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Research ArticleBrain

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

H. Vrenken, J.J.G. Geurts, D.L. Knol, C.H. Polman, J.A. Castelijns, P.J.W. Pouwels and F. Barkhof
American Journal of Neuroradiology October 2006, 27 (9) 2005-2011;
H. Vrenken
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J.J.G. Geurts
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D.L. Knol
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C.H. Polman
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J.A. Castelijns
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P.J.W. Pouwels
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F. Barkhof
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    Fig 1.

    T2-weighted images coregistered to the T1 maps illustrating the definition of pixel classes in 1 female patient with primary progressive MS (aged 59.5 years; disease duration, 8.3 years; cerebral lesion volume, 14.9 mL; EDSS score, 4.0; MSFC score, 0.54). For greater clarity, the 2 pixel classes, lesion core and lesion rim, are displayed as a single class (Lesions) in this figure. The perilesional NAWM pixel classes (Layer 1 through Layer 4) are defined as consecutive layers of a single pixel width around these lesion masks. Distant NAWM consists of NAWM pixels that are at least 4 mm away from the lesion masks in all directions. Details of the definition of the pixel classes are provided in the text. Note that the coregistration of the lesion masks to the T1 maps was chosen to overestimate the lesions, to be conservative toward NAWM. Note also that because of less-reliable segmentation in deep gray matter and periventricular regions, these regions were excluded from the NAWM pixel classes. As a result, there are several lesions in this region without perilesional NAWM pixel layers around them (visible mainly in the images in the second row).

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    Fig 2.

    MTR (A) and T1 (B) histogram peak positions for the 7 pixel classes in each of the 3 MS groups. The horizontal lines indicate the mean and SD of the values for control white matter. Statistically significant differences with distant NAWM, averaged over disease types, are indicated with black asterisks (*). Statistically significant differences with control white matter are indicated for each of the 3 MS disease types by daggers (†) in the corresponding color. See also Table 2. Details of the applied general linear mixed model are provided in the text. PP indicates primary progressive, RR, relapsing-remitting; SP, secondary progressive.

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    Table 1:

    Subject group characteristics

    PPMSRRMSSPMSCombined MS groupControls
    Subjects (M/F)11 (7/4)34 (10/24)18 (7/11)63 (24/39)22 (12/10)
    Age (y)58.4 ± 6.039.4 ± 7.144.3 ± 10.544.1 ± 10.630.7 ± 7.6
    Disease duration (y)11.8 ± 5.19.1 ± 5.315.8 ± 9.011.6 ± 7.2
    Median EDSS (range)4.5 (3.0–6.5)2.0 (1.5–4.0)6.0 (2.5–8.0)3.0 (1.5–8.0)
    MSFC0.15 ± 0.530.57 ± 0.30−0.27 ± 0.720.26 ± 0.61
    NBV (L)1.41 ± 0.041.48 ± 0.061.41 ± 0.051.45 ± 0.061.52 ± 0.04
    Median lesion load, mL (range)6.8 (0.2–27.8)5.6 (0.3–41.2)10.8 (2.5–54.7)6.8 (0.2–54.7)
    • Note:—MS indicates multiple sclerosis, specified by type as primary progressive (PPMS), relapsing-remitting (RRMS), and secondary progressive (SPMS); EDSS, Expanded Disability Status Scale; MSFC, Multiple Sclerosis Functional Composite; NBV, normalized brain volume.

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    Table 2:

    Magnetization transfer ratio (MTR) and T1 histogram parameters of lesion and normal-appearing white matter (NAWM) pixel classes and of control white matter (WM)

    Pixel classType of MST1MTR
    Peak position (ms)Peak height (10−3)Peak position (%)Peak height (10−3)
    Lesion corePP1050 ± 173**††1.9 ± 1.1**††26.1 ± 3.8**††7.2 ± 2.1**††
    RR1053 ± 144**††1.8 ± 0.5**††24.5 ± 3.1**††7.2 ± 1.6**††
    SP1020 ± 129**††1.6 ± 0.4**††25.1 ± 2.7**††6.6 ± 0.7**††
    Lesion rimPP833 ± 49**††3.0 ± 0.9**††30.1 ± 1.3**††8.4 ± 1.5**††
    RR851 ± 54**††2.8 ± 0.7**††29.5 ± 2.1**††8.4 ± 1.2**††
    SP868 ± 46**††2.7 ± 0.6**††28.8 ± 1.7**††8.4 ± 1.1**††
    NAWM Layer 1PP777 ± 236.2 ± 0.9**31.9 ± 0.9**12.7 ± 1.5*
    RR782 ± 28†6.8 ± 1.4**31.6 ± 1.1**†13.1 ± 1.3*
    SP804 ± 36†6.0 ± 1.0**31.0 ± 1.4**†12.9 ± 1.2*
    NAWM Layer 2PP764 ± 177.0 ± 0.8*32.5 ± 1.0*13.0 ± 1.4*
    RR770 ± 217.2 ± 1.0*32.2 ± 1.0*13.8 ± 1.5*†
    SP797 ± 34†6.3 ± 1.0*31.5 ± 1.3*13.3 ± 1.1*
    NAWM Layer 3PP757 ± 187.1 ± 0.9*32.4 ± 0.712.9 ± 1.4*
    RR768 ± 307.0 ± 0.8*32.5 ± 0.913.9 ± 1.2*†
    SP791 ± 38†6.2 ± 1.0*31.7 ± 1.213.2 ± 1.1*
    NAWM Layer 4PP744 ± 496.8 ± 0.8*32.6 ± 0.612.9 ± 1.3*
    RR770 ± 266.9 ± 0.8*32.4 ± 0.913.9 ± 1.3*†
    SP796 ± 43†6.1 ± 1.0*31.9 ± 1.013.2 ± 1.1*
    Distant NAWMPP756 ± 176.1 ± 1.032.6 ± 0.611.8 ± 1.6
    RR764 ± 256.0 ± 0.9†32.8 ± 0.812.8 ± 1.1
    SP793 ± 37†5.0 ± 1.2††32.0 ± 1.011.9 ± 1.0
    Control WM747 ± 227.0 ± 0.732.8 ± 1.012.6 ± 1.1
    • Note:—Values are observed means and SDs. Symbols indicate statistically significant differences:

    • * P < .05,

    • ** P < .001 versus distant NAWM,

    • † P < .05,

    • †† P < .001 versus control WM. Details of the applied linear mixed model are given in the text. MS indicates multiple sclerosis; PP, primary progressive; RR, relapsing-remitting; SP, secondary progressive.

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American Journal of Neuroradiology: 27 (9)
American Journal of Neuroradiology
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H. Vrenken, J.J.G. Geurts, D.L. Knol, C.H. Polman, J.A. Castelijns, P.J.W. Pouwels, F. Barkhof
Normal-Appearing White Matter Changes Vary with Distance to Lesions in Multiple Sclerosis
American Journal of Neuroradiology Oct 2006, 27 (9) 2005-2011;

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Normal-Appearing White Matter Changes Vary with Distance to Lesions in Multiple Sclerosis
H. Vrenken, J.J.G. Geurts, D.L. Knol, C.H. Polman, J.A. Castelijns, P.J.W. Pouwels, F. Barkhof
American Journal of Neuroradiology Oct 2006, 27 (9) 2005-2011;
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