Nonlinear magic: Multiphoton microscopy in the biosciences

Nature Biotechnology

Volumn 21, Issue 11, 2003, Pages 1369-1377

  Zipfel, Warren R ^a   Williams, Rebecca M ^a   Webb, Watt W ^a  

^a School of Civil and Environmental Engineering   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

FLUORESCENCE; LIGHT SCATTERING; NONLINEAR OPTICS; PHOTOCHEMICAL REACTIONS; PHOTONS;

MULTIPHOTON MICROSCOPY (MPM);

BIOTECHNOLOGY;

COLLAGEN FIBRIL;

BIOMEDICINE; BLOOD CELL; BLOOD FLOW; BRAIN; CAPILLARY; FLUORESCENCE MICROSCOPY; GENETIC CODE; LIGHT SCATTERING; MICROSCOPY; NONHUMAN; NONLINEAR SYSTEM; OPTICS; PHOTOCHEMISTRY; PHOTON; PRIORITY JOURNAL; REVIEW; TRANSGENIC MOUSE;

BIOLOGICAL SCIENCES; EQUIPMENT DESIGN; IMAGE ENHANCEMENT; IMAGING, THREE-DIMENSIONAL; MICROSCOPY, CONFOCAL; MICROSCOPY, FLUORESCENCE, MULTIPHOTON; NONLINEAR DYNAMICS; TRANSDUCERS;

ANIMALIA; MUS MUSCULUS;

EID: 0242353872     PISSN: 10870156     EISSN: None     Source Type: Journal    
DOI: 10.1038/nbt899     Document Type: Review

References (144)

