Abstract

Minimally invasive, specific measurement of cellular energy metabolism is crucial for understanding cerebral pathophysiology. Here, we present high-resolution, in vivo observations of autofluorescence lifetime as a biomarker of cerebral energy metabolism in exposed rat cortices. We describe a customized two-photon imaging system with time correlated single photon counting detection and specialized software for modeling multiple-component fits of fluorescence decay and monitoring their transient behaviors. In vivo cerebral NADH fluorescence suggests the presence of four distinct components, which respond differently to brief periods of anoxia and likely indicate different enzymatic formulations. Individual components show potential as indicators of specific molecular pathways involved in oxidative metabolism.

© 2013 OSA

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  1. L. Sokoloff, “The physiological and biochemical bases of functional brain imaging,” Cogn Neurodyn2(1), 1–5 (2008).
    [CrossRef] [PubMed]
  2. D. C. Wallace, “A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine,” Annu. Rev. Genet.39(1), 359–407 (2005).
    [CrossRef] [PubMed]
  3. M. Monsalve, S. Borniquel, I. Valle, and S. Lamas, “Mitochondrial dysfunction in human pathologies,” Front. Biosci.12(1), 1131–1153 (2007).
    [CrossRef] [PubMed]
  4. M. R. Duchen, “Mitochondria in health and disease: perspectives on a new mitochondrial biology,” Mol. Aspects Med.25(4), 365–451 (2004).
    [CrossRef] [PubMed]
  5. F. Hyder, “Dynamic imaging of brain function,” in Dynamic Brain Imaging: Multi-Modal Methods and In vivo Applications, F. Hyder, ed. (Humana, Totowa, NJ, 2009), pp. 3–21.
  6. B. Chance, P. Cohen, F. Jobsis, and B. Schoener, “Intracellular oxidation-reduction states in vivo: the microfluorometry of pyridine nucleotide gives a continuous measurement of the oxidation state,” Science137(3529), 499–508 (1962).
    [CrossRef] [PubMed]
  7. A. A. Heikal, “Intracellular coenzymes as natural biomarkers for metabolic activities and mitochondrial anomalies,” Biomarkers Med.4(2), 241–263 (2010).
    [CrossRef] [PubMed]
  8. B. Chance and B. Thorell, “Localization and kinetics of reduced pyridine nucleotide in living cells by microfluorometry,” J. Biol. Chem.234, 3044–3050 (1959).
    [PubMed]
  9. K. Svoboda and R. Yasuda, “Principles of two-photon excitation microscopy and its applications to neuroscience,” Neuron50(6), 823–839 (2006).
    [CrossRef] [PubMed]
  10. G. H. Patterson, S. M. Knobel, P. Arkhammar, O. Thastrup, and D. W. Piston, “Separation of the glucose-stimulated cytoplasmic and mitochondrial NAD(P)H responses in pancreatic islet β cells,” Proc. Natl. Acad. Sci. U.S.A.97(10), 5203–5207 (2000).
    [CrossRef] [PubMed]
  11. S. Huang, A. A. Heikal, and W. W. Webb, “Two-photon fluorescence spectroscopy and microscopy of NAD(P)H and flavoprotein,” Biophys. J.82(5), 2811–2825 (2002).
    [CrossRef] [PubMed]
  12. W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, “Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation,” Proc. Natl. Acad. Sci. U.S.A.100(12), 7075–7080 (2003).
    [CrossRef] [PubMed]
  13. K. A. Kasischke, H. D. Vishwasrao, P. J. Fisher, W. R. Zipfel, and W. W. Webb, “Neural activity triggers neuronal oxidative metabolism followed by astrocytic glycolysis,” Science305(5680), 99–103 (2004).
    [CrossRef] [PubMed]
  14. W. Becker, Advanced Time-Correlated Single Photon Counting Techniques (Springer, Berlin, 2005).
  15. M. Y. Berezin and S. Achilefu, “Fluorescence lifetime measurements and biological imaging,” Chem. Rev.110(5), 2641–2684 (2010).
    [CrossRef] [PubMed]
  16. J. R. Lakowicz, Principles of Fluorescence Spectroscopy (Springer, New York, 2006).
  17. D. F. Eaton, “Recommended methods for fluorescence decay analysis,” Pure Appl. Chem.62(8), 1631–1648 (1990).
    [CrossRef]
  18. R. Niesner, B. Peker, P. Schlüsche, and K.-H. Gericke, “Noniterative biexponential fluorescence lifetime imaging in the investigation of cellular metabolism by means of NAD(P)H autofluorescence,” ChemPhysChem5(8), 1141–1149 (2004).
    [CrossRef] [PubMed]
  19. H. D. Vishwasrao, A. A. Heikal, K. A. Kasischke, and W. W. Webb, “Conformational dependence of intracellular NADH on metabolic state revealed by associated fluorescence anisotropy,” J. Biol. Chem.280(26), 25119–25126 (2005).
    [CrossRef] [PubMed]
  20. Q. Yu and A. A. Heikal, “Two-photon autofluorescence dynamics imaging reveals sensitivity of intracellular NADH concentration and conformation to cell physiology at the single-cell level,” J. Photochem. Photobiol. B95(1), 46–57 (2009).
    [CrossRef] [PubMed]
  21. T. H. Chia, A. Williamson, D. D. Spencer, and M. J. Levene, “Multiphoton fluorescence lifetime imaging of intrinsic fluorescence in human and rat brain tissue reveals spatially distinct NADH binding,” Opt. Express16(6), 4237–4249 (2008).
    [CrossRef] [PubMed]
  22. M. C. Skala, K. M. Riching, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, J. G. White, and N. Ramanujam, “In vivo multiphoton microscopy of NADH and FAD redox states, fluorescence lifetimes, and cellular morphology in precancerous epithelia,” Proc. Natl. Acad. Sci. U.S.A.104(49), 19494–19499 (2007).
    [CrossRef] [PubMed]
  23. C. Stringari, A. Cinquin, O. Cinquin, M. A. Digman, P. J. Donovan, and E. Gratton, “Phasor approach to fluorescence lifetime microscopy distinguishes different metabolic states of germ cells in a live tissue,” Proc. Natl. Acad. Sci. U.S.A.108(33), 13582–13587 (2011).
    [CrossRef] [PubMed]
  24. S. Sakadžić, E. Roussakis, M. A. Yaseen, E. T. Mandeville, V. J. Srinivasan, K. Arai, S. Ruvinskaya, A. Devor, E. H. Lo, S. A. Vinogradov, and D. A. Boas, “Two-photon high-resolution measurement of partial pressure of oxygen in cerebral vasculature and tissue,” Nat. Methods7(9), 755–759 (2010).
    [CrossRef] [PubMed]
  25. M. A. Yaseen, V. J. Srinivasan, S. Sakadžić, H. Radhakrishnan, I. Gorczynska, W. Wu, J. G. Fujimoto, and D. A. Boas, “Microvascular oxygen tension and flow measurements in rodent cerebral cortex during baseline conditions and functional activation,” J. Cereb. Blood Flow Metab.31(4), 1051–1063 (2011).
    [CrossRef] [PubMed]
  26. L. K. Klaidman, A. C. Leung, and J. D. Adams., “High-performance liquid chromatography analysis of oxidized and reduced pyridine dinucleotides in specific brain regions,” Anal. Biochem.228(2), 312–317 (1995).
    [CrossRef] [PubMed]
  27. R. Guarneri and V. Bonavita, “Nicotinamide adenine dinucleotides in the developing rat brain,” Brain Res.2(2), 145–150 (1966).
    [CrossRef] [PubMed]
  28. Y. Avi-Dor, J. M. Olson, M. D. Doherty, and N. O. Kaplan, “Fluorescence of pyridine nucleotides in mitochondria,” J. Biol. Chem.237, 2377–2383 (1962).
  29. V. V. Ghukasyan and F.-J. Kao, “Monitoring cellular metabolism with fluorescence lifetime of reduced nicotinamide adenine dinucleotide,” J. Phys. Chem. C113(27), 11532–11540 (2009).
    [CrossRef]
  30. E. Gratton, S. Breusegem, J. Sutin, Q. Ruan, and N. Barry, “Fluorescence lifetime imaging for the two-photon microscope: time-domain and frequency-domain methods,” J. Biomed. Opt.8(3), 381–390 (2003).
    [CrossRef] [PubMed]
  31. M. Van Den Zegel, N. Boens, D. Daems, and F. C. De Schryver, “Possibilities and limitations of the time-correlated single photon counting technique: a comparative study of correction methods for the wavelength dependence of the instrument response function,” Chem. Phys.101(2), 311–335 (1986).
    [CrossRef]
  32. A. Habenicht, J. Hjelm, E. Mukhtar, F. Bergström, and L. B.-Å. Johansson, “Two-photon excitation and time-resolved fluorescence: I. The proper response function for analysing single-photon counting experiments,” Chem. Phys. Lett.354(5-6), 367–375 (2002).
    [CrossRef]
  33. K. Blinova, S. Carroll, S. Bose, A. V. Smirnov, J. J. Harvey, J. R. Knutson, and R. S. Balaban, “Distribution of mitochondrial NADH fluorescence lifetimes: steady-state kinetics of matrix NADH interactions,” Biochemistry44(7), 2585–2594 (2005).
    [CrossRef] [PubMed]
  34. E. Baraghis, A. Devor, Q. Fang, V. J. Srinivasan, W. Wu, F. Lesage, C. Ayata, K. A. Kasischke, D. A. Boas, and S. Sakadzić, “Two-photon microscopy of cortical NADH fluorescence intensity changes: correcting contamination from the hemodynamic response,” J. Biomed. Opt.16(10), 106003 (2011).
    [CrossRef] [PubMed]
  35. A. Nimmerjahn, F. Kirchhoff, J. N. D. Kerr, and F. Helmchen, “Sulforhodamine 101 as a specific marker of astroglia in the neocortex in vivo,” Nat. Methods1(1), 31–37 (2004).
    [CrossRef] [PubMed]
  36. A. Gafni and L. Brand, “Fluorescence decay studies of reduced nicotinamide adenine dinucleotide in solution and bound to liver alcohol dehydrogenase,” Biochemistry15(15), 3165–3171 (1976).
    [CrossRef] [PubMed]
  37. M. Wakita, G. Nishimura, and M. Tamura, “Some characteristics of the fluorescence lifetime of reduced pyridine nucleotides in isolated mitochondria, isolated hepatocytes, and perfused rat liver in situ,” J. Biochem.118(6), 1151–1160 (1995).
    [PubMed]
  38. T. G. Scott, R. D. Spencer, N. J. Leonard, and G. Weber, “Synthetic spectroscopic models related to coenzymes and base pairs. V. Emission properties of NADH. Studies of fluorescence lifetimes and quantum efficiencies of NADH, AcPyADH, [reduced acetylpyridineadenine dinucleotide] and simplified synthetic models,” J. Am. Chem. Soc.92(3), 687–695 (1970).
    [CrossRef]
  39. D. K. Bird, L. Yan, K. M. Vrotsos, K. W. Eliceiri, E. M. Vaughan, P. J. Keely, J. G. White, and N. Ramanujam, “Metabolic mapping of MCF10A human breast cells via multiphoton fluorescence lifetime imaging of the coenzyme NADH,” Cancer Res.65(19), 8766–8773 (2005).
    [CrossRef] [PubMed]
  40. V. K. Ramanujan, J. A. Jo, G. Cantu, and B. A. Herman, “Spatially resolved fluorescence lifetime mapping of enzyme kinetics in living cells,” J. Microsc.230(3), 329–338 (2008).
    [CrossRef] [PubMed]
  41. D. Li, W. Zheng, and J. Y. Qu, “Time-resolved spectroscopic imaging reveals the fundamentals of cellular NADH fluorescence,” Opt. Lett.33(20), 2365–2367 (2008).
    [CrossRef] [PubMed]
  42. M. W. Conklin, P. P. Provenzano, K. W. Eliceiri, R. Sullivan, and P. J. Keely, “Fluorescence lifetime imaging of endogenous fluorophores in histopathology sections reveals differences between normal and tumor epithelium in carcinoma in situ of the breast,” Cell Biochem. Biophys.53(3), 145–157 (2009).
    [CrossRef] [PubMed]
  43. Y. Sun, J. Phipps, D. S. Elson, H. Stoy, S. Tinling, J. Meier, B. Poirier, F. S. Chuang, D. G. Farwell, and L. Marcu, “Fluorescence lifetime imaging microscopy: in vivo application to diagnosis of oral carcinoma,” Opt. Lett.34(13), 2081–2083 (2009).
    [CrossRef] [PubMed]
  44. C. A. Thorling, X. Liu, F. J. Burczynski, L. M. Fletcher, G. C. Gobe, and M. S. Roberts, “Multiphoton microscopy can visualize zonal damage and decreased cellular metabolic activity in hepatic ischemia-reperfusion injury in rats,” J. Biomed. Opt.16(11), 116011 (2011).
    [CrossRef] [PubMed]
  45. D. L. Nelson and M. M. Cox, Lehninger Principles of Biochemistry (W.H. Freeman, New York, 2008).
  46. A. Devor, S. Sakadžić, P. A. Saisan, M. A. Yaseen, E. Roussakis, V. J. Srinivasan, S. A. Vinogradov, B. R. Rosen, R. B. Buxton, A. M. Dale, and D. A. Boas, “‘Overshoot’ of O₂ is required to maintain baseline tissue oxygenation at locations distal to blood vessels,” J. Neurosci.31(38), 13676–13681 (2011).
    [CrossRef] [PubMed]
  47. B. Chance, B. Schoener, R. Oshino, F. Itshak, and Y. Nakase, “Oxidation-reduction ratio studies of mitochondria in freeze-trapped samples. NADH and flavoprotein fluorescence signals,” J. Biol. Chem.254(11), 4764–4771 (1979).
    [PubMed]
  48. N. D. Kirkpatrick, C. Zou, M. A. Brewer, W. R. Brands, R. A. Drezek, and U. Utzinger, “Endogenous fluorescence spectroscopy of cell suspensions for chemopreventive drug monitoring,” Photochem. Photobiol.81(1), 125–134 (2005).
    [CrossRef] [PubMed]
  49. T. A. Wang, Y. V. Yu, G. Govindaiah, X. Ye, L. Artinian, T. P. Coleman, J. V. Sweedler, C. L. Cox, and M. U. Gillette, “Circadian rhythm of redox state regulates excitability in suprachiasmatic nucleus neurons,” Science337(6096), 839–842 (2012).
    [CrossRef] [PubMed]
  50. S. K. Shankar, “Biology of aging brain,” Indian J. Pathol. Microbiol.53(4), 595–604 (2010).
    [CrossRef] [PubMed]
  51. J. V. Rocheleau, W. S. Head, and D. W. Piston, “Quantitative NAD(P)H/flavoprotein autofluorescence imaging reveals metabolic mechanisms of pancreatic islet pyruvate response,” J. Biol. Chem.279(30), 31780–31787 (2004).
    [CrossRef] [PubMed]
  52. J. R. Lakowicz, ed., Principles of Fluorescence Spectroscopy (Springer, New York, 2006).
  53. M. vandeVen, M. Ameloot, B. Valeur, and N. Boens, “Pitfalls and their remedies in time-resolved fluorescence spectroscopy and microscopy,” J. Fluoresc.15(3), 377–413 (2005).
    [CrossRef] [PubMed]
  54. M. Köllner and J. Wolfrum, “How many photons are necessary for fluorescence-lifetime measurements?” Chem. Phys. Lett.200(1-2), 199–204 (1992).
    [CrossRef]

