Abstract

This paper is intended to give a comprehensive review of light-sheet (LS) microscopy from an optics perspective. As such, emphasis is placed on the advantages that LS microscope configurations present, given the degree of freedom gained by uncoupling the excitation and detection arms. The new imaging properties are first highlighted in terms of optical parameters and how these have enabled several biomedical applications. Then, the basics are presented for understanding how a LS microscope works. This is followed by a presentation of a tutorial for LS microscope designs, each working at different resolutions and for different applications. Then, based on a numerical Fourier analysis and given the multiple possibilities for generating the LS in the microscope (using Gaussian, Bessel, and Airy beams in the linear and nonlinear regimes), a systematic comparison of their optical performance is presented. Finally, based on advances in optics and photonics, the novel optical implementations possible in a LS microscope are highlighted.

© 2018 Optical Society of America

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2017 (7)

R. M. Power and J. Huisken, “A guide to light-sheet fluorescence microscopy for multiscale imaging,” Nat. Methods 14, 360–373 (2017).
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P. P. Laissue, R. A. Alghamdi, P. Tomancak, E. G. Reynaud, and H. Shroff, “Assessing phototoxicity in live fluorescence imaging,” Nat. Methods 14, 657–661 (2017).

J. Andilla, R. Jorand, O. E. Olarte, A. C. Dufour, M. Cazales, Y. L. E. Montagner, R. Ceolato, N. Riviere, J.-C. Olivo-Marin, P. Loza-Alvarez, and C. Lorenzo, “Imaging tissue-mimic with light sheet microscopy: a comparative guideline,” Sci. Rep. 7, 44939 (2017).
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E. Zagato, T. Brans, S. Verstuyft, D. van Thourhout, J. Missinne, G. van Steenberge, J. Demeester, S. De Smedt, K. Remaut, K. Neyts, and K. Braeckmans, “Microfabricated devices for single objective single plane illumination microscopy (SoSPIM),” Opt. Express 25, 1732–1745 (2017).
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A. Rohrbacher, O. E. Olarte, V. Villamaina, P. Loza-Alvarez, and B. Resan, “Multiphoton imaging with blue-diode-pumped SESAM-modelocked Ti:sapphire oscillator generating 5 nJ 82 fs pulses,” Opt. Express 25, 10677–10684 (2017).
[Crossref]

N. Ji, “Adaptive optical fluorescence microscopy,” Nat. Methods 14, 374–380 (2017).
[Crossref]

B.-J. Chang, V. D. P. Meza, and E. H. K. Stelzer, “csiLSFM combines light-sheet fluorescence microscopy and coherent structured illumination for a lateral resolution below 100 nm,” Proc. Natl. Acad. Sci. USA 114, 4869–4874 (2017).
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2016 (14)

J. D. Manton and E. J. Rees, “triSPIM: light sheet microscopy with isotropic super-resolution,” Opt. Lett. 41, 4170–4173 (2016).
[Crossref]

D. Di Battista, D. Ancora, H. Zhang, K. Lemonaki, E. Marakis, E. Liapis, S. Tzortzakis, and G. Zacharakis, “Tailored light sheets through opaque cylindrical lenses,” Optica 3, 1237–1240 (2016).
[Crossref]

W. R. Legant, L. Shao, J. B. Grimm, T. A. Brown, D. E. Milkie, B. B. Avants, L. D. Lavis, and E. Betzig, “High-density three-dimensional localization microscopy across large volumes,” Nat. Methods 13, 359–365 (2016).
[Crossref]

P. Hoyer, G. de Medeiros, B. Balázs, N. Norlin, C. Besir, J. Hanne, H.-G. Kräusslich, J. Engelhardt, S. J. Sahl, S. W. Hell, and L. Hufnagel, “Breaking the diffraction limit of light-sheet fluorescence microscopy by RESOLFT,” Proc. Natl. Acad. Sci. USA 113, 3442–3446 (2016).
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L. A. Royer, W. C. Lemon, R. K. Chhetri, Y. Wan, M. Coleman, E. W. Myers, and P. J. Keller, “Adaptive light-sheet microscopy for long-term, high-resolution imaging in living organisms,” Nat. Biotechnol. 34, 1267–1278 (2016).
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P. Theer, D. Dragneva, and M. Knop, “πSPIM: high NA high resolution isotropic light-sheet imaging in cell culture dishes,” Sci. Rep. 6, 32880 (2016).
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S. L. Reidt, D. J. O’Brien, K. Wood, and M. P. MacDonald, “Polarised light sheet tomography,” Opt. Express 24, 11239–11249 (2016).
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T. Meinert, O. Tietz, K. J. Palme, and A. Rohrbach, “Separation of ballistic and diffusive fluorescence photons in confocal light-sheet microscopy of Arabidopsis roots,” Sci. Rep. 6, 30378 (2016).
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J. Nylk, K. McCluskey, S. Aggarwal, J. A. Tello, and K. Dholakia, “Enhancement of image quality and imaging depth with Airy light-sheet microscopy in cleared and non-cleared neural tissue,” Biomed. Opt. Express 7, 4021–4033 (2016).
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M. B. M. Meddens, S. Liu, P. S. Finnegan, T. L. Edwards, C. D. James, and K. A. Lidke, “Single objective light-sheet microscopy for high-speed whole-cell 3D super-resolution,” Biomed. Opt. Express 7, 2219–2236 (2016).
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S. Quirin, N. Vladimirov, C.-T. Yang, D. S. Peterka, R. Yuste, and M. Ahrens, “Calcium imaging of neural circuits with extended depth-of-field light-sheet microscopy,” Opt. Lett. 41, 855–858 (2016).
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W. Müller, M. Kielhorn, M. Schmitt, J. Popp, and R. Heintzmann, “Light sheet Raman micro-spectroscopy,” Optica 3, 452–457 (2016).
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E. S. Welf, M. K. Driscoll, K. M. Dean, C. Schäfer, J. Chu, M. W. Davidson, M. Z. Lin, G. Danuser, and R. Fiolka, “Quantitative multiscale cell imaging in controlled 3D microenvironments,” Dev. Cell 36, 462–475 (2016).
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P. Paiè, F. Bragheri, A. Bassi, and R. Osellame, “Selective plane illumination microscopy on a chip,” Lab Chip 16, 1556–1560 (2016).
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2015 (20)

B. Schmid and J. Huisken, “Real-time multi-view deconvolution,” Bioinformatics 31, 3398–3400 (2015).
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I. Golub, B. Chebbi, and J. Golub, “Toward the optical ‘magic carpet’: reducing the divergence of a light sheet below the diffraction limit,” Opt. Lett. 40, 5121–5124 (2015).
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W. Zong, J. Zhao, X. Chen, Y. Lin, H. Ren, Y. Zhang, M. Fan, Z. Zhou, H. Cheng, Y. Sun, and L. Chen, “Large-field high-resolution two-photon digital scanned light-sheet microscopy,” Cell Res. 25, 254–257 (2015).
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N. Scherf and J. Huisken, “The smart and gentle microscope,” Nat. Biotechnol. 33, 815–818 (2015).
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P. Weber, S. Schickinger, M. Wagner, B. Angres, T. Bruns, and H. Schneckenburger, “Monitoring of apoptosis in 3D cell cultures by FRET and light sheet fluorescence microscopy,” Int. J. Mol. Sci. 16, 5375–5385 (2015).
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W. Jahr, B. Schmid, C. Schmied, F. O. Fahrbach, and J. Huisken, “Hyperspectral light sheet microscopy,” Nat. Commun. 6, 7990 (2015).
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I. Rocha-Mendoza, J. Licea-Rodriguez, M. Marro, O. E. Olarte, M. Plata-Sanchez, and P. Loza-Alvarez, “Rapid spontaneous Raman light sheet microscopy using cw-lasers and tunable filters,” Biomed. Opt. Express 6, 3449–3461 (2015).
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M. B. Bouchard, V. Voleti, C. S. Mendes, C. Lacefield, W. B. Grueber, R. S. Mann, R. M. Bruno, and E. M. C. Hillman, “Swept confocally-aligned planar excitation (SCAPE) microscopy for high-speed volumetric imaging of behaving organisms,” Nat. Photonics 9, 113–119 (2015).
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O. E. Olarte, J. Andilla, D. Artigas, and P. Loza-Alvarez, “Decoupled illumination detection in light sheet microscopy for fast volumetric imaging,” Optica 2, 702–705 (2015).
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O. E. Olarte, J. Andilla, D. Artigas, and P. Loza-Alvarez, “Decoupled illumination-detection microscopy,” Opt. Photon. News 26(12), 41 (2015), special issue on Optics in 2015.

