Special Section on Coherent Raman Imaging Techniques and Biomedical Applications

Multimodal coherent anti-Stokes Raman scattering microscopy reveals microglia-associated myelin and axonal dysfunction in multiple sclerosis-like lesions in mice

[+] Author Affiliations
Jaime Imitola, Stine Rasmussen, Yingru Liu, Tanuja Chitnis, Samia J. Khoury

Brigham and Women's Hospital, Center for Neurologic Diseases, Partner Multiple Sclerosis Center, Harvard Medical School, Department of Neurology, Boston, Massachusetts 02115

Daniel Côté

Massachusetts General Hospital, Advanced Microscopy Program, Center for Systems Biology and Wellman Center for Photomedicine, BHX 630, Harvard Medical School, 50 Blossom Street, Boston, Massachusetts 02114

Université Laval, Centre de Recherche Université Laval Robert Giffard and Centre d’Optique Photonique et Laser, Québec City, Québec G1J 2G3, Canada

X. Sunney Xie, Charles. P. Lin

Massachusetts General Hospital, Advanced Microscopy Program, Center for Systems Biology and Wellman Center for Photomedicine, BHX 630, Harvard Medical School, 50 Blossom Street, Boston, Massachusetts 02114

Richard L. Sidman

Beth Israel Deaconess Medical Center, Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115

J. Biomed. Opt. 16(2), 021109 (February 17, 2011). doi:10.1117/1.3533312
History: Received March 24, 2010; Revised September 15, 2010; Accepted September 30, 2010; Published February 17, 2011; Online February 17, 2011
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Myelin loss and axonal degeneration predominate in many neurological disorders; however, methods to visualize them simultaneously in live tissue are unavailable. We describe a new imaging strategy combining video rate reflectance and fluorescence confocal imaging with coherent anti-Stokes Raman scattering (CARS) microscopy tuned to CH2 vibration of myelin lipids, applied in live tissue of animals with chronic experimental autoimmune encephalomyelitis (EAE). Our method allows monitoring over time of demyelination and neurodegeneration in brain slices with high spatial resolution and signal-to-noise ratio. Local areas of severe loss of lipid signal indicative of demyelination and loss of the reflectance signal from axons were seen in the corpus callosum and spinal cord of EAE animals. Even in myelinated areas of EAE mice, the intensity of myelin lipid signals is significantly reduced. Using heterozygous knock-in mice in which green fluorescent protein replaces the CX3CR1 coding sequence that labels central nervous system microglia, we find areas of activated microglia colocalized with areas of altered reflectance and CARS signals reflecting axonal injury and demyelination. Our data demonstrate the use of multimodal CARS microscopy for characterization of demyelinating and neurodegenerative pathology in a mouse model of multiple sclerosis, and further confirm the critical role of microglia in chronic inflammatory neurodegeneration.

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© 2011 Society of Photo-Optical Instrumentation Engineers (SPIE)

Citation

Jaime Imitola ; Daniel Côté ; Stine Rasmussen ; X. Sunney Xie ; Yingru Liu, et al.
"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(2), 021109 (February 17, 2011). ; http://dx.doi.org/10.1117/1.3533312


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