2012

T. A. Wang, Y. V. Yu, G. Govindaiah, X. Ye, L. Artinian, T. P. Coleman, J. V. Sweedler, C. L. Cox, and M. U. Gillette, “Circadian rhythm of redox state regulates excitability in suprachiasmatic nucleus neurons,” Science337(6096), 839–842 (2012).
[CrossRef] [PubMed]

2011

C. A. Thorling, X. Liu, F. J. Burczynski, L. M. Fletcher, G. C. Gobe, and M. S. Roberts, “Multiphoton microscopy can visualize zonal damage and decreased cellular metabolic activity in hepatic ischemia-reperfusion injury in rats,” J. Biomed. Opt.16(11), 116011 (2011).
[CrossRef] [PubMed]

A. Devor, S. Sakadžić, P. A. Saisan, M. A. Yaseen, E. Roussakis, V. J. Srinivasan, S. A. Vinogradov, B. R. Rosen, R. B. Buxton, A. M. Dale, and D. A. Boas, “‘Overshoot’ of O₂ is required to maintain baseline tissue oxygenation at locations distal to blood vessels,” J. Neurosci.31(38), 13676–13681 (2011).
[CrossRef] [PubMed]

M. A. Yaseen, V. J. Srinivasan, S. Sakadžić, H. Radhakrishnan, I. Gorczynska, W. Wu, J. G. Fujimoto, and D. A. Boas, “Microvascular oxygen tension and flow measurements in rodent cerebral cortex during baseline conditions and functional activation,” J. Cereb. Blood Flow Metab.31(4), 1051–1063 (2011).
[CrossRef] [PubMed]

C. Stringari, A. Cinquin, O. Cinquin, M. A. Digman, P. J. Donovan, and E. Gratton, “Phasor approach to fluorescence lifetime microscopy distinguishes different metabolic states of germ cells in a live tissue,” Proc. Natl. Acad. Sci. U.S.A.108(33), 13582–13587 (2011).
[CrossRef] [PubMed]

E. Baraghis, A. Devor, Q. Fang, V. J. Srinivasan, W. Wu, F. Lesage, C. Ayata, K. A. Kasischke, D. A. Boas, and S. Sakadzić, “Two-photon microscopy of cortical NADH fluorescence intensity changes: correcting contamination from the hemodynamic response,” J. Biomed. Opt.16(10), 106003 (2011).
[CrossRef] [PubMed]

2010

S. Sakadžić, E. Roussakis, M. A. Yaseen, E. T. Mandeville, V. J. Srinivasan, K. Arai, S. Ruvinskaya, A. Devor, E. H. Lo, S. A. Vinogradov, and D. A. Boas, “Two-photon high-resolution measurement of partial pressure of oxygen in cerebral vasculature and tissue,” Nat. Methods7(9), 755–759 (2010).
[CrossRef] [PubMed]

A. A. Heikal, “Intracellular coenzymes as natural biomarkers for metabolic activities and mitochondrial anomalies,” Biomarkers Med.4(2), 241–263 (2010).
[CrossRef] [PubMed]

M. Y. Berezin and S. Achilefu, “Fluorescence lifetime measurements and biological imaging,” Chem. Rev.110(5), 2641–2684 (2010).
[CrossRef] [PubMed]

S. K. Shankar, “Biology of aging brain,” Indian J. Pathol. Microbiol.53(4), 595–604 (2010).
[CrossRef] [PubMed]

2009

M. W. Conklin, P. P. Provenzano, K. W. Eliceiri, R. Sullivan, and P. J. Keely, “Fluorescence lifetime imaging of endogenous fluorophores in histopathology sections reveals differences between normal and tumor epithelium in carcinoma in situ of the breast,” Cell Biochem. Biophys.53(3), 145–157 (2009).
[CrossRef] [PubMed]

Y. Sun, J. Phipps, D. S. Elson, H. Stoy, S. Tinling, J. Meier, B. Poirier, F. S. Chuang, D. G. Farwell, and L. Marcu, “Fluorescence lifetime imaging microscopy: in vivo application to diagnosis of oral carcinoma,” Opt. Lett.34(13), 2081–2083 (2009).
[CrossRef] [PubMed]

Q. Yu and A. A. Heikal, “Two-photon autofluorescence dynamics imaging reveals sensitivity of intracellular NADH concentration and conformation to cell physiology at the single-cell level,” J. Photochem. Photobiol. B95(1), 46–57 (2009).
[CrossRef] [PubMed]

V. V. Ghukasyan and F.-J. Kao, “Monitoring cellular metabolism with fluorescence lifetime of reduced nicotinamide adenine dinucleotide,” J. Phys. Chem. C113(27), 11532–11540 (2009).
[CrossRef]

2008

2007

M. Monsalve, S. Borniquel, I. Valle, and S. Lamas, “Mitochondrial dysfunction in human pathologies,” Front. Biosci.12(1), 1131–1153 (2007).
[CrossRef] [PubMed]

M. C. Skala, K. M. Riching, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, J. G. White, and N. Ramanujam, “In vivo multiphoton microscopy of NADH and FAD redox states, fluorescence lifetimes, and cellular morphology in precancerous epithelia,” Proc. Natl. Acad. Sci. U.S.A.104(49), 19494–19499 (2007).
[CrossRef] [PubMed]

2006

K. Svoboda and R. Yasuda, “Principles of two-photon excitation microscopy and its applications to neuroscience,” Neuron50(6), 823–839 (2006).
[CrossRef] [PubMed]

2005

D. C. Wallace, “A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine,” Annu. Rev. Genet.39(1), 359–407 (2005).
[CrossRef] [PubMed]

H. D. Vishwasrao, A. A. Heikal, K. A. Kasischke, and W. W. Webb, “Conformational dependence of intracellular NADH on metabolic state revealed by associated fluorescence anisotropy,” J. Biol. Chem.280(26), 25119–25126 (2005).
[CrossRef] [PubMed]

K. Blinova, S. Carroll, S. Bose, A. V. Smirnov, J. J. Harvey, J. R. Knutson, and R. S. Balaban, “Distribution of mitochondrial NADH fluorescence lifetimes: steady-state kinetics of matrix NADH interactions,” Biochemistry44(7), 2585–2594 (2005).
[CrossRef] [PubMed]

D. K. Bird, L. Yan, K. M. Vrotsos, K. W. Eliceiri, E. M. Vaughan, P. J. Keely, J. G. White, and N. Ramanujam, “Metabolic mapping of MCF10A human breast cells via multiphoton fluorescence lifetime imaging of the coenzyme NADH,” Cancer Res.65(19), 8766–8773 (2005).
[CrossRef] [PubMed]

M. vandeVen, M. Ameloot, B. Valeur, and N. Boens, “Pitfalls and their remedies in time-resolved fluorescence spectroscopy and microscopy,” J. Fluoresc.15(3), 377–413 (2005).
[CrossRef] [PubMed]

N. D. Kirkpatrick, C. Zou, M. A. Brewer, W. R. Brands, R. A. Drezek, and U. Utzinger, “Endogenous fluorescence spectroscopy of cell suspensions for chemopreventive drug monitoring,” Photochem. Photobiol.81(1), 125–134 (2005).
[CrossRef] [PubMed]

2004

J. V. Rocheleau, W. S. Head, and D. W. Piston, “Quantitative NAD(P)H/flavoprotein autofluorescence imaging reveals metabolic mechanisms of pancreatic islet pyruvate response,” J. Biol. Chem.279(30), 31780–31787 (2004).
[CrossRef] [PubMed]

A. Nimmerjahn, F. Kirchhoff, J. N. D. Kerr, and F. Helmchen, “Sulforhodamine 101 as a specific marker of astroglia in the neocortex in vivo,” Nat. Methods1(1), 31–37 (2004).
[CrossRef] [PubMed]

M. R. Duchen, “Mitochondria in health and disease: perspectives on a new mitochondrial biology,” Mol. Aspects Med.25(4), 365–451 (2004).
[CrossRef] [PubMed]

K. A. Kasischke, H. D. Vishwasrao, P. J. Fisher, W. R. Zipfel, and W. W. Webb, “Neural activity triggers neuronal oxidative metabolism followed by astrocytic glycolysis,” Science305(5680), 99–103 (2004).
[CrossRef] [PubMed]

R. Niesner, B. Peker, P. Schlüsche, and K.-H. Gericke, “Noniterative biexponential fluorescence lifetime imaging in the investigation of cellular metabolism by means of NAD(P)H autofluorescence,” ChemPhysChem5(8), 1141–1149 (2004).
[CrossRef] [PubMed]

2003

W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, “Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation,” Proc. Natl. Acad. Sci. U.S.A.100(12), 7075–7080 (2003).
[CrossRef] [PubMed]

E. Gratton, S. Breusegem, J. Sutin, Q. Ruan, and N. Barry, “Fluorescence lifetime imaging for the two-photon microscope: time-domain and frequency-domain methods,” J. Biomed. Opt.8(3), 381–390 (2003).
[CrossRef] [PubMed]

2002

A. Habenicht, J. Hjelm, E. Mukhtar, F. Bergström, and L. B.-Å. Johansson, “Two-photon excitation and time-resolved fluorescence: I. The proper response function for analysing single-photon counting experiments,” Chem. Phys. Lett.354(5-6), 367–375 (2002).
[CrossRef]

S. Huang, A. A. Heikal, and W. W. Webb, “Two-photon fluorescence spectroscopy and microscopy of NAD(P)H and flavoprotein,” Biophys. J.82(5), 2811–2825 (2002).
[CrossRef] [PubMed]

2000

G. H. Patterson, S. M. Knobel, P. Arkhammar, O. Thastrup, and D. W. Piston, “Separation of the glucose-stimulated cytoplasmic and mitochondrial NAD(P)H responses in pancreatic islet β cells,” Proc. Natl. Acad. Sci. U.S.A.97(10), 5203–5207 (2000).
[CrossRef] [PubMed]

1995

M. Wakita, G. Nishimura, and M. Tamura, “Some characteristics of the fluorescence lifetime of reduced pyridine nucleotides in isolated mitochondria, isolated hepatocytes, and perfused rat liver in situ,” J. Biochem.118(6), 1151–1160 (1995).
[PubMed]

L. K. Klaidman, A. C. Leung, and J. D. Adams., “High-performance liquid chromatography analysis of oxidized and reduced pyridine dinucleotides in specific brain regions,” Anal. Biochem.228(2), 312–317 (1995).
[CrossRef] [PubMed]

1992

M. Köllner and J. Wolfrum, “How many photons are necessary for fluorescence-lifetime measurements?” Chem. Phys. Lett.200(1-2), 199–204 (1992).
[CrossRef]

1990

D. F. Eaton, “Recommended methods for fluorescence decay analysis,” Pure Appl. Chem.62(8), 1631–1648 (1990).
[CrossRef]

1986

M. Van Den Zegel, N. Boens, D. Daems, and F. C. De Schryver, “Possibilities and limitations of the time-correlated single photon counting technique: a comparative study of correction methods for the wavelength dependence of the instrument response function,” Chem. Phys.101(2), 311–335 (1986).
[CrossRef]

1979

B. Chance, B. Schoener, R. Oshino, F. Itshak, and Y. Nakase, “Oxidation-reduction ratio studies of mitochondria in freeze-trapped samples. NADH and flavoprotein fluorescence signals,” J. Biol. Chem.254(11), 4764–4771 (1979).
[PubMed]

1976

A. Gafni and L. Brand, “Fluorescence decay studies of reduced nicotinamide adenine dinucleotide in solution and bound to liver alcohol dehydrogenase,” Biochemistry15(15), 3165–3171 (1976).
[CrossRef] [PubMed]

1970

T. G. Scott, R. D. Spencer, N. J. Leonard, and G. Weber, “Synthetic spectroscopic models related to coenzymes and base pairs. V. Emission properties of NADH. Studies of fluorescence lifetimes and quantum efficiencies of NADH, AcPyADH, [reduced acetylpyridineadenine dinucleotide] and simplified synthetic models,” J. Am. Chem. Soc.92(3), 687–695 (1970).
[CrossRef]

1966

R. Guarneri and V. Bonavita, “Nicotinamide adenine dinucleotides in the developing rat brain,” Brain Res.2(2), 145–150 (1966).
[CrossRef] [PubMed]

1962

Y. Avi-Dor, J. M. Olson, M. D. Doherty, and N. O. Kaplan, “Fluorescence of pyridine nucleotides in mitochondria,” J. Biol. Chem.237, 2377–2383 (1962).

B. Chance, P. Cohen, F. Jobsis, and B. Schoener, “Intracellular oxidation-reduction states in vivo: the microfluorometry of pyridine nucleotide gives a continuous measurement of the oxidation state,” Science137(3529), 499–508 (1962).
[CrossRef] [PubMed]

1959

B. Chance and B. Thorell, “Localization and kinetics of reduced pyridine nucleotide in living cells by microfluorometry,” J. Biol. Chem.234, 3044–3050 (1959).
[PubMed]

Achilefu, S.

