Abstract

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.

© 2013 OSA

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    [CrossRef] [PubMed]

2013 (2)

R. Cicchi, N. Vogler, D. Kapsokalyvas, B. Dietzek, J. Popp, and F. S. Pavone, “From molecular structure to tissue architecture: collagen organization probed by SHG microscopy,” J. Biophotonics6, 129–142 (2013).
[CrossRef]

A. Ghazaryan, H. F. Tsai, G. Hayrapetyan, W.-L. Chen, Y.-F. Chen, M. Y. Jeong, C.-S. Kim, S.-J. Chen, and C.-Y. Dong, “Analysis of collagen fiber domain organization by Fourier second harmonic generation microscopy,” J. Biomed. Opt.18, 31105 (2013).
[CrossRef]

2012 (3)

M. Filippi, M. A. Rocca, F. Barkhof, W. Brück, J. T. Chen, G. Comi, G. DeLuca, N. De Stefano, B. J. Erickson, N. Evangelou, F. Fazekas, J. J. G. Geurts, C. Lucchinetti, D. H. Miller, D. Pelletier, B. F. G. Popescu, and H. Lassmann, “Association between pathological and MRI findings in multiple sclerosis,” Lancet Neurol.11, 349–360 (2012).
[CrossRef] [PubMed]

C. W. Freudiger, R. Pfannl, D. A. Orringer, B. G. Saar, M. Ji, Q. Zeng, L. Ottoboni, Y. Wei, W. Ying, C. Waeber, J. R. Sims, P. L. De Jager, O. Sagher, M. A. Philbert, X. Xu, S. Kesari, X. S. Xie, and G. S. Young, “Multicolored stain-free histopathology with coherent Raman imaging,” Lab. Invest.92, 1492–1502 (2012).
[CrossRef] [PubMed]

E. Bélanger, J. Crépeau, S. Laffray, R. Vallée, Y. De Koninck, and D. Côté, “Live animal myelin histomorphometry of the spinal cord with video-rate multimodal nonlinear microendoscopy,” J. Biomed. Opt.17, 021107 (2012).
[CrossRef] [PubMed]

2011 (6)

E. Bélanger, F. P. Henry, R. Vallée, M. A. Randolph, I. E. Kochevar, J. M. Winograd, C. P. Lin, and D. Côté, “In vivo evaluation of demyelination and remyelination in a nerve crush injury model,” Biomed. Opt. Express2, 2698–2708 (2011).

B. A. ’t Hart, B. Gran, and R. Weissert, “EAE: imperfect but useful models of multiple sclerosis,” Trends Mol. Med.17, 119–125 (2011).
[CrossRef] [PubMed]

J. P. Pezacki, J. A. Blake, D. C. Danielson, D. C. Kennedy, R. K. Lyn, and R. Singaravelu, “Chemical contrast for imaging living systems: molecular vibrations drive CARS microscopy,” Nat. Chem. Biol.7, 137–145 (2011).
[CrossRef] [PubMed]

J. Imitola, D. Côté, S. Rasmussen, X. S. Xie, Y. Liu, T. Chitnis, R. L. Sidman, C. P. Lin, and S. J. Khoury, “Multimodal coherent anti-Stokes Raman scattering microscopy reveals microglia-associated myelin and axonal dysfunction in multiple sclerosis-like lesions in mice,” J. Biomed. Opt.16, 021109 (2011).

Y. Fu, T. J. Frederick, T. B. Huff, G. E. Goings, S. D. Miller, and J.-X. Cheng, “Paranodal myelin retraction in relapsing experimental autoimmune encephalomyelitis visualized by coherent anti-Stokes Raman scattering microscopy,” J. Biomed. Opt.16, 106006 (2011).

Y. Shi, D. Zhang, T. B. Huff, X. Wang, R. Shi, X.-M. Xu, and J.-X. Cheng, “Longitudinal in vivo coherent anti-Stokes Raman scattering imaging of demyelination and remyelination in injured spinal cord,” J. Biomed. Opt.16, 106012 (2011).

2010 (2)

E. Mix, H. Meyer-Rienecker, H.-P. Hartung, and U. K. Zettl, “Animal models of multiple sclerosis–potentials and limitations,” Prog. Neurobiol.92, 386–404 (2010).
[CrossRef] [PubMed]

K.-A. Nave, “Myelination and the trophic support of long axons,” Nat. Rev. Neurosci.11, 275–283 (2010).
[CrossRef] [PubMed]

2009 (7)

I. L. King, T. L. Dickendesher, and B. M. Segal, “Circulating Ly-6C+ myeloid precursors migrate to the CNS and play a pathogenic role during autoimmune demyelinating disease,” Blood113, 3190–3197 (2009).

P. van der Valk and S. Amor, “Preactive lesions in multiple sclerosis,” Curr. Opin. Neurol.22, 207–213 (2009).
[PubMed]

S. Bégin, E. Bélanger, S. Laffray, R. Vallée, and D. Côté, “In vivo optical monitoring of tissue pathologies and diseases with vibrational contrast,” J. Biophotonics2, 632–642 (2009).
[CrossRef] [PubMed]

P. Matteini, F. Ratto, F. Rossi, R. Cicchi, C. Stringari, D. Kapsokalyvas, F. S. Pavone, and R. Pini, “Photothermally-induced disordered patterns of corneal collagen revealed by SHG imaging,” Opt. Express17, 4868–4878 (2009).
[CrossRef] [PubMed]

R. A. Rao, M. R. Mehta, and K. C. Toussaint, “Fourier transform-second-harmonic generation imaging of biological tissues,” Opt. Express17, 14534–14542 (2009).
[CrossRef] [PubMed]

E. Bélanger, S. Bégin, S. Laffray, Y. De Koninck, R. Vallée, and D. Côté, “Quantitative myelin imaging with coherent anti-Stokes Raman scattering microscopy: alleviating the excitation polarization dependence with circularly polarized laser beams,” Opt. Express17, 18419–18432 (2009).
[CrossRef]

S. Preibisch, S. Saalfeld, and P. Tomancak, “Globally optimal stitching of tiled 3D microscopic image acquisitions,” Bioinformatics25, 1463–1465 (2009).

