Table 1.
Disease duration based on patient report of symptom onset to time of baseline scan.
Fig 1.
A flow diagram for the data analysis process used in this study.
FreeSurfer was used to parcellate and segment the T1W data into 82 distinct cortical and sub-cortical brain regions based on the Deskian-Killiany atlas. For each region, t-statistics of the volumetric difference between the ALS patient group and the control group were estimated. The t-statistics were measured between control subjects and ALS patients at baseline, ALS patients at baseline and at six-month follow-up, and ALS patients at six-month follow-up and at twelve-month follow-up. The structural connectome data were obtained from the existing IIT Human Brain Atlas (V.5.0). Based on the repeated seeding approach, NDM was implemented to identify the epicentre of the disease. For each brain region, the network diffusion model was used to estimate the diffusion at all other regions. The association between NDM estimates (predicted atrophy) and t-statistics (measured atrophy) were investigated using Parsons’s correlation. The maximum correlation value for each seed region was used to estimate the likelihood of that region being involved in the spread of the pathology in ALS. ALS T1: ALS baseline scan. ALS T2: ALS six-month follow-up scan. ALS T3: ALS twelve-month follow-up scan.
Fig 2.
Visual representation of the measured atrophy in ALS patients.
(A) The measured atrophy at baseline compared to controls, (B) at six months follow-up compared to baseline (B), and (C) at twelve-months follow-up compared to six-month follow-up. The displayed atrophy pattern is based on the t-value of the difference in grey-matter volume in the 82 parcels from the Desikan-Killiany atlas. The darker red colour in the colour range represents the region of greatest atrophy. L, R and S represent left, right, and superior view.
Fig 3.
Prediction of atrophy pattern at baseline.
(A) Scatter plot of the correlation between predicated and measured atrophy, when measured atrophy was estimated between ALS patients at baseline and control subjects. Pearson’s correlation coefficient (r) and the significance of the correlation (p) are shown, p is family-wise error (FWE) corrected. (B) Visual representation of maximum correlation obtained for each node, when measured atrophy was estimated between ALS patients at baseline and control subjects. The size of the ball corresponds to the maximum correlation between predicted and measured atrophy. The colour of the balls ranges from light yellow (for smallest) to dark red (for biggest). L is left and R is Right. a.u. is arbitrary unit.
Table 2.
Seed regions identified by NDM at baseline (atrophy measured at baseline compared to controls), at six-month follow-up (atrophy measured at six-month follow-up compared to the baseline) and at twelve-month follow-up (atrophy measured at twelve- month follow-up compared to the six-month follow-up).
R is Pearson’s correlation. p values are family-wise error (FWE) corrected). The symbol * denotes significant p value.
Fig 4.
Prediction of atrophy pattern at six-month follow-up.
(A) Scatter plot of the correlation between predicated and measured atrophy, when measured atrophy was estimated between ALS patients at six-month follow-up and ALS patients at baseline. Pearson’s correlation coefficient (r) and the significance of the correlation (p) are shown, p is family-wise error (FWE) corrected. (B) Visual representation of maximum correlation obtained for each node, when measured atrophy was estimated between ALS patients at six-month follow-up and ALS patients at baseline. The size of the ball corresponds to the maximum correlation between predicted and measured atrophy. The colour of the balls ranges from light yellow (for smallest) to dark red (for biggest biggest). L is left and R is Right. a.u. is arbitrary unit.
Fig 5.
Prediction of atrophy pattern at twelve-month follow-up.
(A) Scatter plot of the correlation between predicated and measured atrophy, when measured atrophy was estimated between ALS patients at twelve-month follow-up and ALS patients at six-month follow-up. Pearson’s correlation coefficient (r) and the significance of the correlation (p) are shown, p is family-wise error (FWE) corrected. (B) Visual representation of maximum correlation obtained for each node, when measured atrophy was estimated between ALS patients at twelve-month follow-up and ALS patients at six-month follow-up. The size of the ball corresponds to the maximum correlation between predicted and measured atrophy. The colour of the balls ranges from light yellow (for smallest) to dark red (for biggest biggest). L is left and R is Right. a.u. is arbitrary unit.