M. Y. Berezin and S. Achilefu, “Fluorescence lifetime measurements and biological imaging,” Chem. Rev.110(5), 2641–2684 (2010).
[CrossRef] [PubMed]

Adams, J. D.

L. K. Klaidman, A. C. Leung, and J. D. Adams., “High-performance liquid chromatography analysis of oxidized and reduced pyridine dinucleotides in specific brain regions,” Anal. Biochem.228(2), 312–317 (1995).
[CrossRef] [PubMed]

Ameloot, M.

M. vandeVen, M. Ameloot, B. Valeur, and N. Boens, “Pitfalls and their remedies in time-resolved fluorescence spectroscopy and microscopy,” J. Fluoresc.15(3), 377–413 (2005).
[CrossRef] [PubMed]

Arai, K.

S. Sakadžić, E. Roussakis, M. A. Yaseen, E. T. Mandeville, V. J. Srinivasan, K. Arai, S. Ruvinskaya, A. Devor, E. H. Lo, S. A. Vinogradov, and D. A. Boas, “Two-photon high-resolution measurement of partial pressure of oxygen in cerebral vasculature and tissue,” Nat. Methods7(9), 755–759 (2010).
[CrossRef] [PubMed]

Arkhammar, P.

G. H. Patterson, S. M. Knobel, P. Arkhammar, O. Thastrup, and D. W. Piston, “Separation of the glucose-stimulated cytoplasmic and mitochondrial NAD(P)H responses in pancreatic islet β cells,” Proc. Natl. Acad. Sci. U.S.A.97(10), 5203–5207 (2000).
[CrossRef] [PubMed]

Artinian, L.

T. A. Wang, Y. V. Yu, G. Govindaiah, X. Ye, L. Artinian, T. P. Coleman, J. V. Sweedler, C. L. Cox, and M. U. Gillette, “Circadian rhythm of redox state regulates excitability in suprachiasmatic nucleus neurons,” Science337(6096), 839–842 (2012).
[CrossRef] [PubMed]

Avi-Dor, Y.

Y. Avi-Dor, J. M. Olson, M. D. Doherty, and N. O. Kaplan, “Fluorescence of pyridine nucleotides in mitochondria,” J. Biol. Chem.237, 2377–2383 (1962).

Ayata, C.

E. Baraghis, A. Devor, Q. Fang, V. J. Srinivasan, W. Wu, F. Lesage, C. Ayata, K. A. Kasischke, D. A. Boas, and S. Sakadzić, “Two-photon microscopy of cortical NADH fluorescence intensity changes: correcting contamination from the hemodynamic response,” J. Biomed. Opt.16(10), 106003 (2011).
[CrossRef] [PubMed]

Balaban, R. S.

K. Blinova, S. Carroll, S. Bose, A. V. Smirnov, J. J. Harvey, J. R. Knutson, and R. S. Balaban, “Distribution of mitochondrial NADH fluorescence lifetimes: steady-state kinetics of matrix NADH interactions,” Biochemistry44(7), 2585–2594 (2005).
[CrossRef] [PubMed]

Baraghis, E.

E. Baraghis, A. Devor, Q. Fang, V. J. Srinivasan, W. Wu, F. Lesage, C. Ayata, K. A. Kasischke, D. A. Boas, and S. Sakadzić, “Two-photon microscopy of cortical NADH fluorescence intensity changes: correcting contamination from the hemodynamic response,” J. Biomed. Opt.16(10), 106003 (2011).
[CrossRef] [PubMed]

Barry, N.

E. Gratton, S. Breusegem, J. Sutin, Q. Ruan, and N. Barry, “Fluorescence lifetime imaging for the two-photon microscope: time-domain and frequency-domain methods,” J. Biomed. Opt.8(3), 381–390 (2003).
[CrossRef] [PubMed]

Berezin, M. Y.

M. Y. Berezin and S. Achilefu, “Fluorescence lifetime measurements and biological imaging,” Chem. Rev.110(5), 2641–2684 (2010).
[CrossRef] [PubMed]

Bergström, F.

A. Habenicht, J. Hjelm, E. Mukhtar, F. Bergström, and L. B.-Å. Johansson, “Two-photon excitation and time-resolved fluorescence: I. The proper response function for analysing single-photon counting experiments,” Chem. Phys. Lett.354(5-6), 367–375 (2002).
[CrossRef]

Bird, D. K.

D. K. Bird, L. Yan, K. M. Vrotsos, K. W. Eliceiri, E. M. Vaughan, P. J. Keely, J. G. White, and N. Ramanujam, “Metabolic mapping of MCF10A human breast cells via multiphoton fluorescence lifetime imaging of the coenzyme NADH,” Cancer Res.65(19), 8766–8773 (2005).
[CrossRef] [PubMed]

Blinova, K.

K. Blinova, S. Carroll, S. Bose, A. V. Smirnov, J. J. Harvey, J. R. Knutson, and R. S. Balaban, “Distribution of mitochondrial NADH fluorescence lifetimes: steady-state kinetics of matrix NADH interactions,” Biochemistry44(7), 2585–2594 (2005).
[CrossRef] [PubMed]

Boas, D. A.

E. Baraghis, A. Devor, Q. Fang, V. J. Srinivasan, W. Wu, F. Lesage, C. Ayata, K. A. Kasischke, D. A. Boas, and S. Sakadzić, “Two-photon microscopy of cortical NADH fluorescence intensity changes: correcting contamination from the hemodynamic response,” J. Biomed. Opt.16(10), 106003 (2011).
[CrossRef] [PubMed]

M. A. Yaseen, V. J. Srinivasan, S. Sakadžić, H. Radhakrishnan, I. Gorczynska, W. Wu, J. G. Fujimoto, and D. A. Boas, “Microvascular oxygen tension and flow measurements in rodent cerebral cortex during baseline conditions and functional activation,” J. Cereb. Blood Flow Metab.31(4), 1051–1063 (2011).
[CrossRef] [PubMed]

A. Devor, S. Sakadžić, P. A. Saisan, M. A. Yaseen, E. Roussakis, V. J. Srinivasan, S. A. Vinogradov, B. R. Rosen, R. B. Buxton, A. M. Dale, and D. A. Boas, “‘Overshoot’ of O₂ is required to maintain baseline tissue oxygenation at locations distal to blood vessels,” J. Neurosci.31(38), 13676–13681 (2011).
[CrossRef] [PubMed]

S. Sakadžić, E. Roussakis, M. A. Yaseen, E. T. Mandeville, V. J. Srinivasan, K. Arai, S. Ruvinskaya, A. Devor, E. H. Lo, S. A. Vinogradov, and D. A. Boas, “Two-photon high-resolution measurement of partial pressure of oxygen in cerebral vasculature and tissue,” Nat. Methods7(9), 755–759 (2010).
[CrossRef] [PubMed]

Boens, N.

M. vandeVen, M. Ameloot, B. Valeur, and N. Boens, “Pitfalls and their remedies in time-resolved fluorescence spectroscopy and microscopy,” J. Fluoresc.15(3), 377–413 (2005).
[CrossRef] [PubMed]

M. Van Den Zegel, N. Boens, D. Daems, and F. C. De Schryver, “Possibilities and limitations of the time-correlated single photon counting technique: a comparative study of correction methods for the wavelength dependence of the instrument response function,” Chem. Phys.101(2), 311–335 (1986).
[CrossRef]

Bonavita, V.

R. Guarneri and V. Bonavita, “Nicotinamide adenine dinucleotides in the developing rat brain,” Brain Res.2(2), 145–150 (1966).
[CrossRef] [PubMed]

Borniquel, S.

M. Monsalve, S. Borniquel, I. Valle, and S. Lamas, “Mitochondrial dysfunction in human pathologies,” Front. Biosci.12(1), 1131–1153 (2007).
[CrossRef] [PubMed]

Bose, S.

K. Blinova, S. Carroll, S. Bose, A. V. Smirnov, J. J. Harvey, J. R. Knutson, and R. S. Balaban, “Distribution of mitochondrial NADH fluorescence lifetimes: steady-state kinetics of matrix NADH interactions,” Biochemistry44(7), 2585–2594 (2005).
[CrossRef] [PubMed]

Brand, L.

A. Gafni and L. Brand, “Fluorescence decay studies of reduced nicotinamide adenine dinucleotide in solution and bound to liver alcohol dehydrogenase,” Biochemistry15(15), 3165–3171 (1976).
[CrossRef] [PubMed]

Brands, W. R.

N. D. Kirkpatrick, C. Zou, M. A. Brewer, W. R. Brands, R. A. Drezek, and U. Utzinger, “Endogenous fluorescence spectroscopy of cell suspensions for chemopreventive drug monitoring,” Photochem. Photobiol.81(1), 125–134 (2005).
[CrossRef] [PubMed]

Breusegem, S.

E. Gratton, S. Breusegem, J. Sutin, Q. Ruan, and N. Barry, “Fluorescence lifetime imaging for the two-photon microscope: time-domain and frequency-domain methods,” J. Biomed. Opt.8(3), 381–390 (2003).
[CrossRef] [PubMed]

Brewer, M. A.

N. D. Kirkpatrick, C. Zou, M. A. Brewer, W. R. Brands, R. A. Drezek, and U. Utzinger, “Endogenous fluorescence spectroscopy of cell suspensions for chemopreventive drug monitoring,” Photochem. Photobiol.81(1), 125–134 (2005).
[CrossRef] [PubMed]

Burczynski, F. J.

C. A. Thorling, X. Liu, F. J. Burczynski, L. M. Fletcher, G. C. Gobe, and M. S. Roberts, “Multiphoton microscopy can visualize zonal damage and decreased cellular metabolic activity in hepatic ischemia-reperfusion injury in rats,” J. Biomed. Opt.16(11), 116011 (2011).
[CrossRef] [PubMed]

Buxton, R. B.

A. Devor, S. Sakadžić, P. A. Saisan, M. A. Yaseen, E. Roussakis, V. J. Srinivasan, S. A. Vinogradov, B. R. Rosen, R. B. Buxton, A. M. Dale, and D. A. Boas, “‘Overshoot’ of O₂ is required to maintain baseline tissue oxygenation at locations distal to blood vessels,” J. Neurosci.31(38), 13676–13681 (2011).
[CrossRef] [PubMed]

Cantu, G.

V. K. Ramanujan, J. A. Jo, G. Cantu, and B. A. Herman, “Spatially resolved fluorescence lifetime mapping of enzyme kinetics in living cells,” J. Microsc.230(3), 329–338 (2008).
[CrossRef] [PubMed]

Carroll, S.

K. Blinova, S. Carroll, S. Bose, A. V. Smirnov, J. J. Harvey, J. R. Knutson, and R. S. Balaban, “Distribution of mitochondrial NADH fluorescence lifetimes: steady-state kinetics of matrix NADH interactions,” Biochemistry44(7), 2585–2594 (2005).
[CrossRef] [PubMed]

Chance, B.

B. Chance, B. Schoener, R. Oshino, F. Itshak, and Y. Nakase, “Oxidation-reduction ratio studies of mitochondria in freeze-trapped samples. NADH and flavoprotein fluorescence signals,” J. Biol. Chem.254(11), 4764–4771 (1979).
[PubMed]

B. Chance, P. Cohen, F. Jobsis, and B. Schoener, “Intracellular oxidation-reduction states in vivo: the microfluorometry of pyridine nucleotide gives a continuous measurement of the oxidation state,” Science137(3529), 499–508 (1962).
[CrossRef] [PubMed]

B. Chance and B. Thorell, “Localization and kinetics of reduced pyridine nucleotide in living cells by microfluorometry,” J. Biol. Chem.234, 3044–3050 (1959).
[PubMed]

Chia, T. H.

Christie, R.

W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, “Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation,” Proc. Natl. Acad. Sci. U.S.A.100(12), 7075–7080 (2003).
[CrossRef] [PubMed]

Chuang, F. S.

Cinquin, A.

C. Stringari, A. Cinquin, O. Cinquin, M. A. Digman, P. J. Donovan, and E. Gratton, “Phasor approach to fluorescence lifetime microscopy distinguishes different metabolic states of germ cells in a live tissue,” Proc. Natl. Acad. Sci. U.S.A.108(33), 13582–13587 (2011).
[CrossRef] [PubMed]

Cinquin, O.

C. Stringari, A. Cinquin, O. Cinquin, M. A. Digman, P. J. Donovan, and E. Gratton, “Phasor approach to fluorescence lifetime microscopy distinguishes different metabolic states of germ cells in a live tissue,” Proc. Natl. Acad. Sci. U.S.A.108(33), 13582–13587 (2011).
[CrossRef] [PubMed]

Cohen, P.

B. Chance, P. Cohen, F. Jobsis, and B. Schoener, “Intracellular oxidation-reduction states in vivo: the microfluorometry of pyridine nucleotide gives a continuous measurement of the oxidation state,” Science137(3529), 499–508 (1962).
[CrossRef] [PubMed]

Coleman, T. P.

T. A. Wang, Y. V. Yu, G. Govindaiah, X. Ye, L. Artinian, T. P. Coleman, J. V. Sweedler, C. L. Cox, and M. U. Gillette, “Circadian rhythm of redox state regulates excitability in suprachiasmatic nucleus neurons,” Science337(6096), 839–842 (2012).
[CrossRef] [PubMed]

Conklin, M. W.

M. W. Conklin, P. P. Provenzano, K. W. Eliceiri, R. Sullivan, and P. J. Keely, “Fluorescence lifetime imaging of endogenous fluorophores in histopathology sections reveals differences between normal and tumor epithelium in carcinoma in situ of the breast,” Cell Biochem. Biophys.53(3), 145–157 (2009).
[CrossRef] [PubMed]

Cox, C. L.

T. A. Wang, Y. V. Yu, G. Govindaiah, X. Ye, L. Artinian, T. P. Coleman, J. V. Sweedler, C. L. Cox, and M. U. Gillette, “Circadian rhythm of redox state regulates excitability in suprachiasmatic nucleus neurons,” Science337(6096), 839–842 (2012).
[CrossRef] [PubMed]

Daems, D.

