E-Tables

Table e-1: Mean values for brain structure volumes, DTI indices, and MTR.

Healthy Volunteers
(n = 26) / All MS
(n = 117) / Relapsing-remitting MS
(n = 66) / Secondary Progressive MS (n = 30) / Primary Progressive MS
(n = 21)
Mean CVF (SD) / 0.815 (0.018) / 0.789 (0.027)* / 0.794 (0.027) / 0.777 (0.025)** / 0.790 (0.027)
Mean Normalized Cerebral WM Volume (SD) / 0.320 (0.0163) / 0.316 (0.020) / 0.316 (0.019) / 0.310 (0.017) / 0.323 (0.024)†
Mean Normalized Cerebral GM Volume (SD) / 0.364 (0.019) / 0.344 (0.017)* / 0.347 (0.019) / 0.341 (0.013) / 0.342 (0.013)
Mean Normalized T2 Lesion Volume (SD) / n/a / 0.009 (0.009) / 0.008 (0.009) / 0.010 (0.007) / 0.010 (0.010)
Mean Normalized Caudate Volume (SD) / 0.009 (0.001) / 0.008 (0.002)* / 0.007 (0.001) / 0.008 (0.002)** / 0.007 (0.001)**
Mean Normalized Thalamus Volume (SD) / 0.011 (0.001) / 0.009 (0.002)* / 0.010 (0.003) / 0.009 (0.002) / 0.009 (0.002)
Mean Normalized Putamen Volume (SD) / 0.010 (0.001) / 0.009 (0.001)* / 0.009 (0.002) / 0.009 (0.001) / 0.008 (0.001)
Mean Normalized Brainstem Volume (SD) / 0.016 (0.001) / 0.015 (0.002) / 0.016 (0.002) / 0.015 (0.002)** / 0.014 (0.001)**
Mean Normalized Cerebellum Volume (SD) / 0.086 (0.006) / 0.087 (0.007) / 0.088 (0.007) / 0.087 (0.009) / 0.086 (0.006)
Mean Supratentorial FA (SD) / 0.270 (0.011) / 0.259 (0.014)* / 0.258 (0.014) / 0.257 (0.013) / 0.264 (0.017)
Mean Supratentorial MD, µm2/ms (SD) / 0.891 (0.017) / 0.925 (0.0328)* / 0.921 (0.034) / 0.934 (0.031) / 0.922 (0.033)
Mean Supratentorial λ║, µm2/ms (SD) / 1.136 (0.013) / 1.165 (0.030)* / 1.161 (0.031) / 1.172 (0.029) / 1.167 (0.028)
Mean Supratentorial λ┴, µm2/ms (SD) / 0.769 (0.002) / 0.805 (0.004)* / 0.802 (0.004) / 0.814 (0.003) / 0.800 (0.004)
Mean Supratentorial, MTR (SD) / 0.399 (0.007) / 0.390 (0.010)* / 0.391 (0.009) / 0.388 (0.010) / 0.393 (0.011)
Mean Corpus Callosum FA (SD) / 0.570 (0.033) / 0.514 (0.044)* / 0.517 (0.046) / 0.504 (0.042) / 0.522 (0.039)
Mean Corpus Callosum MD, µm2/ms (SD) / 0.903 (0.070) / 1.045 (0.011)* / 1.031 (0.109) / 1.087 (0.099)** / 1.031 (0.096)
Mean Corpus Callosum λ║, µm2/ms (SD) / 1.54 (0.083) / 1.673 (0.118)* / 1.656 (0.117) / 1.716 (0.115)** / 1.663 (0.117)
Mean Corpus Callosum λ┴, µm2/ms (SD) / 0.582 (0.068) / 0.732 (0.108)* / 0.719 (0.113) / 0.773 (0.100)** / 0.716 (0.094)†
Mean Corpus Callosum MTR (SD) / 0.442 (0.013) / 0.419 (0.021)* / 0.420 (0.021) / 0.415 (0.020) / 0.420 (0.023)
Mean Optic Radiations FA (SD) / 0.521 (0.029) / 0.461 (0.041)* / 0.467 (0.040) / 0.447 (0.036)** / 0.462 (0.045)
Mean Optic Radiations MD, µm2/ms (SD) / 0.863 (0.050) / 0.971 (0.086)* / 0.952 (0.081) / 1.009 (0.074)** / 0.980 (0.010)
Mean Optic Radiations λ║, µm2/ms (SD) / 1.398 (0.057) / 1.484 (0.085)* / 1.465 (0.080) / 1.516 (0.076)** / 1.501 (0.096)
Mean Optic Radiations λ┴, µm2/ms (SD) / 0.596 (0.051) / 0.715 (0.089)* / 0.695 (0.085) / 0.756 (0.076)** / 0.720 (0.104)
Mean Optic Radiations MTR (SD) / 0.445 (0.014) / 0.420 (0.025)* / 0.425 (0.020) / 0.412 (0.023)** / 0.419 (0.036)
Mean Corticospinal Tract FA (SD) / 0.532 (0.019) / 0.528 (0.024) / 0.532 (0.024) / 0.520 (0.022)** / 0.530 (0.027)
Mean Corticospinal Tract MD, µm2/ms (SD) / 0.788 (0.022) / 0.827 (0.040)* / 0.821 (0.039) / 0.837 (0.040) / 0.831 (0.042)
Mean Corticospinal Tract λ║, µm2/ms (SD) / 1.310 (0.037) / 1.363 (0.058)* / 1.360 (0.0580) / 1.364 (0.059) / 1.371 (0.057)
Mean Corticospinal Tract λ┴, µm2/ms (SD) / 0.523 (0.024) / 0.560 (0.039)* / 0.552 (0.0371) / 0.0573 (0.038)** / 0.562 (0.043)
Mean Corticospinal Tract MTR (SD) / 0.454 (0.007) / 0.446 (0.011)* / 0.447 (0.010) / 0.444 (0.010) / 0.445 (0.014)

* p < 0.05 for comparison to healthy volunteers. ** p < 0.05 for comparison to RRMS † p < 0.05 for comparison to SPMS

Table e-2: Correlation between CVF and T2 lesion volume and disability measures.

