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Improved Turnaround Times | Median time to first decision: 12 days

Research ArticleAdult Brain

Unraveling Deep Gray Matter Atrophy and Iron and Myelin Changes in Multiple Sclerosis

G. Pontillo, M. Petracca, S. Monti, M. Quarantelli, C. Criscuolo, R. Lanzillo, E. Tedeschi, A. Elefante, V. Brescia Morra, A. Brunetti, S. Cocozza and G. Palma
American Journal of Neuroradiology April 2021, DOI: https://doi.org/10.3174/ajnr.A7093
G. Pontillo
aFrom the Departments of Advanced Biomedical Sciences (G.P., E.T., A.E., A.B., S.C.)
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M. Petracca
bNeurosciences and Reproductive and Odontostomatological Sciences (M.P., C.C., R.L., V.B.M.), University “Federico II,” Naples, Italy
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S. Monti
cInstitute of Biostructure and Bioimaging, (S.M., M.Q., G.P.) National Research Council, Naples, Italy
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M. Quarantelli
cInstitute of Biostructure and Bioimaging, (S.M., M.Q., G.P.) National Research Council, Naples, Italy
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C. Criscuolo
bNeurosciences and Reproductive and Odontostomatological Sciences (M.P., C.C., R.L., V.B.M.), University “Federico II,” Naples, Italy
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R. Lanzillo
bNeurosciences and Reproductive and Odontostomatological Sciences (M.P., C.C., R.L., V.B.M.), University “Federico II,” Naples, Italy
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E. Tedeschi
aFrom the Departments of Advanced Biomedical Sciences (G.P., E.T., A.E., A.B., S.C.)
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A. Elefante
aFrom the Departments of Advanced Biomedical Sciences (G.P., E.T., A.E., A.B., S.C.)
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V. Brescia Morra
bNeurosciences and Reproductive and Odontostomatological Sciences (M.P., C.C., R.L., V.B.M.), University “Federico II,” Naples, Italy
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A. Brunetti
aFrom the Departments of Advanced Biomedical Sciences (G.P., E.T., A.E., A.B., S.C.)
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S. Cocozza
aFrom the Departments of Advanced Biomedical Sciences (G.P., E.T., A.E., A.B., S.C.)
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G. Palma
cInstitute of Biostructure and Bioimaging, (S.M., M.Q., G.P.) National Research Council, Naples, Italy
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  • FIG 1.
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    FIG 1.

    Image shows voxelwise analyses of iron maps. Clusters of significant between-group differences regarding unmodulated (top panel) and modulated (lower panel) iron maps for both the MS>HC (red-yellow, according to 1 - P value) and MS<HC (blue-light blue, according to 1 - P value) contrasts are presented, superimposed on the QSM template in the MNI space. Reprinted by permission from Springer Nature Customer Service Center GmbH: Springer Nature, Neuroradiology, European Society of Neuroradiology 2020, Copyright 2020, Springer-Verlag GmbH Germany, part of Springer Nature.

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    FIG 2.

    Image shows voxelwise analyses of myelin maps. Clusters of significant between-group difference regarding modulated myelin maps for the MS<HC (blue-light blue, according to 1 - P value) contrast are presented, superimposed on the QSM template in the MNI space. No significant differences emerged for the MS>HC contrast or for unmodulated myelin maps. Reprinted by permission from Springer Nature Customer Service Center GmbH: Springer Nature, Neuroradiology, European Society of Neuroradiology 2020, Copyright 2020, Springer-Verlag GmbH Germany, part of Springer Nature.

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    FIG 3.

    Between-group comparisons of MRI features regarding thalamic subnuclei. Boxplots at the y-axis show z scores (adjusted for the effect of age and sex in HC) of iron concentration and content (upper panel), myelin concentration and content (middle panel), and normalized volume (lower panel) of the corresponding thalamic subregions shown at the x-axis for both the MS and HC groups. Red asterisks mark significant between-group differences.