M. Van Den Zegel, N. Boens, D. Daems, and F. C. De Schryver, “Possibilities and limitations of the time-correlated single photon counting technique: a comparative study of correction methods for the wavelength dependence of the instrument response function,” Chem. Phys.101(2), 311–335 (1986).
[CrossRef]

Dale, A. M.

A. Devor, S. Sakadžić, P. A. Saisan, M. A. Yaseen, E. Roussakis, V. J. Srinivasan, S. A. Vinogradov, B. R. Rosen, R. B. Buxton, A. M. Dale, and D. A. Boas, “‘Overshoot’ of O₂ is required to maintain baseline tissue oxygenation at locations distal to blood vessels,” J. Neurosci.31(38), 13676–13681 (2011).
[CrossRef] [PubMed]

De Schryver, F. C.

M. Van Den Zegel, N. Boens, D. Daems, and F. C. De Schryver, “Possibilities and limitations of the time-correlated single photon counting technique: a comparative study of correction methods for the wavelength dependence of the instrument response function,” Chem. Phys.101(2), 311–335 (1986).
[CrossRef]

Devor, A.

E. Baraghis, A. Devor, Q. Fang, V. J. Srinivasan, W. Wu, F. Lesage, C. Ayata, K. A. Kasischke, D. A. Boas, and S. Sakadzić, “Two-photon microscopy of cortical NADH fluorescence intensity changes: correcting contamination from the hemodynamic response,” J. Biomed. Opt.16(10), 106003 (2011).
[CrossRef] [PubMed]

A. Devor, S. Sakadžić, P. A. Saisan, M. A. Yaseen, E. Roussakis, V. J. Srinivasan, S. A. Vinogradov, B. R. Rosen, R. B. Buxton, A. M. Dale, and D. A. Boas, “‘Overshoot’ of O₂ is required to maintain baseline tissue oxygenation at locations distal to blood vessels,” J. Neurosci.31(38), 13676–13681 (2011).
[CrossRef] [PubMed]

S. Sakadžić, E. Roussakis, M. A. Yaseen, E. T. Mandeville, V. J. Srinivasan, K. Arai, S. Ruvinskaya, A. Devor, E. H. Lo, S. A. Vinogradov, and D. A. Boas, “Two-photon high-resolution measurement of partial pressure of oxygen in cerebral vasculature and tissue,” Nat. Methods7(9), 755–759 (2010).
[CrossRef] [PubMed]

Digman, M. A.

C. Stringari, A. Cinquin, O. Cinquin, M. A. Digman, P. J. Donovan, and E. Gratton, “Phasor approach to fluorescence lifetime microscopy distinguishes different metabolic states of germ cells in a live tissue,” Proc. Natl. Acad. Sci. U.S.A.108(33), 13582–13587 (2011).
[CrossRef] [PubMed]

Doherty, M. D.

Y. Avi-Dor, J. M. Olson, M. D. Doherty, and N. O. Kaplan, “Fluorescence of pyridine nucleotides in mitochondria,” J. Biol. Chem.237, 2377–2383 (1962).

Donovan, P. J.

C. Stringari, A. Cinquin, O. Cinquin, M. A. Digman, P. J. Donovan, and E. Gratton, “Phasor approach to fluorescence lifetime microscopy distinguishes different metabolic states of germ cells in a live tissue,” Proc. Natl. Acad. Sci. U.S.A.108(33), 13582–13587 (2011).
[CrossRef] [PubMed]

Drezek, R. A.

N. D. Kirkpatrick, C. Zou, M. A. Brewer, W. R. Brands, R. A. Drezek, and U. Utzinger, “Endogenous fluorescence spectroscopy of cell suspensions for chemopreventive drug monitoring,” Photochem. Photobiol.81(1), 125–134 (2005).
[CrossRef] [PubMed]

Duchen, M. R.

M. R. Duchen, “Mitochondria in health and disease: perspectives on a new mitochondrial biology,” Mol. Aspects Med.25(4), 365–451 (2004).
[CrossRef] [PubMed]

Eaton, D. F.

D. F. Eaton, “Recommended methods for fluorescence decay analysis,” Pure Appl. Chem.62(8), 1631–1648 (1990).
[CrossRef]

Eickhoff, J.

M. C. Skala, K. M. Riching, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, J. G. White, and N. Ramanujam, “In vivo multiphoton microscopy of NADH and FAD redox states, fluorescence lifetimes, and cellular morphology in precancerous epithelia,” Proc. Natl. Acad. Sci. U.S.A.104(49), 19494–19499 (2007).
[CrossRef] [PubMed]

Eliceiri, K. W.

M. W. Conklin, P. P. Provenzano, K. W. Eliceiri, R. Sullivan, and P. J. Keely, “Fluorescence lifetime imaging of endogenous fluorophores in histopathology sections reveals differences between normal and tumor epithelium in carcinoma in situ of the breast,” Cell Biochem. Biophys.53(3), 145–157 (2009).
[CrossRef] [PubMed]

M. C. Skala, K. M. Riching, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, J. G. White, and N. Ramanujam, “In vivo multiphoton microscopy of NADH and FAD redox states, fluorescence lifetimes, and cellular morphology in precancerous epithelia,” Proc. Natl. Acad. Sci. U.S.A.104(49), 19494–19499 (2007).
[CrossRef] [PubMed]

D. K. Bird, L. Yan, K. M. Vrotsos, K. W. Eliceiri, E. M. Vaughan, P. J. Keely, J. G. White, and N. Ramanujam, “Metabolic mapping of MCF10A human breast cells via multiphoton fluorescence lifetime imaging of the coenzyme NADH,” Cancer Res.65(19), 8766–8773 (2005).
[CrossRef] [PubMed]

Elson, D. S.

Fang, Q.

E. Baraghis, A. Devor, Q. Fang, V. J. Srinivasan, W. Wu, F. Lesage, C. Ayata, K. A. Kasischke, D. A. Boas, and S. Sakadzić, “Two-photon microscopy of cortical NADH fluorescence intensity changes: correcting contamination from the hemodynamic response,” J. Biomed. Opt.16(10), 106003 (2011).
[CrossRef] [PubMed]

Farwell, D. G.

Fisher, P. J.

K. A. Kasischke, H. D. Vishwasrao, P. J. Fisher, W. R. Zipfel, and W. W. Webb, “Neural activity triggers neuronal oxidative metabolism followed by astrocytic glycolysis,” Science305(5680), 99–103 (2004).
[CrossRef] [PubMed]

Fletcher, L. M.

C. A. Thorling, X. Liu, F. J. Burczynski, L. M. Fletcher, G. C. Gobe, and M. S. Roberts, “Multiphoton microscopy can visualize zonal damage and decreased cellular metabolic activity in hepatic ischemia-reperfusion injury in rats,” J. Biomed. Opt.16(11), 116011 (2011).
[CrossRef] [PubMed]

Fujimoto, J. G.

M. A. Yaseen, V. J. Srinivasan, S. Sakadžić, H. Radhakrishnan, I. Gorczynska, W. Wu, J. G. Fujimoto, and D. A. Boas, “Microvascular oxygen tension and flow measurements in rodent cerebral cortex during baseline conditions and functional activation,” J. Cereb. Blood Flow Metab.31(4), 1051–1063 (2011).
[CrossRef] [PubMed]

Gafni, A.

A. Gafni and L. Brand, “Fluorescence decay studies of reduced nicotinamide adenine dinucleotide in solution and bound to liver alcohol dehydrogenase,” Biochemistry15(15), 3165–3171 (1976).
[CrossRef] [PubMed]

Gendron-Fitzpatrick, A.

M. C. Skala, K. M. Riching, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, J. G. White, and N. Ramanujam, “In vivo multiphoton microscopy of NADH and FAD redox states, fluorescence lifetimes, and cellular morphology in precancerous epithelia,” Proc. Natl. Acad. Sci. U.S.A.104(49), 19494–19499 (2007).
[CrossRef] [PubMed]

Gericke, K.-H.

R. Niesner, B. Peker, P. Schlüsche, and K.-H. Gericke, “Noniterative biexponential fluorescence lifetime imaging in the investigation of cellular metabolism by means of NAD(P)H autofluorescence,” ChemPhysChem5(8), 1141–1149 (2004).
[CrossRef] [PubMed]

Ghukasyan, V. V.

V. V. Ghukasyan and F.-J. Kao, “Monitoring cellular metabolism with fluorescence lifetime of reduced nicotinamide adenine dinucleotide,” J. Phys. Chem. C113(27), 11532–11540 (2009).
[CrossRef]

Gillette, M. U.

T. A. Wang, Y. V. Yu, G. Govindaiah, X. Ye, L. Artinian, T. P. Coleman, J. V. Sweedler, C. L. Cox, and M. U. Gillette, “Circadian rhythm of redox state regulates excitability in suprachiasmatic nucleus neurons,” Science337(6096), 839–842 (2012).
[CrossRef] [PubMed]

Gobe, G. C.

C. A. Thorling, X. Liu, F. J. Burczynski, L. M. Fletcher, G. C. Gobe, and M. S. Roberts, “Multiphoton microscopy can visualize zonal damage and decreased cellular metabolic activity in hepatic ischemia-reperfusion injury in rats,” J. Biomed. Opt.16(11), 116011 (2011).
[CrossRef] [PubMed]

Gorczynska, I.

M. A. Yaseen, V. J. Srinivasan, S. Sakadžić, H. Radhakrishnan, I. Gorczynska, W. Wu, J. G. Fujimoto, and D. A. Boas, “Microvascular oxygen tension and flow measurements in rodent cerebral cortex during baseline conditions and functional activation,” J. Cereb. Blood Flow Metab.31(4), 1051–1063 (2011).
[CrossRef] [PubMed]

Govindaiah, G.

T. A. Wang, Y. V. Yu, G. Govindaiah, X. Ye, L. Artinian, T. P. Coleman, J. V. Sweedler, C. L. Cox, and M. U. Gillette, “Circadian rhythm of redox state regulates excitability in suprachiasmatic nucleus neurons,” Science337(6096), 839–842 (2012).
[CrossRef] [PubMed]

Gratton, E.

C. Stringari, A. Cinquin, O. Cinquin, M. A. Digman, P. J. Donovan, and E. Gratton, “Phasor approach to fluorescence lifetime microscopy distinguishes different metabolic states of germ cells in a live tissue,” Proc. Natl. Acad. Sci. U.S.A.108(33), 13582–13587 (2011).
[CrossRef] [PubMed]

E. Gratton, S. Breusegem, J. Sutin, Q. Ruan, and N. Barry, “Fluorescence lifetime imaging for the two-photon microscope: time-domain and frequency-domain methods,” J. Biomed. Opt.8(3), 381–390 (2003).
[CrossRef] [PubMed]

Guarneri, R.

R. Guarneri and V. Bonavita, “Nicotinamide adenine dinucleotides in the developing rat brain,” Brain Res.2(2), 145–150 (1966).
[CrossRef] [PubMed]

Habenicht, A.

A. Habenicht, J. Hjelm, E. Mukhtar, F. Bergström, and L. B.-Å. Johansson, “Two-photon excitation and time-resolved fluorescence: I. The proper response function for analysing single-photon counting experiments,” Chem. Phys. Lett.354(5-6), 367–375 (2002).
[CrossRef]

Harvey, J. J.

K. Blinova, S. Carroll, S. Bose, A. V. Smirnov, J. J. Harvey, J. R. Knutson, and R. S. Balaban, “Distribution of mitochondrial NADH fluorescence lifetimes: steady-state kinetics of matrix NADH interactions,” Biochemistry44(7), 2585–2594 (2005).
[CrossRef] [PubMed]

Head, W. S.

J. V. Rocheleau, W. S. Head, and D. W. Piston, “Quantitative NAD(P)H/flavoprotein autofluorescence imaging reveals metabolic mechanisms of pancreatic islet pyruvate response,” J. Biol. Chem.279(30), 31780–31787 (2004).
[CrossRef] [PubMed]

Heikal, A. A.

A. A. Heikal, “Intracellular coenzymes as natural biomarkers for metabolic activities and mitochondrial anomalies,” Biomarkers Med.4(2), 241–263 (2010).
[CrossRef] [PubMed]

Q. Yu and A. A. Heikal, “Two-photon autofluorescence dynamics imaging reveals sensitivity of intracellular NADH concentration and conformation to cell physiology at the single-cell level,” J. Photochem. Photobiol. B95(1), 46–57 (2009).
[CrossRef] [PubMed]

H. D. Vishwasrao, A. A. Heikal, K. A. Kasischke, and W. W. Webb, “Conformational dependence of intracellular NADH on metabolic state revealed by associated fluorescence anisotropy,” J. Biol. Chem.280(26), 25119–25126 (2005).
[CrossRef] [PubMed]

S. Huang, A. A. Heikal, and W. W. Webb, “Two-photon fluorescence spectroscopy and microscopy of NAD(P)H and flavoprotein,” Biophys. J.82(5), 2811–2825 (2002).
[CrossRef] [PubMed]

Helmchen, F.

A. Nimmerjahn, F. Kirchhoff, J. N. D. Kerr, and F. Helmchen, “Sulforhodamine 101 as a specific marker of astroglia in the neocortex in vivo,” Nat. Methods1(1), 31–37 (2004).
[CrossRef] [PubMed]

Herman, B. A.

V. K. Ramanujan, J. A. Jo, G. Cantu, and B. A. Herman, “Spatially resolved fluorescence lifetime mapping of enzyme kinetics in living cells,” J. Microsc.230(3), 329–338 (2008).
[CrossRef] [PubMed]

Hjelm, J.

A. Habenicht, J. Hjelm, E. Mukhtar, F. Bergström, and L. B.-Å. Johansson, “Two-photon excitation and time-resolved fluorescence: I. The proper response function for analysing single-photon counting experiments,” Chem. Phys. Lett.354(5-6), 367–375 (2002).
[CrossRef]

Huang, S.

S. Huang, A. A. Heikal, and W. W. Webb, “Two-photon fluorescence spectroscopy and microscopy of NAD(P)H and flavoprotein,” Biophys. J.82(5), 2811–2825 (2002).
[CrossRef] [PubMed]

Hyman, B. T.

W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, “Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation,” Proc. Natl. Acad. Sci. U.S.A.100(12), 7075–7080 (2003).
[CrossRef] [PubMed]

Itshak, F.

