Subvoxel light-sheet microscopy for high-resolution high-throughput volumetric imaging of large biomedical specimens

Abstract. A key challenge when imaging whole biomedical specimens is how to quickly obtain massive cellular information over a large field of view (FOV). We report a subvoxel light-sheet microscopy (SLSM) method enabling high-throughput volumetric imaging of mesoscale specimens at cellular resolution. A nonaxial, continuous scanning strategy is developed to rapidly acquire a stack of large-FOV images with three-dimensional (3-D) nanoscale shifts encoded. Then, by adopting a subvoxel-resolving procedure, the SLSM method models these low-resolution, cross-correlated images in the spatial domain and can iteratively recover a 3-D image with improved resolution throughout the sample. This technique can surpass the optical limit of a conventional light-sheet microscope by more than three times, with high acquisition speeds of gigavoxels per minute. By fast reconstruction of 3-D cultured cells, intact organs, and live embryos, SLSM method presents a convenient way to circumvent the trade-off between mapping large-scale tissue (>100  mm3) and observing single cell (∼1-μm resolution). It also eliminates the need of complicated mechanical stitching or modulated illumination, using a simple light-sheet setup and fast graphics processing unit-based computation to achieve high-throughput, high-resolution 3-D microscopy, which could be tailored for a wide range of biomedical applications in pathology, histology, neuroscience, etc.

[1]  Sabine Süsstrunk,et al.  A Frequency Domain Approach to Registration of Aliased Images with Application to Super-resolution , 2006, EURASIP J. Adv. Signal Process..

[2]  Matthew A. Brown,et al.  Automatic Panoramic Image Stitching using Invariant Features , 2007, International Journal of Computer Vision.

[3]  Stephan Preibisch,et al.  Efficient Bayesian-based multiview deconvolution , 2013, Nature Methods.

[4]  Loïc Denis,et al.  Inline hologram reconstruction with sparsity constraints. , 2009, Optics letters.

[5]  A. Diaspro,et al.  Influence of refractive-index mismatch in high-resolution three-dimensional confocal microscopy. , 2002, Applied optics.

[6]  D. Sampson,et al.  High-resolution, wide-field object reconstruction with synthetic aperture Fourier holographic optical microscopy. , 2009, Optics express.

[7]  Scott E. Fraser,et al.  Digitizing life at the level of the cell: high-performance laser-scanning microscopy and image analysis for in toto imaging of development , 2003, Mechanisms of Development.

[8]  Philipp J. Keller,et al.  Fast, high-contrast imaging of animal development with scanned light sheet–based structured-illumination microscopy , 2010, Nature Methods.

[9]  Philipp J. Keller,et al.  Whole-brain functional imaging at cellular resolution using light-sheet microscopy , 2013, Nature Methods.

[10]  H. Seung,et al.  Serial two-photon tomography: an automated method for ex-vivo mouse brain imaging , 2011, Nature Methods.

[11]  Joris J J Dirckx,et al.  Tomographic imaging of macroscopic biomedical objects in high resolution and three dimensions using orthogonal-plane fluorescence optical sectioning. , 2009, Applied optics.

[12]  C.-C. Jay Kuo,et al.  Amendment history : Corrigendum ( August 2016 ) 4-Dimensional light-sheet microscopy to elucidate shear stress modulation of cardiac trabeculation , 2018 .

[13]  Matthias Hillenbrand,et al.  Thin-sheet laser imaging microscopy for optical sectioning of thick tissues. , 2009, BioTechniques.

[14]  A. Ozcan,et al.  Pixel super-resolution using wavelength scanning , 2015, Light: Science & Applications.

[15]  M. Chalfie,et al.  Green fluorescent protein as a marker for gene expression. , 1994, Science.

[16]  M Rajadhyaksha,et al.  Analysis of spherical aberration of a water immersion objective: application to specimens with refractive indices 1.33–1.40 , 2000, Journal of microscopy.

[17]  Philipp J. Keller,et al.  Light-sheet functional imaging in fictively behaving zebrafish , 2014, Nature Methods.

[18]  Guoan Zheng,et al.  The ePetri dish, an on-chip cell imaging platform based on subpixel perspective sweeping microscopy (SPSM) , 2011, Proceedings of the National Academy of Sciences.

[19]  Aydogan Ozcan,et al.  Field-portable wide-field microscopy of dense samples using multi-height pixel super-resolution based lensfree imaging. , 2012, Lab on a chip.