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    Table 1:

    Demographic, clinical, and conventional MRI characteristics of the studied populationa

    MS (n = 91)HC (n = 55)P Value (MS vs HC)
    Age (yr)38.3 (SD, 11.1)41.6 (SD, 13.9).14
    Female sexb54 (59.3)27 (49.1).23
    Use of DMTb83 (91.2)––
    Progressive courseb20 (22.0)––
    DD (yr)11.2 (SD, 7.0)––
    EDSSc3.5 (2.5–4.5)––
    T2-LL (mL)11.4 (SD, 13.3)––
    Normalized brain volume (mL)1485.8 (SD, 88.6)1552.9 (SD, 76.4)<.001
    Normalized GM volume (mL)755.6 (SD, 62.8)794.7 (SD, 57.5)<.001
    Normalized WM volume (mL)730.2 (SD, 36.5)758.2 (SD, 31.7)<.001
    • Note:—– indicates not applicable; DMT, disease-modifying treatment.

    • ↵a Unless otherwise indicated, data are expressed as means (SD). Between-group differences regarding MRI measures are adjusted for age and sex.

    • ↵b Data are the number of subjects, with percentages in parentheses.

    • ↵c Data are medians, with interquartile range in parentheses.

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    Table 2:

    Results of the ANCOVA analyses for the between-group comparisons regarding DGM structuresa

    MS (n = 91)HC (n = 55)Cohen’s DFP Value
    Normalized volume (mL)
     Thalamus19.2 (SD, 2.8)21.7 (SD, 1.9)1.1445.75<.001
     Caudate8.7 (SD, 1.5)9.7 (SD, 1.3)0.8827.10<.001
     Putamen12.6 (SD, 1.9)13.8 (SD, 1.6)0.8223.83<.001
     Globus pallidus4.5 (SD, 0.6)4.9 (SD, 0.4)0.7620.55<.001
    Iron concentration (mg/kg[DW])
     Thalamus5 (SD, 59)38 (SD, 51)0.6213.64<.001
     Caudate310 (SD, 103)271 (SD, 76)0.405.55.02b
     Putamen276 (SD, 112)243 (SD, 94)0.518.94.03b
     Globus pallidus786 (SD, 135)697 (SD, 128)0.6816.51<.001
    Myelin concentration (MVF[DW])
     Thalamus0.24 (SD, 0.06)0.22 (SD, 0.08)0.191.25.27
     Caudate0.19 (SD, 0.06)0.20 (SD, 0.08)0.060.10.76
     Putamen0.23 (SD, 0.06)0.22 (SD, 0.08)0.090.29.59
     Globus pallidus0.21 (SD, 0.06)0.20 (SD, 0.08)0.110.49.48
    Iron content (µg)
     Thalamus0.2 (SD, 1.1)0.8 (SD, 1.1)0.6313.93<.001
     Caudate2.7 (SD, 1.0)2.6 (SD, 0.8)0.030.04.84
     Putamen3.4 (SD, 1.4)3.3 (SD, 1.2)0.252.13.15
     Globus pallidus3.5 (SD, 6.8)3.4 (SD, 6.9)0.140.75.39
    Myelin content (mL)
     Thalamus4.6 (SD, 1.4)4.8 (SD, 1.7)0.211.51.22
     Caudate1.7 (SD, 0.8)1.9 (SD, 0.7)0.292.94.09
     Putamen2.9 (SD, 1.0)3.1 (SD, 1.0)0.191.32.25
     Globus pallidus0.9 (SD, 0.3)1.0 (SD, 0.4)0.090.34.56
    • Note:—degrees of freedom (df) , 141.

    • ↵a Descriptive statistics (mean [SD]) for DGM-related MRI features are reported, along with the effect sizes (Cohen’s D), test statistics (F), and exact probability (P value) values regarding between-group (MS versus HC) comparisons.

    • ↵b Not significant after false discovery rate correction.

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G. Pontillo, M. Petracca, S. Monti, M. Quarantelli, C. Criscuolo, R. Lanzillo, E. Tedeschi, A. Elefante, V. Brescia Morra, A. Brunetti, S. Cocozza, G. Palma
Unraveling Deep Gray Matter Atrophy and Iron and Myelin Changes in Multiple Sclerosis
American Journal of Neuroradiology Apr 2021, DOI: 10.3174/ajnr.A7093

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Unraveling Deep Gray Matter Atrophy and Iron and Myelin Changes in Multiple Sclerosis
G. Pontillo, M. Petracca, S. Monti, M. Quarantelli, C. Criscuolo, R. Lanzillo, E. Tedeschi, A. Elefante, V. Brescia Morra, A. Brunetti, S. Cocozza, G. Palma
American Journal of Neuroradiology Apr 2021, DOI: 10.3174/ajnr.A7093
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