2010) The corticothalamocortical circuit drives higher-order cortex in the mouse. Nat Neurosci 13(1):84–88. doi:10.1038/nn.2449, pii: nn.2449

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Benson RC, Meyer RA, Zaruba ME et al (1979) Cellular autofluorescence—is it due to flavins? J Histochem Cytochem 27(1):44–48

    Article  CAS  PubMed  Google Scholar 

  33. Lee IY, Chance B (1968) Activation of malate-linked reductions of NAD and flavoproteins in Ascaris muscle mitochondria by phosphate. Biochem Biophys Res Commun 32(3):547–553

    Article  CAS  PubMed  Google Scholar 

  34. Hassinen I, Chance B (1968) Oxidation-reduction properties of the mitochondrial flavoprotein chain. Biochem Biophys Res Commun 31(6):895–900

    Article  CAS  PubMed  Google Scholar 

  35. 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(7):951–957

    Article  CAS  PubMed  Google Scholar 

  36. Lee IY, Chance B (1977) Regulatory factors of acetaldehyde metabolism in isolated rat liver mitochondria. Adv Exp Med Biol 85A:203–224

    Article  CAS  PubMed  Google Scholar 

  37. Barlow CH, Harden WR III, Harken AH et al (1979) Fluorescence mapping of mitochondrial redox changes in heart and brain. Crit Care Med 7(9):402–406

    Article  CAS  PubMed  Google Scholar 

  38. Rehncrona S, Mela L, Chance B (1979) Cerebral energy state, mitochondrial function, and redox state measurements in transient ischemia. Fed Proc 38(11):2489–2492

    CAS  PubMed  Google Scholar 

  39. Duchen MR, Biscoe TJ (1992) Mitochondrial function in type I cells isolated from rabbit arterial chemoreceptors. J Physiol 450:13–31

    CAS  PubMed Central  PubMed  Google Scholar 

  40. Kosterin P, Kim GH, Muschol M et al (2005) Changes in FAD and NADH fluorescence in neurosecretory terminals are triggered by calcium entry and by ADP production. J Membr Biol 208(2):113–124. doi:10.1007/s00232-005-0824-x

    Article  CAS  PubMed  Google Scholar 

  41. Takano T, Tian G-F, Peng W et al (2007) Cortical spreading depression causes and coincides with tissue hypoxia. Nat Neurosci 10(6):754–762

    Article  CAS  PubMed  Google Scholar 

  42. Zhao M, Nguyen J, Ma H et al (2011) Preictal and ictal neurovascular and metabolic coupling surrounding a seizure focus. J Neurosci 31(37):13292–13300. doi:10.1523/jneurosci.2597-11.2011

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  43. Prakash N, Biag JD, Sheth SA et al (2007) Temporal profiles and 2-dimensional oxy-, deoxy-, and total-hemoglobin somatosensory maps in rat versus mouse cortex. Neuroimage 37(suppl 1):S27–S36, http://dx.doi.org/10.1016/j.neuroimage.2007.04.063

    Article  PubMed Central  PubMed  Google Scholar 

  44. Kozberg MG, Chen BR, DeLeo SE et al (2013) Resolving the transition from negative to positive blood oxygen level-dependent responses in the developing brain. Proc Natl Acad Sci. doi:10.1073/pnas.1212785110

    PubMed Central  PubMed  Google Scholar 

  45. Sun R, Bouchard MB, Hillman EM (2010) SPLASSH: open source software for camera-based high-speed, multispectral in-vivo optical image acquisition. Biomed Opt Express 1(2):385–397. doi:10.1364/boe.1.000385

    Article  PubMed Central  PubMed  Google Scholar 

  46. Bouchard MB, Chen BR, Burgess SA et al (2009) Ultra-fast multispectral optical imaging of cortical oxygenation, blood flow, and intracellular calcium dynamics. Opt Express 17(18):15670–15678

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  47. Zhao M, Suh M, Ma H et al (2007) Focal increases in perfusion and decreases in hemoglobin oxygenation precede seizure onset in spontaneous human epilepsy. Epilepsia 48(11):2059–2067. doi:10.1111/j.1528-1167.2007.01229.x, pii: EPI1229

    Article  PubMed  Google Scholar 

  48. Ma H, Zhao M, Suh M et al (2009) Hemodynamic surrogates for excitatory membrane potential change during interictal epileptiform events in rat neocortex. J Neurophysiol 101(5):2550–2562. doi:10.1152/jn.90694.2008, pii: 90694.2008

    Article  PubMed Central  PubMed  Google Scholar 

  49. Ratzlaff EH, Grinvald A (1991) A tandem-lens epifluorescence macroscope: hundred-fold brightness advantage for wide-field imaging. J Neurosci Methods 36(2–3): 127–137

    Article  CAS  PubMed  Google Scholar 

  50. Sato C, Nemoto M, Tamura M (2002) Reassessment of activity-related optical signals in somatosensory cortex by an algorithm with wavelength-dependent path length. Jpn J Physiol 52(3):301–312

    Article  CAS  PubMed  Google Scholar 

  51. Zhao M, Ma H, Suh M et al (2009) Spatiotemporal dynamics of perfusion and oximetry during ictal discharges in the rat neocortex. J Neurosci 29(9):2814–2823. doi:10.1523/JNEUROSCI.4667-08.2009, pii: 29/9/2814