2008 (2)

C. L. Evans and X. S. Xie, “Coherent anti-Stokes Raman scattering microscopy: chemical imaging for biology and medicine,” Annu. Rev. Anal. Chem.1, 883–909 (2008).
[CrossRef]

I. Veilleux, J. A. Spencer, D. P. Biss, D. Côté, and C. P. Lin, “In vivo cell tracking with video rate multimodality laser scanning microscopy,” IEEE J. Sel. Top. Quantum Electron.14, 10–18 (2008).
[CrossRef]

2007 (2)

D. A. Brown and P. E. Sawchenko, “Time course and distribution of inflammatory and neurodegenerative events suggest structural bases for the pathogenesis of experimental autoimmune encephalomyelitis,” J. Comp. Neurol.502, 236–260 (2007).
[CrossRef] [PubMed]

Y. Fu, H. Wang, T. B. Huff, R. Shi, and J.-X. Cheng, “Coherent anti-Stokes Raman scattering imaging of myelin degradation reveals a calcium-dependent pathway in lyso-PtdCho-induced demyelination,” J. Neurosci. Res.85, 2870–2881 (2007).
[CrossRef] [PubMed]

2005 (1)

H. Wang, Y. Fu, P. Zickmund, R. Shi, and J.-X. Cheng, “Coherent anti-Stokes Raman scattering imaging of axonal myelin in live spinal tissues,” Biophys. J.89, 581–591 (2005).
[CrossRef] [PubMed]

2003 (1)

P. L. Rosin, “Measuring shape: ellipticity, rectangularity, and triangularity,” Mach. Vis. Appl.14, 172–184 (2003).

1999 (1)

A. Zumbusch, G. R. Holtom, and X. S. Xie, “Three-dimensional vibrational imaging by coherent anti-Stokes Raman scattering,” Phys. Rev. Lett.82, 4142–4145 (1999).
[CrossRef]

1993 (1)

J. Flusser and T. Suk, “Pattern recognition by affine moment invariants,” Pattern Recogn.26, 167–174 (1993).
[CrossRef]

1982 (1)

1964 (1)

A. Savitzky and M. J. Golay, “Smoothing and differentiation of data by simplified least squares procedures,” Anal. Chem.36, 1627–1639 (1964).
[CrossRef]

’t Hart, B. A.

B. A. ’t Hart, B. Gran, and R. Weissert, “EAE: imperfect but useful models of multiple sclerosis,” Trends Mol. Med.17, 119–125 (2011).
[CrossRef] [PubMed]

Amor, S.

P. van der Valk and S. Amor, “Preactive lesions in multiple sclerosis,” Curr. Opin. Neurol.22, 207–213 (2009).
[PubMed]

Barkhof, F.

M. Filippi, M. A. Rocca, F. Barkhof, W. Brück, J. T. Chen, G. Comi, G. DeLuca, N. De Stefano, B. J. Erickson, N. Evangelou, F. Fazekas, J. J. G. Geurts, C. Lucchinetti, D. H. Miller, D. Pelletier, B. F. G. Popescu, and H. Lassmann, “Association between pathological and MRI findings in multiple sclerosis,” Lancet Neurol.11, 349–360 (2012).
[CrossRef] [PubMed]

Bégin, S.

Bélanger, E.

E. Bélanger, J. Crépeau, S. Laffray, R. Vallée, Y. De Koninck, and D. Côté, “Live animal myelin histomorphometry of the spinal cord with video-rate multimodal nonlinear microendoscopy,” J. Biomed. Opt.17, 021107 (2012).
[CrossRef] [PubMed]

E. Bélanger, F. P. Henry, R. Vallée, M. A. Randolph, I. E. Kochevar, J. M. Winograd, C. P. Lin, and D. Côté, “In vivo evaluation of demyelination and remyelination in a nerve crush injury model,” Biomed. Opt. Express2, 2698–2708 (2011).

S. Bégin, E. Bélanger, S. Laffray, R. Vallée, and D. Côté, “In vivo optical monitoring of tissue pathologies and diseases with vibrational contrast,” J. Biophotonics2, 632–642 (2009).
[CrossRef] [PubMed]

E. Bélanger, S. Bégin, S. Laffray, Y. De Koninck, R. Vallée, and D. Côté, “Quantitative myelin imaging with coherent anti-Stokes Raman scattering microscopy: alleviating the excitation polarization dependence with circularly polarized laser beams,” Opt. Express17, 18419–18432 (2009).
[CrossRef]

Biss, D. P.

I. Veilleux, J. A. Spencer, D. P. Biss, D. Côté, and C. P. Lin, “In vivo cell tracking with video rate multimodality laser scanning microscopy,” IEEE J. Sel. Top. Quantum Electron.14, 10–18 (2008).
[CrossRef]

Blake, J. A.

