Axonal injury in the cerebral normal-appearing white matter of patients with multiple sclerosis is related to concurrent demyelination in lesions but not to concurrent demyelination in normal-appearing white matter

Sridar Narayanan, Simon J. Francis, John G. Sled, A. C. Santos, Samson Antel, Ives Levesque, Steven Brass, Yves Lapierre, Dominique Sappey-Marinier, G. Bruce Pike, Douglas L. Arnold

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Abstract

We assessed axonal injury and demyelination in the cerebral normal-appearing white matter (NAWM) of MS patients in a pilot study using proton magnetic resonance spectroscopic imaging and quantitative magnetization transfer (MT) imaging. Resonance intensities of N-acetylaspartate (NAA) relative to creatine (Cr) were measured in a large central brain volume. NAA/Cr in NAWM was estimated by regression of the NAA/Cr in each voxel against white matter fraction and extrapolation to a white matter fraction of 1. The fractional size of the semi-solid pool (F) was obtained from the binary spin bath model of MT by computing the model parameters from multiple MT-weighted and relaxometry acquisitions. F in NAWM was significantly smaller in the patients [0.109 (0.009)] relative to controls [0.123 (0.007), P = 0.011], but did not differ between RR [0.1085] and SP [0.1087] patients [P > 0.99]. NAA/Cr and F in the NAWM were not correlated (r = 0.16, P > 0.7), mainly due to a lack of variation in F among patients. This may indicate a floor to the extent of myelin pathology that can occur in NAWM before a lesion appears, or that axonal damage is not strictly related to demyelination. The correlation between NAWM NAA/Cr and T2w lesion volume was not significant (P > 0.1). However, dividing the lesion volumes by the mean F in T2w lesions resulted in a quantity that correlated well with NAWM NAA/Cr (r = -0.78, P = 0.038), possibly reflecting the association of Wallerian degeneration in the NAWM with axonal transection associated with demyelination within lesions.

Original languageEnglish (US)
Pages (from-to)637-642
Number of pages6
JournalNeuroImage
Volume29
Issue number2
DOIs
StatePublished - Jan 15 2006
Externally publishedYes

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ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Neurology

Cite this

Narayanan, S., Francis, S. J., Sled, J. G., Santos, A. C., Antel, S., Levesque, I., Brass, S., Lapierre, Y., Sappey-Marinier, D., Pike, G. B., & Arnold, D. L. (2006). Axonal injury in the cerebral normal-appearing white matter of patients with multiple sclerosis is related to concurrent demyelination in lesions but not to concurrent demyelination in normal-appearing white matter. NeuroImage, 29(2), 637-642. https://doi.org/10.1016/j.neuroimage.2005.07.017