R. Galland, G. Grenci, A. Aravind, V. Viasnoff, V. Studer, and J.-B. Sibarita, “3D high- and super-resolution imaging using single-objective SPIM,” Nat. Methods 12, 641–644 (2015).
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P. Strnad, S. Gunther, J. Reichmann, U. Krzic, B. Balazs, G. de Medeiros, N. Norlin, T. Hiiragi, L. Hufnagel, and J. Ellenberg, “Inverted light-sheet microscope for imaging mouse pre-implantation development,” Nat. Methods 13, 139–142 (2015).
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R. K. Chhetri, F. Amat, Y. Wan, B. Höckendorf, W. C. Lemon, and P. J. Keller, “Whole-animal functional and developmental imaging with isotropic spatial resolution,” Nat. Methods 12, 1171–1178 (2015).
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E. J. Gualda, H. Pereira, T. Vale, M. Falcão Estrada, C. Brito, and N. Moreno, “SPIM-fluid: open source light-sheet based platform for high-throughput imaging,” Biomed. Opt. Express 6, 4447–4456 (2015).
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V. Trivedi, T. V. Truong, L. A. Trinh, D. B. Holland, M. Liebling, and S. E. Fraser, “Dynamic structure and protein expression of the live embryonic heart captured by 2-photon light sheet microscopy and retrospective registration,” Biomed. Opt. Express 6, 2056–2066 (2015).
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L. Gao, “Optimization of the excitation light sheet in selective plane illumination microscopy,” Biomed. Opt. Express 6, 881–890 (2015).
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Z. Yang, L. Mei, F. Xia, Q. Luo, L. Fu, and H. Gong, “Dual-slit confocal light sheet microscopy for in vivo whole-brain imaging of zebrafish,” Biomed. Opt. Express 6, 1797–1811 (2015).
[Crossref]

J.-H. Spille, T. P. Kaminski, K. Scherer, J. S. Rinne, A. Heckel, and U. Kubitscheck, “Direct observation of mobility state transitions in RNA trajectories by sensitive single molecule feedback tracking,” Nucleic Acids Res. 43, e14 (2015).
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R. Tomer, M. Lovett-Barron, I. Kauvar, A. Andalman, V. M. Burns, S. Sankaran, L. Grosenick, M. Broxton, S. Yang, and K. Deisseroth, “SPED light sheet microscopy: fast mapping of biological system structure and function,” Cell 163, 1796–1806 (2015).
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K. F. Tehrani, J. Xu, Y. Zhang, P. Shen, and P. Kner, “Adaptive optics stochastic optical reconstruction microscopy (AO-STORM) using a genetic algorithm,” Opt. Express 23, 13677–13692 (2015).
[Crossref]

2014 (20)

K. Wang, D. E. Milkie, A. Saxena, P. Engerer, T. Misgeld, M. E. Bronner, J. Mumm, and E. Betzig, “Rapid adaptive optical recovery of optimal resolution over large volumes,” Nat. Methods 11, 625–628 (2014).
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J. W. Krieger, A. P. Singh, C. S. Garbe, T. Wohland, and J. Langowski, “Dual-color fluorescence cross-correlation spectroscopy on a single plane illumination microscope (SPIM-FCCS),” Opt. Express 22, 2358–2375 (2014).
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B. Patra, Y.-S. Peng, C.-C. Peng, W.-H. Liao, Y.-A. Chen, K.-H. Lin, Y.-C. Tung, and C.-H. Lee, “Migration and vascular lumen formation of endothelial cells in cancer cell spheroids of various sizes,” Biomicrofluidics 8, 052109 (2014).
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E. Rebollo, K. Karkali, F. Mangione, and E. Martin-Blanco, “Live imaging in Drosophila: the optical and genetic toolkits,” Methods 68, 48–59 (2014).
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E. H. K. Stelzer, “Light-sheet fluorescence microscopy for quantitative biology,” Nat. Methods 12, 23–26 (2014).
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E. G. Reynaud, J. Peychl, J. Huisken, and P. Tomancak, “Guide to light-sheet microscopy for adventurous biologists,” Nat. Methods 12, 30–34 (2014).
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F. Pampaloni, R. Kroschewski, U. Berge, A. Marmaras, P. Horvath, and E. H. K. Stelzer, “Tissue-culture light sheet fluorescence microscopy (TC-LSFM) allows long-term imaging of three-dimensional cell cultures under controlled conditions,” Integr. Biol. 6, 988–998 (2014).
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T. Vettenburg, H. I. C. Dalgarno, J. Nylk, C. Coll-Lladó, D. E. K. Ferrier, T. Čižmár, F. J. Gunn-Moore, and K. Dholakia, “Light-sheet microscopy using an Airy beam,” Nat. Methods 11, 541–544 (2014).
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P. Zhang, M. E. Phipps, P. M. Goodwin, and J. H. Werner, “Confocal line scanning of a Bessel beam for fast 3D imaging,” Opt. Lett. 39, 3682–3685 (2014).
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B.-C. Chen, W. R. Legant, K. Wang, L. Shao, D. E. Milkie, M. W. Davidson, C. Janetopoulos, X. S. Wu, J. A. Hammer, Z. Liu, B. P. English, Y. Mimori-Kiyosue, D. P. Romero, A. T. Ritter, J. Lippincott-Schwartz, L. Fritz-Laylin, R. D. Mullins, D. M. Mitchell, J. N. Bembenek, A.-C. Reymann, R. Boehme, S. W. Grill, J. T. Wang, G. Seydoux, U. S. Tulu, D. P. Kiehart, and E. Betzig, “Lattice light-sheet microscopy: imaging molecules to embryos at high spatiotemporal resolution,” Science 346, 1257998 (2014).
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L. Gao, L. Shao, B.-C. Chen, and E. Betzig, “3D live fluorescence imaging of cellular dynamics using Bessel beam plane illumination microscopy,” Nat. Protoc. 9, 1083–1101 (2014).
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P. Mahou, J. Vermot, E. Beaurepaire, and W. Supatto, “Multicolor two-photon light-sheet microscopy,” Nat. Methods 11, 600–601 (2014).
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M. Zhao, H. Zhang, Y. Li, A. Ashok, R. Liang, W. Zhou, and L. Peng, “Cellular imaging of deep organ using two-photon Bessel light-sheet nonlinear structured illumination microscopy,” Biomed. Opt. Express 5, 1296–1308 (2014).
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A. Kumar, Y. Wu, R. Christensen, P. Chandris, W. Gandler, E. McCreedy, A. Bokinsky, D. A. Colón-Ramos, Z. Bao, M. McAuliffe, G. Rondeau, and H. Shroff, “Dual-view plane illumination microscopy for rapid and spatially isotropic imaging,” Nat. Protoc. 9, 2555–2573 (2014).
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M. Mickoleit, B. Schmid, M. Weber, F. O. Fahrbach, S. Hombach, S. Reischauer, and J. Huisken, “High-resolution reconstruction of the beating zebrafish heart,” Nat. Methods 11, 919–922 (2014).
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A. Maruyama, Y. Oshima, H. Kajiura-Kobayashi, S. Nonaka, T. Imamura, and K. Naruse, “Wide field intravital imaging by two-photon-excitation digital-scanned light-sheet microscopy (2p-DSLM) with a high-pulse energy laser,” Biomed. Opt. Express 5, 3311–3325 (2014).
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J. Mayer, A. Robert-Moreno, R. Danuser, J. V. Stein, J. Sharpe, and J. Swoger, “OPTiSPIM: integrating optical projection tomography in light sheet microscopy extends specimen characterization to nonfluorescent contrasts,” Opt. Lett. 39, 1053–1056 (2014).
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Z. Yang, M. Prokopas, J. Nylk, C. Coll-Lladó, F. J. Gunn-Moore, D. E. K. Ferrier, T. Vettenburg, and K. Dholakia, “A compact Airy beam light sheet microscope with a tilted cylindrical lens,” Biomed. Opt. Express 5, 3434–3442 (2014).
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R. Regmi, K. Mohan, and P. P. Mondal, “High resolution light-sheet based high-throughput imaging cytometry system enables visualization of intra-cellular organelles,” AIP Adv. 4, 097125 (2014).
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S. Preibisch, F. Amat, E. Stamataki, M. Sarov, R. H. Singer, E. Myers, and P. Tomancak, “Efficient Bayesian-based multiview deconvolution,” Nat. Methods 11, 645–648 (2014).
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2013 (30)