J. P. Pezacki, J. A. Blake, D. C. Danielson, D. C. Kennedy, R. K. Lyn, and R. Singaravelu, “Chemical contrast for imaging living systems: molecular vibrations drive CARS microscopy,” Nat. Chem. Biol.7, 137–145 (2011).
[CrossRef] [PubMed]

Brown, D. A.

D. A. Brown and P. E. Sawchenko, “Time course and distribution of inflammatory and neurodegenerative events suggest structural bases for the pathogenesis of experimental autoimmune encephalomyelitis,” J. Comp. Neurol.502, 236–260 (2007).
[CrossRef] [PubMed]

Brück, W.

M. Filippi, M. A. Rocca, F. Barkhof, W. Brück, J. T. Chen, G. Comi, G. DeLuca, N. De Stefano, B. J. Erickson, N. Evangelou, F. Fazekas, J. J. G. Geurts, C. Lucchinetti, D. H. Miller, D. Pelletier, B. F. G. Popescu, and H. Lassmann, “Association between pathological and MRI findings in multiple sclerosis,” Lancet Neurol.11, 349–360 (2012).
[CrossRef] [PubMed]

Chen, J. T.

M. Filippi, M. A. Rocca, F. Barkhof, W. Brück, J. T. Chen, G. Comi, G. DeLuca, N. De Stefano, B. J. Erickson, N. Evangelou, F. Fazekas, J. J. G. Geurts, C. Lucchinetti, D. H. Miller, D. Pelletier, B. F. G. Popescu, and H. Lassmann, “Association between pathological and MRI findings in multiple sclerosis,” Lancet Neurol.11, 349–360 (2012).
[CrossRef] [PubMed]

Chen, S.-J.

A. Ghazaryan, H. F. Tsai, G. Hayrapetyan, W.-L. Chen, Y.-F. Chen, M. Y. Jeong, C.-S. Kim, S.-J. Chen, and C.-Y. Dong, “Analysis of collagen fiber domain organization by Fourier second harmonic generation microscopy,” J. Biomed. Opt.18, 31105 (2013).
[CrossRef]

Chen, W.-L.

A. Ghazaryan, H. F. Tsai, G. Hayrapetyan, W.-L. Chen, Y.-F. Chen, M. Y. Jeong, C.-S. Kim, S.-J. Chen, and C.-Y. Dong, “Analysis of collagen fiber domain organization by Fourier second harmonic generation microscopy,” J. Biomed. Opt.18, 31105 (2013).
[CrossRef]

Chen, Y.-F.

A. Ghazaryan, H. F. Tsai, G. Hayrapetyan, W.-L. Chen, Y.-F. Chen, M. Y. Jeong, C.-S. Kim, S.-J. Chen, and C.-Y. Dong, “Analysis of collagen fiber domain organization by Fourier second harmonic generation microscopy,” J. Biomed. Opt.18, 31105 (2013).
[CrossRef]

Cheng, J.-X.

Y. Fu, T. J. Frederick, T. B. Huff, G. E. Goings, S. D. Miller, and J.-X. Cheng, “Paranodal myelin retraction in relapsing experimental autoimmune encephalomyelitis visualized by coherent anti-Stokes Raman scattering microscopy,” J. Biomed. Opt.16, 106006 (2011).

Y. Shi, D. Zhang, T. B. Huff, X. Wang, R. Shi, X.-M. Xu, and J.-X. Cheng, “Longitudinal in vivo coherent anti-Stokes Raman scattering imaging of demyelination and remyelination in injured spinal cord,” J. Biomed. Opt.16, 106012 (2011).

Y. Fu, H. Wang, T. B. Huff, R. Shi, and J.-X. Cheng, “Coherent anti-Stokes Raman scattering imaging of myelin degradation reveals a calcium-dependent pathway in lyso-PtdCho-induced demyelination,” J. Neurosci. Res.85, 2870–2881 (2007).
[CrossRef] [PubMed]

H. Wang, Y. Fu, P. Zickmund, R. Shi, and J.-X. Cheng, “Coherent anti-Stokes Raman scattering imaging of axonal myelin in live spinal tissues,” Biophys. J.89, 581–591 (2005).
[CrossRef] [PubMed]

Chitnis, T.

J. Imitola, D. Côté, S. Rasmussen, X. S. Xie, Y. Liu, T. Chitnis, R. L. Sidman, C. P. Lin, and S. J. Khoury, “Multimodal coherent anti-Stokes Raman scattering microscopy reveals microglia-associated myelin and axonal dysfunction in multiple sclerosis-like lesions in mice,” J. Biomed. Opt.16, 021109 (2011).

Cicchi, R.

R. Cicchi, N. Vogler, D. Kapsokalyvas, B. Dietzek, J. Popp, and F. S. Pavone, “From molecular structure to tissue architecture: collagen organization probed by SHG microscopy,” J. Biophotonics6, 129–142 (2013).
[CrossRef]

P. Matteini, F. Ratto, F. Rossi, R. Cicchi, C. Stringari, D. Kapsokalyvas, F. S. Pavone, and R. Pini, “Photothermally-induced disordered patterns of corneal collagen revealed by SHG imaging,” Opt. Express17, 4868–4878 (2009).
[CrossRef] [PubMed]

Comi, G.

