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Research ArticleADULT BRAIN
Open Access

Lesion Heterogeneity on High-Field Susceptibility MRI Is Associated with Multiple Sclerosis Severity

D.M. Harrison, X. Li, H. Liu, C.K. Jones, B. Caffo, P.A. Calabresi and P. van Zijl
American Journal of Neuroradiology August 2016, 37 (8) 1447-1453; DOI: https://doi.org/10.3174/ajnr.A4726
D.M. Harrison
aFrom the Department of Neurology (D.M.H.), University of Maryland School of Medicine, Baltimore, Maryland
bDepartments of Neurology (D.M.H., P.A.C.)
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X. Li
cRadiology and Radiological Science (X.L., C.K.J., P.v.Z.)
eF.M. Kirby Research Center for Functional Brain Imaging (X.L., H.L., C.K.J., P.v.Z.), Kennedy Krieger Institute, Baltimore, Maryland
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H. Liu
eF.M. Kirby Research Center for Functional Brain Imaging (X.L., H.L., C.K.J., P.v.Z.), Kennedy Krieger Institute, Baltimore, Maryland
fDepartment of Radiology (H.L.), Guangdong Academy of Medical Sciences, Guangdong General Hospital, Guangzhou, China.
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C.K. Jones
cRadiology and Radiological Science (X.L., C.K.J., P.v.Z.)
eF.M. Kirby Research Center for Functional Brain Imaging (X.L., H.L., C.K.J., P.v.Z.), Kennedy Krieger Institute, Baltimore, Maryland
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B. Caffo
dBiostatistics (B.C.), Johns Hopkins University School of Medicine, Baltimore, Maryland
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P.A. Calabresi
bDepartments of Neurology (D.M.H., P.A.C.)
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P. van Zijl
cRadiology and Radiological Science (X.L., C.K.J., P.v.Z.)
eF.M. Kirby Research Center for Functional Brain Imaging (X.L., H.L., C.K.J., P.v.Z.), Kennedy Krieger Institute, Baltimore, Maryland
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  • Fig 1.
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    Fig 1.

    Examples of lesions seen on FLAIR, R2*, phase, and QSM. Each colored arrow indicates the same lesion seen on each of the 4 image contrasts. Lesions were initially identified on FLAIR images. Quantitative gray-scale values (ranging from black to white) for the above images are as follows: R2* = 0–283.78 Hz, phase = −48.69 to 40.00 Hz, QSM = −0.58 to 0.40 ppm.

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    Fig 2.

    Examples of common lesion patterns on R2*, phase, and QSM. Yellow arrows indicate lesions identified and shown here as samples of common lesion patterns found on each image contrast. Lesions were identified by the intensity of their core and outer rim when visually compared with surrounding white matter. Only a small portion of lesions were invisible on R2* (6%), whereas a larger proportion were invisible on phase (42%) and QSM (36%).

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    Fig 3.

    Quantitative comparison of lesion susceptibility values by disease subtype and level of disability. Box-and-whisker plots showing a quantitative comparison of mean lesion R2*, frequency (from phase), and relative susceptibility (from QSM) between subjects with RRMS and SPMS/PPMS (left column) and those with lower-versus-higher levels of disability based on the EDSS score (right column). Lesion R2* values were significantly lower in SPMS/PPMS and EDSS ≥ 5.0, and mean lesion relative susceptibility was lower in SPMS/PPMS. Lesion values were taken as the mean of all voxels within each lesion. Red lines indicate the median value for all lesions in each group. P values represent the results of Wilcoxon rank sum testing.

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    Fig 4.

    Relationship between EDSS and quantitative R2*, frequency, and relative susceptibility values. Shown are the results of linear mixed-model regression (adjusted for age and sex) for prediction of the quantitative MR imaging index value by the Expanded Disability Status Scale score as represented by a fitted-values plot. A significant inverse relationship was found between R2* and EDSS and for a combined index of R2* + relative susceptibility and EDSS. The open circles represent fitted values based on the fixed and random effects from the model, with each circle thus representing 1 subject and the size of the circle weighted for the number of lesions that particular subject contributed to the model. The regression coefficient for the fixed-effects portion of the model is shown in each panel, along with the P value for the significance of that coefficient. To place all quantitative values in an equivalent space, we converted all values to z score units (based on mean and SD from all lesions).

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    Table 1:

    Demographic and clinical characteristics of study sample

    Demographics/Characteristics
    No. of subjects24
    No. of lesions306
    Lesions per subject analyzed (median) (range)12 (2–29)
    Age (mean) (SD) (yr)44.3 (10.0)
    Sex (No.) (%)
        Female12 (50%)
        Male12 (50%)
    Disease duration (mean) (SD) (yr)11.2 (7.6)
    Clinical phenotype (No.) (%)
        Relapsing-remitting21 (88%)
        Secondary-progressive2 (8%)
        Primary-progressive1 (4%)
    On MS treatment (No.) (%)19 (79%)
    EDSS score (median) (range)3.0 (1.5–6.5)
    MFIS score (mean) (SD)37.7 (19.3)
    9-HPT, dominant hand (mean) (SD)23.0 (6.6) seconds
    9-HPT, nondominant hand (mean) (SD)27.7 (17.9) seconds
    Timed 25-ft walk (mean) (SD)5.3 (2.4) seconds
    PASAT-3 score (mean) (SD)46.3 (9.8)
    MSFC z score (mean) (SD)−0.27 (1.54)
    • Note:—9-HPT indicates Nine Hole Peg Test; PASAT-3, Paced Auditory Serial Addition Test, 3-second delay.

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    Table 2:

    Hypothesized alterations in myelin and iron content in MS lesions associated with commonly observed R2*/QSM lesion contrast patterns

    R2* IntensityQSM IntensityAlteration in Myelin ContentAlteration in Iron Content
    HypoHyper↓↔
    HypoIso↓↓
    IsoHyper↓↑
    • Note:—Hypo indicates hypointensity; Hyper, hyperintensity; Iso, isointensity; ↑, increase; ↓, decrease; ↔, little-to-no change.

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American Journal of Neuroradiology: 37 (8)
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Cite this article
D.M. Harrison, X. Li, H. Liu, C.K. Jones, B. Caffo, P.A. Calabresi, P. van Zijl
Lesion Heterogeneity on High-Field Susceptibility MRI Is Associated with Multiple Sclerosis Severity
American Journal of Neuroradiology Aug 2016, 37 (8) 1447-1453; DOI: 10.3174/ajnr.A4726

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Lesion Heterogeneity on High-Field Susceptibility MRI Is Associated with Multiple Sclerosis Severity
D.M. Harrison, X. Li, H. Liu, C.K. Jones, B. Caffo, P.A. Calabresi, P. van Zijl
American Journal of Neuroradiology Aug 2016, 37 (8) 1447-1453; DOI: 10.3174/ajnr.A4726
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