title: 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.
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.
authors.affiliation: Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, Montreal, Quebec, Canada H3A 2B4. sridar@mrs.mni.mcgill.ca
authors.forename: Sridar
authors.initials: S
authors.lastname: Narayanan
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Francis
authors.forename: John G
authors.initials: JG
authors.lastname: Sled
authors.forename: A C
authors.initials: AC
authors.lastname: Santos
authors.forename: Samson
authors.initials: S
authors.lastname: Antel
authors.forename: Ives
authors.initials: I
authors.lastname: Levesque
authors.forename: Steven
authors.initials: S
authors.lastname: Brass
authors.forename: Yves
authors.initials: Y
authors.lastname: Lapierre
authors.forename: Dominique
authors.initials: D
authors.lastname: Sappey-Marinier
authors.forename: G Bruce
authors.initials: GB
authors.lastname: Pike
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Arnold
mesh_terms: D000328:Adult; D001369:Axons / Q000473:pathology*; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000473:pathology*; D003711:Demyelinating Diseases / Q000473:pathology*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology*; D009186:Myelin Sheath / Q000473:pathology