M. Filippi, M. A. Rocca, F. Barkhof, W. Brück, J. T. Chen, G. Comi, G. DeLuca, N. De Stefano, B. J. Erickson, N. Evangelou, F. Fazekas, J. J. G. Geurts, C. Lucchinetti, D. H. Miller, D. Pelletier, B. F. G. Popescu, and H. Lassmann, “Association between pathological and MRI findings in multiple sclerosis,” Lancet Neurol.11, 349–360 (2012).
[CrossRef] [PubMed]

Côté, D.

E. Bélanger, J. Crépeau, S. Laffray, R. Vallée, Y. De Koninck, and D. Côté, “Live animal myelin histomorphometry of the spinal cord with video-rate multimodal nonlinear microendoscopy,” J. Biomed. Opt.17, 021107 (2012).
[CrossRef] [PubMed]

J. Imitola, D. Côté, S. Rasmussen, X. S. Xie, Y. Liu, T. Chitnis, R. L. Sidman, C. P. Lin, and S. J. Khoury, “Multimodal coherent anti-Stokes Raman scattering microscopy reveals microglia-associated myelin and axonal dysfunction in multiple sclerosis-like lesions in mice,” J. Biomed. Opt.16, 021109 (2011).

E. Bélanger, F. P. Henry, R. Vallée, M. A. Randolph, I. E. Kochevar, J. M. Winograd, C. P. Lin, and D. Côté, “In vivo evaluation of demyelination and remyelination in a nerve crush injury model,” Biomed. Opt. Express2, 2698–2708 (2011).

S. Bégin, E. Bélanger, S. Laffray, R. Vallée, and D. Côté, “In vivo optical monitoring of tissue pathologies and diseases with vibrational contrast,” J. Biophotonics2, 632–642 (2009).
[CrossRef] [PubMed]

E. Bélanger, S. Bégin, S. Laffray, Y. De Koninck, R. Vallée, and D. Côté, “Quantitative myelin imaging with coherent anti-Stokes Raman scattering microscopy: alleviating the excitation polarization dependence with circularly polarized laser beams,” Opt. Express17, 18419–18432 (2009).
[CrossRef]

I. Veilleux, J. A. Spencer, D. P. Biss, D. Côté, and C. P. Lin, “In vivo cell tracking with video rate multimodality laser scanning microscopy,” IEEE J. Sel. Top. Quantum Electron.14, 10–18 (2008).
[CrossRef]

Crépeau, J.

E. Bélanger, J. Crépeau, S. Laffray, R. Vallée, Y. De Koninck, and D. Côté, “Live animal myelin histomorphometry of the spinal cord with video-rate multimodal nonlinear microendoscopy,” J. Biomed. Opt.17, 021107 (2012).
[CrossRef] [PubMed]

Danielson, D. C.

J. P. Pezacki, J. A. Blake, D. C. Danielson, D. C. Kennedy, R. K. Lyn, and R. Singaravelu, “Chemical contrast for imaging living systems: molecular vibrations drive CARS microscopy,” Nat. Chem. Biol.7, 137–145 (2011).
[CrossRef] [PubMed]

De Jager, P. L.

C. W. Freudiger, R. Pfannl, D. A. Orringer, B. G. Saar, M. Ji, Q. Zeng, L. Ottoboni, Y. Wei, W. Ying, C. Waeber, J. R. Sims, P. L. De Jager, O. Sagher, M. A. Philbert, X. Xu, S. Kesari, X. S. Xie, and G. S. Young, “Multicolored stain-free histopathology with coherent Raman imaging,” Lab. Invest.92, 1492–1502 (2012).
[CrossRef] [PubMed]

De Koninck, Y.

E. Bélanger, J. Crépeau, S. Laffray, R. Vallée, Y. De Koninck, and D. Côté, “Live animal myelin histomorphometry of the spinal cord with video-rate multimodal nonlinear microendoscopy,” J. Biomed. Opt.17, 021107 (2012).
[CrossRef] [PubMed]

E. Bélanger, S. Bégin, S. Laffray, Y. De Koninck, R. Vallée, and D. Côté, “Quantitative myelin imaging with coherent anti-Stokes Raman scattering microscopy: alleviating the excitation polarization dependence with circularly polarized laser beams,” Opt. Express17, 18419–18432 (2009).
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Y. Shi, D. Zhang, T. B. Huff, X. Wang, R. Shi, X.-M. Xu, and J.-X. Cheng, “Longitudinal in vivo coherent anti-Stokes Raman scattering imaging of demyelination and remyelination in injured spinal cord,” J. Biomed. Opt.16, 106012 (2011).

Sidman, R. L.

J. Imitola, D. Côté, S. Rasmussen, X. S. Xie, Y. Liu, T. Chitnis, R. L. Sidman, C. P. Lin, and S. J. Khoury, “Multimodal coherent anti-Stokes Raman scattering microscopy reveals microglia-associated myelin and axonal dysfunction in multiple sclerosis-like lesions in mice,” J. Biomed. Opt.16, 021109 (2011).

Sims, J. R.

C. W. Freudiger, R. Pfannl, D. A. Orringer, B. G. Saar, M. Ji, Q. Zeng, L. Ottoboni, Y. Wei, W. Ying, C. Waeber, J. R. Sims, P. L. De Jager, O. Sagher, M. A. Philbert, X. Xu, S. Kesari, X. S. Xie, and G. S. Young, “Multicolored stain-free histopathology with coherent Raman imaging,” Lab. Invest.92, 1492–1502 (2012).
[CrossRef] [PubMed]

Singaravelu, R.