1. Denk, W., Strickler, J.H. & Webb, W.W. Two-photon laser scanning fluorescence microscopy. Science 248, 73-76 (1990).
2. Yuste, R. & Denk, W. Dendritic spines as basic functional units of neuronal integration. Nature 375, 682-684 (1995).
3. Mainen, Z.F., Malinow, R. & Svoboda, K. Synaptic calcium transients in single spines indicate that NMDA receptors are not saturated. Nature 399, 151-155 (1999).
4. + imaging in spines and fine dendrites of central neurons. Pflugers Arch. 439, 201-207 (1999).
5. 2+ concentration rises in rat cerebellar basket cell axons. J. Physiol. 520 Pt 1, 65-78 (1999).
6. Cox, C.L., Denk, W., Tank, D.W. & Svoboda, K. Action potentials reliably invade axonal arbors of rat neocortical neurons. Proc. Natl. Acad. Sci. USA 97, 9724-9728 (2000).
7. Majewska, A., Tashiro, A. & Yuste, R. Regulation of spine calcium dynamics by rapid spine motility. J. Neurosci. 20, 8262-8268 (2000).
8. Oertner, T.G. Functional imaging of single synapses in brain slices. Exp. Physiol. 87, 733-736 (2002).
9. 2+ signals by small oblique dendrites of CA1 pyramidal neurons. J. Neurosci. 23, 3243-3250 (2003).
10. Lendvai, B., Zelles, T., Rozsa, B. & Vizi, E.S. A vinca alkaloid enhances morphological dynamics of dendritic spines of neocortical layer 2/3 pyramidal cells. Brain Res. Bull. 59, 257-260 (2003).
11. Sabatini, B.L. & Svoboda, K. Analysis of calcium channels in single spines using optical fluctuation analysis. Nature 408, 589-593 (2000).
12. Svoboda, K., Denk, W., Kleinfeld, D. & Tank, D.W. In vivodendritic calcium dynamics in neocortical pyramidal neurons. Nature 385, 161-165 (1997).
13. Helmchen, F., Svoboda, K., Denk, W. & Tank, D.W. In vivo dendritic calcium dynamics in deep-layer cortical pyramidal neurons. Nat. Neurosci. 2, 989-996 (1999).
14. Stosiek, C., Garaschuk, O., Holthoff, K. & Konnerth, A. In vivo two-photon calcium imaging of neuronal networks. Proc. Natl. Acad. Sci. USA 100, 7319-7324 (2003).
15. Helmchen, F. & Waters, J. Ca(2+) imaging in the mammalian brain in vivo. Eur. J. Pharmacol. 447, 119-129 (2002).
16. Svoboda, K., Tank, D.W. & Denk, W. Direct measurement of coupling between dendritic spines and shafts. Science 272, 716-719 (1996).
17. Ladewig, T. et al. Spatial profiles of store-dependent calcium release in motoneurones of the nucleus hypoglossus from newborn mouse. J. Physiol. 547, 775-787 (2003).
18. Christie, R.H. et al. Growth arrest of individual senile plaques in a model of Alzheimer's disease observed by in vivo multiphoton microscopy. J. Neurosci. 21, 858-864 (2001).
19. Bacskai, B.J. et al. Non-Fc-mediated mechanisms are involved in clearance of amyloid-beta in vivo by immunotherapy. J. Neurosci. 22, 7873-7878 (2002).
20. D'Amore, J.D. et al. In vivo multiphoton imaging of a transgenic mouse model of Alzheimer disease reveals marked thioflavine-S-associated alterations in neurite trajectories. J. Neuropathol. Exp. Neurol. 62, 137-145 (2003).
21. Bacskai, B.J. et al. Imaging of amyloid-beta deposits in brains of living mice permits direct observation of clearance of plaques with immunotherapy. Nat. Med. 7, 369-372 (2001).
22. Brown, E.B. et al. In vivo measurement of gene expression, angiogenesis and physiological function in tumors using multiphoton laser scanning microscopy. Nat. Med. 7, 864-868 (2001).
23. McDonald, D.M. & Choyke, P.L. Imaging of angiogenesis: from microscope to clinic. Nat. Med. 9, 713-725 (2003).
24. Wang, W. et al. Single cell behavior in metastatic primary mammary tumors correlated with gene expression patterns revealed by molecular profiling. Cancer Res. 62, 6278-6288 (2002).
25. Wolf, K. et al. Compensation mechanism in tumor cell migration: mesenchymal-amoeboid transition after blocking of pericellular proteolysis. J. Cell Biol. 160, 267-277 (2003).
26. Cahalan, M.D., Parker, I., Wei, S.H. & Miller, M.J. Two-photon tissue imaging: seeing the immune system in a fresh light. Nat. Rev. Immunol. 2, 872-880 (2002).