J. Wu and R. K. Y. Chan, “A fast fluorescence imaging flow cytometer for phytoplankton analysis,” Opt. Express 21, 23921–23926 (2013).
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J. Wu, J. Li, and R. K. Y. Chan, “A light sheet based high throughput 3D-imaging flow cytometer for phytoplankton analysis,” Opt. Express 21, 14474–14480 (2013).
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E. J. Gualda, T. Vale, P. Almada, J. A. Feijó, G. G. Martins, and N. Moreno, “OpenSpinMicroscopy: an open-source integrated microscopy platform,” Nat. Methods 10, 599–600 (2013).
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S. L. Jacques, “Optical properties of biological tissues: a review,” Phys. Med. Biol. 58, R37–R61 (2013).
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Z. Yang, H. Downie, E. Rozbicki, L. X. Dupuy, and M. P. MacDonald, “Light sheet tomography (LST) for in situ imaging of plant roots,” Opt. Express 21, 16239–16247 (2013).
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Z. Lavagnino, F. C. Zanacchi, E. Ronzitti, and A. Diaspro, “Two-photon excitation selective plane illumination microscopy (2PE-SPIM) of highly scattering samples: characterization and application,” Opt. Express 21, 5998–6008 (2013).
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Y. Wu, P. Wawrzusin, J. Senseney, R. S. Fischer, R. Christensen, A. Santella, A. G. York, P. W. Winter, C. M. Waterman, Z. Bao, D. A. Colon-Ramos, M. McAuliffe, and H. Shroff, “Spatially isotropic four-dimensional imaging with dual-view plane illumination microscopy,” Nat. Biotechnol. 31, 1032–1038 (2013).
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F. O. Fahrbach, F. F. Voigt, B. Schmid, F. Helmchen, and J. Huisken, “Rapid 3D light-sheet microscopy with a tunable lens,” Opt. Express 21, 21010–21026 (2013).
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J. C. M. Gebhardt, D. M. Suter, R. Roy, Z. W. Zhao, A. R. Chapman, S. Basu, T. Maniatis, and X. S. Xie, “Single-molecule imaging of transcription factor binding to DNA in live mammalian cells,” Nat. Methods 10, 421–426 (2013).
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M. B. Ahrens, M. B. Orger, D. N. Robson, J. M. Li, and P. J. Keller, “Whole-brain functional imaging at cellular resolution using light-sheet microscopy,” Nat. Methods 10, 413–420 (2013).
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T. Panier, S. A. Romano, R. Olive, T. Pietri, G. Sumbre, R. Candelier, and G. Debregeas, “Fast functional imaging of multiple brain regions in intact zebrafish larvae using selective plane illumination microscopy,” Front. Neural Circuits 7, 65 (2013).
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A. Desmaison, C. Lorenzo, J. Rouquette, B. Ducommun, and V. Lobjois, “A versatile sample holder for single plane illumination microscopy,” J. Microsc. 251, 128–132 (2013).
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F. Amat and P. J. Keller, “Towards comprehensive cell lineage reconstructions in complex organisms using light-sheet microscopy,” Dev. Growth Differ. 55, 563–578 (2013).
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P. G. Sappl and M. G. Heisler, “Live-imaging of plant development: latest approaches,” Curr. Opin. Plant Biol. 16, 33–40 (2013).
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F. O. Fahrbach, V. Gurchenkov, K. Alessandri, P. Nassoy, and A. Rohrbach, “Light-sheet microscopy in thick media using scanned Bessel beams and two-photon fluorescence excitation,” Opt. Express 21, 13824–13839 (2013).
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F. Pampaloni, N. Ansari, and E. H. K. Stelzer, “High-resolution deep imaging of live cellular spheroids with light-sheet-based fluorescence microscopy,” Cell Tissue Res. 352, 161–177 (2013).
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A. Ertürk and F. Bradke, “High-resolution imaging of entire organs by 3-dimensional imaging of solvent cleared organs (3DISCO),” Exp. Neurol. 242, 57–64 (2013).
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M. Jemielita, M. J. Taormina, A. DeLaurier, C. B. Kimmel, and R. Parthasarathy, “Comparing phototoxicity during the development of a zebrafish craniofacial bone using confocal and light sheet fluorescence microscopy techniques,” J. Biophoton. 6, 920–928 (2013).
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Y. Wu, R. Christensen, D. Colon-Ramos, and H. Shroff, “Advanced optical imaging techniques for neurodevelopment,” Curr. Opin. Neurobiol. 23, 1090–1097 (2013).
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J. H. Hoh, W. F. Heinz, and J. L. Werbin, “Spatial information dynamics during early zebrafish development,” Dev. Biol. 377, 126–137 (2013).
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P. J. Keller, “In vivo imaging of zebrafish embryogenesis,” Methods 62, 268–278 (2013).
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F. Pinto-Teixeira, M. Muzzopappa, J. Swoger, A. Mineo, J. Sharpe, and H. Lopez-Schier, “Intravital imaging of hair-cell development and regeneration in the zebrafish,” Front. Neuroanat. 7, 33 (2013).
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R. Fickentscher, P. Struntz, and M. Weiss, “Mechanical cues in the early embryogenesis of Caenorhabditis elegans,” Biophys. J. 105, 1805–1811 (2013).
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T. Ichikawa, K. Nakazato, P. J. Keller, H. Kajiura-Kobayashi, E. H. K. Stelzer, A. Mochizuki, and S. Nonaka, “Live imaging of whole mouse embryos during gastrulation: migration analyses of epiblast and mesodermal cells,” PLoS ONE 8, e64506 (2013).
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B. Schmid, G. Shah, N. Scherf, M. Weber, K. Thierbach, C. P. Campos, I. Roeder, P. Aanstad, and J. Huisken, “High-speed panoramic light-sheet microscopy reveals global endodermal cell dynamics,” Nat. Commun. 4, 2207 (2013).
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A. P. Singh, J. W. Krieger, J. Buchholz, E. Charbon, J. Langowski, and T. Wohland, “The performance of 2D array detectors for light sheet based fluorescence correlation spectroscopy,” Opt. Express 21, 8652–8668 (2013).
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Y. S. Hu, Q. Zhu, K. Elkins, K. Tse, Y. Li, J. A. J. Fitzpatrick, I. M. Verma, and H. Cang, “Light-sheet Bayesian microscopy enables deep-cell super-resolution imaging of heterochromatin in live human embryonic stem cells,” Opt. Nanosc. 2, 7 (2013).
[Crossref]