J. P. Pezacki, J. A. Blake, D. C. Danielson, D. C. Kennedy, R. K. Lyn, and R. Singaravelu, “Chemical contrast for imaging living systems: molecular vibrations drive CARS microscopy,” Nat. Chem. Biol.7, 137–145 (2011).
[CrossRef] [PubMed]

Spencer, J. A.

I. Veilleux, J. A. Spencer, D. P. Biss, D. Côté, and C. P. Lin, “In vivo cell tracking with video rate multimodality laser scanning microscopy,” IEEE J. Sel. Top. Quantum Electron.14, 10–18 (2008).
[CrossRef]

Stringari, C.

Suk, T.

J. Flusser and T. Suk, “Pattern recognition by affine moment invariants,” Pattern Recogn.26, 167–174 (1993).
[CrossRef]

Tibshirani, R. J.

B. Efron and R. J. Tibshirani, An Introduction to the Bootstrap (Chapman & Hall, New York, 1993).

Tomancak, P.

S. Preibisch, S. Saalfeld, and P. Tomancak, “Globally optimal stitching of tiled 3D microscopic image acquisitions,” Bioinformatics25, 1463–1465 (2009).

Toussaint, K. C.

Tsai, H. F.

A. Ghazaryan, H. F. Tsai, G. Hayrapetyan, W.-L. Chen, Y.-F. Chen, M. Y. Jeong, C.-S. Kim, S.-J. Chen, and C.-Y. Dong, “Analysis of collagen fiber domain organization by Fourier second harmonic generation microscopy,” J. Biomed. Opt.18, 31105 (2013).
[CrossRef]

Vallée, R.

E. Bélanger, J. Crépeau, S. Laffray, R. Vallée, Y. De Koninck, and D. Côté, “Live animal myelin histomorphometry of the spinal cord with video-rate multimodal nonlinear microendoscopy,” J. Biomed. Opt.17, 021107 (2012).
[CrossRef] [PubMed]

E. Bélanger, F. P. Henry, R. Vallée, M. A. Randolph, I. E. Kochevar, J. M. Winograd, C. P. Lin, and D. Côté, “In vivo evaluation of demyelination and remyelination in a nerve crush injury model,” Biomed. Opt. Express2, 2698–2708 (2011).

S. Bégin, E. Bélanger, S. Laffray, R. Vallée, and D. Côté, “In vivo optical monitoring of tissue pathologies and diseases with vibrational contrast,” J. Biophotonics2, 632–642 (2009).
[CrossRef] [PubMed]

E. Bélanger, S. Bégin, S. Laffray, Y. De Koninck, R. Vallée, and D. Côté, “Quantitative myelin imaging with coherent anti-Stokes Raman scattering microscopy: alleviating the excitation polarization dependence with circularly polarized laser beams,” Opt. Express17, 18419–18432 (2009).
[CrossRef]

van der Valk, P.

P. van der Valk and S. Amor, “Preactive lesions in multiple sclerosis,” Curr. Opin. Neurol.22, 207–213 (2009).
[PubMed]

Veilleux, I.

I. Veilleux, J. A. Spencer, D. P. Biss, D. Côté, and C. P. Lin, “In vivo cell tracking with video rate multimodality laser scanning microscopy,” IEEE J. Sel. Top. Quantum Electron.14, 10–18 (2008).
[CrossRef]

Vogler, N.

R. Cicchi, N. Vogler, D. Kapsokalyvas, B. Dietzek, J. Popp, and F. S. Pavone, “From molecular structure to tissue architecture: collagen organization probed by SHG microscopy,” J. Biophotonics6, 129–142 (2013).
[CrossRef]

Waeber, C.

C. W. Freudiger, R. Pfannl, D. A. Orringer, B. G. Saar, M. Ji, Q. Zeng, L. Ottoboni, Y. Wei, W. Ying, C. Waeber, J. R. Sims, P. L. De Jager, O. Sagher, M. A. Philbert, X. Xu, S. Kesari, X. S. Xie, and G. S. Young, “Multicolored stain-free histopathology with coherent Raman imaging,” Lab. Invest.92, 1492–1502 (2012).
[CrossRef] [PubMed]

Wang, H.

Y. Fu, H. Wang, T. B. Huff, R. Shi, and J.-X. Cheng, “Coherent anti-Stokes Raman scattering imaging of myelin degradation reveals a calcium-dependent pathway in lyso-PtdCho-induced demyelination,” J. Neurosci. Res.85, 2870–2881 (2007).
[CrossRef] [PubMed]

H. Wang, Y. Fu, P. Zickmund, R. Shi, and J.-X. Cheng, “Coherent anti-Stokes Raman scattering imaging of axonal myelin in live spinal tissues,” Biophys. J.89, 581–591 (2005).
[CrossRef] [PubMed]

Wang, X.

Y. Shi, D. Zhang, T. B. Huff, X. Wang, R. Shi, X.-M. Xu, and J.-X. Cheng, “Longitudinal in vivo coherent anti-Stokes Raman scattering imaging of demyelination and remyelination in injured spinal cord,” J. Biomed. Opt.16, 106012 (2011).

Wei, Y.

C. W. Freudiger, R. Pfannl, D. A. Orringer, B. G. Saar, M. Ji, Q. Zeng, L. Ottoboni, Y. Wei, W. Ying, C. Waeber, J. R. Sims, P. L. De Jager, O. Sagher, M. A. Philbert, X. Xu, S. Kesari, X. S. Xie, and G. S. Young, “Multicolored stain-free histopathology with coherent Raman imaging,” Lab. Invest.92, 1492–1502 (2012).
[CrossRef] [PubMed]

Weissert, R.

