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Research ArticleAdult Brain

Improved Precision of Automatic Brain Volume Measurements in Patients with Clinically Isolated Syndrome and Multiple Sclerosis Using Edema Correction

J.B.M. Warntjes, A. Tisell, I. Håkansson, P. Lundberg and J. Ernerudh
American Journal of Neuroradiology February 2018, 39 (2) 296-302; DOI: https://doi.org/10.3174/ajnr.A5476
J.B.M. Warntjes
aFrom the Center for Medical Image Science and Visualization (J.B.M.W., A.T., P.L.)
bDivision of Cardiovascular Medicine (J.B.M.W.)
gSyntheticMR AB (J.B.M.W.), Linköping, Sweden.
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A. Tisell
aFrom the Center for Medical Image Science and Visualization (J.B.M.W., A.T., P.L.)
cRadiation Physics (A.T., P.L.), Department of Medical and Health Sciences
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I. Håkansson
dDepartment of Neurology (I.H.), Department of Clinical and Experimental Medicine
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P. Lundberg
aFrom the Center for Medical Image Science and Visualization (J.B.M.W., A.T., P.L.)
cRadiation Physics (A.T., P.L.), Department of Medical and Health Sciences
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J. Ernerudh
eDepartment of Clinical Immunology and Transfusion Medicine (J.E.)
fDepartment of Clinical and Experimental Medicine (J.E.), Linköping University, Sweden
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    Fig 1.

    Typical output of the SyMRI software: A, Synthetic T2-weighted image of a section of the brain of one of the patients. This synthetic image was generated from the R1, R2, and PD maps in combination with a TE/TR = 100/4500 ms. B, PD map on a scale of 0%–100%, in which 100% corresponds to pure water at 37°C. C, Automatically generated intracranial mask (ICV). D, Automatically generated CSF partial volume map on a scale of 0%–100%. The brain parenchymal volume is calculated as the sum of all ICV minus the sum of all CSF. The brain parenchymal fraction is calculated as BPV/ICV.

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    Fig 2.

    Brain parenchymal fraction of all subjects at all times. The 4 time points of each individual are connected with a line. The gray line indicates the linear regression slope.

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    Fig 3.

    Relative difference of intracranial volume (A), brain parenchymal volume (B), and brain parenchymal fraction (C) of all subjects as a function of time after inclusion of the study. D, The relative difference in BPF of all subjects is shown again as a function of time after inclusion is shown, but corrected for PD. This figure is comparable with C, albeit with less variation in the data. The gray lines indicate the linear regression slopes.

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    Fig 4.

    Observed mean R1 (A), mean R2 (B), and mean proton density (C) of the entire brain (triangles), gray matter (dots), and white matter (squares) as a function of age for all subjects.

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    Table 1:

    Patient diagnoses, relapse status, and treatment status at baseline and at follow-up MRI

    Clinical and Laboratory DataBaseline1 Year2 Years4 Years
    Diagnosis (CIS/RRMS/PPMS)16/19/310/25/37/28/35/30/3
    Relapse within last 2 mo before MRI (yes/no)13/253/351/372/36
    Treatmenta (No. of subjects)
        No DMT38171818
        Interferon-β 1b016125
        Interferon-β 1a0111
        Dimethyl fumarate0002
        Fingolimod0113
        Natalizumab0369
    • Note:—CIS indicates clinically isolated syndrome; RRMS, relapsing-remitting MS; PPMS, primary-progressive MS; DMT, disease modifying therapy.

    • ↵a In addition, 1 patient received temporary relapse-controlling corticosteroid treatment within 2 months prior to baseline.

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    Table 2:

    Observed correlation slopes SR1, SR2, and SPD of the relative change in BPF as a function of relative change in R1, R2, and PD of the entire brain and gray and white matter

    BrainGray MatterWhite Matter
    SR1 value (%/%)−0.198−0.133−0.364
    SR1 (95% CI) (%/%)(−0.242 to −0.152)(−0.222 to −0.044)(−0.4376 to −0.290)
    SR1 P value<.001.02<.001
    SR2 value (%/%)0.1560.3030.090
    SR2 (95% CI) (%/%)(0.039–0.274)(0.228–0.378)(−0.016–0.196)
    SR2 P value.04<.001.2
    SPD value (%/%)0.488.396.655
    SPD (95% CI) (%/%)(0.382–0.594)(0.146–0.645)(0.535–0.776)
    SPD P value<.001.003<.001
    • View popup
    Table 3:

    Observed mean values and slopes of R1, R2, and PD of the entire brain and gray and white matter as a function of subject age

    BrainGray MatterWhite Matter
    R1 intercept (s−1)1.1510.8971.495
    R1 slope (s−1/y)0.000540.00015−0.00063
    R1 slope (95% CI) (s−1/y)(0.0002–0.0010)(−0.0001–0.0002)(−0.0011–0.0002)
    R1 slope P value.04.4.2
    R2 intercept (s−1)11.4410.5712.62
    R2 slope (s−1/y)−0.0001−0.0018−0.0056
    R2 slope (95% CI) (s−1/y)(−0.004–0.002)(−0.004–0.001)(−0.009–0.000)
    R2 slope P value.5.3.05
    PD intercept (%)75.6582.4467.44
    PD slope (%/y)−0.026−0.0190.009
    PD slope (95% CI) (%/y)(−0.039–0.013)(−0.025 to −0.013)(−0.003–0.020)
    PD slope P value<.001<.001.2
    • Note:—y indicates year.

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    Table 4:

    Observed SDs of the relative changes in BPF at baseline and at 1, 2, and 4 years after inclusiona

    Baseline (%)1 Year (%)2 Years (%)4 Years (%)
    Uncorrected0.5080.5260.4540.687
    Corr. for brain R10.362 (28.8%)0.506 (3.7%)0.327 (28.1%)0.599 (12.8%)
    Corr. for brain PD0.385 (24.2%)0.500 (4.9%)0.303 (33.3%)0.567 (17.4%)
    Corr. for GM R20.506 (0.4%)0.465 (11.5%)0.297 (34.7%)0.561 (16.2%)
    Corr. for GM PD0.481 (5.3%)0.539 (−2.4%)0.398 (12.5%)0.673 (1.9%)
    Corr. for WM R10.343 (32.6%)0.463 (12.0%)0.349 (23.2%)0.568 (17.3%)
    Corr. for WM PD0.399 (21.5%)0.474 (9.8%)0.326 (28.3%)0.492 (28.3%)
    • Note:—Corr. indicates corrected.

    • ↵a When BPF is corrected for average R1, R2, or PD values for brain, GM, or WM, the SDs of the observations decrease. The percentage reduction is given in parentheses. Corrections were only included when a high significance was found in Table 2.

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American Journal of Neuroradiology: 39 (2)
American Journal of Neuroradiology
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1 Feb 2018
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J.B.M. Warntjes, A. Tisell, I. Håkansson, P. Lundberg, J. Ernerudh
Improved Precision of Automatic Brain Volume Measurements in Patients with Clinically Isolated Syndrome and Multiple Sclerosis Using Edema Correction
American Journal of Neuroradiology Feb 2018, 39 (2) 296-302; DOI: 10.3174/ajnr.A5476

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Improved Precision of Automatic Brain Volume Measurements in Patients with Clinically Isolated Syndrome and Multiple Sclerosis Using Edema Correction
J.B.M. Warntjes, A. Tisell, I. Håkansson, P. Lundberg, J. Ernerudh
American Journal of Neuroradiology Feb 2018, 39 (2) 296-302; DOI: 10.3174/ajnr.A5476
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