D. Turaga and T. E. Holy, “Aberrations and their correction in light-sheet microscopy: a low-dimensional parametrization,” Biomed. Opt. Express 4, 1654–1661 (2013).
[Crossref]

A. Costa, A. Candeo, L. Fieramonti, G. Valentini, and A. Bassi, “Calcium dynamics in root cells of Arabidopsis thaliana visualized with selective plane illumination microscopy,” PLoS ONE 8, e75646 (2013).
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F. O. Fahrbach, V. Gurchenkov, K. Alessandri, P. Nassoy, and A. Rohrbach, “Self-reconstructing sectioned Bessel beams offer submicron optical sectioning for large fields of view in light-sheet microscopy,” Opt. Express 21, 11425–11440 (2013).
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2012 (23)

L. Silvestri, A. Bria, L. Sacconi, G. Iannello, and F. S. Pavone, “Confocal light sheet microscopy: micron-scale neuroanatomy of the entire mouse brain,” Opt. Express 20, 20582–20598 (2012).
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H. I. C. Dalgarno, T. Cizmar, T. Vettenburg, J. Nylk, F. J. Gunn-Moore, and K. Dholakia, “Wavefront corrected light sheet microscopy in turbid media,” Appl. Phys. Lett. 100, 191108 (2012).
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I. Izeddin, M. E. Beheiry, J. Andilla, D. Ciepielewski, X. Darzacq, and M. Dahan, “PSF shaping using adaptive optics for three-dimensional single-molecule super-resolution imaging and tracking,” Opt. Express 20, 4957–4967 (2012).
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J.-H. Spille, T. Kaminski, H.-P. Königshoven, and U. Kubitscheck, “Dynamic three-dimensional tracking of single fluorescent nanoparticles deep inside living tissue,” Opt. Express 20, 19697–19707 (2012).
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P. Sengupta, S. Van Engelenburg, and J. Lippincott-Schwartz, “Visualizing cell structure and function with point-localization superresolution imaging,” Dev. Cell 23, 1092–1102 (2012).
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J. Michaelson, H. Choi, P. So, and H. Huang, “Depth-resolved cellular microrheology using HiLo microscopy,” Biomed. Opt. Express 3, 1241–1255 (2012).
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R. Opitz, E. Maquet, J. Huisken, F. Antonica, A. Trubiroha, G. Pottier, V. Janssens, and S. Costagliola, “Transgenic zebrafish illuminate the dynamics of thyroid morphogenesis and its relationship to cardiovascular development,” Dev. Biol. 372, 203–216 (2012).
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A. Kaufmann, M. Mickoleit, M. Weber, and J. Huisken, “Multilayer mounting enables long-term imaging of zebrafish development in a light sheet microscope,” Development 139, 3242–3247 (2012).
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L. Gao, L. Shao, C. D. Higgins, J. S. Poulton, M. Peifer, M. W. Davidson, X. Wu, B. Goldstein, and E. Betzig, “Noninvasive imaging beyond the diffraction limit of 3D dynamics in thickly fluorescent specimens,” Cell 151, 1370–1385 (2012).
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R. Jorand, G. Le Corre, J. Andilla, A. Maandhui, C. Frongia, V. Lobjois, B. Ducommun, and C. Lorenzo, “Deep and clear optical imaging of thick inhomogeneous samples,” PLoS ONE 7, e35795 (2012).
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A. Ertürk, K. Becker, N. Jährling, C. P. Mauch, C. D. Hojer, J. G. Egen, F. Hellal, F. Bradke, M. Sheng, and H.-U. Dodt, “Three-dimensional imaging of solvent-cleared organs using 3DISCO,” Nat. Protoc. 7, 1983–1995 (2012).
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K. Mellman, J. Huisken, C. Dinsmore, C. Hoppe, and D. Y. Stainier, “Fibrillin-2b regulates endocardial morphogenesis in zebrafish,” Dev. Biol. 372, 111–119 (2012).
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T. Bruns, S. Schickinger, R. Wittig, and H. Schneckenburger, “Preparation strategy and illumination of three-dimensional cell cultures in light sheet-based fluorescence microscopy,” J. Biomed. Opt. 17, 1015181 (2012).
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P. J. Keller and H.-U. Dodt, “Light sheet microscopy of living or cleared specimens,” Curr. Opin. Neurobiol. 22, 138–143 (2012).
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O. E. Olarte, J. Licea-Rodriguez, J. A. Palero, E. J. Gualda, D. Artigas, J. Mayer, J. Swoger, J. Sharpe, I. Rocha-Mendoza, R. Rangel-Rojo, and P. Loza-Alvarez, “Image formation by linear and nonlinear digital scanned light-sheet fluorescence microscopy with Gaussian and Bessel beam profiles,” Biomed. Opt. Express 3, 1492–1505 (2012).
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U. Krzic, S. Gunther, T. E. Saunders, S. J. Streichan, and L. Hufnagel, “Multiview light-sheet microscope for rapid in toto imaging,” Nat. Methods 9, 730–733 (2012).
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R. Tomer, K. Khairy, F. Amat, and P. J. Keller, “Quantitative high-speed imaging of entire developing embryos with simultaneous multiview light-sheet microscopy,” Nat. Methods 9, 755–763 (2012).
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F. Cutrale and E. Gratton, “Inclined selective plane illumination microscopy adaptor for conventional microscopes,” Microsc. Res. Tech. 75, 1461–1466 (2012).
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Y. Oshima, H. Kajiura-Kobayashi, and S. Nonaka, “Multimodal light-sheet microscopy for fluorescence live imaging,” Proc. SPIE 8227, 82271H (2012).

