Advanced

AJNR - American Journal of Neuroradiology

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Vrenken, H. Articles by Barkhof, F. Search for Related Content PubMed PubMed Citation Articles by Vrenken, H. Articles by Barkhof, F.

American Journal of Neuroradiology 27:2005-2011, October 2006
© 2006 American Society of Neuroradiology

BRAIN

Normal-Appearing White Matter Changes Vary with Distance to Lesions in Multiple Sclerosis

H. Vrenken^a, J.J.G. Geurts^a, D.L. Knol^b, C.H. Polman^c, J.A. Castelijns^a, P.J.W. Pouwels^d and F. Barkhof^a

^a Department of Radiology, MR Center for MS Research, VU University Medical Center, Amsterdam, the Netherlands
^b Department of Clinical Epidemiology and Biostatistics, MR Center for MS Research, VU University Medical Center, Amsterdam, the Netherlands
^c Department of Neurology, MR Center for MS Research, VU University Medical Center, Amsterdam, the Netherlands
^d Department of Physics and Medical Technology, MR Center for MS Research, VU University Medical Center, Amsterdam, the Netherlands

Please address correspondence to H. Vrenken, PhD, VU University Medical Center, Department of Radiology, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands; e-mail: h.vrenken{at}vumc.nl

BACKGROUND AND PURPOSE: Multiple sclerosis (MS) disease processes in normal-appearing white matter (NAWM) may be different close to MR-visible lesions than farther from these lesions. We aimed to investigate the relationship of NAWM changes to the distance to the lesions.

METHODS: We measured B₁-corrected T1 and magnetization transfer ratio (MTR) maps in 63 patients with MS (11 primary progressive, 34 relapsing-remitting, 18 secondary progressive). We used histogram analyses to assess the global properties of lesions, of 4 consecutive 1-mm pixel layers of NAWM around the lesions, and of distant NAWM located at least 4-mm from lesions in all directions. In 22 healthy controls, we measured white matter MTR and T1 histograms. Histogram parameters were statistically analyzed by using a linear mixed model.

RESULTS: The first and second NAWM pixel layers around the lesions had a significantly lower MTR histogram peak position than distant NAWM, whereas T1 histogram peak position was similar between all types of NAWM. Furthermore, MTR histograms of distant NAWM were statistically indistinguishable from those of control white matter, whereas T1 histograms of distant NAWM had significantly decreased peak height for relapsing-remitting MS and secondary progressive MS and significantly increased peak position for secondary progressive MS.

CONCLUSION: Our results may suggest that axonal damage and demyelination in NAWM mainly arise as a secondary result of visible lesions, with the largest effect close to these lesions. NAWM disease farther from the lesions may be mainly characterized by subtle blood-brain barrier damage, with leakage of fibrinogen into the parenchyma and microplaque formation, processes that are detected with T1 but not with MTR.

This article has been cited by other articles:

				I I Kirov, V Patil, J S Babb, H Rusinek, J Herbert, and O Gonen MR spectroscopy indicates diffuse multiple sclerosis activity during remission J. Neurol. Neurosurg. Psychiatry, December 1, 2009; 80(12): 1330 - 1336. [Abstract] [Full Text] [PDF]

				C. Di Perri, M. Battaglini, M. L. Stromillo, M. L. Bartolozzi, L. Guidi, A. Federico, and N. De Stefano Voxel-Based Assessment of Differences in Damage and Distribution of White Matter Lesions Between Patients With Primary Progressive and Relapsing-Remitting Multiple Sclerosis Arch Neurol, February 1, 2008; 65(2): 236 - 243. [Abstract] [Full Text] [PDF]

				T. Zeis, U. Graumann, R. Reynolds, and N. Schaeren-Wiemers Normal-appearing white matter in multiple sclerosis is in a subtle balance between inflammation and neuroprotection Brain, January 1, 2008; 131(1): 288 - 303. [Abstract] [Full Text] [PDF]