B. A. ’t Hart, B. Gran, and R. Weissert, “EAE: imperfect but useful models of multiple sclerosis,” Trends Mol. Med.17, 119–125 (2011).
[CrossRef] [PubMed]

Winograd, J. M.

Xie, X. S.

C. W. Freudiger, R. Pfannl, D. A. Orringer, B. G. Saar, M. Ji, Q. Zeng, L. Ottoboni, Y. Wei, W. Ying, C. Waeber, J. R. Sims, P. L. De Jager, O. Sagher, M. A. Philbert, X. Xu, S. Kesari, X. S. Xie, and G. S. Young, “Multicolored stain-free histopathology with coherent Raman imaging,” Lab. Invest.92, 1492–1502 (2012).
[CrossRef] [PubMed]

J. Imitola, D. Côté, S. Rasmussen, X. S. Xie, Y. Liu, T. Chitnis, R. L. Sidman, C. P. Lin, and S. J. Khoury, “Multimodal coherent anti-Stokes Raman scattering microscopy reveals microglia-associated myelin and axonal dysfunction in multiple sclerosis-like lesions in mice,” J. Biomed. Opt.16, 021109 (2011).

C. L. Evans and X. S. Xie, “Coherent anti-Stokes Raman scattering microscopy: chemical imaging for biology and medicine,” Annu. Rev. Anal. Chem.1, 883–909 (2008).
[CrossRef]

A. Zumbusch, G. R. Holtom, and X. S. Xie, “Three-dimensional vibrational imaging by coherent anti-Stokes Raman scattering,” Phys. Rev. Lett.82, 4142–4145 (1999).
[CrossRef]

Xu, X.

C. W. Freudiger, R. Pfannl, D. A. Orringer, B. G. Saar, M. Ji, Q. Zeng, L. Ottoboni, Y. Wei, W. Ying, C. Waeber, J. R. Sims, P. L. De Jager, O. Sagher, M. A. Philbert, X. Xu, S. Kesari, X. S. Xie, and G. S. Young, “Multicolored stain-free histopathology with coherent Raman imaging,” Lab. Invest.92, 1492–1502 (2012).
[CrossRef] [PubMed]

Xu, X.-M.

Y. Shi, D. Zhang, T. B. Huff, X. Wang, R. Shi, X.-M. Xu, and J.-X. Cheng, “Longitudinal in vivo coherent anti-Stokes Raman scattering imaging of demyelination and remyelination in injured spinal cord,” J. Biomed. Opt.16, 106012 (2011).

Ying, W.

C. W. Freudiger, R. Pfannl, D. A. Orringer, B. G. Saar, M. Ji, Q. Zeng, L. Ottoboni, Y. Wei, W. Ying, C. Waeber, J. R. Sims, P. L. De Jager, O. Sagher, M. A. Philbert, X. Xu, S. Kesari, X. S. Xie, and G. S. Young, “Multicolored stain-free histopathology with coherent Raman imaging,” Lab. Invest.92, 1492–1502 (2012).
[CrossRef] [PubMed]

Young, G. S.

C. W. Freudiger, R. Pfannl, D. A. Orringer, B. G. Saar, M. Ji, Q. Zeng, L. Ottoboni, Y. Wei, W. Ying, C. Waeber, J. R. Sims, P. L. De Jager, O. Sagher, M. A. Philbert, X. Xu, S. Kesari, X. S. Xie, and G. S. Young, “Multicolored stain-free histopathology with coherent Raman imaging,” Lab. Invest.92, 1492–1502 (2012).
[CrossRef] [PubMed]

Zeng, Q.

C. W. Freudiger, R. Pfannl, D. A. Orringer, B. G. Saar, M. Ji, Q. Zeng, L. Ottoboni, Y. Wei, W. Ying, C. Waeber, J. R. Sims, P. L. De Jager, O. Sagher, M. A. Philbert, X. Xu, S. Kesari, X. S. Xie, and G. S. Young, “Multicolored stain-free histopathology with coherent Raman imaging,” Lab. Invest.92, 1492–1502 (2012).
[CrossRef] [PubMed]

Zettl, U. K.

E. Mix, H. Meyer-Rienecker, H.-P. Hartung, and U. K. Zettl, “Animal models of multiple sclerosis–potentials and limitations,” Prog. Neurobiol.92, 386–404 (2010).
[CrossRef] [PubMed]

Zhang, D.

Y. Shi, D. Zhang, T. B. Huff, X. Wang, R. Shi, X.-M. Xu, and J.-X. Cheng, “Longitudinal in vivo coherent anti-Stokes Raman scattering imaging of demyelination and remyelination in injured spinal cord,” J. Biomed. Opt.16, 106012 (2011).

Zickmund, P.

H. Wang, Y. Fu, P. Zickmund, R. Shi, and J.-X. Cheng, “Coherent anti-Stokes Raman scattering imaging of axonal myelin in live spinal tissues,” Biophys. J.89, 581–591 (2005).
[CrossRef] [PubMed]

Zumbusch, A.