B. Chance, B. Schoener, R. Oshino, F. Itshak, and Y. Nakase, “Oxidation-reduction ratio studies of mitochondria in freeze-trapped samples. NADH and flavoprotein fluorescence signals,” J. Biol. Chem.254(11), 4764–4771 (1979).
[PubMed]

Jo, J. A.

V. K. Ramanujan, J. A. Jo, G. Cantu, and B. A. Herman, “Spatially resolved fluorescence lifetime mapping of enzyme kinetics in living cells,” J. Microsc.230(3), 329–338 (2008).
[CrossRef] [PubMed]

Jobsis, F.

B. Chance, P. Cohen, F. Jobsis, and B. Schoener, “Intracellular oxidation-reduction states in vivo: the microfluorometry of pyridine nucleotide gives a continuous measurement of the oxidation state,” Science137(3529), 499–508 (1962).
[CrossRef] [PubMed]

Johansson, L. B.-Å.

A. Habenicht, J. Hjelm, E. Mukhtar, F. Bergström, and L. B.-Å. Johansson, “Two-photon excitation and time-resolved fluorescence: I. The proper response function for analysing single-photon counting experiments,” Chem. Phys. Lett.354(5-6), 367–375 (2002).
[CrossRef]

Kao, F.-J.

V. V. Ghukasyan and F.-J. Kao, “Monitoring cellular metabolism with fluorescence lifetime of reduced nicotinamide adenine dinucleotide,” J. Phys. Chem. C113(27), 11532–11540 (2009).
[CrossRef]

Kaplan, N. O.

Y. Avi-Dor, J. M. Olson, M. D. Doherty, and N. O. Kaplan, “Fluorescence of pyridine nucleotides in mitochondria,” J. Biol. Chem.237, 2377–2383 (1962).

Kasischke, K. A.

E. Baraghis, A. Devor, Q. Fang, V. J. Srinivasan, W. Wu, F. Lesage, C. Ayata, K. A. Kasischke, D. A. Boas, and S. Sakadzić, “Two-photon microscopy of cortical NADH fluorescence intensity changes: correcting contamination from the hemodynamic response,” J. Biomed. Opt.16(10), 106003 (2011).
[CrossRef] [PubMed]

H. D. Vishwasrao, A. A. Heikal, K. A. Kasischke, and W. W. Webb, “Conformational dependence of intracellular NADH on metabolic state revealed by associated fluorescence anisotropy,” J. Biol. Chem.280(26), 25119–25126 (2005).
[CrossRef] [PubMed]

K. A. Kasischke, H. D. Vishwasrao, P. J. Fisher, W. R. Zipfel, and W. W. Webb, “Neural activity triggers neuronal oxidative metabolism followed by astrocytic glycolysis,” Science305(5680), 99–103 (2004).
[CrossRef] [PubMed]

Keely, P. J.

M. W. Conklin, P. P. Provenzano, K. W. Eliceiri, R. Sullivan, and P. J. Keely, “Fluorescence lifetime imaging of endogenous fluorophores in histopathology sections reveals differences between normal and tumor epithelium in carcinoma in situ of the breast,” Cell Biochem. Biophys.53(3), 145–157 (2009).
[CrossRef] [PubMed]

D. K. Bird, L. Yan, K. M. Vrotsos, K. W. Eliceiri, E. M. Vaughan, P. J. Keely, J. G. White, and N. Ramanujam, “Metabolic mapping of MCF10A human breast cells via multiphoton fluorescence lifetime imaging of the coenzyme NADH,” Cancer Res.65(19), 8766–8773 (2005).
[CrossRef] [PubMed]

Kerr, J. N. D.

A. Nimmerjahn, F. Kirchhoff, J. N. D. Kerr, and F. Helmchen, “Sulforhodamine 101 as a specific marker of astroglia in the neocortex in vivo,” Nat. Methods1(1), 31–37 (2004).
[CrossRef] [PubMed]

Kirchhoff, F.

A. Nimmerjahn, F. Kirchhoff, J. N. D. Kerr, and F. Helmchen, “Sulforhodamine 101 as a specific marker of astroglia in the neocortex in vivo,” Nat. Methods1(1), 31–37 (2004).
[CrossRef] [PubMed]

Kirkpatrick, N. D.

N. D. Kirkpatrick, C. Zou, M. A. Brewer, W. R. Brands, R. A. Drezek, and U. Utzinger, “Endogenous fluorescence spectroscopy of cell suspensions for chemopreventive drug monitoring,” Photochem. Photobiol.81(1), 125–134 (2005).
[CrossRef] [PubMed]

Klaidman, L. K.

L. K. Klaidman, A. C. Leung, and J. D. Adams., “High-performance liquid chromatography analysis of oxidized and reduced pyridine dinucleotides in specific brain regions,” Anal. Biochem.228(2), 312–317 (1995).
[CrossRef] [PubMed]

Knobel, S. M.

G. H. Patterson, S. M. Knobel, P. Arkhammar, O. Thastrup, and D. W. Piston, “Separation of the glucose-stimulated cytoplasmic and mitochondrial NAD(P)H responses in pancreatic islet β cells,” Proc. Natl. Acad. Sci. U.S.A.97(10), 5203–5207 (2000).
[CrossRef] [PubMed]

Knutson, J. R.

K. Blinova, S. Carroll, S. Bose, A. V. Smirnov, J. J. Harvey, J. R. Knutson, and R. S. Balaban, “Distribution of mitochondrial NADH fluorescence lifetimes: steady-state kinetics of matrix NADH interactions,” Biochemistry44(7), 2585–2594 (2005).
[CrossRef] [PubMed]

Köllner, M.

M. Köllner and J. Wolfrum, “How many photons are necessary for fluorescence-lifetime measurements?” Chem. Phys. Lett.200(1-2), 199–204 (1992).
[CrossRef]

Lamas, S.

M. Monsalve, S. Borniquel, I. Valle, and S. Lamas, “Mitochondrial dysfunction in human pathologies,” Front. Biosci.12(1), 1131–1153 (2007).
[CrossRef] [PubMed]

Leonard, N. J.

T. G. Scott, R. D. Spencer, N. J. Leonard, and G. Weber, “Synthetic spectroscopic models related to coenzymes and base pairs. V. Emission properties of NADH. Studies of fluorescence lifetimes and quantum efficiencies of NADH, AcPyADH, [reduced acetylpyridineadenine dinucleotide] and simplified synthetic models,” J. Am. Chem. Soc.92(3), 687–695 (1970).
[CrossRef]

Lesage, F.

E. Baraghis, A. Devor, Q. Fang, V. J. Srinivasan, W. Wu, F. Lesage, C. Ayata, K. A. Kasischke, D. A. Boas, and S. Sakadzić, “Two-photon microscopy of cortical NADH fluorescence intensity changes: correcting contamination from the hemodynamic response,” J. Biomed. Opt.16(10), 106003 (2011).
[CrossRef] [PubMed]

Leung, A. C.

L. K. Klaidman, A. C. Leung, and J. D. Adams., “High-performance liquid chromatography analysis of oxidized and reduced pyridine dinucleotides in specific brain regions,” Anal. Biochem.228(2), 312–317 (1995).
[CrossRef] [PubMed]

Levene, M. J.

Li, D.

Liu, X.

C. A. Thorling, X. Liu, F. J. Burczynski, L. M. Fletcher, G. C. Gobe, and M. S. Roberts, “Multiphoton microscopy can visualize zonal damage and decreased cellular metabolic activity in hepatic ischemia-reperfusion injury in rats,” J. Biomed. Opt.16(11), 116011 (2011).
[CrossRef] [PubMed]

Lo, E. H.

S. Sakadžić, E. Roussakis, M. A. Yaseen, E. T. Mandeville, V. J. Srinivasan, K. Arai, S. Ruvinskaya, A. Devor, E. H. Lo, S. A. Vinogradov, and D. A. Boas, “Two-photon high-resolution measurement of partial pressure of oxygen in cerebral vasculature and tissue,” Nat. Methods7(9), 755–759 (2010).
[CrossRef] [PubMed]

Mandeville, E. T.

S. Sakadžić, E. Roussakis, M. A. Yaseen, E. T. Mandeville, V. J. Srinivasan, K. Arai, S. Ruvinskaya, A. Devor, E. H. Lo, S. A. Vinogradov, and D. A. Boas, “Two-photon high-resolution measurement of partial pressure of oxygen in cerebral vasculature and tissue,” Nat. Methods7(9), 755–759 (2010).
[CrossRef] [PubMed]

Marcu, L.

Meier, J.

Monsalve, M.

M. Monsalve, S. Borniquel, I. Valle, and S. Lamas, “Mitochondrial dysfunction in human pathologies,” Front. Biosci.12(1), 1131–1153 (2007).
[CrossRef] [PubMed]

Mukhtar, E.

A. Habenicht, J. Hjelm, E. Mukhtar, F. Bergström, and L. B.-Å. Johansson, “Two-photon excitation and time-resolved fluorescence: I. The proper response function for analysing single-photon counting experiments,” Chem. Phys. Lett.354(5-6), 367–375 (2002).
[CrossRef]

Nakase, Y.

B. Chance, B. Schoener, R. Oshino, F. Itshak, and Y. Nakase, “Oxidation-reduction ratio studies of mitochondria in freeze-trapped samples. NADH and flavoprotein fluorescence signals,” J. Biol. Chem.254(11), 4764–4771 (1979).
[PubMed]

Niesner, R.

R. Niesner, B. Peker, P. Schlüsche, and K.-H. Gericke, “Noniterative biexponential fluorescence lifetime imaging in the investigation of cellular metabolism by means of NAD(P)H autofluorescence,” ChemPhysChem5(8), 1141–1149 (2004).
[CrossRef] [PubMed]

Nikitin, A. Y.

W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, “Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation,” Proc. Natl. Acad. Sci. U.S.A.100(12), 7075–7080 (2003).
[CrossRef] [PubMed]

Nimmerjahn, A.

A. Nimmerjahn, F. Kirchhoff, J. N. D. Kerr, and F. Helmchen, “Sulforhodamine 101 as a specific marker of astroglia in the neocortex in vivo,” Nat. Methods1(1), 31–37 (2004).
[CrossRef] [PubMed]

Nishimura, G.

M. Wakita, G. Nishimura, and M. Tamura, “Some characteristics of the fluorescence lifetime of reduced pyridine nucleotides in isolated mitochondria, isolated hepatocytes, and perfused rat liver in situ,” J. Biochem.118(6), 1151–1160 (1995).
[PubMed]

Olson, J. M.

Y. Avi-Dor, J. M. Olson, M. D. Doherty, and N. O. Kaplan, “Fluorescence of pyridine nucleotides in mitochondria,” J. Biol. Chem.237, 2377–2383 (1962).

Oshino, R.

B. Chance, B. Schoener, R. Oshino, F. Itshak, and Y. Nakase, “Oxidation-reduction ratio studies of mitochondria in freeze-trapped samples. NADH and flavoprotein fluorescence signals,” J. Biol. Chem.254(11), 4764–4771 (1979).
[PubMed]

Patterson, G. H.

G. H. Patterson, S. M. Knobel, P. Arkhammar, O. Thastrup, and D. W. Piston, “Separation of the glucose-stimulated cytoplasmic and mitochondrial NAD(P)H responses in pancreatic islet β cells,” Proc. Natl. Acad. Sci. U.S.A.97(10), 5203–5207 (2000).
[CrossRef] [PubMed]

Peker, B.

R. Niesner, B. Peker, P. Schlüsche, and K.-H. Gericke, “Noniterative biexponential fluorescence lifetime imaging in the investigation of cellular metabolism by means of NAD(P)H autofluorescence,” ChemPhysChem5(8), 1141–1149 (2004).
[CrossRef] [PubMed]

Phipps, J.

Piston, D. W.

J. V. Rocheleau, W. S. Head, and D. W. Piston, “Quantitative NAD(P)H/flavoprotein autofluorescence imaging reveals metabolic mechanisms of pancreatic islet pyruvate response,” J. Biol. Chem.279(30), 31780–31787 (2004).
[CrossRef] [PubMed]

G. H. Patterson, S. M. Knobel, P. Arkhammar, O. Thastrup, and D. W. Piston, “Separation of the glucose-stimulated cytoplasmic and mitochondrial NAD(P)H responses in pancreatic islet β cells,” Proc. Natl. Acad. Sci. U.S.A.97(10), 5203–5207 (2000).
[CrossRef] [PubMed]

Poirier, B.

Provenzano, P. P.

M. W. Conklin, P. P. Provenzano, K. W. Eliceiri, R. Sullivan, and P. J. Keely, “Fluorescence lifetime imaging of endogenous fluorophores in histopathology sections reveals differences between normal and tumor epithelium in carcinoma in situ of the breast,” Cell Biochem. Biophys.53(3), 145–157 (2009).
[CrossRef] [PubMed]

Qu, J. Y.

Radhakrishnan, H.

M. A. Yaseen, V. J. Srinivasan, S. Sakadžić, H. Radhakrishnan, I. Gorczynska, W. Wu, J. G. Fujimoto, and D. A. Boas, “Microvascular oxygen tension and flow measurements in rodent cerebral cortex during baseline conditions and functional activation,” J. Cereb. Blood Flow Metab.31(4), 1051–1063 (2011).
[CrossRef] [PubMed]

Ramanujam, N.

M. C. Skala, K. M. Riching, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, J. G. White, and N. Ramanujam, “In vivo multiphoton microscopy of NADH and FAD redox states, fluorescence lifetimes, and cellular morphology in precancerous epithelia,” Proc. Natl. Acad. Sci. U.S.A.104(49), 19494–19499 (2007).
[CrossRef] [PubMed]

D. K. Bird, L. Yan, K. M. Vrotsos, K. W. Eliceiri, E. M. Vaughan, P. J. Keely, J. G. White, and N. Ramanujam, “Metabolic mapping of MCF10A human breast cells via multiphoton fluorescence lifetime imaging of the coenzyme NADH,” Cancer Res.65(19), 8766–8773 (2005).
[CrossRef] [PubMed]

Ramanujan, V. K.