27. Miller, M.J., Wei, S.H., Parker, I. & Cahalan, M.D. Two-photon imaging of lymphocyte motility and antigen response in intact lymph node. Science 296, 1869-1873 (2002).
28. Wei, S.H., Miller, M.J., Cahalan, M.D. & Parker, I. Two-photon imaging in intact lymphoid tissue. Adv. Exp. Med. Biol. 512, 203-208 (2002).
29. Miller, M.J., Wei, S.H., Cahalan, M.D. Parker, I. Autonomous T cell trafficking examined in vivo with intravital two-photon microscopy. Proc. Natl. Acad. Sci. USA 100, 2604-2609 (2003).
30. Acuto, O. T cell-dendritic cell interaction in vivo: random encounters favor development of long-lasting ties. Science STKE 2003, PE28 (2003).
31. Squirrell, J.M., Wokosin, D.L., White, J.G. & Bavister, B.D. Long-term two-photon fluorescence imaging of mammalian embryos without compromising viability. Nat. Biotechnol. 17, 763-767 (1999).
32. Gryczynski, I., Szmacinski, H. & Lakowicz, J.R. On the possibility of calcium imaging using Indo-1 with three-photon excitation. Photochem. Photobiol. 62, 804-808 (1995).
33. Lakowicz, J.R. et al. Time-resolved fluorescence spectroscopy and imaging of DNA labeled with DAPI and Hoechst 33342 using three-photon excitation. Biophys. J. 72, 567-578 (1997).
34. Maiti, S., Shear, J.B., Williams, R.M., Zipfel, W.R. & Webb, W.W. Measuring serotonin distribution in live cells with three-photon excitation. Science 275, 530-532 (1997).
35. Williams, R.M., Shear, J.B., Zipfel, W.R., Maiti, S. & Webb, W.W. Mucosal mast cell secretion processes imaged using three-photon microscopy of 5-hydroxytryptamine autofluorescence. Biophys. J. 76, 1835-1846 (1999).
36. Xu, C., Zipfel, W., Shear, J.B., Williams, R.M. & Webb, W.W. Multiphoton fluorescence excitation: new spectral windows for biological nonlinear microscopy. Proc. Natl. Acad. Sci. USA 93, 10763-10768 (1996).
37. Zipfel, W.R. et al. Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation. Proc. Natl. Acad. Sci. USA 100, 7075-7080 (2003).
38. Freund, I. & Deutsch, M. 2nd-harmonic microscopy of biological tissue. Opt. Lett. 11, 94-96 (1986).
39. Campagnola, P.J., Clark, H.A., Mohler, W.A., Lewis, A. & Loew, L.M. Second-harmonic imaging microscopy of living cells. J. Biomed. Opt. 6, 277-286 (2001).
40. Mertz, J. & Moreaux, L. Second-harmonic generation by focused excitation of inhomogeneously distributed scatterers. Opt. Commun. 196, 325-330 (2001).
41. Moreaux, L., Sandre, O., Charpak, S., Blanchard-Desce, M. & Mertz, J. Coherent scattering in multi-harmonic light microscopy. Biophys. J. 80, 1568-1574 (2001).
42. Campagnola, P.J. et al. Three-dimensional high-resolution second-harmonic generation imaging of endogenous structural proteins in biological tissues. Biophys. J. 82, 493-508 (2002).
43. Campagnola, P.J., Mohler, W. & Millard, A.E. 3-dimensional high-resolution second harmonic generation imaging of endogenous structural proteins in biological tissues. Biophys. J. 82, 175a-175a (2002).
44. Dombeck, D.A. et al. Uniform polarity microtubule assemblies imaged in native brain tissue by second-harmonic generation microscopy. Proc. Natl. Acad. Sci. USA 100, 7081-7086 (2003).
45. Zoumi, A., Yeh, A. & Tromberg, B.J. Imaging cells and extracellular matrix in vivo by using second-harmonic generation and two-photon excited fluorescence. Proc. Natl. Acad. Sci. USA 99, 11014-11019 (2002).
46. Barad, Y., Eisenberg, H., Horowitz, M. & Silberberg, Y. Nonlinear scanning laser microscopy by third harmonic generation. Appl. Phys. Lett. 70, 922-924 (1997).
47. Muller, M., Squier, J., Wilson, K.R. & Brakenhoff, G.J. 3D microscopy of transparent objects using third-harmonic generation. J. Microsc. 191, 266-274 (1998).
48. Yelin, D., Oron, D., Korkotian, E., Segal, M. & Silbergerg, Y. Third-harmonic microscopy with a titanium-sapphire laser. Appl. Phys. B-Lasers O 74, S97-S101 (2002).
49. Sheppard, C.J.R. & Kompfner, R. Resonant scanning optical microscope. Appl. Optics 17, 2879-2882 (1978).
50. Duncan, M.D., Reintjes, J. & Manuccia, T.J. Scanning coherent anti-Stokes Raman microscope. Opt. Lett. 7, 350-352 (1982).