[20]  David D Sampson,et al.  Coherent aperture-synthesis, wide-field, high-resolution holographic microscopy of biological tissue. , 2010, Optics letters.

[21]  R. Dobarzić,et al.  [Fluorescence microscopy]. , 1975, Plucne bolesti i tuberkuloza.

[22]  T. Holy,et al.  Fast Three-Dimensional Fluorescence Imaging of Activity in Neural Populations by Objective-Coupled Planar Illumination Microscopy , 2008, Neuron.

[23]  Aydogan Ozcan,et al.  Increased space-bandwidth product in pixel super-resolved lensfree on-chip microscopy , 2013, Scientific Reports.

[24]  F. Del Bene,et al.  Optical Sectioning Deep Inside Live Embryos by Selective Plane Illumination Microscopy , 2004, Science.

[25]  Jan Huisken,et al.  Multi-view image fusion improves resolution in three-dimensional microscopy. , 2007, Optics express.

[26]  Stephan Saalfeld,et al.  Software for bead-based registration of selective plane illumination microscopy data , 2010, Nature Methods.

[27]  Lawrence D. True,et al.  Light-sheet microscopy for slide-free non-destructive pathology of large clinical specimens , 2017, Nature Biomedical Engineering.

[28]  J. Rodenburg,et al.  Optical ptychography: a practical implementation with useful resolution. , 2010, Optics letters.

[29]  N. Plesnila,et al.  Shrinkage-mediated imaging of entire organs and organisms using uDISCO , 2016, Nature Methods.

[30]  R. Horstmeyer,et al.  Wide-field, high-resolution Fourier ptychographic microscopy , 2013, Nature Photonics.

[31]  James H. Resau.  Book Review: Handbook of Biological Confocal Microscopy , 2008 .

[32]  Wesley R. Legant,et al.  Lattice light-sheet microscopy: Imaging molecules to embryos at high spatiotemporal resolution , 2014, Science.

[33]  W Xu,et al.  Digital in-line holography for biological applications , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[34]  Peng Fei,et al.  Light-sheet fluorescence imaging to localize cardiac lineage and protein distribution , 2017, Scientific Reports.

[35]  Hao Jiang,et al.  Compact plane illumination plugin device to enable light sheet fluorescence imaging of multi-cellular organisms on an inverted wide-field microscope. , 2016, Biomedical optics express.

[36]  J. Huisken,et al.  A guide to light-sheet fluorescence microscopy for multiscale imaging , 2017, Nature Methods.

[37]  Rajan P Kulkarni,et al.  Single-Cell Phenotyping within Transparent Intact Tissue through Whole-Body Clearing , 2014, Cell.

[38]  Michael Elad,et al.  Fast and robust multiframe super resolution , 2004, IEEE Transactions on Image Processing.

[39]  E. Susaki,et al.  Whole-Brain Imaging with Single-Cell Resolution Using Chemical Cocktails and Computational Analysis , 2014, Cell.

[40]  Misha B. Ahrens,et al.  Visualizing Whole-Brain Activity and Development at the Single-Cell Level Using Light-Sheet Microscopy , 2015, Neuron.

[41]  K. Deisseroth,et al.  Advanced CLARITY for rapid and high-resolution imaging of intact tissues , 2014, Nature Protocols.

[42]  George Paxinos,et al.  The Mouse Brain in Stereotaxic Coordinates , 2001 .

[43]  M. Schmid.  Principles Of Optics Electromagnetic Theory Of Propagation Interference And Diffraction Of Light , 2016 .

[44]  Aaron S. Andalman,et al.  Structural and molecular interrogation of intact biological systems , 2013, Nature.

[45]  Michael Elad,et al.  A fast super-resolution reconstruction algorithm for pure translational motion and common space-invariant blur , 2001, IEEE Trans. Image Process..

[46]  Philipp J. Keller,et al.  Reconstruction of Zebrafish Early Embryonic Development by Scanned Light Sheet Microscopy , 2008, Science.

[47]  Yongjin Sung,et al.  High-speed synthetic aperture microscopy for live cell imaging. , 2011, Optics letters.

[48]  Zeev Zalevsky,et al.  Space–bandwidth product of optical signals and systems , 1996 .

[49]  C.-C. Jay Kuo,et al.  Cardiac Light-Sheet Fluorescent Microscopy for Multi-Scale and Rapid Imaging of Architecture and Function , 2016, Scientific Reports.