Y. Oshima, H. Sato, H. Kajiura-Kobayashi, T. Kimura, K. Naruse, and S. Nonaka, “Light sheet-excited spontaneous Raman imaging of a living fish by optical sectioning in a wide field Raman microscope,” Opt. Express 20, 16195–16204 (2012).
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J. Fehrenbach, P. Weiss, and C. Lorenzo, “Variational algorithms to remove stationary noise: applications to microscopy imaging,” IEEE Trans. Image Process. 21, 4420–4430 (2012).
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E. Baumgart and U. Kubitscheck, “Scanned light sheet microscopy with confocal slit detection,” Opt. Express 20, 21805–21814 (2012).
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F. O. Fahrbach and A. Rohrbach, “Propagation stability of self-reconstructing Bessel beams enables contrast-enhanced imaging in thick media,” Nat. Commun. 3, 632 (2012).
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2011 (20)

M. Drobizhev, N. S. Makarov, S. E. Tillo, T. E. Hughes, and A. Rebane, “Two-photon absorption properties of fluorescent proteins,” Nat. Methods 8, 393–399 (2011).
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M. Friedrich, Q. Gan, V. Ermolayev, and G. S. Harms, “STED-SPIM: stimulated emission depletion improves sheet illumination microscopy resolution,” Biophys. J. 100, L43–L45 (2011).
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L. Shao, P. Kner, E. H. Rego, and M. G. L. Gustafsson, “Super-resolution 3D microscopy of live whole cells using structured illumination,” Nat. Methods 8, 1044–1046 (2011).
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K. Greger, M. J. Neetz, E. G. Reynaud, and E. H. K. Stelzer, “Three-dimensional fluorescence lifetime imaging with a single plane illumination microscope provides an improved signal to noise ratio,” Opt. Express 19, 20743–20750 (2011).
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T. A. Planchon, L. Gao, D. E. Milkie, M. W. Davidson, J. A. Galbraith, C. G. Galbraith, and E. Betzig, “Rapid three-dimensional isotropic imaging of living cells using Bessel beam plane illumination,” Nat. Methods 8, 417–423 (2011).
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T. V. Truong, W. Supatto, D. S. Koos, J. M. Choi, and S. E. Fraser, “Deep and fast live imaging with two-photon scanned light-sheet microscopy,” Nat. Methods 8, 757–760 (2011).
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J. Capoulade, M. Wachsmuth, L. Hufnagel, and M. Knop, “Quantitative fluorescence imaging of protein diffusion and interaction in living cells,” Nat. Biotechnol. 29, 835–839 (2011).
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F. C. Zanacchi, Z. Lavagnino, M. P. Donnorso, A. D. Bue, L. Furia, M. Faretta, and A. Diaspro, “Live-cell 3D super-resolution imaging in thick biological samples,” Nat. Methods 8, 1047–1049 (2011).
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C. Lorenzo, C. Frongia, R. Jorand, J. Fehrenbach, P. Weiss, A. Maandhui, G. Gay, B. Ducommun, and V. Lobjois, “Live cell division dynamics monitoring in 3D large spheroid tumor models using light sheet microscopy,” Cell Div. 6, 22 (2011).
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M. Weber and J. Huisken, “Light sheet microscopy for real-time developmental biology,” Curr. Opin. Genet. Dev. 21, 566–572 (2011).
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F. Pampaloni, N. Ansari, P. Girard, and E. H. K. Stelzer, “Light sheet-based fluorescence microscopy (LSFM) reduces phototoxic effects and provides new means for the modern life sciences,” Adv. Microsc. Tech. II 8086, 80860Y (2011).
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Y. Wu, A. Ghitani, R. Christensen, A. Santella, Z. Du, G. Rondeau, Z. Bao, D. Colón-Ramos, and H. Shroff, “Inverted selective plane illumination microscopy (iSPIM) enables coupled cell identity lineaging and neurodevelopmental imaging in Caenorhabditis elegans,” Proc. Natl. Acad. Sci. USA 108, 17708–17713 (2011).
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J. Swoger, M. Muzzopappa, H. López-Schier, and J. Sharpe, “4D retrospective lineage tracing using SPIM for zebrafish organogenesis studies,” J. Biophoton. 4, 122–134 (2011).
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G. Sena, Z. Frentz, K. D. Birnbaum, and S. Leibler, “Quantitation of cellular dynamics in growing Arabidopsis roots with light sheet microscopy,” PLoS ONE 6, e21303 (2011).
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P. J. Keller, A. D. Schmidt, J. Wittbrodt, and E. H. K. Stelzer, “Digital scanned laser light-sheet fluorescence microscopy (DSLM) of zebrafish and Drosophila embryonic development,” Cold Spring Harb. Protoc. 2011, 1235–1243 (2011).
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C. Conrad, A. Wünsche, T. H. Tan, J. Bulkescher, F. Sieckmann, F. Verissimo, A. Edelstein, T. Walter, U. Liebel, R. Pepperkok, and J. Ellenberg, “Micropilot: automation of fluorescence microscopy-based imaging for systems biology,” Nat. Methods 8, 246–249 (2011).
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X. Tao, B. Fernandez, O. Azucena, M. Fu, D. Garcia, Y. Zuo, D. C. Chen, and J. Kubby, “Adaptive optics confocal microscopy using direct wavefront sensing,” Opt. Lett. 36, 1062–1064 (2011).
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R. Aviles-Espinosa, J. Andilla, R. Porcar-Guezenec, O. E. Olarte, M. Nieto, X. Levecq, D. Artigas, and P. Loza-Alvarez, “Measurement and correction of in vivo sample aberrations employing a nonlinear guide-star in two-photon excited fluorescence microscopy,” Biomed. Opt. Express 2, 3135–3149 (2011).
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Z. Xu and T. E. Holy, “Development of low-coherence light sheet illumination microscope for fluorescence-free bioimaging,” Proc. SPIE 8129, 812908 (2011).
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2010 (13)

T. Wohland, X. Shi, J. Sankaran, and E. H. K. Stelzer, “Single plane illumination fluorescence correlation spectroscopy (SPIM-FCS) probes inhomogeneous three-dimensional environments,” Opt. Express 18, 10627–10641 (2010).
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J. G. Ritter, R. Veith, A. Veenendaal, J. P. Siebrasse, and U. Kubitscheck, “Light sheet microscopy for single molecule tracking in living tissue,” PLoS ONE 5, e11639 (2010).
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J. Mertz and J. Kim, “Scanning light-sheet microscopy in the whole mouse brain with HiLo background rejection,” J. Biomed. Opt. 15, 016027 (2010).
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N. Jahrling, K. Becker, C. Schonbauer, F. Schnorrer, and H.-U. Dodt, “Three-dimensional reconstruction and segmentation of intact Drosophila by ultramicroscopy,” Front. Syst. Neurosci. 4, 1–6 (2010).
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P. J. Keller, A. D. Schmidt, A. Santella, K. Khairy, Z. Bao, J. Wittbrodt, and E. H. K. Stelzer, “Fast, high-contrast imaging of animal development with scanned light sheet-based structured-illumination microscopy,” Nat. Methods 7, 637–642 (2010).
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J. Palero, S. I. C. O. Santos, D. Artigas, and P. Loza-Alvarez, “A simple scanless two-photon fluorescence microscope using selective plane illumination,” Opt. Express 18, 8491–8498 (2010).
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S. Preibisch, S. Saalfeld, J. Schindelin, and P. Tomancak, “Software for bead-based registration of selective plane illumination microscopy data,” Nat. Methods 7, 418–419 (2010).
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F. O. Fahrbach and A. Rohrbach, “A line scanned light-sheet microscope with phase shaped self-reconstructing beams,” Opt. Express 18, 24229–24244 (2010).
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N. N. Boustany, S. A. Boppart, and V. Backman, “Microscopic imaging and spectroscopy with scattered light,” Annu. Rev. Biomed. Eng. 12, 285–314 (2010).
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S. Saghafi, K. Becker, N. Jaehrling, M. Richter, E. R. Kramer, and H.-U. Dodt, “Image enhancement in ultramicroscopy by improved laser light sheets,” J. Biophoton. 3, 686–695 (2010).
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P. J. Keller and E. H. K. Stelzer, “Digital scanned laser light sheet fluorescence microscopy,” Cold Spring Harb. Protoc. 2010, pdb.top78 (2010).
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F. O. Fahrbach, P. Simon, and A. Rohrbach, “Microscopy with self-reconstructing beams,” Nat. Photonics 4, 780–785 (2010).
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I. Barman, K. M. Tan, and G. P. Singh, “Optical sectioning using single-plane-illumination Raman imaging,” J. Raman Spectrosc. 41, 1099–1101 (2010).
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2009 (4)

