Development of a head-mount fiber scanning system for imaging in vivo

In this thesis I will describe the basic concepts necessary for acquiring functional data from nerve tissue by application of two-photon laser scanning microscopy and its miniaturization for in vivo imaging in freely moving animals. The construction of a laser with enhanced repetition rate and the design of a novel non-resonant fiber scanning technique is emphasized. The increased repetition rate of the femtosecond laser source should decrease undesirable non-linear effects when transmitting ultra-short pulses with a single mode fiber. By implementing the prototype of a head-mounted microscope involving the novel fiber scanner and testing with fluorescent probes I can demonstrate its feasibility - not only for imaging in freely moving animals but for mobile laser scanning microscopy in general.

[1]  T. Brabec,et al.  Mode locking in solitary lasers. , 1991, Optics letters.

[2]  T Dekorsy,et al.  Femtosecond Ti:sapphire ring laser with a 2-GHz repetition rate and its application in time-resolved spectroscopy. , 1999, Optics letters.

[3]  V. Ghiglieri,et al.  Electrophysiological and pharmacological characteristics of nigral dopaminergic neurons in the conscious, head‐restrained rat , 2003, Synapse.

[4]  J. Edeline,et al.  Evoked oscillations in the thalamo-cortical auditory system are present in anesthetized but not in unanesthetized rats. , 2003, Journal of neurophysiology.

[5]  S. Silvestri,et al.  Astigmatism in Gaussian-beam self-focusing and in resonators for Kerr-lens mode locking , 1995 .

[6]  C. Stosiek,et al.  In vivo two-photon calcium imaging of neuronal networks , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[7]  Maria Goeppert-Mayer.  Über Elementarakte mit zwei Quantensprüngen , 1931 .

[8]  A Bartels,et al.  Generation of a broadband continuum by a Ti:sapphire femtosecond oscillator with a 1-GHz repetition rate. , 2002, Optics letters.

[9]  F. Duarte.  Generalized multiple-prism dispersion theory for pulse compression in ultrafast dye lasers , 1987 .

[10]  R. E. Sherriff.  Analytic expressions for group-delay dispersion and cubic dispersion in arbitrary prism sequences , 1998 .

[11]  Mark Gumbleton,et al.  Coming out of the dark: the evolving role of fluorescence imaging in drug delivery research. , 2005, Advanced drug delivery reviews.

[12]  D. Tank,et al.  Dendritic Integration in Mammalian Neurons, a Century after Cajal , 1996, Neuron.

[13]  Sandro De Silvestri,et al.  ABCD matrix analysis of propagation of gaussian beams through Kerr media , 1993 .

[14]  Mj Martin Bastiaans.  ABCD law for partially coherent Gaussian light, propagating through first-order optical systems , 1992, Optical Society of America Annual Meeting.

[15]  W. Webb,et al.  IN VIVO MULTIPHOTON IMAGING OF AMYLOID DEPOSITION IN TRANSGENIC MICE , 1999 .

[16]  W. Webb,et al.  Multiphoton fluorescence excitation: new spectral windows for biological nonlinear microscopy. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[17]  B Sakmann,et al.  Patch clamp techniques for studying ionic channels in excitable membranes. , 1984, Annual review of physiology.

[18]  D. Tank,et al.  Enhanced two-photon excitation through optical fiber by single-mode propagation in a large core. , 2002, Applied optics.

[19]  W. Webb,et al.  Molecular dynamics in living cells observed by fluorescence correlation spectroscopy with one- and two-photon excitation. , 1999, Biophysical journal.

[20]  F. Duarte.  Multiple-prism arrays in laser optics , 2000 .

[21]  Ai Kah Soh,et al.  Three-dimensional electromechanical responses of a parallel piezoelectric bimorph , 2001 .

[22]  Govind P. Agrawal,et al.  Nonlinear Fiber Optics , 1989 .

[23]  Fritjof Helmchen,et al.  Miniaturization of Fluorescence Microscopes Using Fibre Optics , 2002, Experimental physiology.

[24]  W. Nasalski.  Complex ray tracing of nonlinear propagation , 1995 .

[25]  E Neher,et al.  Fast scanning and efficient photodetection in a simple two-photon microscope , 1999, Journal of Neuroscience Methods.

[26]  Bartlett W. Mel,et al.  Towards the memory capacity of neurons with active dendrites , 1999, Neurocomputing.

[27]  D. M. Kane.  Ti:sapphire laser cavity mode and pump-laser mode calculations. , 1994, Applied Optics.

[28]  Jack Waters,et al.  Ca2+ imaging in the mammalian brain in vivo. , 2002, European journal of pharmacology.

[29]  Self-mode locking of four-mirror-cavity solid-state lasers by Kerr self-focusing , 1995 .

[30]  D. Muller,et al.  A simple method for organotypic cultures of nervous tissue , 1991, Journal of Neuroscience Methods.

[31]  Analytical expression for the complex radius of curvature tensor Q for generalized gaussian beams , 1991 .

[32]  D. Kleinfeld,et al.  Anatomical and functional imaging of neurons using 2-photon laser scanning microscopy , 1994, Journal of Neuroscience Methods.

[33]  Sooyoung Chung,et al.  Functional imaging with cellular resolution reveals precise micro-architecture in visual cortex , 2005, Nature.

[34]  J. Gordon,et al.  Optical resonator with negative dispersion. , 1984, Optics letters.

[35]  D. Kleinfeld,et al.  In vivo dendritic calcium dynamics in neocortical pyramidal neurons , 1997, Nature.

[36]  J G Fujimoto,et al.  High-resolution optical coherence microscopy for high-speed, in vivo cellular imaging. , 2003, Optics letters.

