Table 3.
Associations of MTR and R2* Layer-Specific Z-Scores and CSF-In Z-Score Changes per Layer With Demographic, Clinical, and Conventional MRI Metrics in Patients With Multiple Sclerosis in Cortex, Thalamus, and Caudate
| Cortex | ||||||||
| MTR | R2* | |||||||
| βa (SE) | p (FDR-p) | βb (SE) | p (FDR-p) | βa (SE) | p (FDR-p) | βb (SE) | p (FDR-p) | |
| Age (×10−1) | ||||||||
| Outer | −0.60 (0.18) | 0.002 (0.027) | 0.18 (0.05) | <0.001 (0.016) | −0.27 (0.15) | 0.082 (0.255) | 0.05 (0.05) | 0.264 (0.469) |
| Middle | −0.40 (0.15) | 0.013 (0.09) | −0.18 (0.17) | 0.301 (0.517) | ||||
| Inner | −0.24 (0.14) | 0.087 (0.262) | −0.16 (0.19) | 0.391 (0.598) | ||||
| DD (×10−1) | ||||||||
| Outer | −0.42 (0.17) | 0.015 (0.095) | 0.09 (0.05) | 0.058 (0.200) | −0.21 (0.13) | 0.117 (0.314) | 0.00 (0.04) | 0.967 (0.967) |
| Middle | −0.33 (0.13) | 0.018 (0.099) | −0.20 (0.15) | 0.184 (0.420) | ||||
| Inner | −0.24 (0.12) | 0.053 (0.197) | −0.20 (0.16) | 0.210 (0.423) | ||||
| EDSS | ||||||||
| Outer | −0.23 (0.08) | 0.009 (0.073) | 0.06 (0.02) | 0.014 (0.091) | −0.09 (0.07) | 0.195 (0.420) | 0.05 (0.02) | 0.011 (0.085) |
| Middle | −0.15 (0.07) | 0.028 (0.128) | −0.01 (0.08) | 0.868 (0.940) | ||||
| Inner | −0.11 (0.06) | 0.078 (0.249) | 0.01 (0.08) | 0.880 (0.941) | ||||
| WMLV | ||||||||
| Outer | −0.52 (0.11) | <0.001 (0.002) | 0.12 (0.03) | 0.001 (0.016) | −0.23 (0.10) | 0.027 (0.128) | 0.04 (0.03) | 0.195 (0.420) |
| Middle | −0.37 (0.10) | <0.001 (0.011) | −0.14 (0.12) | 0.243 (0.450) | ||||
| Inner | −0.28 (0.09) | 0.002 (0.027) | −0.15 (0.13) | 0.256 (0.460) | ||||
| CLV | ||||||||
| Outer | −1.13 (0.92) | 0.227 (0.428) | 0.33 (0.25) | 0.194 (0.420) | −1.51 (0.68) | 0.031 (0.140) | 0.05 (0.21) | 0.816 (0.916) |
| Middle | −0.65 (0.75) | 0.390 (0.598) | −1.24 (0.78) | 0.118 (0.314) | ||||
| Inner | −0.46 (0.66) | 0.483 (0.692) | −1.41 (0.85) | 0.104 (0.289) | ||||
| NBV (×10−2) | ||||||||
| Outer | 1.55 (0.29) | <0.001 (<0.001) | −0.48 (0.07) | <0.001 (<0.001) | 0.81 (0.25) | 0.002 (0.027) | −0.10 (0.08) | 0.249 (0.456) |
| Middle | 0.92 (0.26) | <0.001 (0.018) | 0.61 (0.30) | 0.047 (0.175) | ||||
| Inner | 0.60 (0.24) | 0.017 (0.099) | 0.62 (0.33) | 0.064 (0.212) | ||||
| Cth | ||||||||
| Outer | 6.86 (2.02) | 0.001 (0.023) | −2.42 (0.51) | <0.001 (0.001) | 0.92 (1.69) | 0.589 (0.782) | −1.51 (0.46) | 0.002 (0.027) |
| Middle | 3.99 (1.71) | 0.024 (0.119) | −1.63 (1.90) | 0.393 (0.598) | ||||
| Inner | 2.01 (1.55) | 0.199 (0.420) | −2.10 (2.06) | 0.313 (0.528) | ||||
| NCPV (×10−2) | ||||||||
| Outer | −0.01 (0.03) | 0.712 (0.86) | 0.02 (0.01) | 0.079 (0.249) | 0.02 (0.03) | 0.409 (0.608) | 0.01 (0.01) | 0.500 (0.701) |
| Middle | 0.01 (0.03) | 0.777 (0.888) | 0.03 (0.03) | 0.317 (0.528) | ||||
| Inner | 0.02 (0.03) | 0.397 (0.600) | 0.03 (0.03) | 0.330 (0.533) | ||||
| Thalamus | ||||||||
| MTR | R2* | |||||||
| βa (SE) | p (FDR-p) | βb (SE) | p (FDR-p) | βa (SE) | p (FDR-p) | βb (SE) | p (FDR-p) | |
| Age (×10−1) | ||||||||
| Outer | −0.29 (0.19) | 0.140 (0.354) | 0.09 (0.04) | 0.036 (0.149) | −0.26 (0.20) | 0.202 (0.420) | 0.06 (0.05) | 0.220 (0.426) |
