Local assessment of myelin health in a multiple sclerosis mouse model using a 2D Fourier transform approach.

We present an automated two-dimensional Fourier transform (2D-FT) approach to analyze the local organization of myelinated axons in the spinal cord. Coherent anti-Stokes Raman scattering (CARS) microscopy was used to observe lesions in a commonly used animal model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE). A 2D-FT was applied on the CARS images to find the average orientation and directional anisotropy of the fibers within contiguous image domains. We introduce the corrected correlation parameter (CCP), a measure of the correlation between orientations of adjacent domains. We show that in the EAE animal model of MS, the CCP can be used to quantify the degree of organization/disorganization in the myelin structure. This analysis was applied to a large image dataset from animals at different clinical scores and we show that some descriptors of the CCP probability density function are strongly correlated with the clinical scores. This procedure, compatible with live animal imaging, has been developed to perform local in situ evaluation of myelinated axons afflicted by EAE.

[1]  P. Sawchenko,et al.  Time course and distribution of inflammatory and neurodegenerative events suggest structural bases for the pathogenesis of experimental autoimmune encephalomyelitis , 2007, The Journal of comparative neurology.

[2]  R. Shi,et al.  Coherent anti‐stokes Raman scattering imaging of myelin degradation reveals a calcium‐dependent pathway in lyso‐PtdCho‐induced demyelination , 2007, Journal of neuroscience research.

[3]  Riyi Shi,et al.  Longitudinal in vivo coherent anti-Stokes Raman scattering imaging of demyelination and remyelination in injured spinal cord. , 2011, Journal of biomedical optics.

[4]  Stine Rasmussen,et al.  Multimodal coherent anti-Stokes Raman scattering microscopy reveals microglia-associated myelin and axonal dysfunction in multiple sclerosis-like lesions in mice. , 2011, Journal of biomedical optics.

[5]  I. Veilleux,et al.  In Vivo Cell Tracking With Video Rate Multimodality Laser Scanning Microscopy , 2008, IEEE Journal of Selected Topics in Quantum Electronics.

[6]  S. Amor,et al.  Preactive lesions in multiple sclerosis , 2009, Current opinion in neurology.

[7]  Riyi Shi,et al.  Coherent anti-stokes Raman scattering imaging of axonal myelin in live spinal tissues. , 2005, Biophysical journal.

[8]  D. Côté,et al.  Quantitative myelin imaging with coherent anti-Stokes Raman scattering microscopy: alleviating the excitation polarization dependence with circularly polarized laser beams. , 2009, Optics express.

[9]  M D Duncan,et al.  Scanning coherent anti-Stokes Raman microscope. , 1982, Optics letters.

[10]  Ji-Xin Cheng,et al.  Paranodal myelin retraction in relapsing experimental autoimmune encephalomyelitis visualized by coherent anti-Stokes Raman scattering microscopy. , 2011, Journal of biomedical optics.

[11]  R. Vallée,et al.  In vivo evaluation of demyelination and remyelination in a nerve crush injury model , 2011, Biomedical optics express.

[12]  Jürgen Popp,et al.  From molecular structure to tissue architecture: collagen organization probed by SHG microscopy , 2013, Journal of biophotonics.

[13]  Réal Vallée,et al.  Live animal myelin histomorphometry of the spinal cord with video-rate multimodal nonlinear microendoscopy. , 2012, Journal of biomedical optics.

[14]  Jane A Dickerson,et al.  Current Applications of Liquid Chromatography / Mass Spectrometry in Pharmaceutical Discovery After a Decade of Innovation , 2008 .

[15]  Paul L. Rosin Measuring shape: ellipticity, rectangularity, and triangularity , 2003, Machine Vision and Applications.

[16]  Jan Flusser,et al.  Pattern recognition by affine moment invariants , 1993, Pattern Recognit..

[17]  Klaus-Armin Nave,et al.  Myelination and the trophic support of long axons , 2010, Nature Reviews Neuroscience.

[18]  S. Laffray,et al.  In vivo optical monitoring of tissue pathologies and diseases with vibrational contrast , 2009, Journal of biophotonics.

[19]  H. Hartung,et al.  Animal models of multiple sclerosis—Potentials and limitations , 2010, Progress in Neurobiology.

[20]  Massimo Filippi,et al.  Association between pathological and MRI findings in multiple sclerosis , 2012, The Lancet Neurology.

[21]  Irah L. King,et al.  Circulating Ly-6C+ myeloid precursors migrate to the CNS and play a pathogenic role during autoimmune demyelinating disease. , 2009, Blood.

[22]  John Paul Pezacki,et al.  Chemical contrast for imaging living systems: molecular vibrations drive CARS microscopy , 2011, Nature chemical biology.

[23]  X. Xie,et al.  Multicolored Stain-free Histopathology with Coherent Raman Imaging , 2012, Laboratory Investigation.

[24]  Monal R. Mehta,et al.  Fourier transform-second-harmonic generation imaging of biological tissues. , 2009, Optics express.

[25]  B. '. ’t Hart,et al.  EAE: imperfect but useful models of multiple sclerosis. , 2011, Trends in molecular medicine.

[26]  Stephan Saalfeld,et al.  Globally optimal stitching of tiled 3D microscopic image acquisitions , 2009, Bioinform..

[27]  Chang-Seok Kim,et al.  Analysis of collagen fiber domain organization by Fourier second harmonic generation microscopy , 2012, Journal of biomedical optics.

[28]  Roberto Pini,et al.  Photothermally-induced disordered patterns of corneal collagen revealed by SHG imaging. , 2009, Optics express.

[29]  W. R. Wiley,et al.  Three-Dimensional Vibrational Imaging by Coherent Anti-Stokes Raman Scattering , 1999 .

[30]  A. Savitzky,et al.  Smoothing and Differentiation of Data by Simplified Least Squares Procedures. , 1964 .