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Research ArticleAdult Brain
Open Access

Evaluation of the Sensitivity of Inhomogeneous Magnetization Transfer (ihMT) MRI for Multiple Sclerosis

E. Van Obberghen, S. Mchinda, A. le Troter, V.H. Prevost, P. Viout, M. Guye, G. Varma, D.C. Alsop, J.-P. Ranjeva, J. Pelletier, O. Girard and G. Duhamel
American Journal of Neuroradiology April 2018, 39 (4) 634-641; DOI: https://doi.org/10.3174/ajnr.A5563
E. Van Obberghen
aFrom Aix-Marseille Université (E.V.O., S.M., A.l.T., V.H.P., P.V., M.G., J.-P.R., J.P., O.G., G.D.), Centre de Résonance Magnétique Biologique et Médicale (CRMBM), UMR 7339 Centre National de Recherche Scientifique (CNRS), Marseille, France
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S. Mchinda
aFrom Aix-Marseille Université (E.V.O., S.M., A.l.T., V.H.P., P.V., M.G., J.-P.R., J.P., O.G., G.D.), Centre de Résonance Magnétique Biologique et Médicale (CRMBM), UMR 7339 Centre National de Recherche Scientifique (CNRS), Marseille, France
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A. le Troter
aFrom Aix-Marseille Université (E.V.O., S.M., A.l.T., V.H.P., P.V., M.G., J.-P.R., J.P., O.G., G.D.), Centre de Résonance Magnétique Biologique et Médicale (CRMBM), UMR 7339 Centre National de Recherche Scientifique (CNRS), Marseille, France
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V.H. Prevost
aFrom Aix-Marseille Université (E.V.O., S.M., A.l.T., V.H.P., P.V., M.G., J.-P.R., J.P., O.G., G.D.), Centre de Résonance Magnétique Biologique et Médicale (CRMBM), UMR 7339 Centre National de Recherche Scientifique (CNRS), Marseille, France
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P. Viout
aFrom Aix-Marseille Université (E.V.O., S.M., A.l.T., V.H.P., P.V., M.G., J.-P.R., J.P., O.G., G.D.), Centre de Résonance Magnétique Biologique et Médicale (CRMBM), UMR 7339 Centre National de Recherche Scientifique (CNRS), Marseille, France
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M. Guye
aFrom Aix-Marseille Université (E.V.O., S.M., A.l.T., V.H.P., P.V., M.G., J.-P.R., J.P., O.G., G.D.), Centre de Résonance Magnétique Biologique et Médicale (CRMBM), UMR 7339 Centre National de Recherche Scientifique (CNRS), Marseille, France
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G. Varma
bDepartment of Radiology (G.V., D.C.A.), Division of MR Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
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D.C. Alsop
bDepartment of Radiology (G.V., D.C.A.), Division of MR Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
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J.-P. Ranjeva
aFrom Aix-Marseille Université (E.V.O., S.M., A.l.T., V.H.P., P.V., M.G., J.-P.R., J.P., O.G., G.D.), Centre de Résonance Magnétique Biologique et Médicale (CRMBM), UMR 7339 Centre National de Recherche Scientifique (CNRS), Marseille, France
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J. Pelletier
aFrom Aix-Marseille Université (E.V.O., S.M., A.l.T., V.H.P., P.V., M.G., J.-P.R., J.P., O.G., G.D.), Centre de Résonance Magnétique Biologique et Médicale (CRMBM), UMR 7339 Centre National de Recherche Scientifique (CNRS), Marseille, France
cAix-Marseille University (J.P.), Assistance Publique des Hôpitaux de Marseille (APHM), Hôpital de La Timone, Pôle de Neurosciences Cliniques, Service de Neurologie, Marseille, France.
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O. Girard
aFrom Aix-Marseille Université (E.V.O., S.M., A.l.T., V.H.P., P.V., M.G., J.-P.R., J.P., O.G., G.D.), Centre de Résonance Magnétique Biologique et Médicale (CRMBM), UMR 7339 Centre National de Recherche Scientifique (CNRS), Marseille, France
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G. Duhamel
aFrom Aix-Marseille Université (E.V.O., S.M., A.l.T., V.H.P., P.V., M.G., J.-P.R., J.P., O.G., G.D.), Centre de Résonance Magnétique Biologique et Médicale (CRMBM), UMR 7339 Centre National de Recherche Scientifique (CNRS), Marseille, France
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    Fig 1.

    A, Postprocessing pipeline. Step 1: Quantitative MTR and ihMTR map calculation for controls and patients with RRMS. Step 2: Manual segmentation of WM lesions on the multislice T2W images and reslicing to the single-slice 2D ihMT reference space. Step 3: Construction of the ihMT average template by realignment of the ihMT images of the control and RRMS subjects into a new common reference space. Construction of the ihMT atlas was based on the ihMT average template by manual segmentation of frontal, temporal, and occipital WM, internal capsule, corpus callosum, thalami, and putamen. Step 4: Automatic segmentation of individual ihMT images by projection of the ihMT atlas onto the individual native space of each control and patient. Individual lesion masks obtained in step 2 were removed from the ihMT atlas to generate normal-appearing tissue ROIs. Step 5: Quantitative measurement of ihMTR and MTR in the ROIs and lesions. B, Lesion-load map calculated over all the patients with RRMS and superimposed over the ihMT average template. The histogram shows the percentage of lesions within each brain structure.