A. Zumbusch, G. R. Holtom, and X. S. Xie, “Three-dimensional vibrational imaging by coherent anti-Stokes Raman scattering,” Phys. Rev. Lett.82, 4142–4145 (1999).
[CrossRef]

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A. Savitzky and M. J. Golay, “Smoothing and differentiation of data by simplified least squares procedures,” Anal. Chem.36, 1627–1639 (1964).
[CrossRef]

Annu. Rev. Anal. Chem. (1)

C. L. Evans and X. S. Xie, “Coherent anti-Stokes Raman scattering microscopy: chemical imaging for biology and medicine,” Annu. Rev. Anal. Chem.1, 883–909 (2008).
[CrossRef]

Bioinformatics (1)

S. Preibisch, S. Saalfeld, and P. Tomancak, “Globally optimal stitching of tiled 3D microscopic image acquisitions,” Bioinformatics25, 1463–1465 (2009).

Biomed. Opt. Express (1)

Biophys. J. (1)

H. Wang, Y. Fu, P. Zickmund, R. Shi, and J.-X. Cheng, “Coherent anti-Stokes Raman scattering imaging of axonal myelin in live spinal tissues,” Biophys. J.89, 581–591 (2005).
[CrossRef] [PubMed]

Blood (1)

I. L. King, T. L. Dickendesher, and B. M. Segal, “Circulating Ly-6C+ myeloid precursors migrate to the CNS and play a pathogenic role during autoimmune demyelinating disease,” Blood113, 3190–3197 (2009).

Curr. Opin. Neurol. (1)

P. van der Valk and S. Amor, “Preactive lesions in multiple sclerosis,” Curr. Opin. Neurol.22, 207–213 (2009).
[PubMed]

IEEE J. Sel. Top. Quantum Electron. (1)

I. Veilleux, J. A. Spencer, D. P. Biss, D. Côté, and C. P. Lin, “In vivo cell tracking with video rate multimodality laser scanning microscopy,” IEEE J. Sel. Top. Quantum Electron.14, 10–18 (2008).
[CrossRef]

J. Biomed. Opt. (5)

E. Bélanger, J. Crépeau, S. Laffray, R. Vallée, Y. De Koninck, and D. Côté, “Live animal myelin histomorphometry of the spinal cord with video-rate multimodal nonlinear microendoscopy,” J. Biomed. Opt.17, 021107 (2012).
[CrossRef] [PubMed]

A. Ghazaryan, H. F. Tsai, G. Hayrapetyan, W.-L. Chen, Y.-F. Chen, M. Y. Jeong, C.-S. Kim, S.-J. Chen, and C.-Y. Dong, “Analysis of collagen fiber domain organization by Fourier second harmonic generation microscopy,” J. Biomed. Opt.18, 31105 (2013).
[CrossRef]

J. Imitola, D. Côté, S. Rasmussen, X. S. Xie, Y. Liu, T. Chitnis, R. L. Sidman, C. P. Lin, and S. J. Khoury, “Multimodal coherent anti-Stokes Raman scattering microscopy reveals microglia-associated myelin and axonal dysfunction in multiple sclerosis-like lesions in mice,” J. Biomed. Opt.16, 021109 (2011).

Y. Fu, T. J. Frederick, T. B. Huff, G. E. Goings, S. D. Miller, and J.-X. Cheng, “Paranodal myelin retraction in relapsing experimental autoimmune encephalomyelitis visualized by coherent anti-Stokes Raman scattering microscopy,” J. Biomed. Opt.16, 106006 (2011).

Y. Shi, D. Zhang, T. B. Huff, X. Wang, R. Shi, X.-M. Xu, and J.-X. Cheng, “Longitudinal in vivo coherent anti-Stokes Raman scattering imaging of demyelination and remyelination in injured spinal cord,” J. Biomed. Opt.16, 106012 (2011).

J. Biophotonics (2)

S. Bégin, E. Bélanger, S. Laffray, R. Vallée, and D. Côté, “In vivo optical monitoring of tissue pathologies and diseases with vibrational contrast,” J. Biophotonics2, 632–642 (2009).
[CrossRef] [PubMed]

R. Cicchi, N. Vogler, D. Kapsokalyvas, B. Dietzek, J. Popp, and F. S. Pavone, “From molecular structure to tissue architecture: collagen organization probed by SHG microscopy,” J. Biophotonics6, 129–142 (2013).
[CrossRef]

J. Comp. Neurol. (1)

D. A. Brown and P. E. Sawchenko, “Time course and distribution of inflammatory and neurodegenerative events suggest structural bases for the pathogenesis of experimental autoimmune encephalomyelitis,” J. Comp. Neurol.502, 236–260 (2007).
[CrossRef] [PubMed]

J. Neurosci. Res. (1)

Y. Fu, H. Wang, T. B. Huff, R. Shi, and J.-X. Cheng, “Coherent anti-Stokes Raman scattering imaging of myelin degradation reveals a calcium-dependent pathway in lyso-PtdCho-induced demyelination,” J. Neurosci. Res.85, 2870–2881 (2007).
[CrossRef] [PubMed]

Lab. Invest. (1)

C. W. Freudiger, R. Pfannl, D. A. Orringer, B. G. Saar, M. Ji, Q. Zeng, L. Ottoboni, Y. Wei, W. Ying, C. Waeber, J. R. Sims, P. L. De Jager, O. Sagher, M. A. Philbert, X. Xu, S. Kesari, X. S. Xie, and G. S. Young, “Multicolored stain-free histopathology with coherent Raman imaging,” Lab. Invest.92, 1492–1502 (2012).
[CrossRef] [PubMed]

Lancet Neurol. (1)

M. Filippi, M. A. Rocca, F. Barkhof, W. Brück, J. T. Chen, G. Comi, G. DeLuca, N. De Stefano, B. J. Erickson, N. Evangelou, F. Fazekas, J. J. G. Geurts, C. Lucchinetti, D. H. Miller, D. Pelletier, B. F. G. Popescu, and H. Lassmann, “Association between pathological and MRI findings in multiple sclerosis,” Lancet Neurol.11, 349–360 (2012).
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P. L. Rosin, “Measuring shape: ellipticity, rectangularity, and triangularity,” Mach. Vis. Appl.14, 172–184 (2003).

