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. 2024 Jun 19;11(4):e200271. doi: 10.1212/NXI.0000000000200271

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.

a

β regression coefficient, quantifying the estimated mean change in the layer-specific z-score, associated with a one-unit increase in the predictor.

b

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.