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    Fig 2.

    Representative anatomic T2W images (A and D) and MTR (B and E) and ihMTR (C and F) maps obtained on a control subject and a patient with RRMS after step 1 of the postprocessing procedure. Decrease of MTR and ihMTR signals is clear in patients (E and F) relative to controls (B and C) in the FWM and OCCWM (orange arrows). Brain areas encompassing lesions (white arrows) are shown in inserts for each technique. T2W hyperintensities and MTR/ihMTR hypointensities are clearly visible in lesions.

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    Fig 3.

    Mean MTR and ihMTR values measured in the 7 ROIs of the ihMT atlas (TEMPWM, FWM, OCCWM, CC, thalami, and putamen) for each control (blue markers) and patient with RRMS (pink markers). For patients, mean values measured in lesions are also reported. Boxplots indicate the median, upper and lower quartiles, and the minimum and maximum values excluding outliers. The asterisk indicates a significant difference (P < .05) in values between controls and patients (comparison assessed by the nonparametric Wilcoxon rank test [α = .05] corrected by the Holm-Bonferroni method for multiple comparisons [m = 7 brain structures]).

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    Fig 4.

    Radar plot of mean ihMTR and MTR z scores of patients with RRMS relative to control subjects calculated for each brain structure of the ihMT atlas. A tendency (not significant, P > .1) for lower values was observed with MTR compared with ihMTR in the IC, TEMPWM, OCCWM, CC, and thalami.

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    Fig 5.

    Representative ihMTR and MTR maps obtained after step 1 of the postprocessing procedure for a control subject and for patients with RRMS with various values of EDSS. Progressive loss of signal with increasing EDSS is noticed in occipital WM for both MTR and ihMTR (pink arrows). In frontal WM though, the decrease in values is more apparent with ihMTR (white arrows).

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    Fig 6.

    Correlation analysis of ihMTR versus EDSS scores of patients with RRMS. Mean MTR (pink markers) and ihMTR (blue markers) values measured in each structure of the ihMT atlas plotted as a function of the EDSS score and the density ellipses (α = .95) are shown. Bar plots indicate the Spearman correlation coefficient: The asterisk indicates statistically significant (α = .05, corrected by the Holm-Bonferroni method for multiple comparisons [m = 6 brain structures]). For ihMTR, significant negative correlations with EDSS were obtained in all structures (except the OCCWM); conversely, for the MTR, only a trend for low negative correlations with EDSS was obtained in all structures.

Tables

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  • Mean ihMTR and MTR values calculated in the 7 ROIs of the ihMT atlas and in lesionsa

    Brain StructureihMTR (%)MTR (%)
    ControlsPatientsControlsPatients
    IC7.8 ± 0.37.6 ± 0.445.2 ± 0.644.7 ± 0.8
    P = .16P = .02b
    TEMPWM8.0 ± 0.37.3 ± 0.746.3 ± 0.644.2 ± 1.9
    P < .001bP < .001b
    FWM7.7 ± 0.37.4 ± 0.547.5 ± 0.746.2 ± 1.4
    P = .01bP = .01b
    OCCWM7.6 ± 0.47.0 ± 0.644.6 ± 0.743.4 ± 1.5
    P = .004bP = .005b
    CC6.5 ± 0.66.0 ± 0.743.7 ± 2.241.9 ± 2.7
    P = .09P = .07
    Thalami5.6 ± 0.25.1 ± 0.443.3 ± 0.841.0 ± 2.2
    P < .001bP < .001b
    Putamen4.6 ± 0.34.9 ± 0.442.0 ± 0.842.4 ± 0.7
    P =.03P = .09
    LesionsNA6.3 ± 0.9cNA39.9 ± 3.6c
    • Note:—NA indicates not applicable.

    • ↵a ihMTR and MTR data are expressed as mean value ± SD. Between-group comparison (P value): comparison of mean ihMTR and MTR between patients with RRMS and controls was assessed by the nonparametric Wilcoxon rank test (α = .05) corrected by the Holm-Bonferroni method for multiple comparisons (m = 7 brain structures).

    • ↵b Statistically significant.

    • ↵c Within-patient group: ihMTR and MTR values in lesions statistically different (Kruskal-Wallis test corrected for multiple comparisons using the Steel-Dwass procedure) from values in all normal-appearing WM structures (P < .05) except the corpus callosum (P > .5).

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American Journal of Neuroradiology: 39 (4)
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E. Van Obberghen, S. Mchinda, A. le Troter, V.H. Prevost, P. Viout, M. Guye, G. Varma, D.C. Alsop, J.-P. Ranjeva, J. Pelletier, O. Girard, G. Duhamel
Evaluation of the Sensitivity of Inhomogeneous Magnetization Transfer (ihMT) MRI for Multiple Sclerosis
American Journal of Neuroradiology Apr 2018, 39 (4) 634-641; DOI: 10.3174/ajnr.A5563

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Evaluation of the Sensitivity of Inhomogeneous Magnetization Transfer (ihMT) MRI for Multiple Sclerosis
E. Van Obberghen, S. Mchinda, A. le Troter, V.H. Prevost, P. Viout, M. Guye, G. Varma, D.C. Alsop, J.-P. Ranjeva, J. Pelletier, O. Girard, G. Duhamel
American Journal of Neuroradiology Apr 2018, 39 (4) 634-641; DOI: 10.3174/ajnr.A5563
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