N. Jaehrling, K. Becker, and H.-U. Dodt, “3D-reconstruction of blood vessels by ultramicroscopy,” Organogenesis 5, 227–230 (2009).
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J. Huisken and D. Y. R. Stainier, “Selective plane illumination microscopy techniques in developmental biology,” Development 136, 1963–1975 (2009).
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E. H. K. Stelzer, “Light sheet based fluorescence microscopes (LSFM, SPIM, DSLM) reduce phototoxic effects by several orders of magnitude,” Mech. Dev. 126, S36 (2009).
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M. A. Bandres, “Accelerating beams,” Opt. Lett. 34, 3791–3793 (2009).
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2008 (10)

M. Tokunaga, N. Imamoto, and K. Sakata-Sogawa, “Highly inclined thin illumination enables clear single-molecule imaging in cells,” Nat. Methods 5, 159–161 (2008).
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C. A. Konopka and S. Y. Bednarek, “Variable-angle epifluorescence microscopy: a new way to look at protein dynamics in the plant cell cortex,” Plant J. 53, 186–196 (2008).
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E. G. Reynaud, U. Kržič, K. Greger, and E. H. K. Stelzer, “Light sheet-based fluorescence microscopy: more dimensions, more photons, and less photodamage,” HFSP J. 2, 266–275 (2008).
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J. Vermot, S. E. Fraser, and M. Liebling, “Fast fluorescence microscopy for imaging the dynamics of embryonic development,” HFSP J. 2, 143–155 (2008).
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P. J. Keller, A. D. Schmidt, J. Wittbrodt, and E. H. K. Stelzer, “Reconstruction of zebrafish early embryonic development by scanned light sheet microscopy,” Science 322, 1065–1069 (2008).
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P. J. Scherz, J. Huisken, P. Sahai-Hernandez, and D. Y. R. Stainier, “High-speed imaging of developing heart valves reveals interplay of morphogenesis and function,” Development 135, 1179–1187 (2008).
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C. Dunsby, “Optically sectioned imaging by oblique plane microscopy,” Opt. Express 16, 20306–20316 (2008).
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K. Becker, N. Jaehrling, E. R. Kramer, E. Schnorrer, and H.-U. Dodt, “Ultramicroscopy: 3D reconstruction of large microscopical specimens,” J. Biophoton. 1, 36–42 (2008).
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P. J. Keller and E. H. Stelzer, “Quantitative in vivo imaging of entire embryos with digital scanned laser light sheet fluorescence microscopy,” Curr. Opin. Neurobiol. 18, 624–632 (2008).
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T. F. Holekamp, D. Turaga, and T. E. Holy, “Fast three-dimensional fluorescence imaging of activity in neural populations by objective-coupled planar illumination microscopy,” Neuron 57, 661–672 (2008).
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2007 (9)

K. Greger, J. Swoger, and E. H. K. Stelzer, “Basic building units and properties of a fluorescence single plane illumination microscope,” Rev. Sci. Instrum. 78, 023705 (2007).
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J. Huisken and D. Y. R. Stainier, “Even fluorescence excitation by multidirectional selective plane illumination microscopy (mSPIM),” Opt. Lett. 32, 2608–2610 (2007).
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J. Swoger, P. Verveer, K. Greger, J. Huisken, and E. H. K. Stelzer, “Multi-view image fusion improves resolution in three-dimensional microscopy,” Opt. Express 15, 8029–8042 (2007).
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C. J. Engelbrecht, K. Greger, E. G. Reynaud, U. Kržič, J. Colombelli, and E. H. Stelzer, “Three-dimensional laser microsurgery in light-sheet based microscopy (SPIM),” Opt. Express 15, 6420–6430 (2007).
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P. J. Keller, F. Pampaloni, and E. H. K. Stelzer, “Three-dimensional preparation and imaging reveal intrinsic microtubule properties,” Nat. Methods 4, 843–846 (2007).
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P. J. Verveer, J. Swoger, F. Pampaloni, K. Greger, M. Marcello, and E. H. K. Stelzer, “High-resolution three-dimensional imaging of large specimens with light sheet-based microscopy,” Nat. Methods 4, 311–313 (2007).
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G. A. Siviloglou and D. N. Christodoulides, “Accelerating finite energy Airy beams,” Opt. Lett. 32, 979–981 (2007).
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G. A. Siviloglou, J. Broky, A. Dogariu, and D. N. Christodoulides, “Observation of accelerating Airy beams,” Phys. Rev. Lett. 99, 213901 (2007).
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2006 (4)

E. Betzig, G. H. Patterson, R. Sougrat, O. W. Lindwasser, S. Olenych, J. S. Bonifacino, M. W. Davidson, J. Lippincott-Schwartz, and H. F. Hess, “Imaging intracellular fluorescent proteins at nanometer resolution,” Science 313, 1642–1645 (2006).
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S. Bolte and F. P. Cordelières, “A guided tour into subcellular colocalization analysis in light microscopy,” J. Microsc. 224, 213–232 (2006).
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P. J. Keller, F. Pampaloni, and E. H. Stelzer, “Life sciences require the third dimension,” Curr. Opin. Cell Biol. 18, 117–124 (2006).
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C. J. Engelbrecht and E. H. Stelzer, “Resolution enhancement in a light-sheet-based microscope (SPIM),” Opt. Lett. 31, 1477–1479 (2006).
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2005 (1)

H. Wallrabe and A. Periasamy, “Imaging protein molecules using FRET and FLIM microscopy,” Curr. Opin. Biotechnol. 16, 19–27 (2005).
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2004 (2)

H. Urey, “Spot size, depth-of-focus, and diffraction ring intensity formulas for truncated Gaussian beams,” Appl. Opt. 43, 620–625 (2004).
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J. Huisken, J. Swoger, F. Del Bene, J. Wittbrodt, and E. H. K. Stelzer, “Optical sectioning deep inside live embryos by selective plane illumination microscopy,” Science 305, 1007–1009 (2004).
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2000 (1)

M. G. Gustafsson, “Surpassing the lateral resolution limit by a factor of two using structured illumination microscopy,” J. Microsc. 198, 82–87 (2000).
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1999 (1)

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S. Lindek and E. H. K. Stelzer, “Optical transfer functions for confocal theta fluorescence microscopy,” J. Opt. Soc. Am. A 13, 479–482 (1996).
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R. P. MacDonald, S. A. Boothroyd, T. Okamoto, J. Chrostowski, and B. A. Syrett, “Interboard optical data distribution by Bessel beam shadowing,” Opt. Commun. 122, 169–177 (1996).
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1995 (1)

1994 (3)

S. W. Hell and J. Wichmann, “Breaking the diffraction resolution limit by stimulated emission: stimulated-emission-depletion fluorescence microscopy,” Opt. Lett. 19, 780–782 (1994).
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1993 (2)

A. H. Voie, D. H. Burns, and F. A. Spelman, “Orthogonal-plane fluorescence optical sectioning: three-dimensional imaging of macroscopic biological specimens,” J. Microsc. 170, 229–236 (1993).
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1989 (1)

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1987 (2)

1984 (1)

N. Streibl, “Depth transfer by an imaging system,” Opt. Acta 31, 1233–1241 (1984).
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1982 (1)