| Middle | −0.17 (0.17) | 0.319 (0.528) | −0.21 (0.22) | 0.326 (0.530) | ||||
| Inner | −0.11 (0.17) | 0.499 (0.701) | −0.15 (0.21) | 0.487 (0.692) | ||||
| DD (×10−1) | ||||||||
| Outer | −0.13 (0.17) | 0.430 (0.634) | 0.08 (0.03) | 0.019 (0.100) | −0.35 (0.17) | 0.046 (0.175) | −0.02 (0.04) | 0.570 (0.771) |
| Middle | −0.02 (0.15) | 0.918 (0.943) | −0.44 (0.18) | 0.017 (0.099) | ||||
| Inner | 0.03 (0.14) | 0.826 (0.917) | −0.40 (0.18) | 0.028 (0.128) | ||||
| EDSS | ||||||||
| Outer | −0.16 (0.08) | 0.056 (0.200) | 0.04 (0.02) | 0.046 (0.175) | −0.18 (0.09) | 0.041 (0.163) | 0.05 (0.02) | 0.009 (0.073) |
| Middle | −0.12 (0.07) | 0.095 (0.273) | −0.12 (0.09) | 0.213 (0.423) | ||||
| Inner | −0.09 (0.07) | 0.227 (0.428) | −0.08 (0.09) | 0.402 (0.604) | ||||
| WM LV | ||||||||
| Outer | −0.16 (0.13) | 0.209 (0.423) | 0.06 (0.03) | 0.018 (0.099) | −0.37 (0.13) | 0.007 (0.070) | 0.07 (0.03) | 0.035 (0.148) |
| Middle | −0.08 (0.12) | 0.474 (0.691) | −0.31 (0.14) | 0.033 (0.141) | ||||
| Inner | −0.03 (0.11) | 0.764 (0.888) | −0.23 (0.14) | 0.103 (0.289) | ||||
| TLV | ||||||||
| Outer | −1.63 (1.31) | 0.219 (0.426) | 0.12 (0.28) | 0.665 (0.829) | 0.51 (1.43) | 0.724 (0.869) | 1.05 (0.29) | 0.001 (0.016) |
| Middle | −1.52 (1.16) | 0.197 (0.420) | 1.96 (1.48) | 0.191 (0.420) | ||||
| Inner | −1.38 (1.13) | 0.227 (0.428) | 2.60 (1.43) | 0.075 (0.245) | ||||
| NBV (×10−2) | ||||||||
| Outer | 0.73 (0.33) | 0.033 (0.141) | −0.23 (0.07) | 0.002 (0.024) | 0.36 (0.37) | 0.334 (0.534) | −0.16 (0.08) | 0.062 (0.208) |
| Middle | 0.49 (0.30) | 0.112 (0.306) | 0.21 (0.39) | 0.591 (0.782) | ||||
| Inner | 0.28 (0.30) | 0.358 (0.564) | 0.05 (0.38) | 0.896 (0.941) | ||||
| NTV | ||||||||
| Outer | 0.25 (0.09) | 0.006 (0.059) | −0.05 (0.02) | 0.012 (0.087) | 0.10 (0.10) | 0.324 (0.530) | −0.05 (0.02) | 0.014 (0.091) |
| Middle | 0.19 (0.08) | 0.019 (0.100) | 0.04 (0.10) | 0.671 (0.831) | ||||
| Inner | 0.15 (0.08) | 0.058 (0.200) | −0.01 (0.10) | 0.926 (0.946) | ||||
| NCPV (×10−2) | ||||||||
| Outer | 0.00 (0.04) | 0.910 (0.942) | 0.01 (0.01) | 0.486 (0.692) | −0.01 (0.04) | 0.769 (0.888) | 0.01 (0.01) | 0.361 (0.564) |
| Middle | 0.01 (0.03) | 0.663 (0.829) | −0.01 (0.04) | 0.897 (0.941) | ||||
| Inner | 0.01 (0.03) | 0.653 (0.825) | 0.00 (0.04) | 0.934 (0.949) | ||||
| Caudate | ||||||||
| MTR | R2* | |||||||
| βa (SE) | p (FDR-p) | βb (SE) | p (FDR-p) | βa (SE) | p (FDR-p) | βb (SE) | p (FDR-p) | |
| Age (×10−1) | ||||||||
| Outer | −0.30 (0.21) | 0.149 (0.372) | 0.02 (0.04) | 0.632 (0.820) | 0.03 (0.19) | 0.872 (0.940) | 0.06 (0.04) | 0.157 (0.386) |
| Middle | −0.27 (0.20) | 0.189 (0.420) | 0.10 (0.19) | 0.596 (0.783) | ||||
| Inner | −0.26 (0.19) | 0.176 (0.412) | 0.14 (0.20) | 0.475 (0.691) | ||||
| DD (×10−1) | ||||||||
| Outer | −0.24 (0.18) | 0.180 (0.417) | 0.02 (0.04) | 0.682 (0.839) | −0.10 (0.16) | 0.540 (0.740) | 0.02 (0.03) | 0.513 (0.709) |
| Middle | −0.2 (0.17) | 0.268 (0.472) | −0.09 (0.16) | 0.589 (0.782) | ||||