V. K. Ramanujan, J. A. Jo, G. Cantu, and B. A. Herman, “Spatially resolved fluorescence lifetime mapping of enzyme kinetics in living cells,” J. Microsc.230(3), 329–338 (2008).
[CrossRef] [PubMed]

Riching, K. M.

M. C. Skala, K. M. Riching, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, J. G. White, and N. Ramanujam, “In vivo multiphoton microscopy of NADH and FAD redox states, fluorescence lifetimes, and cellular morphology in precancerous epithelia,” Proc. Natl. Acad. Sci. U.S.A.104(49), 19494–19499 (2007).
[CrossRef] [PubMed]

Roberts, M. S.

C. A. Thorling, X. Liu, F. J. Burczynski, L. M. Fletcher, G. C. Gobe, and M. S. Roberts, “Multiphoton microscopy can visualize zonal damage and decreased cellular metabolic activity in hepatic ischemia-reperfusion injury in rats,” J. Biomed. Opt.16(11), 116011 (2011).
[CrossRef] [PubMed]

Rocheleau, J. V.

J. V. Rocheleau, W. S. Head, and D. W. Piston, “Quantitative NAD(P)H/flavoprotein autofluorescence imaging reveals metabolic mechanisms of pancreatic islet pyruvate response,” J. Biol. Chem.279(30), 31780–31787 (2004).
[CrossRef] [PubMed]

Rosen, B. R.

A. Devor, S. Sakadžić, P. A. Saisan, M. A. Yaseen, E. Roussakis, V. J. Srinivasan, S. A. Vinogradov, B. R. Rosen, R. B. Buxton, A. M. Dale, and D. A. Boas, “‘Overshoot’ of O₂ is required to maintain baseline tissue oxygenation at locations distal to blood vessels,” J. Neurosci.31(38), 13676–13681 (2011).
[CrossRef] [PubMed]

Roussakis, E.

A. Devor, S. Sakadžić, P. A. Saisan, M. A. Yaseen, E. Roussakis, V. J. Srinivasan, S. A. Vinogradov, B. R. Rosen, R. B. Buxton, A. M. Dale, and D. A. Boas, “‘Overshoot’ of O₂ is required to maintain baseline tissue oxygenation at locations distal to blood vessels,” J. Neurosci.31(38), 13676–13681 (2011).
[CrossRef] [PubMed]

S. Sakadžić, E. Roussakis, M. A. Yaseen, E. T. Mandeville, V. J. Srinivasan, K. Arai, S. Ruvinskaya, A. Devor, E. H. Lo, S. A. Vinogradov, and D. A. Boas, “Two-photon high-resolution measurement of partial pressure of oxygen in cerebral vasculature and tissue,” Nat. Methods7(9), 755–759 (2010).
[CrossRef] [PubMed]

Ruan, Q.

E. Gratton, S. Breusegem, J. Sutin, Q. Ruan, and N. Barry, “Fluorescence lifetime imaging for the two-photon microscope: time-domain and frequency-domain methods,” J. Biomed. Opt.8(3), 381–390 (2003).
[CrossRef] [PubMed]

Ruvinskaya, S.

S. Sakadžić, E. Roussakis, M. A. Yaseen, E. T. Mandeville, V. J. Srinivasan, K. Arai, S. Ruvinskaya, A. Devor, E. H. Lo, S. A. Vinogradov, and D. A. Boas, “Two-photon high-resolution measurement of partial pressure of oxygen in cerebral vasculature and tissue,” Nat. Methods7(9), 755–759 (2010).
[CrossRef] [PubMed]

Saisan, P. A.

A. Devor, S. Sakadžić, P. A. Saisan, M. A. Yaseen, E. Roussakis, V. J. Srinivasan, S. A. Vinogradov, B. R. Rosen, R. B. Buxton, A. M. Dale, and D. A. Boas, “‘Overshoot’ of O₂ is required to maintain baseline tissue oxygenation at locations distal to blood vessels,” J. Neurosci.31(38), 13676–13681 (2011).
[CrossRef] [PubMed]

Sakadzic, S.

E. Baraghis, A. Devor, Q. Fang, V. J. Srinivasan, W. Wu, F. Lesage, C. Ayata, K. A. Kasischke, D. A. Boas, and S. Sakadzić, “Two-photon microscopy of cortical NADH fluorescence intensity changes: correcting contamination from the hemodynamic response,” J. Biomed. Opt.16(10), 106003 (2011).
[CrossRef] [PubMed]

Sakadžic, S.

M. A. Yaseen, V. J. Srinivasan, S. Sakadžić, H. Radhakrishnan, I. Gorczynska, W. Wu, J. G. Fujimoto, and D. A. Boas, “Microvascular oxygen tension and flow measurements in rodent cerebral cortex during baseline conditions and functional activation,” J. Cereb. Blood Flow Metab.31(4), 1051–1063 (2011).
[CrossRef] [PubMed]

A. Devor, S. Sakadžić, P. A. Saisan, M. A. Yaseen, E. Roussakis, V. J. Srinivasan, S. A. Vinogradov, B. R. Rosen, R. B. Buxton, A. M. Dale, and D. A. Boas, “‘Overshoot’ of O₂ is required to maintain baseline tissue oxygenation at locations distal to blood vessels,” J. Neurosci.31(38), 13676–13681 (2011).
[CrossRef] [PubMed]

S. Sakadžić, E. Roussakis, M. A. Yaseen, E. T. Mandeville, V. J. Srinivasan, K. Arai, S. Ruvinskaya, A. Devor, E. H. Lo, S. A. Vinogradov, and D. A. Boas, “Two-photon high-resolution measurement of partial pressure of oxygen in cerebral vasculature and tissue,” Nat. Methods7(9), 755–759 (2010).
[CrossRef] [PubMed]

Schlüsche, P.

R. Niesner, B. Peker, P. Schlüsche, and K.-H. Gericke, “Noniterative biexponential fluorescence lifetime imaging in the investigation of cellular metabolism by means of NAD(P)H autofluorescence,” ChemPhysChem5(8), 1141–1149 (2004).
[CrossRef] [PubMed]

Schoener, B.

B. Chance, B. Schoener, R. Oshino, F. Itshak, and Y. Nakase, “Oxidation-reduction ratio studies of mitochondria in freeze-trapped samples. NADH and flavoprotein fluorescence signals,” J. Biol. Chem.254(11), 4764–4771 (1979).
[PubMed]

B. Chance, P. Cohen, F. Jobsis, and B. Schoener, “Intracellular oxidation-reduction states in vivo: the microfluorometry of pyridine nucleotide gives a continuous measurement of the oxidation state,” Science137(3529), 499–508 (1962).
[CrossRef] [PubMed]

Scott, T. G.

T. G. Scott, R. D. Spencer, N. J. Leonard, and G. Weber, “Synthetic spectroscopic models related to coenzymes and base pairs. V. Emission properties of NADH. Studies of fluorescence lifetimes and quantum efficiencies of NADH, AcPyADH, [reduced acetylpyridineadenine dinucleotide] and simplified synthetic models,” J. Am. Chem. Soc.92(3), 687–695 (1970).
[CrossRef]

Shankar, S. K.

S. K. Shankar, “Biology of aging brain,” Indian J. Pathol. Microbiol.53(4), 595–604 (2010).
[CrossRef] [PubMed]

Skala, M. C.

M. C. Skala, K. M. Riching, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, J. G. White, and N. Ramanujam, “In vivo multiphoton microscopy of NADH and FAD redox states, fluorescence lifetimes, and cellular morphology in precancerous epithelia,” Proc. Natl. Acad. Sci. U.S.A.104(49), 19494–19499 (2007).
[CrossRef] [PubMed]

Smirnov, A. V.

K. Blinova, S. Carroll, S. Bose, A. V. Smirnov, J. J. Harvey, J. R. Knutson, and R. S. Balaban, “Distribution of mitochondrial NADH fluorescence lifetimes: steady-state kinetics of matrix NADH interactions,” Biochemistry44(7), 2585–2594 (2005).
[CrossRef] [PubMed]

Sokoloff, L.

L. Sokoloff, “The physiological and biochemical bases of functional brain imaging,” Cogn Neurodyn2(1), 1–5 (2008).
[CrossRef] [PubMed]

Spencer, D. D.

Spencer, R. D.

T. G. Scott, R. D. Spencer, N. J. Leonard, and G. Weber, “Synthetic spectroscopic models related to coenzymes and base pairs. V. Emission properties of NADH. Studies of fluorescence lifetimes and quantum efficiencies of NADH, AcPyADH, [reduced acetylpyridineadenine dinucleotide] and simplified synthetic models,” J. Am. Chem. Soc.92(3), 687–695 (1970).
[CrossRef]

Srinivasan, V. J.

E. Baraghis, A. Devor, Q. Fang, V. J. Srinivasan, W. Wu, F. Lesage, C. Ayata, K. A. Kasischke, D. A. Boas, and S. Sakadzić, “Two-photon microscopy of cortical NADH fluorescence intensity changes: correcting contamination from the hemodynamic response,” J. Biomed. Opt.16(10), 106003 (2011).
[CrossRef] [PubMed]

M. A. Yaseen, V. J. Srinivasan, S. Sakadžić, H. Radhakrishnan, I. Gorczynska, W. Wu, J. G. Fujimoto, and D. A. Boas, “Microvascular oxygen tension and flow measurements in rodent cerebral cortex during baseline conditions and functional activation,” J. Cereb. Blood Flow Metab.31(4), 1051–1063 (2011).
[CrossRef] [PubMed]

A. Devor, S. Sakadžić, P. A. Saisan, M. A. Yaseen, E. Roussakis, V. J. Srinivasan, S. A. Vinogradov, B. R. Rosen, R. B. Buxton, A. M. Dale, and D. A. Boas, “‘Overshoot’ of O₂ is required to maintain baseline tissue oxygenation at locations distal to blood vessels,” J. Neurosci.31(38), 13676–13681 (2011).
[CrossRef] [PubMed]

S. Sakadžić, E. Roussakis, M. A. Yaseen, E. T. Mandeville, V. J. Srinivasan, K. Arai, S. Ruvinskaya, A. Devor, E. H. Lo, S. A. Vinogradov, and D. A. Boas, “Two-photon high-resolution measurement of partial pressure of oxygen in cerebral vasculature and tissue,” Nat. Methods7(9), 755–759 (2010).
[CrossRef] [PubMed]

Stoy, H.

Stringari, C.

C. Stringari, A. Cinquin, O. Cinquin, M. A. Digman, P. J. Donovan, and E. Gratton, “Phasor approach to fluorescence lifetime microscopy distinguishes different metabolic states of germ cells in a live tissue,” Proc. Natl. Acad. Sci. U.S.A.108(33), 13582–13587 (2011).
[CrossRef] [PubMed]

Sullivan, R.

M. W. Conklin, P. P. Provenzano, K. W. Eliceiri, R. Sullivan, and P. J. Keely, “Fluorescence lifetime imaging of endogenous fluorophores in histopathology sections reveals differences between normal and tumor epithelium in carcinoma in situ of the breast,” Cell Biochem. Biophys.53(3), 145–157 (2009).
[CrossRef] [PubMed]

Sun, Y.

Sutin, J.

E. Gratton, S. Breusegem, J. Sutin, Q. Ruan, and N. Barry, “Fluorescence lifetime imaging for the two-photon microscope: time-domain and frequency-domain methods,” J. Biomed. Opt.8(3), 381–390 (2003).
[CrossRef] [PubMed]

Svoboda, K.

K. Svoboda and R. Yasuda, “Principles of two-photon excitation microscopy and its applications to neuroscience,” Neuron50(6), 823–839 (2006).
[CrossRef] [PubMed]

Sweedler, J. V.

T. A. Wang, Y. V. Yu, G. Govindaiah, X. Ye, L. Artinian, T. P. Coleman, J. V. Sweedler, C. L. Cox, and M. U. Gillette, “Circadian rhythm of redox state regulates excitability in suprachiasmatic nucleus neurons,” Science337(6096), 839–842 (2012).
[CrossRef] [PubMed]

Tamura, M.

M. Wakita, G. Nishimura, and M. Tamura, “Some characteristics of the fluorescence lifetime of reduced pyridine nucleotides in isolated mitochondria, isolated hepatocytes, and perfused rat liver in situ,” J. Biochem.118(6), 1151–1160 (1995).
[PubMed]

Thastrup, O.

G. H. Patterson, S. M. Knobel, P. Arkhammar, O. Thastrup, and D. W. Piston, “Separation of the glucose-stimulated cytoplasmic and mitochondrial NAD(P)H responses in pancreatic islet β cells,” Proc. Natl. Acad. Sci. U.S.A.97(10), 5203–5207 (2000).
[CrossRef] [PubMed]

Thorell, B.

B. Chance and B. Thorell, “Localization and kinetics of reduced pyridine nucleotide in living cells by microfluorometry,” J. Biol. Chem.234, 3044–3050 (1959).
[PubMed]

Thorling, C. A.

C. A. Thorling, X. Liu, F. J. Burczynski, L. M. Fletcher, G. C. Gobe, and M. S. Roberts, “Multiphoton microscopy can visualize zonal damage and decreased cellular metabolic activity in hepatic ischemia-reperfusion injury in rats,” J. Biomed. Opt.16(11), 116011 (2011).
[CrossRef] [PubMed]

Tinling, S.

Utzinger, U.

N. D. Kirkpatrick, C. Zou, M. A. Brewer, W. R. Brands, R. A. Drezek, and U. Utzinger, “Endogenous fluorescence spectroscopy of cell suspensions for chemopreventive drug monitoring,” Photochem. Photobiol.81(1), 125–134 (2005).
[CrossRef] [PubMed]

Valeur, B.

M. vandeVen, M. Ameloot, B. Valeur, and N. Boens, “Pitfalls and their remedies in time-resolved fluorescence spectroscopy and microscopy,” J. Fluoresc.15(3), 377–413 (2005).
[CrossRef] [PubMed]

Valle, I.

M. Monsalve, S. Borniquel, I. Valle, and S. Lamas, “Mitochondrial dysfunction in human pathologies,” Front. Biosci.12(1), 1131–1153 (2007).
[CrossRef] [PubMed]

Van Den Zegel, M.

