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Journal of Biomedical Optics • Open Access

Multimodal coherent anti-Stokes Raman scattering microscopy reveals microglia-associated myelin and axonal dysfunction in multiple sclerosis-like lesions in mice
Author(s): Jaime Imitola; Stine Rasmussen; Yingru Liu; Tanuja Chitnis; Samia Khoury; Daniel Côté; X. Sunney Xie; Charles P. Lin; Richard L. Sidman

Paper Abstract

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.

Paper Details

Date Published: 1 February 2011
PDF: 11 pages
J. Biomed. Opt. 16(2) 021109 doi: 10.1117/1.3533312
Published in: Journal of Biomedical Optics Volume 16, Issue 2
Show Author Affiliations
Jaime Imitola, Brigham and Women's Hospital (United States)
Stine Rasmussen, Brigham and Women's Hospital (United States)
Yingru Liu, Brigham and Women's Hospital (United States)
Tanuja Chitnis, Brigham and Women's Hospital (United States)
Samia Khoury, Brigham and Women's Hospital (United States)
Daniel Côté, Massachusetts General Hospital (United States)
X. Sunney Xie, Massachusetts General Hospital (United States)
Charles P. Lin, Massachusetts General Hospital (United States)
Richard L. Sidman, Beth Israel Deaconess Medical Ctr. (United States)

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