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Diffusion fMRI detects white-matter dysfunction in mice with acute optic neuritis.

Tsen-Hsuan Lin1, William M Spees2, Chia-Wen Chiang3

  • 1Department of Physics, Washington University, St. Louis, MO 63130, USA.

Neurobiology of Disease
|March 18, 2014
PubMed
Summary

Diffusion functional MRI (fMRI) reveals reduced white matter activation in optic neuritis models. This technique shows promise for assessing multiple sclerosis (MS) dysfunction and treatment efficacy.

Keywords:
Diffusion fMRIEAEOptic neuritisVisual acuityWhite matter

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Area of Science:

  • Neuroscience
  • Medical Imaging
  • Immunology

Background:

  • Optic neuritis is an early indicator of multiple sclerosis (MS).
  • Conventional MRI assesses MS pathologies like demyelination and axonal injury.
  • Directly probing white matter function non-invasively could clarify disease mechanisms.

Purpose of the Study:

  • To investigate the relationship between visual acuity, optic nerve pathology, and diffusion fMRI in experimental autoimmune encephalomyelitis (EAE) mice.
  • To apply a previously established diffusion fMRI technique to an MS model.

Main Methods:

  • Diffusion fMRI was used to measure the apparent diffusion coefficient of water perpendicular to axonal fibers (ADC⊥) during visual stimulation in EAE mice and controls.
  • Post-MRI immunohistochemistry assessed optic nerve pathologies.
  • Visual acuity was evaluated.

Main Results:

  • A significant ADC⊥ decrease (25%) was observed in sham EAE optic nerves with visual stimulation.
  • EAE mice with optic neuritis showed a markedly reduced ADC⊥ decrease (7%) during visual stimulation.
  • Reduced ADC⊥ response correlated with inflammation, demyelination, and axonal injury.
  • A negative correlation was found between the activation-associated ADC⊥ response and visual acuity.

Conclusions:

  • Reduced diffusion fMRI activation reflects impaired axonal function in EAE mice with optic neuritis.
  • Diffusion fMRI offers a promising method for in vivo assessment of white matter dysfunction and therapeutic response in MS.