Table 2.
Cross-sectional and longitudinal outputs for the panel of imaging metrics
| Cross-sectional (Main effect: Group) | Longitudinal (Interaction: Time x Group) | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Right hemisphere | Left hemisphere | Right hemisphere | Left hemisphere | |||||||||
| Esti-mate | t / F-value | p-value | esti-mate | t / F-value | p-value | esti-mate | t / F-value | p-value | esti-mate | t-value | p-value | |
| ALS vs. HC | ||||||||||||
| Vol | – 6.75e-5 | – 1.505 | 0.133 | n.a. | n.a. | n.a. | – 3.20e-5 | – 1.263 | 0.208 | n.a. | n.a. | n.a. |
| CT | – 0.076 | – 3.375 | 8.34e-4* | – 0.088 | – 4.315 | <.001* | – 0.022 | – 1.686 | 0.093 | – 6.20e-3 | – 0.639 | 0.524 |
| RD | – 2.26e-5 | – 1.376 | 0.170 | – 7.63e-6 | – 0.454 | 0.651 | 2.58e-5 | 2.030 | 0.044* | 2.07e-5 | 1.626 | 0.105 |
| AD | – 7.58e-5 | – 2.151 | 0.032* | – 4.74e-5 | – 1.320 | 0.188 | 6.01e-5 | 2.210 | 0.028* | 4.35e-5 | 1.567 | 0.118 |
| FC | 0.026 | 1.035 | 0.302 | 0.005 | 0.185 | 0.853 | – 0.048 | – 2.187 | 0.030* | 0.004 | 0.174 | 0.862 |
| C9+ vs. C9-/HC | ||||||||||||
| Vol | 9.40e-7 | 3.427 | 0.034* | n.a. | n.a. | n.a. | 5.82e-6 | 0.161 | 0.872 | n.a. | n.a. | n.a. |
| CT | 0.920 | 14.11 | <.001* | 0.709 | 12.85 | <.001* | – 0.029 | – 2.040 | 0.042* | – 0.044 | – 3.505 | <.001* |
| RD | 9.30e-8 | 2.533 | 0.081+ | 4.40e-8 | 1.144 | 0.320 | – 1.56e-5 | – 0.746 | 0.456 | 2.04e-8 | 9.75e-4 | 0.999 |
| AD | 5.57e-7 | 3.276 | 0.039* | 3.17e-7 | 1.794 | 0.168 | – 2.72e-5 | – 0.597 | 0.551 | – 1.50e-5 | – 0.325 | 0.745 |
| FC | 0.050 | 0.599 | 0.550 | 0.006 | 0.079 | 0.924 | – 0.003 | – 0.074 | 0.941 | – 0.024 | – 0.651 | 0.515 |
| BA/BS vs. HC (C9- patients only) | ||||||||||||
| Vol | 1.03e-6 | 3.813 | 0.023* | n.a. | n.a. | n.a. | 3.80e-5 | 1.543 | 0.124 | n.a. | n.a. | n.a. |
| CT | 0.300 | 4.707 | 0.010* | 0.433 | 8.233 | <.001* | 0.0172 | 1.654 | 0.100+ | 1.03e-4 | 0.011 | 0.991 |
| RD | 1.65e-7 | 4.460 | 0.012* | 1.18e-7 | 3.042 | 0.049* | – 3.11e-5 | – 2.183 | 0.030* | – 3.97e-6 | – 0.318 | 0.095+ |
| AD | 1.03e-6 | 6.074 | 0.003* | 8.01e-7 | 4.500 | 0.012* | – 6.96e-5 | – 2.304 | 0.022* | – 5.45-e5 | – 1.778 | 0.077+ |
| FC | 0.076 | 0.905 | 0.406 | 0.043 | 0.507 | 0.603 | 0.048 | 1.961 | 0.051+ | – 0.021 | – 0.862 | 0.390 |
| MRI-clinical correlations (ALSFRS-r bulbar score) | ||||||||||||
| Vol | 266.22 | 0.361 | 0.7193 | n.a. | n.a. | n.a. | 3.59e-05 | 0.809 | 0.421 | n.a. | n.a. | n.a. |
| CT | – 0.638 | – 0.565 | 0.574 | – 0.567 | 0.508 | 0.613 | – 5.12e-4 | – 0.027 | 0.978 | – 0.012 | – 0.949 | 0.346 |
| RD | 1.58e3 | 0.868 | 0.389 | 8.18e2 | 0.454 | 0.651 | – 3.14e-5 | – 1.286 | 0.202 | – 1.58e-5 | – 0.578 | 0.565 |
| AD | 689.01 | 0.808 | 0.422 | 711.43 | 0.843 | 0.402 | – 5.17e-5 | – 0.974 | 0.333 | – 3.10e-5 | – 0.541 | 0.590 |
| FC | 1.032 | 0.883 | 0.380 | -0.324 | – 0.251 | 0.802 | 9.88e-4 | 0.022 | 0.982 | 5.57e-3 | – 0.119 | 0.906 |
| Receiver operating characteristics (ROC) | ||||||||||||
| ROI | AUC at baseline | AUC at 12 months | ||||||||||
| Medulla volume | 0.611 | 0.642 | ||||||||||
| CT right | 0.567 | 0.624 | ||||||||||
| CT left | 0.619 | 0.685 | ||||||||||
| RD right | 0.606 | 0.670 | ||||||||||
| RD left | 0.606 | 0.682 | ||||||||||
| AD right | 0.563 | 0.645 | ||||||||||
| AD left | 0.467 | 0.612 | ||||||||||
| FC left | 0.504 | 0.535 | ||||||||||
| FC right | 0.521 | 0.553 |
For unilateral structures, such as the medulla, relevant values are presented in the “left hemisphere” columns. For the cross-sectional comparisons “ALS vs. HC” and the “MRI-clinical correlations”, t-tests are reported; for the cross-sectional comparisons “C9 + vs. C9/HC” and “BA/BS vs. HC” we F-tests (analyses of variance) are reported. Where the F-test was significant for cross-sectional comparisons, we performed pairwise post-hoc tests. Significant post-hoc differences are indicated in Figs. 4 and 5 using asterisks. AD axial diffusivity, ALS amyotrophic lateral sclerosis, AUC area under the curve, BA bulbar asymptomatic, defined as C9orf72 negative with spinal onset disease an no bulbar symptom at baseline, BS bulbar symptomatic, defined as C9orf72 negative patient with bulbar symptoms at baseline, C9 + hexanucleotide repeat expansion carrier in C9orf72, C9- tested negative for hexanucleotide repeat expansions in C9orf72, CT cortical thickness, FC functional connectivity, HC healthy control, MRI magnetic resonance imaging, n.a. not applicable, RD radial diffusivity, ROC receiver operating characteristics, Vol medullary volume, +approaching significace at an alpha-level of p ≤ 0.10, *significant at an alpha-level of p ≤ 0.05