W. J. Alford, R. D. VanderNeut, and V. J. Zaleckas, “Laser scanning microscopy,” Proc. IEEE 70, 641–651 (1982).
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P. Weber, S. Schickinger, M. Wagner, B. Angres, T. Bruns, and H. Schneckenburger, “Monitoring of apoptosis in 3D cell cultures by FRET and light sheet fluorescence microscopy,” Int. J. Mol. Sci. 16, 5375–5385 (2015).
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F. Pampaloni, N. Ansari, P. Girard, and E. H. K. Stelzer, “Light sheet-based fluorescence microscopy (LSFM) reduces phototoxic effects and provides new means for the modern life sciences,” Adv. Microsc. Tech. II 8086, 80860Y (2011).
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Figures (28)

Figure 1.
Figure 1. Basic schematic of a LSFM.
Figure 2.
Figure 2. Electronic energy level scheme showing the different excitation processes: one-photon (linear) absorption and two-photon (nonlinear) absorption.
Figure 3.
Figure 3. Schematic of the illumination and detection arm in a LSFM.
Figure 4.
Figure 4. LSFM setups: (a) macro LS configuration, (b) cylindrical lens (CL) configuration, and (c) DSLM configuration. See the main text for a detailed description.
Figure 5.
Figure 5. Examples of four different LSFM architectures. (a) Multiple objectives: mSPIM has double side illumination and single side detection, all lenses in a plane parallel to the table. Sample (thinner cylinder in front of the objectives) can be positioned from the top, using a capillary (thick cylinder, entering the scene from the top). (b) Double side illumination and double side detection with only two objective lenses on a 45° configuration in diSPIM, both lenses in a plane orthogonal to the table. (c) A single objective lens and a micro-machined mirror is used in a soSPIM microscope to both excite and detect emission from fluorophores. (d) Two en face objectives and an AFM tip mirror are used in RSLM; excitation objective not shown. The LS is represented in blue and the detection cone in green.
Figure 6.
Figure 6. Examples of four different sample scanning approaches on LSFM systems. (a) Standard sample scanning by mechanically translating the sample across the LS plane. (b) Opto-mechanic solution where the sample remains static. A galvo mirror scans the LS over the sample in coordination with a piezo stage that refocuses the detection objective. Published by The Optical Society under the terms of the Creative Commons Attribution 4.0 License. Further distribution of this work must maintain attribution to the author(s) and the published article’s title, journal citation, and DOI. (c) The detection objective depth of field is extended using a cubic phase mask to extend its depth of field, allowing all the planes of the sample to be in focus simultaneously. During acquisition a galvo mirror scans the sample, illuminating different planes. (d) Samples flow inside a FEP capillary across the LS plane on the SPIM-Fluid system. The system allows imaging of, in an automated way, hundreds of samples providing high-throughput capabilities. Adapted from [2,42,84,89], respectively. Figure (a) from Huisken et al., Science 305, 1007–1009 (2004) [2]. Reprinted with permission from AAAS.
Figure 7.
Figure 7. Basic imaging properties of a WFM, (a) PSF and (b) MTF. See the main text for a complete description. Color intensity values are normalized to their maximum; darker colors indicate higher intensities.
Figure 8.
Figure 8. Gaussian beams with different truncation ratios T. Beam properties (a) FOVi and (b) Dbeam, according to Eqs. (6) and (7). These curves were generated using the approximation formulas for truncated Gaussian beams reported in Ref. [138]. See the main text for more detail.
Figure 9.
Figure 9. Examples of pupil amplitude masks for the generation of LSs based on (a) cylindrical lenses, and scanned (b) Gaussian and (c) Bessel beams. The white corresponds to a 100% transmission and the red dashed lines indicate k for maximum NA available in the excitation objective. For details on the parameters see Table 3 in the main text.
Figure 10.
Figure 10. Example of a LS generated using a cylindrical lens. (a) Detection objective PSF, (b) LS intensity profile at the center of the FOV, (c) overall MTF, and (d) axial profile of the MTF (ky=0). Color intensity values are normalized to their maximum; darker colors indicate higher intensities.
Figure 11.
Figure 11. Example of a 2P-LSFM generated using a cylindrical lens. (a) Detection objective intensity PSF, (b) LS intensity profile at the center of the FOV, (c) overall MTF, and (d) MTF axial profile (ky=0) for 2P-LSFM (orange) and LS (blue). Color intensity values are normalized to their maximum; darker colors indicate higher intensities.
Figure 12.
Figure 12. Examples of beam profiles for DSLM LS generation. (a) Gaussian and (b) Bessel generating the same FOV width of around 60 μm. (c) Bessel beam generating twice the original FOV width of (a). The square root of the beam intensity is shown for better visualization. Color intensity values are normalized to their maximum; darker colors indicate higher intensities.
Figure 13.
Figure 13. Example of LS generated for DSLM using Gaussian beams. The zy sections of (a) the excitation beam profile and (b) the LS (scanned-beam) intensity profile, at the center of the FOV. Overall (c) MTF and (d) MTF axial profile (ky=0) for DSLM (orange) and LSFM (blue). Color maps for intensity values are normalized to the maximum; darker colors indicate higher intensities. See the description in the main text.
Figure 14.
Figure 14. Example of 2P-DSLM generation using Gaussian beams. The zy sections of (a) the excitation beam profile and (b) the LS (scanned-beam) intensity profile, at the center of the FOV. Overall (c) MTF and (d) MTF axial profile (ky=0) for 2P-DSLM (orange) and LSFM (blue). Color maps for intensity values are normalized to the maximum; darker colors indicate higher intensities. See the description in the main text.
Figure 15.
Figure 15. Example of LS generation for DSLM with Bessel beams. The zy sections of (a) the excitation beam profile and (b) the LS (scanned-beam) intensity profile, at the center of the FOV. Overall (c) MTF and (d) MTF axial profile (ky=0) for DSLM with Bessel beams (orange) and LSFM (blue). Color maps for intensity values are normalized to the maximum, darker colors indicate higher intensities. See the description in the main text.
Figure 16.
Figure 16. Example of LS generation for 2P-DSLM with Bessel beams. The zy sections of (a) the excitation beam profile and (b) the LS (scanned-beam) intensity profile, at the center of the FOV. Overall (c) MTF and (d) MTF axial profile (ky=0) for 2P-DSLM with Bessel beams (orange) and LSFM (blue). Color maps for intensity values are normalized to the maximum; darker colors indicate higher intensities. See the description in the main text.
Figure 17.
Figure 17. Examples of pupil amplitude masks for the generation of Bessel-like beams for scanned DSLM, based on (a) sectioned Bessel beams, and (b) optical lattices. The white color corresponds to a transmissivity T=1.0, the red dotted lines indicate the maximum NA available in the excitation objective, and the green lines the limits of the base Bessel ring.
Figure 18.
Figure 18. Example of LS generation for DSLM with SBBs. The zy sections of (a) the excitation beam profile and (b) the LS (scanned-beam) intensity profile, at the center of the FOV. Overall (c) MTF and (d) MTF axial profile (ky=0) for 1P-DSLM with SBB (orange) and LSFM (blue). Color maps for intensity values are normalized to the maximum; darker colors indicate higher intensities. See the description in the main text.
Figure 19.
Figure 19. Example of LS generation for DSLM with optical lattices, optimized for optical sectioning. The zy sections of (a) the excitation beam profile and (b) the LS (scanned-beam) intensity profile, at the center of the FOV. Overall (c) MTF and (d) MTF axial profile (ky=0) for DSLM with optical lattices (orange) and LSFM (blue). Color maps for intensity values are normalized to the maximum; darker colors indicate higher intensities. See the description in the main text.
Figure 20.
Figure 20. Example of LS generation for DSLM with optical lattices, optimized for structured illumination. The zy sections of (a) the excitation beam profile and (b) the LS (scanned-beam) intensity profile, at the center of the FOV. Overall (c) MTF and (d) MTF axial profile (ky=0) for DSLM with optical lattices (orange) and LSFM (blue). Color maps for intensity values are normalized to the maximum; darker colors indicate higher intensities. See the description in the main text.
Figure 21.
Figure 21. Example of LS generation for DSLM with Airy beams. The zy sections of (a) the excitation beam profile and (b) the LS (scanned-beam) intensity profile, at the center of the FOV. Overall (c) MTF and (d) MTF axial profile (ky=0) for DSLM with Airy beams (orange) and LSFM (blue). Color maps for intensity values are normalized to the maximum; darker colors indicate higher intensities. See the description in the main text.
Figure 22.
Figure 22. Optical setups for (a) multicolor 2P-LSFM, which combines bidirectional multicolor two-photon excitation and multispectral detection on a single camera [68], and (b) hyperspectral LS allowing multiple use of fluorescent markers (adapted with permission from Jahr et al., Nat. Commun. 6, 7990 [2015] [97]), published by The Optical Society under the terms of the Creative Commons Attribution 4.0 License. Further distribution of this work must maintain attribution to the author(s) and the published article’s title, journal citation, and DOI).
Figure 23.
Figure 23. SPIM-FLIM optical setup [94]. See the main text for more details.
Figure 24.
Figure 24. Raman LS optical setups. (a) A CW laser forms the LS on the sample plane using a galvo mirror (DSLM). A tunable filter (TF) scans the spectrum with an edge depending on θ, the tilt angle of the filter. Inset: spectral knife edge (KE) trace extraction from a 2D image stack at a region of interest I(x,y) with N as the total number of images, each taken at a different filter tilt angle [100]. (b) Fourier transform-based Raman LS. The illumination LS is done with a high-power laser and a cylindrical lens. The spectra are recovered using a Fourier-transform imaging spectrometer (red path). See the main text for a detailed description [101].
Figure 25.
Figure 25. Confocal line scanning DSLM. (a) The principle of confocal line scanning by using a DSLM and a sCMOS camera. XY and XZ maximum projection intensity of 3D stacks of a 4 dpf zebrafish expressing H2B-GFP are shown for the (b), (e) Gaussian; (c), (f) Bessel; and (d), (g) Bessel confocal line cases. See the main text for more detail.
Figure 26.
Figure 26. AO for LSFM. (a) The optical setup for correcting the aberrations using AO in the detection path of a LSFM (enclosed in the green square). The main components are: the deformable mirror (DM) that is the active element that can modify the wavefront, and the Hartmann–Shack wavefront sensor (HSWF) that measures the amount of wavefront aberration that should be compensated. (b) Maximum intensity projection of a 3D stack of 100 images (z spacing 1 mm) of a large MCTS expressing a fluorescent nuclear protein, without (w/o AO) and with AO (AO). Scale bar: 50 μm. Adapted with permission from Jorand et al., PLoS ONE 7, e35795 (2012) [50]. Published by The Optical Society under the terms of the Creative Commons Attribution 4.0 License. Further distribution of this work must maintain attribution to the author(s) and the published article’s title, journal citation, and DOI.
Figure 27.
Figure 27. LSFM with an extended DOF. (a) Zoom-in of the optical setup for WFC-LSFM [see also Fig. 6(c)] at the sample space. Some positions of the LS in the axial scanning, from Zo to Zn, are shown in green; the detection PSF is shown in red. (b) Comparison of the effective PSFs for three LS axial positions for WFM (top) and WFC-LSFM (bottom). (c) Comparison of the images obtained with standard LSFM (left) and WFC-LSFM (right). Images are maximum intensity projections of a 3D stack of the fluorescent pharynx of a C. elegans [89]. Insets show different cuts of the data at the marked dotted lines. Scale bar 50 μm.
Figure 28.
Figure 28. LSFM with structured illumination. (a) Example of LS fringe structure generation by interference of two sheets, delimited by yellow and blue boundaries, which cross each other at the center of the FOV. (b) Example of multi-objective structured LS generation [202]. In this case, two complementarily tilted counterpropagating LSs generate a structured illumination pattern that can be rotated for isotropic SR. See text for detailed information.