M. Van Den Zegel, N. Boens, D. Daems, and F. C. De Schryver, “Possibilities and limitations of the time-correlated single photon counting technique: a comparative study of correction methods for the wavelength dependence of the instrument response function,” Chem. Phys.101(2), 311–335 (1986).
[CrossRef]

vandeVen, M.

M. vandeVen, M. Ameloot, B. Valeur, and N. Boens, “Pitfalls and their remedies in time-resolved fluorescence spectroscopy and microscopy,” J. Fluoresc.15(3), 377–413 (2005).
[CrossRef] [PubMed]

Vaughan, E. M.

D. K. Bird, L. Yan, K. M. Vrotsos, K. W. Eliceiri, E. M. Vaughan, P. J. Keely, J. G. White, and N. Ramanujam, “Metabolic mapping of MCF10A human breast cells via multiphoton fluorescence lifetime imaging of the coenzyme NADH,” Cancer Res.65(19), 8766–8773 (2005).
[CrossRef] [PubMed]

Vinogradov, S. A.

A. Devor, S. Sakadžić, P. A. Saisan, M. A. Yaseen, E. Roussakis, V. J. Srinivasan, S. A. Vinogradov, B. R. Rosen, R. B. Buxton, A. M. Dale, and D. A. Boas, “‘Overshoot’ of O₂ is required to maintain baseline tissue oxygenation at locations distal to blood vessels,” J. Neurosci.31(38), 13676–13681 (2011).
[CrossRef] [PubMed]

S. Sakadžić, E. Roussakis, M. A. Yaseen, E. T. Mandeville, V. J. Srinivasan, K. Arai, S. Ruvinskaya, A. Devor, E. H. Lo, S. A. Vinogradov, and D. A. Boas, “Two-photon high-resolution measurement of partial pressure of oxygen in cerebral vasculature and tissue,” Nat. Methods7(9), 755–759 (2010).
[CrossRef] [PubMed]

Vishwasrao, H. D.

H. D. Vishwasrao, A. A. Heikal, K. A. Kasischke, and W. W. Webb, “Conformational dependence of intracellular NADH on metabolic state revealed by associated fluorescence anisotropy,” J. Biol. Chem.280(26), 25119–25126 (2005).
[CrossRef] [PubMed]

K. A. Kasischke, H. D. Vishwasrao, P. J. Fisher, W. R. Zipfel, and W. W. Webb, “Neural activity triggers neuronal oxidative metabolism followed by astrocytic glycolysis,” Science305(5680), 99–103 (2004).
[CrossRef] [PubMed]

Vrotsos, K. M.

D. K. Bird, L. Yan, K. M. Vrotsos, K. W. Eliceiri, E. M. Vaughan, P. J. Keely, J. G. White, and N. Ramanujam, “Metabolic mapping of MCF10A human breast cells via multiphoton fluorescence lifetime imaging of the coenzyme NADH,” Cancer Res.65(19), 8766–8773 (2005).
[CrossRef] [PubMed]

Wakita, M.

M. Wakita, G. Nishimura, and M. Tamura, “Some characteristics of the fluorescence lifetime of reduced pyridine nucleotides in isolated mitochondria, isolated hepatocytes, and perfused rat liver in situ,” J. Biochem.118(6), 1151–1160 (1995).
[PubMed]

Wallace, D. C.

D. C. Wallace, “A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine,” Annu. Rev. Genet.39(1), 359–407 (2005).
[CrossRef] [PubMed]

Wang, T. A.

T. A. Wang, Y. V. Yu, G. Govindaiah, X. Ye, L. Artinian, T. P. Coleman, J. V. Sweedler, C. L. Cox, and M. U. Gillette, “Circadian rhythm of redox state regulates excitability in suprachiasmatic nucleus neurons,” Science337(6096), 839–842 (2012).
[CrossRef] [PubMed]

Webb, W. W.

H. D. Vishwasrao, A. A. Heikal, K. A. Kasischke, and W. W. Webb, “Conformational dependence of intracellular NADH on metabolic state revealed by associated fluorescence anisotropy,” J. Biol. Chem.280(26), 25119–25126 (2005).
[CrossRef] [PubMed]

K. A. Kasischke, H. D. Vishwasrao, P. J. Fisher, W. R. Zipfel, and W. W. Webb, “Neural activity triggers neuronal oxidative metabolism followed by astrocytic glycolysis,” Science305(5680), 99–103 (2004).
[CrossRef] [PubMed]

W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, “Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation,” Proc. Natl. Acad. Sci. U.S.A.100(12), 7075–7080 (2003).
[CrossRef] [PubMed]

S. Huang, A. A. Heikal, and W. W. Webb, “Two-photon fluorescence spectroscopy and microscopy of NAD(P)H and flavoprotein,” Biophys. J.82(5), 2811–2825 (2002).
[CrossRef] [PubMed]

Weber, G.

T. G. Scott, R. D. Spencer, N. J. Leonard, and G. Weber, “Synthetic spectroscopic models related to coenzymes and base pairs. V. Emission properties of NADH. Studies of fluorescence lifetimes and quantum efficiencies of NADH, AcPyADH, [reduced acetylpyridineadenine dinucleotide] and simplified synthetic models,” J. Am. Chem. Soc.92(3), 687–695 (1970).
[CrossRef]

White, J. G.

M. C. Skala, K. M. Riching, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, J. G. White, and N. Ramanujam, “In vivo multiphoton microscopy of NADH and FAD redox states, fluorescence lifetimes, and cellular morphology in precancerous epithelia,” Proc. Natl. Acad. Sci. U.S.A.104(49), 19494–19499 (2007).
[CrossRef] [PubMed]

D. K. Bird, L. Yan, K. M. Vrotsos, K. W. Eliceiri, E. M. Vaughan, P. J. Keely, J. G. White, and N. Ramanujam, “Metabolic mapping of MCF10A human breast cells via multiphoton fluorescence lifetime imaging of the coenzyme NADH,” Cancer Res.65(19), 8766–8773 (2005).
[CrossRef] [PubMed]

Williams, R. M.

W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, “Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation,” Proc. Natl. Acad. Sci. U.S.A.100(12), 7075–7080 (2003).
[CrossRef] [PubMed]

Williamson, A.

Wolfrum, J.

M. Köllner and J. Wolfrum, “How many photons are necessary for fluorescence-lifetime measurements?” Chem. Phys. Lett.200(1-2), 199–204 (1992).
[CrossRef]

Wu, W.

E. Baraghis, A. Devor, Q. Fang, V. J. Srinivasan, W. Wu, F. Lesage, C. Ayata, K. A. Kasischke, D. A. Boas, and S. Sakadzić, “Two-photon microscopy of cortical NADH fluorescence intensity changes: correcting contamination from the hemodynamic response,” J. Biomed. Opt.16(10), 106003 (2011).
[CrossRef] [PubMed]

M. A. Yaseen, V. J. Srinivasan, S. Sakadžić, H. Radhakrishnan, I. Gorczynska, W. Wu, J. G. Fujimoto, and D. A. Boas, “Microvascular oxygen tension and flow measurements in rodent cerebral cortex during baseline conditions and functional activation,” J. Cereb. Blood Flow Metab.31(4), 1051–1063 (2011).
[CrossRef] [PubMed]

Yan, L.

D. K. Bird, L. Yan, K. M. Vrotsos, K. W. Eliceiri, E. M. Vaughan, P. J. Keely, J. G. White, and N. Ramanujam, “Metabolic mapping of MCF10A human breast cells via multiphoton fluorescence lifetime imaging of the coenzyme NADH,” Cancer Res.65(19), 8766–8773 (2005).
[CrossRef] [PubMed]

Yaseen, M. A.

A. Devor, S. Sakadžić, P. A. Saisan, M. A. Yaseen, E. Roussakis, V. J. Srinivasan, S. A. Vinogradov, B. R. Rosen, R. B. Buxton, A. M. Dale, and D. A. Boas, “‘Overshoot’ of O₂ is required to maintain baseline tissue oxygenation at locations distal to blood vessels,” J. Neurosci.31(38), 13676–13681 (2011).
[CrossRef] [PubMed]

M. A. Yaseen, V. J. Srinivasan, S. Sakadžić, H. Radhakrishnan, I. Gorczynska, W. Wu, J. G. Fujimoto, and D. A. Boas, “Microvascular oxygen tension and flow measurements in rodent cerebral cortex during baseline conditions and functional activation,” J. Cereb. Blood Flow Metab.31(4), 1051–1063 (2011).
[CrossRef] [PubMed]

S. Sakadžić, E. Roussakis, M. A. Yaseen, E. T. Mandeville, V. J. Srinivasan, K. Arai, S. Ruvinskaya, A. Devor, E. H. Lo, S. A. Vinogradov, and D. A. Boas, “Two-photon high-resolution measurement of partial pressure of oxygen in cerebral vasculature and tissue,” Nat. Methods7(9), 755–759 (2010).
[CrossRef] [PubMed]

Yasuda, R.

K. Svoboda and R. Yasuda, “Principles of two-photon excitation microscopy and its applications to neuroscience,” Neuron50(6), 823–839 (2006).
[CrossRef] [PubMed]

Ye, X.

T. A. Wang, Y. V. Yu, G. Govindaiah, X. Ye, L. Artinian, T. P. Coleman, J. V. Sweedler, C. L. Cox, and M. U. Gillette, “Circadian rhythm of redox state regulates excitability in suprachiasmatic nucleus neurons,” Science337(6096), 839–842 (2012).
[CrossRef] [PubMed]

Yu, Q.

Q. Yu and A. A. Heikal, “Two-photon autofluorescence dynamics imaging reveals sensitivity of intracellular NADH concentration and conformation to cell physiology at the single-cell level,” J. Photochem. Photobiol. B95(1), 46–57 (2009).
[CrossRef] [PubMed]

Yu, Y. V.

T. A. Wang, Y. V. Yu, G. Govindaiah, X. Ye, L. Artinian, T. P. Coleman, J. V. Sweedler, C. L. Cox, and M. U. Gillette, “Circadian rhythm of redox state regulates excitability in suprachiasmatic nucleus neurons,” Science337(6096), 839–842 (2012).
[CrossRef] [PubMed]

Zheng, W.

Zipfel, W. R.

K. A. Kasischke, H. D. Vishwasrao, P. J. Fisher, W. R. Zipfel, and W. W. Webb, “Neural activity triggers neuronal oxidative metabolism followed by astrocytic glycolysis,” Science305(5680), 99–103 (2004).
[CrossRef] [PubMed]

W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, “Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation,” Proc. Natl. Acad. Sci. U.S.A.100(12), 7075–7080 (2003).
[CrossRef] [PubMed]

Zou, C.

N. D. Kirkpatrick, C. Zou, M. A. Brewer, W. R. Brands, R. A. Drezek, and U. Utzinger, “Endogenous fluorescence spectroscopy of cell suspensions for chemopreventive drug monitoring,” Photochem. Photobiol.81(1), 125–134 (2005).
[CrossRef] [PubMed]

Anal. Biochem.

L. K. Klaidman, A. C. Leung, and J. D. Adams., “High-performance liquid chromatography analysis of oxidized and reduced pyridine dinucleotides in specific brain regions,” Anal. Biochem.228(2), 312–317 (1995).
[CrossRef] [PubMed]

Annu. Rev. Genet.

D. C. Wallace, “A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine,” Annu. Rev. Genet.39(1), 359–407 (2005).
[CrossRef] [PubMed]

Biochemistry

K. Blinova, S. Carroll, S. Bose, A. V. Smirnov, J. J. Harvey, J. R. Knutson, and R. S. Balaban, “Distribution of mitochondrial NADH fluorescence lifetimes: steady-state kinetics of matrix NADH interactions,” Biochemistry44(7), 2585–2594 (2005).
[CrossRef] [PubMed]

A. Gafni and L. Brand, “Fluorescence decay studies of reduced nicotinamide adenine dinucleotide in solution and bound to liver alcohol dehydrogenase,” Biochemistry15(15), 3165–3171 (1976).
[CrossRef] [PubMed]

Biomarkers Med.

A. A. Heikal, “Intracellular coenzymes as natural biomarkers for metabolic activities and mitochondrial anomalies,” Biomarkers Med.4(2), 241–263 (2010).
[CrossRef] [PubMed]

Biophys. J.

S. Huang, A. A. Heikal, and W. W. Webb, “Two-photon fluorescence spectroscopy and microscopy of NAD(P)H and flavoprotein,” Biophys. J.82(5), 2811–2825 (2002).
[CrossRef] [PubMed]

Brain Res.

R. Guarneri and V. Bonavita, “Nicotinamide adenine dinucleotides in the developing rat brain,” Brain Res.2(2), 145–150 (1966).
[CrossRef] [PubMed]

Cancer Res.

D. K. Bird, L. Yan, K. M. Vrotsos, K. W. Eliceiri, E. M. Vaughan, P. J. Keely, J. G. White, and N. Ramanujam, “Metabolic mapping of MCF10A human breast cells via multiphoton fluorescence lifetime imaging of the coenzyme NADH,” Cancer Res.65(19), 8766–8773 (2005).
[CrossRef] [PubMed]

Cell Biochem. Biophys.

M. W. Conklin, P. P. Provenzano, K. W. Eliceiri, R. Sullivan, and P. J. Keely, “Fluorescence lifetime imaging of endogenous fluorophores in histopathology sections reveals differences between normal and tumor epithelium in carcinoma in situ of the breast,” Cell Biochem. Biophys.53(3), 145–157 (2009).
[CrossRef] [PubMed]

Chem. Phys.

M. Van Den Zegel, N. Boens, D. Daems, and F. C. De Schryver, “Possibilities and limitations of the time-correlated single photon counting technique: a comparative study of correction methods for the wavelength dependence of the instrument response function,” Chem. Phys.101(2), 311–335 (1986).
[CrossRef]

Chem. Phys. Lett.

A. Habenicht, J. Hjelm, E. Mukhtar, F. Bergström, and L. B.-Å. Johansson, “Two-photon excitation and time-resolved fluorescence: I. The proper response function for analysing single-photon counting experiments,” Chem. Phys. Lett.354(5-6), 367–375 (2002).
[CrossRef]

M. Köllner and J. Wolfrum, “How many photons are necessary for fluorescence-lifetime measurements?” Chem. Phys. Lett.200(1-2), 199–204 (1992).
[CrossRef]

Chem. Rev.