51. Zumbusch, A., Holtom, G.R. & Xie, X.S. Vibrational mircoscopy using coherent anti-Stokes Raman scattering (1999). Phys. Rev. Lett. 82, 4014-4017 (1999).
52. Muller, M., Squier, J., De Lange, C.A. & Brakenhoff, G.J. CARS microscopy with folded BoxCARS phasematching. J. Microsc. 197 (Pt 2), 150-158 (2000).
53. Piston, D.W., Summers, R.G., Knobel, S.M. & Morrill, J.B. Characterization of involution during sea urchin gastrulation using two-photon excited photorelease and confocal microscopy. Microsc. Microanal. 4, 404-414 (1998).
54. Furuta, T. et al. Brominated 7-hydroxycoumarin-4-ylmethyls: photolabile protecting groups with biologically useful cross-sections for two photon photolysis. Proc. Natl. Acad. Sci. USA 96, 1193-1200 (1999).
55. Matsuzaki, M. et al. Dendritic spine geometry is critical for AMPA receptor expression in hippocampal CA1 pyramidal neurons. Nat. Neurosci. 4, 1086-1092 (2001).
56. Echevarria, W., Leite, M.F., Guerra, M.T., Zipfel, W.R. & Nathanson, M.H. Regulation of calcium signals in the nucleus by a nucleoplasmic reticulum. Nat. Cell. Biol. 5, 440-446 (2003).
57. Berland, K.M., So, P.T. & Gratton, E. Two-photon fluorescence correlation spectroscopy: method and application to the intracellular environment. Biophys. J. 68, 694-701 (1995).
58. Schwille, P., Haupts, U., Maiti, S. & Webb, W.W. Molecular dynamics in living cells observed by fluorescence correlation spectroscopy with one- and two-photon excitation. Biophys. J. 77, 2251-2265 (1999).
59. Brown, E.B., Wu, E.S., Zipfel, W. & Webb, W.W. Measurement of molecular diffusion in solution by multiphoton fluorescence photobleaching recovery. Biophys. J. 77, 2837-2849 (1999).
60. Zipfel, W.R. & Webb, W.W. In vivo diffusion measurements using multiphoton-excited fluorescence photobleaching recovery (MPFPR) and fluorescence correlation spectroscopy (MPFCS) in Methods in Cellular Imaging(ed. Periasamy, A.) 345-376 (Oxford University Press, Oxford, UK, 2001).
61. Stroh, M., Zipfel, W.R., Williams, R.M., Webb, W.W. & Saltzman, W.M. Diffusion of nerve growth factor in rat striatum as determined by multiphoton microscopy. Biophys. J. 85, 581-588 (2003).
62. Heinze, K.G., Koltermann, A. & Schwille, P. Simultaneous two-photon excitation of distinct labels for dual-color fluorescence cross correlation analysis. Proc. Natl. Acad. Sci. USA 97, 10377-10382 (2000).
63. Tirlapur, U.K. & Konig, K. Targeted transfection by femtosecond laser. Nature 418, 290-291 (2002).
64. Konig, K., Riemann, I. & Fritzsche, W. Nanodissection of human chromosomes with near-infrared femtosecond laser pulses. Opt. Lett. 26, 819-821 (2001).
65. Göppert-Mayer, M. Uber elementarakte mit zwei quantensprüngen. Ann. Phys. 9, 273-294 (1931).
66. Xu, C. & Webb, W.W. Multiphoton excitation of molecular fluorophores and nonlinear laser microscopy in Topics in Fluorescence Spectroscopy: Volume 5: Nonlinear and Two-Photon-Induced Fluorescence. (ed. Lakowicz, J.) 471-540 (Plenum Press, New York, 1997).
67. Xu, C. & Webb, W.W. Measurement of two-photon excitation cross sections of molecular fluorophores with data from 690 nm to 1050 nm. J. Opt. Soc. Am. B 13, 481-491 (1996).
68. Steinfeld, J.I. Molecules and Radiation. (MIT Press, Cambridge, MA, 1989).
69. Huang, S., Heikal, A.A. & Webb, W.W. Two-photon fluorescence spectroscopy and microscopy of NAD(P)H and flavoprotein. Biophys. J. 82, 2811-2825 (2002).
70. Piston, D.W., Masters, B.R. & Webb, W.W. Three-dimensionally resolved NAD(P)H cellular metabolic redox imaging of the in situ cornea with two-photon excitation laser scanning microscopy. J. Microsc. 178 (Pt 1), 20-27 (1995).
71. Wong, B.J., Wallace, V., Coleno, M., Benton, H.P. & Tromberg, B.J. Two-photon excitation laser scanning microscopy of human, porcine, and rabbit nasal septal cartilage. Tissue Eng. 7, 599-606 (2001).
72. Noda, M. et al. Switch to anaerobic glucose metabolism with NADH accumulation in the beta-cell model of mitochondrial diabetes. Characteristics of betaHC9 cells deficient in mitochondrial DNA transcription. J. Biol. Chem. 277, 41817-41826 (2002).