Tables (4)

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Table 1. Relation of Components and Parameters Used to Define LSFM in Three Different FOV Regimes

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Table 2. Representative LSFM, Commercially Available

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Table 3. Simulation Parameters for the Different Figures of LS Engineering Approaches

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Table 4. Summary of the LS Superresolution Methods

Equations (43)

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N1p=δ1pN0Iνhν,
Θem=ϕ·N1p·S·l=ϕ·δ1p·N0·Phν·l,
p=δ2pN0Iν1hν1Iν2hν2Iν1=Iν2δ2pN0(Ihν)2,
F(z)=12η1δ2pN0gpfτ1πw0211+(λzπw02)2N2ϑ2,
IRN·I0(ωkω0)4(αρσ)k2,
Raxial=2w0=λπθ=22λfπD=2nλπNA,
FOV=2zr=2πw02λ.
I(z)(J1(z)z)2,
Dbeam=1.22·λillNAill.
I(x)(sin(x)x)2.
Sx=4·n·λillNAill2,
FOVi=1.78·n·λillNAill2.
M=fTLfobj.
RT=0.61·λemNAdet,
Rdet-axial=1.78n·λemNAdet2.
FOVi=FOVdM,
FOVd=#pixelsx·px sizex,
pxsizei=pxsizexM.
RT=2·px sizei=2·pxsizexM.
Dbeam=Rdet-axial.
NAdet=ϵ1.78·n1.22NAill,
Dbeam=λillNAill.
FOVh=Dpfob-illfcl,
MSC=2·NAill·fobj-illDp.
tan(2θGM)=FOVy·MSC2fobj-ill.
i(x,y,z)=o(x,y,z)*|hLS|2,
|hLS|2=|hill|2×|hdet|2.
h=P(KxKy)e2πi(kx+ky)e2πikz(kx,ky)zdkxdky,
kz=(n/λ)(kx2+ky2)
H(kx,ky,kz)=F|hLS|2.
ISB(z,y,x)=1SΠ(yS)*|hbeam(x,y,z)|2.
p=δ2pN0Iν1hν1Iν2hν2Iν1=Iν2δ2pN0(Ihν)2.
I(ρ,ϕ,z,t)hν=Nϵ(ρ,ϕ,z)ϑ(t).
p=d4Ndxdydzdt=d4Nρdρdϕdzdt=δ2pN0ϵ2(ρ,ϕ,z)N2ϑ2(t).
ϵ(ρ,ϕ,z)=ϵ(ρ,z)=1σ2(z)2πe12(ρ2/σ(z)2),
σ(z)=w(z)2=w021+(z(πw02λ))2.
ϑ(t)=ϑ0m=0ne12(tmf)2σt2.
ϑ=1=f+ϑ0e12t2σt2dt=fϑ0σt2π=fϑ0τπ2ln2yieldsϑ0=2ln2fτπϑ,
ϑ2=f+ϑ02e122t2σt2dt=ϑ02fπσt=ϑ02fπτ22ln2=2ln2π1fτϑ2=gpfτϑ2.
d2N=δ2pN0gpfτN2ϑ2ϵ2(ρ,z)ρdρdϕdz.
dNdz=δ2pN0gpfτN2ϑ218π2[ϕ]ϕ1=0ϕ2=2π[eρ2σ(z)2]ρ1=0ρ2=1σ(z)2=δ2pN0gpfτN2ϑ214π1σ(z)2=δ2pN0gpfτ1πw0211+(zzR)2N2