M. Y. Berezin and S. Achilefu, “Fluorescence lifetime measurements and biological imaging,” Chem. Rev.110(5), 2641–2684 (2010).
[CrossRef] [PubMed]

ChemPhysChem

R. Niesner, B. Peker, P. Schlüsche, and K.-H. Gericke, “Noniterative biexponential fluorescence lifetime imaging in the investigation of cellular metabolism by means of NAD(P)H autofluorescence,” ChemPhysChem5(8), 1141–1149 (2004).
[CrossRef] [PubMed]

Cogn Neurodyn

L. Sokoloff, “The physiological and biochemical bases of functional brain imaging,” Cogn Neurodyn2(1), 1–5 (2008).
[CrossRef] [PubMed]

Front. Biosci.

M. Monsalve, S. Borniquel, I. Valle, and S. Lamas, “Mitochondrial dysfunction in human pathologies,” Front. Biosci.12(1), 1131–1153 (2007).
[CrossRef] [PubMed]

Indian J. Pathol. Microbiol.

S. K. Shankar, “Biology of aging brain,” Indian J. Pathol. Microbiol.53(4), 595–604 (2010).
[CrossRef] [PubMed]

J. Am. Chem. Soc.

T. G. Scott, R. D. Spencer, N. J. Leonard, and G. Weber, “Synthetic spectroscopic models related to coenzymes and base pairs. V. Emission properties of NADH. Studies of fluorescence lifetimes and quantum efficiencies of NADH, AcPyADH, [reduced acetylpyridineadenine dinucleotide] and simplified synthetic models,” J. Am. Chem. Soc.92(3), 687–695 (1970).
[CrossRef]

J. Biochem.

M. Wakita, G. Nishimura, and M. Tamura, “Some characteristics of the fluorescence lifetime of reduced pyridine nucleotides in isolated mitochondria, isolated hepatocytes, and perfused rat liver in situ,” J. Biochem.118(6), 1151–1160 (1995).
[PubMed]

J. Biol. Chem.

B. Chance, B. Schoener, R. Oshino, F. Itshak, and Y. Nakase, “Oxidation-reduction ratio studies of mitochondria in freeze-trapped samples. NADH and flavoprotein fluorescence signals,” J. Biol. Chem.254(11), 4764–4771 (1979).
[PubMed]

J. V. Rocheleau, W. S. Head, and D. W. Piston, “Quantitative NAD(P)H/flavoprotein autofluorescence imaging reveals metabolic mechanisms of pancreatic islet pyruvate response,” J. Biol. Chem.279(30), 31780–31787 (2004).
[CrossRef] [PubMed]

B. Chance and B. Thorell, “Localization and kinetics of reduced pyridine nucleotide in living cells by microfluorometry,” J. Biol. Chem.234, 3044–3050 (1959).
[PubMed]

H. D. Vishwasrao, A. A. Heikal, K. A. Kasischke, and W. W. Webb, “Conformational dependence of intracellular NADH on metabolic state revealed by associated fluorescence anisotropy,” J. Biol. Chem.280(26), 25119–25126 (2005).
[CrossRef] [PubMed]

Y. Avi-Dor, J. M. Olson, M. D. Doherty, and N. O. Kaplan, “Fluorescence of pyridine nucleotides in mitochondria,” J. Biol. Chem.237, 2377–2383 (1962).

J. Biomed. Opt.

E. Baraghis, A. Devor, Q. Fang, V. J. Srinivasan, W. Wu, F. Lesage, C. Ayata, K. A. Kasischke, D. A. Boas, and S. Sakadzić, “Two-photon microscopy of cortical NADH fluorescence intensity changes: correcting contamination from the hemodynamic response,” J. Biomed. Opt.16(10), 106003 (2011).
[CrossRef] [PubMed]

E. Gratton, S. Breusegem, J. Sutin, Q. Ruan, and N. Barry, “Fluorescence lifetime imaging for the two-photon microscope: time-domain and frequency-domain methods,” J. Biomed. Opt.8(3), 381–390 (2003).
[CrossRef] [PubMed]

C. A. Thorling, X. Liu, F. J. Burczynski, L. M. Fletcher, G. C. Gobe, and M. S. Roberts, “Multiphoton microscopy can visualize zonal damage and decreased cellular metabolic activity in hepatic ischemia-reperfusion injury in rats,” J. Biomed. Opt.16(11), 116011 (2011).
[CrossRef] [PubMed]

J. Cereb. Blood Flow Metab.

M. A. Yaseen, V. J. Srinivasan, S. Sakadžić, H. Radhakrishnan, I. Gorczynska, W. Wu, J. G. Fujimoto, and D. A. Boas, “Microvascular oxygen tension and flow measurements in rodent cerebral cortex during baseline conditions and functional activation,” J. Cereb. Blood Flow Metab.31(4), 1051–1063 (2011).
[CrossRef] [PubMed]

J. Fluoresc.

M. vandeVen, M. Ameloot, B. Valeur, and N. Boens, “Pitfalls and their remedies in time-resolved fluorescence spectroscopy and microscopy,” J. Fluoresc.15(3), 377–413 (2005).
[CrossRef] [PubMed]

J. Microsc.

V. K. Ramanujan, J. A. Jo, G. Cantu, and B. A. Herman, “Spatially resolved fluorescence lifetime mapping of enzyme kinetics in living cells,” J. Microsc.230(3), 329–338 (2008).
[CrossRef] [PubMed]

J. Neurosci.

A. Devor, S. Sakadžić, P. A. Saisan, M. A. Yaseen, E. Roussakis, V. J. Srinivasan, S. A. Vinogradov, B. R. Rosen, R. B. Buxton, A. M. Dale, and D. A. Boas, “‘Overshoot’ of O₂ is required to maintain baseline tissue oxygenation at locations distal to blood vessels,” J. Neurosci.31(38), 13676–13681 (2011).
[CrossRef] [PubMed]

J. Photochem. Photobiol. B

Q. Yu and A. A. Heikal, “Two-photon autofluorescence dynamics imaging reveals sensitivity of intracellular NADH concentration and conformation to cell physiology at the single-cell level,” J. Photochem. Photobiol. B95(1), 46–57 (2009).
[CrossRef] [PubMed]

J. Phys. Chem. C

V. V. Ghukasyan and F.-J. Kao, “Monitoring cellular metabolism with fluorescence lifetime of reduced nicotinamide adenine dinucleotide,” J. Phys. Chem. C113(27), 11532–11540 (2009).
[CrossRef]

Mol. Aspects Med.

M. R. Duchen, “Mitochondria in health and disease: perspectives on a new mitochondrial biology,” Mol. Aspects Med.25(4), 365–451 (2004).
[CrossRef] [PubMed]

Nat. Methods

S. Sakadžić, E. Roussakis, M. A. Yaseen, E. T. Mandeville, V. J. Srinivasan, K. Arai, S. Ruvinskaya, A. Devor, E. H. Lo, S. A. Vinogradov, and D. A. Boas, “Two-photon high-resolution measurement of partial pressure of oxygen in cerebral vasculature and tissue,” Nat. Methods7(9), 755–759 (2010).
[CrossRef] [PubMed]

A. Nimmerjahn, F. Kirchhoff, J. N. D. Kerr, and F. Helmchen, “Sulforhodamine 101 as a specific marker of astroglia in the neocortex in vivo,” Nat. Methods1(1), 31–37 (2004).
[CrossRef] [PubMed]

Neuron

K. Svoboda and R. Yasuda, “Principles of two-photon excitation microscopy and its applications to neuroscience,” Neuron50(6), 823–839 (2006).
[CrossRef] [PubMed]

Opt. Express

Opt. Lett.

Photochem. Photobiol.

N. D. Kirkpatrick, C. Zou, M. A. Brewer, W. R. Brands, R. A. Drezek, and U. Utzinger, “Endogenous fluorescence spectroscopy of cell suspensions for chemopreventive drug monitoring,” Photochem. Photobiol.81(1), 125–134 (2005).
[CrossRef] [PubMed]

Proc. Natl. Acad. Sci. U.S.A.

M. C. Skala, K. M. Riching, A. Gendron-Fitzpatrick, J. Eickhoff, K. W. Eliceiri, J. G. White, and N. Ramanujam, “In vivo multiphoton microscopy of NADH and FAD redox states, fluorescence lifetimes, and cellular morphology in precancerous epithelia,” Proc. Natl. Acad. Sci. U.S.A.104(49), 19494–19499 (2007).
[CrossRef] [PubMed]

C. Stringari, A. Cinquin, O. Cinquin, M. A. Digman, P. J. Donovan, and E. Gratton, “Phasor approach to fluorescence lifetime microscopy distinguishes different metabolic states of germ cells in a live tissue,” Proc. Natl. Acad. Sci. U.S.A.108(33), 13582–13587 (2011).
[CrossRef] [PubMed]

G. H. Patterson, S. M. Knobel, P. Arkhammar, O. Thastrup, and D. W. Piston, “Separation of the glucose-stimulated cytoplasmic and mitochondrial NAD(P)H responses in pancreatic islet β cells,” Proc. Natl. Acad. Sci. U.S.A.97(10), 5203–5207 (2000).
[CrossRef] [PubMed]

W. R. Zipfel, R. M. Williams, R. Christie, A. Y. Nikitin, B. T. Hyman, and W. W. Webb, “Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation,” Proc. Natl. Acad. Sci. U.S.A.100(12), 7075–7080 (2003).
[CrossRef] [PubMed]

Pure Appl. Chem.

D. F. Eaton, “Recommended methods for fluorescence decay analysis,” Pure Appl. Chem.62(8), 1631–1648 (1990).
[CrossRef]

Science

K. A. Kasischke, H. D. Vishwasrao, P. J. Fisher, W. R. Zipfel, and W. W. Webb, “Neural activity triggers neuronal oxidative metabolism followed by astrocytic glycolysis,” Science305(5680), 99–103 (2004).
[CrossRef] [PubMed]

B. Chance, P. Cohen, F. Jobsis, and B. Schoener, “Intracellular oxidation-reduction states in vivo: the microfluorometry of pyridine nucleotide gives a continuous measurement of the oxidation state,” Science137(3529), 499–508 (1962).
[CrossRef] [PubMed]

T. A. Wang, Y. V. Yu, G. Govindaiah, X. Ye, L. Artinian, T. P. Coleman, J. V. Sweedler, C. L. Cox, and M. U. Gillette, “Circadian rhythm of redox state regulates excitability in suprachiasmatic nucleus neurons,” Science337(6096), 839–842 (2012).
[CrossRef] [PubMed]

Other

J. R. Lakowicz, ed., Principles of Fluorescence Spectroscopy (Springer, New York, 2006).

D. L. Nelson and M. M. Cox, Lehninger Principles of Biochemistry (W.H. Freeman, New York, 2008).

J. R. Lakowicz, Principles of Fluorescence Spectroscopy (Springer, New York, 2006).

W. Becker, Advanced Time-Correlated Single Photon Counting Techniques (Springer, Berlin, 2005).

F. Hyder, “Dynamic imaging of brain function,” in Dynamic Brain Imaging: Multi-Modal Methods and In vivo Applications, F. Hyder, ed. (Humana, Totowa, NJ, 2009), pp. 3–21.

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Figures (3)

Fig. 1
Fig. 1

(a) 2-photon imaging portion of our custom built in vivo imaging system, modified for FLIM measurements. SH: shutter, M: reflecting mirror, P: polarizer, EOM: electro-optic modulator, XY: galvanometer-based scanners, DM: Dichroic Mirror, PCM: photon counting module, PMT: photomultiplier tube. (a) Inset: reflectance image of the sealed cranial window model, approximately 3 mm in diameter at 570 nm. (b) In vivo image of NADH autofluorescence in a cortical astrocyte (Scale bar: 10 µm), with (c) pixel-wide distribution of 2-component fit performed with commercial SPCImage software, clearly showing 4 distinct peaks. (d) Example 4-component lifetime fit of in vivo cortical NADH fluorescence decay, computed with custom software. Blue profile: Collected, binned photon counts, Black-dashed lines: fitting boundaries, Green profile: computed IRF, Red profile: Computed decay profile (e) residuals for computed 2-, 3-, and 4-component lifetime fits to the example in vivo lifetime data, with reduced χ2 errors of 195.16, 2.64, and 2.54, respectively.

Fig. 2
Fig. 2

Spatial distributions of cerebral NADH components in vivo (a-b) Example in vivo intensity images collected from the rat cortex, ~70 µm below the cortical surface. (a) SR101 fluorescence preferentially accumulates within astrocytic cell bodies and processes, enabling distinction between astrocytic cell bodies (yellow ROIs), blood vessels (red ROIs), and neuropil. (b) NADH fluorescence can be seen more uniformly throughout the tissue, though overlying vasculature results in shadows. (c) Distributions of fractional fluorescence for the four computed NADH components and purported scattering component, determined by fitting the fluorescence decays at each pixel and classifying pixels as astrocytes (yellow ROIs) blood vessels (red ROIs), or surrounding neuropil (scale bar: 50 µm, error bars: standard error)

Fig. 3
Fig. 3

NADH transients during anoxia (a) Representative global transients of NADH components (amplitude-weighted lifetime, αiτi), and intensity transients for NADH, SR101, and backscattering. The shaded region corresponds to a 45 s period of anoxia, after which respiration was immediately restored. (b-e) Average component-specific changes in (b) anoxia-induced onset time (c) rise time (d) relative undershoot, and (e) maximal relative change, as measured from 10 trials of anoxia. Error bars denote standard error. * denote statistically significant differences from indicated components, measured with paired t-tests (α = 0.05)

Tables (1)

Tables Icon

Table 1 Computed parameters from profiles modeled with varied levels of added noise

Equations (4)

Equations on this page are rendered with MathJax. Learn more.

I R F ( t ) = F F T 1 ( F F T ( I m e a s u r e d ( t ) ) F F T ( I t h e o r e t i c a l ( t ) ) ) ,
I t h e o r e t i c a l ( t ) = I o f f s e t + i = 1 N α i exp ( t τ i ) ,
I m o d e l ( t ) = I R F ( t ) ( I 0 δ ( t ) + I t h e o r e t i c a l ( t ) ) ,
f k = α k τ k i = 1 N α i τ i .

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