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

• Published in: NeuroImage (Orlando, Fla.) Vol. 29; no. 2; pp. 637 - 642
• Main Authors: Narayanan, Sridar, Francis, Simon J., Sled, John G., Santos, A.C., Antel, Samson, Levesque, Ives, Brass, Steven, Lapierre, Yves, Sappey-Marinier, Dominique, Pike, G. Bruce, Arnold, Douglas L.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15-01-2006; Elsevier Limited; Elsevier
• Subjects: Acoustics; Adult; Axons - pathology; Bioengineering; Brain Mapping; Cerebral Cortex - pathology; Computer Science; Demyelinating Diseases - pathology; Engineering Sciences; Female; Humans; Image Processing; Image Processing, Computer-Assisted; Imaging; Life Sciences; Magnetic Resonance Imaging; Male; Mechanics; Medical Imaging; Medical Physics; Medical research; Metabolites; Middle Aged; Multiple sclerosis; Multiple Sclerosis - pathology; Myelin Sheath - pathology; Nuclear medicine; Pathology; Physics; Signal and Image Processing; Studies
• ISSN: 1053-8119; 1095-9572
• DOI: 10.1016/j.neuroimage.2005.07.017

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.