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  52. Suh M, Bahar S, Mehta AD et al (2005) Temporal dependence in uncoupling of blood volume and oxygenation during interictal epileptiform events in rat neocortex. J Neurosci 25(1):68–77

    Article  CAS  PubMed  Google Scholar 

  53. Arieli A, Shoham D, Hildesheim R et al (1995) Coherent spatiotemporal patterns of ongoing activity revealed by real-time optical imaging coupled with single-unit recording in the cat visual cortex. J Neurophysiol 73(5):2072–2093

    CAS  PubMed  Google Scholar 

  54. Hohman B (2007) LED light source: major advance in fluorescence microscopy. Biomed Instrum Technol 41(6):461–464

    Article  PubMed  Google Scholar 

  55. Albeanu DF, Soucy E, Sato TF et al (2008) LED arrays as cost effective and efficient light sources for widefield microscopy. PLoS One 3(5):e2146. doi:10.1371/journal.pone.0002146

    Article  PubMed Central  PubMed  Google Scholar 

  56. Boison D (2005) Adenosine and epilepsy: from therapeutic rationale to new therapeutic strategies. Neuroscientist 11(1):25–36. doi:10.1177/1073858404269112

    Article  CAS  PubMed  Google Scholar 

  57. Adamantidis AR, Zhang F, Aravanis AM et al (2007) Neural substrates of awakening probed with optogenetic control of hypocretin neurons. Nature 450(7168):420–424

    Article  CAS  PubMed  Google Scholar 

  58. Boison D (2006) Adenosine kinase, epilepsy and stroke: mechanisms and therapies. Trends Pharmacol Sci 27(12):652–658

    Article  CAS  PubMed  Google Scholar 

  59. Zhang F, Wang L-P, Brauner M et al (2007) Multimodal fast optical interrogation of neural circuitry. Nature 446(7136):633–639

    Article  CAS  PubMed  Google Scholar 

  60. Zayat L, Noval MG, Campi J et al (2007) A new inorganic photolabile protecting group for highly efficient visible light GABA uncaging. Chembiochem 8(17):2035–2038. doi:10.1002/cbic.200700354

    Article  CAS  PubMed  Google Scholar 

  61. Deisseroth K, Feng G, Majewska AK et al (2006) Next-generation optical technologies for illuminating genetically targeted brain circuits. J Neurosci 26(41):10380–10386. doi:10.1523/jneurosci.3863-06.2006

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  62. Grinvald A, Shoham D, Shmuel A et al (1999) In-vivo optical imaging of cortical architecture and dynamics. In: Windhorst U, Johansson H (eds) Modern techniques in neuroscience research. Springer, Berlin, pp 893–968

    Chapter  Google Scholar 

  63. Przybyszewski AW, Sato T, Fukuda M (2008) Optical filtering removes non-homogenous illumination artifacts in optical imaging. J Neurosci Methods 168(1):140–145, http://dx.doi.org/10.1016/j.jneumeth.2007.09.006

    Article  PubMed  Google Scholar 

  64. Mayhew JEW, Askew S, Zheng Y et al (1996) Cerebral vasomotion: a 0.1-Hz oscillation in reflected light imaging of neural activity. Neuroimage 4(3):183–193, http://dx.doi.org/10.1006/nimg.1996.0069

    Article  CAS  PubMed  Google Scholar 

  65. Fekete T, Omer DB, Naaman S et al (2009) Removal of spatial biological artifacts in functional maps by local similarity minimization. J Neurosci Methods 178(1):31–39, http://dx.doi.org/10.1016/j.jneumeth.2008.11.020

    Article  PubMed  Google Scholar 

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Acknowledgements

This work was supported by the NINDS RO1 NS49482 (T.H.S), CURE Taking Flight Award (H.M.), the Clinical and Translational Science Center (CTSC) Grant UL1 RR 024996 Pilot Grant (M.Z), and the Cornell University Ithaca-WCMC seed grant (M.Z.). We thank Dr. Yevgeniy B. Sirotin for help with LED setup and AFI analysis.

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Authors and Affiliations

  1. Department of Neurological Surgery, Brain and Mind Research Institute, Weill Cornell Medical College, 1300 York Avenue, New York, NY, 10065, USA

    Mingrui Zhao & Hongtao Ma

  2. Department of Psychology, The University of Sheffield, Sheffield, UK

    Samuel Harris

  3. Department of Neurological Surgery, Weill Cornell Medical College, New York, NY, USA

    Samuel Harris

  4. Department of Neurological Surgery, Brain and Mind Research Institute, Weill Cornell Medical College, New York Presbyterian Hospital, New York, NY, USA

    Theodore H. Schwartz

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  1. Mingrui Zhao
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  2. Hongtao Ma
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  3. Samuel Harris
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  4. Theodore H. Schwartz
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Correspondence to Mingrui Zhao .

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Editors and Affiliations

  1. Weill Cornell Medical College, New York, New York, USA

    Mingrui Zhao

  2. Weill Cornell Medical College, New York, New York, USA

    Hongtao Ma

  3. Weill Cornell Medical College, New York, New York, USA

    Theodore H. Schwartz

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Zhao, M., Ma, H., Harris, S., Schwartz, T.H. (2014). Multi-Spectral Imaging of Blood Volume, Metabolism, Oximetry, and Light Scattering. In: Zhao, M., Ma, H., Schwartz, T. (eds) Neurovascular Coupling Methods. Neuromethods, vol 88. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-0724-3_10

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  • DOI: https://doi.org/10.1007/978-1-4939-0724-3_10

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