73. Zhang, Q., Piston, D.W. & Goodman, R.H. Regulation of corepressor function by nuclear NADH. Science 295, 1895-1897 (2002).
74. Larson, D.R. et al. Water-soluble quantum dots for multiphoton fluorescence imaging in vivo. Science 300, 1434-1436 (2003).
75. Albota, M. et al. Design of organic molecules with large two-photon absorption cross sections. Science 281, 1653-1656 (1998).
76. Wang, X.M. et al. Synthesis of new symmetrically substituted stilbenes with large multiphoton absorption cross section and strong two-photon-induced blue fluorescence. Bull. Chem. Soc. Jpn 74, 1977-1982 (2001).
77. Zhou, X. et al. One- and two-photon absorption properties of novel multi-branched molecules. Phys. Chem. Chem. Phys. 4, 4346-4352 (2002).
78. Heikal, A.A., Hess, S.T. & Webb, W.W. Multiphoton molecular spectroscopy and excited-state dynamics of enhanced green fluorescent protein (EGFP): acid-base specificity. Chem. Phys. 274, 37-55 (2001).
79. Blab, G.A., Lommerse, P.H.M., Cognet, L., Harms, G.S. & Schmidt, T. Two-photon excitation action cross-sections of the autofluorescent proteins. Chem. Phys. Lett. 350, 71-77 (2001).
80. Hanson, G.T. et al. Green fluorescent protein variants as ratiometric dual emission pH sensors. 1. Structural characterization and preliminary application. Biochemistry 41, 15477-15488 (2002).
81. Tsai, P.S. et al. All-optical histology using ultrashort laser pulses. Neuron 39, 27-41 (2003).
82. Mainen, Z.F. et al. Two-photon imaging in living brain slices. Methods 18, 231-239, (1999).
83. Shi, S.H. et al. Rapid spine delivery and redistribution of AMPA receptors after synaptic NMDA receptor activation. Science 284, 1811-1816 (1999).
84. D'Apuzzo, M., Mandolesi, G., Reis, G. & Schuman, E.M. Abundant GFP expression and LTP in hippocampal acute slices by in vivo injection of Sindbis virus. J. Neurophysiol. 86, 1037-1042 (2001).
85. Potter, S.M. et al. Structure and emergence of specific olfactory glomeruli in the mouse. J. Neurosci. 21, 9713-9723 (2001).
86. Strome, S. et al. Spindle dynamics and the role of gamma-tubulin in early Caenorhabditis elegans embryos. Mol. Biol. Cell 12, 1751-1764 (2001).
87. Ahmed, F. et al. GFP expression in the mammary gland for imaging of mammary tumor cells in transgenic mice. Cancer Res. 62, 7166-7169 (2002).
88. Lawson, N.D. & Weinstein, B.M. In vivo imaging of embryonic vascular development using transgenic zebrafish. Dev. Biol. 248, 307-318 (2002).
89. Bestvater, F. et al. Two-photon fluorescence absorption and emission spectra of dyes relevant for cell imaging. J. Microsc. 208, 108-115 (2002).
90. Dickinson, M.E., Simbuerger, E., Zimmermann, B., Waters, C.W. & Fraser, S.E. Multiphoton excitation spectra in biological samples. J. Biomed. Opt. 8, 329-338 (2003).
91. Periasamy, A. Fluorescence resonance energy transfer microscopy: a mini review. J. Biomed. Opt. 6, 287-291 (2001).
92. Majoul, I., Straub, M., Duden, R., Hell, S.W. & Soling, H.D. Fluorescence resonance energy transfer analysis of protein-protein interactions in single living cells by multifocal multiphoton microscopy. J. Biotechnol. 82, 267-277 (2002).
93. Bacskai, B.J., Skoch, J., Hickey, G.A., Allen, R. & Hyman, B.T. Fluorescence resonance energy transfer determinations using multiphoton fluorescence lifetime imaging microscopy to characterize amyloid-beta plaques. J. Biomed. Opt. 8, 368-375 (2003).
94. Gu, M. & Sheppard, C.J.R. Comparison of three-dimensional imaging properties between two-photon and single-photon fluorescence microscopy. J. Microsc. 177, 128-137 (1995).
95. Centonze, V.E. & White, J.G. Multiphoton excitation provides optical sections from deeper within scattering specimens than confocal imaging. Biophys. J. 75, 2015-2024 (1998).
96. Periasamy, A., Skoglund, P., Noakes, C. & Keller, R. An evaluation of two-photon excitation versus confocal and digital deconvolution fluorescence microscopy imaging in Xenopus morphogenesis. Microsc. Res. Technol. 47, 172-181 (1999).