| Inner | −0.21 (0.17) | 0.203 (0.420) | −0.06 (0.17) | 0.741 (0.873) | ||||
| EDSS | ||||||||
| Outer | −0.26 (0.08) | 0.004 (0.040) | 0.05 (0.02) | 0.008 (0.072) | 0.13 (0.08) | 0.127 (0.329) | 0.01 (0.02) | 0.625 (0.816) |
| Middle | −0.19 (0.08) | 0.026 (0.128) | 0.11 (0.08) | 0.175 (0.412) | ||||
| Inner | −0.16 (0.08) | 0.057 (0.200) | 0.14 (0.08) | 0.095 (0.273) | ||||
| WM LV | ||||||||
| Outer | −0.48 (0.13) | <0.001 (0.011) | 0.08 (0.03) | 0.003 (0.033) | −0.04 (0.13) | 0.740 (0.873) | 0.04 (0.03) | 0.089 (0.264) |
| Middle | −0.34 (0.13) | 0.010 (0.081) | 0.01 (0.13) | 0.948 (0.958) | ||||
| Inner | −0.31 (0.12) | 0.015 (0.095) | 0.05 (0.13) | 0.730 (0.870) | ||||
| CaLV | ||||||||
| Outer | −0.87 (2.84) | 0.761 (0.888) | −0.17 (0.59) | 0.774 (0.888) | −0.52 (2.55) | 0.839 (0.926) | 0.60 (0.52) | 0.256 (0.460) |
| Middle | −1.04 (2.73) | 0.706 (0.858) | 0.33 (2.54) | 0.897 (0.941) | ||||
| Inner | −1.21 (2.60) | 0.644 (0.824) | 0.67 (2.65) | 0.800 (0.909) | ||||
| NBV (×10−2) | ||||||||
| Outer | 0.41 (0.38) | 0.281 (0.49) | −0.12 (0.08) | 0.119 (0.314) | −0.35 (0.34) | 0.313 (0.528) | 0.00 (0.07) | 0.964 (0.967) |
| Middle | 0.22 (0.37) | 0.545 (0.743) | −0.22 (0.34) | 0.511 (0.709) | ||||
| Inner | 0.17 (0.35) | 0.636 (0.820) | −0.34 (0.35) | 0.341 (0.542) | ||||
| NCV | ||||||||
| Outer | 0.08 (0.18) | 0.648 (0.824) | −0.05 (0.04) | 0.137 (0.352) | −0.19 (0.16) | 0.233 (0.434) | −0.05 (0.03) | 0.166 (0.399) |
| Middle | −0.02 (0.17) | 0.893 (0.941) | −0.22 (0.16) | 0.164 (0.399) | ||||
| Inner | −0.03 (0.16) | 0.866 (0.940) | −0.28 (0.16) | 0.087 (0.262) | ||||
| NCPV (×10−2) | ||||||||
| Outer | −0.01 (0.04) | 0.913 (0.942) | 0.01 (0.01) | 0.212 (0.423) | −0.01 (0.04) | 0.862 (0.940) | 0.01 (0.01) | 0.288 (0.499) |
| Middle | 0.01 (0.04) | 0.812 (0.916) | 0.00 (0.04) | 0.909 (0.942) | ||||
| Inner | 0.02 (0.04) | 0.689 (0.842) | 0.01 (0.04) | 0.824 (0.917) | ||||
Abbreviations: CLV = cortical lesion volume; CaLV = caudate lesion volume; Cth = cortical thickness; DD = disease duration; EDSS = Expanded Disability Status Scale; EM = estimated mean; FDR = false-discovery rate; HC = healthy controls; LV = lesion volume; MTR = magnetization transfer ratio; NBV = normalized brain volume; NCPV = normalized choroid plexus volume; NCV = normalized caudate volume; NTV = normalized thalamic volume; PMS = progressive multiple sclerosis; RRMS = relapsing-remitting multiple sclerosis; SE = standard error; TLV = thalamic lesion volume; WM = white matter.
Beta-coefficients (β) related to standard errors and p values from linear mixed models are reported. The analysis for lesion volumes was performed on square-root-transformed values. FDR correction (Benjamini-Hochberg procedure) was applied to account for the overall number of tests.
β regression coefficient, quantifying the estimated mean change in the layer-specific z-score, associated with a one-unit increase in the predictor.
β regression coefficient, quantifying the estimated mean change in the CSF-in z-score change per layer, associated with a one-unit increase in the predictor.