Nat. Chem. Biol. (1)

J. P. Pezacki, J. A. Blake, D. C. Danielson, D. C. Kennedy, R. K. Lyn, and R. Singaravelu, “Chemical contrast for imaging living systems: molecular vibrations drive CARS microscopy,” Nat. Chem. Biol.7, 137–145 (2011).
[CrossRef] [PubMed]

Nat. Rev. Neurosci. (1)

K.-A. Nave, “Myelination and the trophic support of long axons,” Nat. Rev. Neurosci.11, 275–283 (2010).
[CrossRef] [PubMed]

Opt. Express (3)

Opt. Lett. (1)

Pattern Recogn. (1)

J. Flusser and T. Suk, “Pattern recognition by affine moment invariants,” Pattern Recogn.26, 167–174 (1993).
[CrossRef]

Phys. Rev. Lett. (1)

A. Zumbusch, G. R. Holtom, and X. S. Xie, “Three-dimensional vibrational imaging by coherent anti-Stokes Raman scattering,” Phys. Rev. Lett.82, 4142–4145 (1999).
[CrossRef]

Prog. Neurobiol. (1)

E. Mix, H. Meyer-Rienecker, H.-P. Hartung, and U. K. Zettl, “Animal models of multiple sclerosis–potentials and limitations,” Prog. Neurobiol.92, 386–404 (2010).
[CrossRef] [PubMed]

Trends Mol. Med. (1)

B. A. ’t Hart, B. Gran, and R. Weissert, “EAE: imperfect but useful models of multiple sclerosis,” Trends Mol. Med.17, 119–125 (2011).
[CrossRef] [PubMed]

Other (2)

J. S. Lim, Two-Dimensional Signal and Image Processing (Prentice Hall, Englewood Cliffs, 1990).

B. Efron and R. J. Tibshirani, An Introduction to the Bootstrap (Chapman & Hall, New York, 1993).

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Figures (7)

Fig. 1
Fig. 1

Median AR (with median absolute deviation) as a function of domain size. For small domain sizes, poor orientation accuracy is due to lack of data on fiber morphology. At large sizes, no additional accuracy is obtained on the orientation although spatial resolution is decreased. The optimal size was thus choosen to be 192 pixels.

Fig. 2
Fig. 2

(a) Three different CARS images of mouse spinal cord surface in the longitudinal orientation. From top to bottom, the tissue becomes progressively afflicted by EAE lesions. (b) Processed 2D-FT of the domains. (c) Segmented objects with superposed equivalent ellipses and main axes. (d) Average fiber orientation overlaid on the images with AR color-coded (AR color code shown right).

Fig. 3
Fig. 3

Two CARS images of healthy (top) and diseased (bottom) spinal cord. (a) The orientation and AR were calculated for square domains of 192×192 pixels. In (b) and (c), the calculated CP and CCP are shown on the bottom right corner as well as color-coded on the images (CP and CCP color code shown at the bottom).

Fig. 4
Fig. 4

The CCP was calculated for twelve images, each divided into 25 domains. The median CCP is shown. (a) Six images typical of healthy-appearing spinal cord tissue. (b) Three images showing a moderate degree of disorganization. (c) Three images showing a severe degree of disorganization.

Fig. 5
Fig. 5

In this large map of spinal cord surface (600×600 μm), we can see that the lesions appear in patches. The difference between the median CCP of the whole image and that of the two subsections highlights the fact that the level of tissue disorganization is heterogeneous throughout the spinal cord.

Fig. 6
Fig. 6

PDF of the CCP for all domains in maps for both control and EAE mice (two mice per condition, blue and orange lines). The number of domains per mouse (NDM1, NDM2) is indicated for all conditions.

Fig. 7
Fig. 7

Different descriptors of the PDF are plotted against the clinical scores in order of decreasing correlation coefficient (rs). The bootstrap percentile confidence interval at 95% shows the sampling error. The line of best fit is plotted to emphasize the correlation.

Equations (9)

Equations on this page are rendered with MathJax. Learn more.

E I = { 16 π 2 I 1 if I 1 1 16 π 2 1 16 π 2 I 1 otherwise ,
I 1 = μ 20 μ 02 μ 11 2 μ 00 4 .
μ p q = x , y ( x x ¯ ) p ( y y ¯ ) q I ( x , y ) ,
S i , j S i + 1 , j = | S i , j | | S i + 1 , j | cos ( θ i , j θ i + 1 , j )
S i , j S i + 1 , j = cos ( θ i , j θ i + 1 , j ) .
C i i + 1 = 2 [ cos 2 ( θ i , j θ i + 1 , j ) 0.5 ] .
CP i , j = C i i 1 + C i i + 1 + C j j 1 + C j j + 1 4 ,
CP i , j = 1 N n b N n b 2 [ cos 2 ( θ i , j θ n b ) 0.5 ] ,
CCP = CP [ 1 AR ] ,

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