97. Schilders, S.P. & Gu, M. Limiting factors on image quality in imaging through turbid media under single-photon and two-photon excitation. Microsc. Microanal. 6, 156-160 (2000).
98. Sheppard, C.J.R. & Gu, M. Image-formation in 2-photon fluorescence microscopy. Optik 86, 104-106 (1990).
99. Richards, B. & Wolf, E. Electromagnetic Diffraction in Optical Systems. 2. Structure of the Image Field in an Aplanatic System. Proc. R. Soc. Lon. Ser. -A 253, 358-379 (1959).
100. Sheppard, C.J.R. & Matthews, H.J. Imaging in high-aperture optical systems. J. Opt. Soc. Am. A 4, 1354-1360 (1987).
101. Beaurepaire, E., Oheim, M. & Mertz, J. Ultra-deep two-photon fluorescence excitation in turbid media. Opt. Commun. 188, 25-29 (2001).
102. Theer, P., Hasan, M.T. & Denk, W. Two-photon imaging to a depth of 1000 microm in living brains by use of a Ti:AI203 regenerative amplifier. Opt. Lett. 28, 1022-1024 (2003).
103. Curley, P.F., Ferguson, A.I., White, J.G. & Amos, W.B. Application of a femtosecond self-sustaining mode-locked Ti:sapphire laser to the field of laser scanning confocal microscopy. Opt. Quant. Electron. 24, 851-859 (1992).
104. Hockberger, P.E. et al. Activation of flavin-containing oxidases underlies light-induced production of H2O2 in mammalian cells. Proc. Natl. Acad. Sci. USA 96, 6255-6260 (1999).
105. Wokosin, D.L., Squirrell, J.M., Eliceiri, K.W. & White, J.G. Optical workstation with concurrent, independent multiphoton imaging and experimental laser microbeam capabilities. Rev. Sci. Instrum. 74, 193-201 (2003).
106. Hopkins, J. & Sibbett, W. Ultrashort lasers: big payoff in a flash. Sci. Am. 283, 73-79 (2000).
107. Soeller, C. & Cannell, M.B. Construction of a two-photon microscope and optimization of illumination pulse duration. Pflugers Arch. 432, 555-561 (1996).
108. Squier, J. & Muller, M. High resolution nonlinear microscopy: A review of sources and methods for achieving optimal imaging. Rev. Sci. Instrum. 72, 2855-2867 (2001).
109. Muller, D., Squier, J. & Brakenhoff, G.J. Measurement of femtosecond pulses in the focal point of a high-numerical-aperture lens by two-photon absorption. Opt. Lett. 20, 1038-1040 (1995).
110. Guild, J.B., Xu, C. & Webb, W.W. Measurement of group delay dispersion of high numerical aperture objective lenses using two-photon excited fluorescence. Appl. Optics 36, 397-401 (1997).
111. Muller, M., Squier, J., Wolleschensky, R., Simon, U. & Brakenhoff, G.J. Dispersion precompensation of 15 femtosecond optical pulses for high-numerical-aperture objectives. J. Microsc. 191, 141-150 (1998).
112. Majewska, A., Yiu, G. & Yuste, R. A custom-made two-photon microscope and deconvolution system. Pflugers Arch. 441, 398-408 (2000).
113. Tsai, P.S. et al. Principles, design and construction of a two photon scanning microscope for in vitro and in vivo studies in Methods for In Vivo Optical Imaging(ed. Frostig, R.) 113-171 (CRC Press, Boca Raton, FL, 2002).
114. Iyer, V., Losavio, B.E. & Saggau, P. Compensation of spatial and temporal dispersion for acousto-optic multiphoton laser-scanning microscopy. J. Biomed. Opt. 8, 460-471 (2003).
115. Pawley, J.B. Handbook of Biological Confocal Microscopy, edn 2. (Plenum Press, New York, 1995).
116. Fan, G.Y. et al. Video-rate scanning two-photon excitation fluorescence microscopy and ratio imaging with cameleons. Biophys. J. 76, 2412-2420 (1999).
117. (2+) imaging. Cell Calcium 30, 383-393 (2001).
118. Gauderon, R., Lukins, P.B. & Sheppard, C.J. Effect of a confocal pinhole in two-photon microscopy. Microsc. Res. Technol. 47, 210-214 (1999).
119. Oheim, M., Beaurepaire, E., Chaigneau, E., Mertz, J. & Charpak, S. Two-photon microscopy in brain tissue: parameters influencing the imaging depth. J. Neurosci. Methods 111, 29-37 (2001).
120. Egner, A., Jakobs, S. & Hell, S.W. Fast 100-nm resolution three-dimensional microscope reveals structural plasticity of mitochondria in live yeast. Proc. Natl. Acad. Sci. USA 99, 3370-3375 (2002).