All MS / Relapsing Remitting MS / Secondary Progressive MS / Primary Progressive MS
EDSS / MSFC z-score / Low Contrast Visual Acuity / EDSS / MSFC z-score / Low Contrast Visual Acuity / EDSS / MSFC z-score / Low Contrast Visual Acuity / EDSS / MSFC z-score / Low Contrast Visual Acuity
CVF / -0.32* / 0.37* / 0.13 / -0.28 / 0.48* / 0.05 / -0.01 / -0.11 / -0.07 / -0.62 / 0.54 / 0.40
T2 Lesion Volume / 0.24 / -0.31* / -0.20 / 0.42* / -0.32 / -0.23 / -.31 / -0.28 / 0.17 / 0.20 / -0.22 / -0.31

Partial correlations, adjusted for age and gender. * p < 0.01 for correlation coefficient.

Table e-3: Comparison of prediction of disability between brain volume, lesion load, and diffusion-tensor-based indices (in RRMS only).

Disability Measure / Prediction of disability (R2) by: / Δ R2 for addition of DTI-derived indices to predictive model
CVF / + / Supratentorial / Corpus Callosum / Optic Radiations / Corticospinal Tract
FA / MD / λ║ / λ┴ / MTR / FA / MD / λ║ / λ┴ / MTR / FA / MD / λ║ / λ┴ / MTR / FA / MD / λ║ / λ┴ / MTR
EDSS / 0.15 / 0.05 / 0.02 / -0.01 / 0.04 / 0.00 / 0.03 / 0.00 / -0.01 / 0.00 / -0.01 / 0.03 / 0.07* / 0.05 / 0.08* / 0.00 / 0.00 / 0.04 / 0.01 / 0.04 / -0.01
MSFC / 0.23 / 0.00 / -0.01 / -0.01 / -0.01 / 0.02 / 0.04 / -0.01 / -0.01 / 0.01 / 0.00 / 0.00 / 0.00 / -0.01 / 0.00 / 0.04 / 0.00 / -0.01 / -0.01 / -0.01 / 0.02
Low Contrast Visual Acuity / -0.04 / 0.01 / 0.01 / -0.01 / 0.02 / -0.01 / 0.04 / -0.02 / 0.00 / -0.02 / 0.01 / 0.16* / 0.07 / 0.00 / 0.11* / 0.07 / 0.07 / 0.07 / -0.01 / 0.13* / 0.10*
T2 Lesion Volume / +
EDSS / 0.26 / 0.0 / -0.01 / -0.01 / 0.00 / 0.00 / 0.00 / 0.00 / -0.01 / 0.00 / 0.00 / -0.01 / 0.02 / 0.00 / 0.03 / 0.01 / 0.01 / 0.00 / 0.00 / -0.01 / 0.00
MSFC / 0.19 / 0.0 / 0.01 / 0.00 / 0.01 / 0.02 / 0.01 / 0.02 / 0.01 / 0.03 / 0.02 / 0.00 / 0.01 / 0.00 / 0.01 / 0.03 / -0.01 / -0.01 / 0.00 / -0.01 / 0.01
Low Contrast Visual Acuity / 0.03 / -0.01 / -0.01 / -0.01 / -0.01 / -0.01 / -0.01 / -0.01 / 0.00 / -0.01 / -0.01 / 0.06* / 0.03 / 0.00 / 0.06* / 0.03 / 0.05* / 0.02 / -0.01 / 0.07* / 0.03
CVF + T2 Lesion Volume / +
EDSS / 0.28 / 0.00 / -0.01 / 0.00 / -0.01 / -0.01 / -0.01 / -0.01 / -0.01 / -0.01 / 0.00 / 0.00 / 0.00 / -0.01 / 0.01 / 0.00 / -0.01 / -0.01 / -0.01 / 0.00 / -0.01
MSFC / 0.21 / -0.01 / -0.01 / -0.02 / -0.01 / 0.00 / -0.01 / -0.01 / -0.01 / -0.01 / -0.00 / -0.01 / -0.01 / -0.02 / -0.01 / 0.01 / -0.02 / -0.02 / -0.01 / -0.02 / 0.00
Low Contrast Visual Acuity / 0.03 / -0.01 / -0.01 / -0.01 / -0.01 / -0.02 / -0.01 / 0.00 / 0.01 / 0.01 / -0.01 / 0.06 / 0.03 / -0.01 / 0.06* / 0.02 / 0.01 / 0.01 / -0.01 / 0.05 / 0.02

Regression performed for prediction of disability measure by CVF, lesion volume, or CVF and lesion volume. DTI-derived indices added to the model to determine if they provided additional predictive information to the nested model (tested by likelihood ratio test). * p < 0.01 for likelihood ratio test.