[37]  A. Mehta,et al.  In vivo mammalian brain imaging using one- and two-photon fluorescence microendoscopy. , 2004, Journal of neurophysiology.

[38]  R. Tobey,et al.  Use of a simple cavity geometry for low and high repetition rate modelocked Ti:sapphire lasers. , 2004, Optics express.

[39]  W. Denk,et al.  Two-photon laser scanning fluorescence microscopy. , 1990, Science.

[40]  P. Richter,et al.  Correction of astigmatism and ellipticity of an astigmatic Gaussian laser beam by symmetrical lenses , 1992 .

[41]  A. Dunaevsky,et al.  Dendritic spine morphogenesis and plasticity. , 2005, Journal of neurobiology.

[42]  A. Marcano O.,et al.  Fluorescence quantum yield of rhodamine 101 in the presence of absorption saturation , 2001 .

[43]  Mark J Schnitzer,et al.  Fiber optic in vivo imaging in the mammalian nervous system , 2004 .

[44]  W. Webb,et al.  Measurement of two-photon excitation cross sections of molecular fluorophores with data from 690 to 1050 nm , 1996 .

[45]  F. Wise,et al.  Fiber delivery of femtosecond pulses from a Ti:sapphire laser. , 2001, Optics letters.

[46]  Frank W. Wise,et al.  Generation of 13‐fs pulses from a mode‐locked Ti:Al2O3 laser with reduced third‐order dispersion , 1993 .

[47]  C. Seidel,et al.  Photobleaching of Fluorescent Dyes under Conditions Used for Single-Molecule Detection:  Evidence of Two-Step Photolysis. , 1998, Analytical chemistry.

[48]  W. Denk,et al.  Two-photon imaging to a depth of 1000 microm in living brains by use of a Ti:Al2O3 regenerative amplifier. , 2003, Optics letters.

[49]  Petra Schwille,et al.  Photobleaching and stabilization of. fluorophores used for single-molecule analysis. with one- and two-photon excitation , 2001 .

[50]  D. Tank,et al.  A Miniature Head-Mounted Two-Photon Microscope High-Resolution Brain Imaging in Freely Moving Animals , 2001, Neuron.

[51]  Ferenc Krausz,et al.  Compression of 2 mJ kilohertz laser pulses to 17.5 fs by pairing double-prism compressor: analysis and performance , 2002 .

[52]  Weihua Wang,et al.  Equation of state of bulk metallic glasses studied by an ultrasonic method , 2001 .

[53]  F. Krausz,et al.  Limits of pulse shortening in solitary lasers. , 1992, Optics letters.

[54]  F. Wise,et al.  Quartz prism sequence for reduction of cubic phase in a mode-locked Ti:Al(2)O(3) laser. , 1992, Optics letters.

[55]  Yinchieh Lai,et al.  Simple analytical method of cavity design for astigmatism-compensated Kerr-lens mode-locked ring lasers and its applications , 1995 .

[56]  D. Debanne,et al.  Organotypic slice cultures: a technique has come of age , 1997, Trends in Neurosciences.

[57]  Sandro De Silvestri,et al.  Closed form gaussian beam analysis of resonators containing a Kerr medium for femtosecond lasers , 1993 .

[58]  Bert Sakmann,et al.  Supralinear Ca2+ Influx into Dendritic Tufts of Layer 2/3 Neocortical Pyramidal Neurons In Vitro and In Vivo , 2003, The Journal of Neuroscience.

[59]  B. Lemoff,et al.  Generation of high-peak-power 20-fs pulses from a regeneratively initiated, self-mode-locked Ti:sapphire laser. , 1992, Optics letters.

[60]  Jing Ma,et al.  Spatial chirp and angular dispersion of a laser crystal for a four-mirror cavity Kerr-lens mode-locked laser. , 2004, Applied optics.

[61]  B Messerschmidt,et al.  Endoscope-compatible confocal microscope using a gradient index-lens system , 2001 .

[62]  Symmetrizing transformation of general astigmatic Gaussian beams , 1994 .

[63]  Winfried Denk,et al.  Coherence-gated wave-front sensing in strongly scattering samples. , 2004, Optics letters.

[64]  G. Patterson,et al.  Photobleaching in two-photon excitation microscopy. , 2000, Biophysical journal.

[65]  Herwig Kogelnik,et al.  On the Propagation of Gaussian Beams of Light Through Lenslike Media Including those with a Loss or Gain Variation , 1965 .

[66]  Borivoj Vojnovic,et al.  Intravital imaging of tumour vascular networks using multi-photon fluorescence microscopy. , 2005, Advanced drug delivery reviews.

[67]  S. Kügler,et al.  Long-term in vivo and in vitro AAV-2-mediated RNA interference in rat retinal ganglion cells and cultured primary neurons. , 2005, Biochemical and biophysical research communications.

[68]  Christian Eggeling,et al.  Single-Molecule Identification of Coumarin-120 by Time-Resolved Fluorescence Detection: Comparison of One- and Two-Photon Excitation in Solution , 1997 .

[69]  J G Fujimoto,et al.  Self-focusing-induced saturable loss for laser mode locking. , 1992, Optics letters.

[70]  Winfried Denk,et al.  New developments in multiphoton microscopy , 2002, Current Opinion in Neurobiology.

[71]  D Onciul.  ABCD propagation law for misaligned general astigmatic Gaussian beams , 1992 .

[72]  J. Fujimoto,et al.  Endoscopic optical coherence tomography , 1996, Conference Proceedings LEOS'96 9th Annual Meeting IEEE Lasers and Electro-Optics Society.

[73]  J. Squier,et al.  Mode locking of Ti:AI(2)O(3) lasers and self-focusing: a Gaussian approximation. , 1991, Optics letters.