121. Tan, Y.P., Llano, I., Hopt, A., Wurriehausen, F. & Neher, E. Fast scanning and efficient photodetection in a simple two-photon microscope. J. Neurosci. Methods 92, 123-135 (1999).
122. Gratton, E., Breusegem, S., Sutin, J., Ruan, Q. & Barry, N. Fluorescence lifetime imaging for the two-photon microscope: time-domain and frequency-domain methods. J. Biomed. Opt. 8, 381-390 (2003).
123. Moreaux, L., Sandre, O. & Mertz, J. Membrane imaging by second-harmonic generation microscopy. J. Opt. Soc. Am. B 17, 1685-1694 (2000).
124. Peleg, G., Lewis, A., Linial, M. & Loew, L.M. Nonlinear optical measurement of membrane potential around single molecules at selected cellular sites. Proc. Natl. Acad. Sci. USA 96, 6700-6704 (1999).
125. Moreaux, L., Sandre, O., Blanchard-Desce, M. & Mertz, J. Membrane imaging by simultaneous second-harmonic generation and two-photon microscopy. Opt. Lett. 25, 320-322 (2000).
126. Millard, A.C., Jin, L., Lewis, A. & Loew, L.M. Direct measurement of the voltage sensitivity of second-harmonic generation from a membrane dye in patch-clamped cells. Opt. Lett. 28, 1221-1223 (2003).
127. Mohler, W., Millard, A.C. & Campagnola, P.J. Second harmonic generation imaging of endogenous structural proteins. Methods 29, 97-109 (2003).
128. Konig, K., So, P.T., Mantulin, W.W., Tromberg, B.J. & Gratton, E. Two-photon excited lifetime imaging of autofluorescence in cells during UVA and NIR photostress. J. Microsc. 183 (Pt 3), 197-204 (1996).
129. 2+ fluorescence imaging with pico- and femtosecond two-photon excitation: signal and photodamage. Biophys. J. 77, 2226-2236 (1999).
130. Hopt, A. & Neher, E. Highly nonlinear photodamage in two-photon fluorescence microscopy. Biophys. J. 80, 2029-2036 (2001).
131. Dittrich, P.S. & Schwille, P. Photobleaching and stabilization of fluorophores used for single-molecule analysis with one- and two-photon excitation. Appl. Phys. B. Lasers O 73, 829-837 (2001).
132. Patterson, G.H. & Piston, D.W. Photobleaching in two-photon excitation microscopy. Biophys. J. 78, 2159-2162 (2000).
133. Neil, M.A. et al. Adaptive aberration correction in a two-photon microscope. J. Microsc. 200 (Pt 2), 105-108 (2000).
134. Booth, M.J., Neil, M.A. & Wilson, T. New modal wave-front sensor: application to adaptive confocal fluorescence microscopy and two-photon excitation fluorescence microscopy. J. Opt. Soc. Am. A Opt. Image Sci. Vis. 19, 2112-2120 (2002).
135. Marsh, P.N., Burns, D. & Girkin, J.M. Practical implementation of adaptive optics in multiphoton microscopy. Opt. Express 11, 1123-1130 (2003).
136. Brunner, F. et al. Diode-pumped femtosecond Yb:KGd(WO/sub 4/)/sub 2/ laser with 1.1-W average power. Opt. Lett. 25, 1119-1121 (2000).
137. Ilday, F.O., Lim, H., Buckley, J.R. & Wise, F.W. Practical all-fiber source of high-power, 120-fs pulses at 1 micron. Opt. Lett. 28, 1362-1364 (2003).
138. Jung, J.C. & Schnitzer, M.J. Multiphoton endoscopy. Opt. Lett. 28, 902-904 (2003).
139. Bird, D. & Gu, M. Two-photon fluorescence endoscopy with a mirco-optic scanning head. Opt. Lett. 28, 1552-1554 (2003).
140. Ouzounov, D.G. et al. Delivery of nanojoule femtosecond pulses through large-core microstructured fibers. Opt. Lett. 27, 1513-1515 (2002).
141. Pastirk, I., Dela Cruz, J.M., Walowicz, K.A., Lozovoy, V.V. & Dantus, M. Selective two-photon microscopy with shaped femtosecond pulses. Opt. Express 11, 1695-1701 (2003).
142. Williams, R.M. & Webb, W.W. Single granule pH cycling in antigen-induced mast cell secretion. J. Cell Sci. 113 (Pt 21), 3839-3850 (2000).
143. (2+) accumulation revealed by multiphoton microscopy in an identified motoneuron and its modulation by dopamine. J. Neurosci. 20, 2523-2533 (2000).
144. Kleinfeld, D., Mitra, P.P., Helmchen, F. & Denk, W. Fluctuations and stimulus-induced changes in blood flow observed in individual capillaries in layers 2 through 4 of rat neocortex. Proc. Natl. Acad. Sci. USA 95, 15741-15746 (1998).