Correlations between radial diffusivity (λr) and NAA/Cr ratio with the ROI T2-LL in RR, PP and all-MS patient groups. (NS = Not significant).

<p>Correlations between radial diffusivity (λr) and NAA/Cr ratio with the ROI T2-LL in RR, PP and all-MS patient groups. (NS = Not significant).</p

Demographics and group characteristics.

<p>Values are expressed as mean (Standard deviation).</p><p>RR: relapsing remitting; SP: secondary progressive; PP: primary progressive; EDSS: expanded disability status scale; ROI T2-LL: T2-lesion load corresponding to the lesion volume measured within the region of interest (ROI); Brain T2-LL: T2-lesion load corresponding to the lesion volume measured in the whole brain.</p

Diffusion and metabolic measures in MS patients and control subjects groups.

<p>Values (Mean ± SD) of mean diffusion (MD), fraction of anisotropy (FA), axial (λa) and radial (λr) diffusivities, N-acetylaspartate (NAA), choline (Cho) and creatine (Cr) (*p<0.05; **p<0.01; ***p<0.001 when compared to controls). RR: relapsing remitting; SP: secondary progressive; PP: primary progressive.</p

ROC curves of the mean diffusion (MD), axial (λa) and radial (λr) diffusivities, NAA/Cho and NAA/Cr ratios in RR (A), SP (B), PP (C) and all-MS patient groups (D).

<p>ROC curves of the mean diffusion (MD), axial (λa) and radial (λr) diffusivities, NAA/Cho and NAA/Cr ratios in RR (A), SP (B), PP (C) and all-MS patient groups (D).</p

Correlation rates (r) between diffusion and metabolic measures and the ROI T2-LL in different groups of MS patients.

<p>Correlation significance (*p<0.05; **p<0.01; ***p<0.001).</p><p>ROI T2-LL: T2-lesion load corresponding to the lesion volume within the region of interest, MD: mean diffusion, FA: fraction of anisotropy, λa: axial diffusivity, λr: radial diffusivity, NAA: N-acetylaspartate, Cr: creatine, RR: relapsing remitting; SP: secondary progressive; PP: primary progressive.</p

Areas under ROC curves analysis of DTI and MRSI derived measures in different groups of MS patients.

<p>Statistical significance (*p<0.05; **p<0.01; ***p<0.001) when comparing areas under ROC curves (AUC) of the following MR metrics: MD: mean diffusivity, λr: radial diffusivity, NAA: N-acetylaspartate, Cr: creatine, RR: relapsing remitting; SP: secondary progressive; PP: primary progressive.</p

Global overview of the “histogram” approach.

<p>As first step <b>(A1)</b> the histogram of the data extracted from time point <i>i</i> and time-point <i>i+p</i> in the same cross-section are fitted using Gaussian mixture model. As second step <b>(A2)</b> our method detects a pathological longitudinal variation between the two time-points in the histogram. The obtained threshold value γ is then used to differentiate between “changed” and “unchanged” fibers <b>(B)</b>. Plotted FA signal profile of the two subset of fiber and cross-sectional view of the labeled fibers <b>(C)</b>.</p

Detection of longitudinal variations by applying the “mean” and “histogram” methods.

<p><b>(A)</b> On the left CST of Patient1 between W1 and W8 time-points, detecting a change in two preexisting lesions (L1, L2); <b>(B)</b> On the right IFOF of Patient2 between W1 and W6 detecting a new lesion; <b>(C)</b> On the right IFOF of Patient2 between W1 and W7 detecting a change in two preexisting lesions (L1, L2) and the apparition of a new lesion (L3). Lesions are shown on FLAIR images. Fiber-subsets labeled as “unchanged” (green) and “changed” (red) are shown on top of FLAIR images.</p

Iterative analysis of the “changed” fiber-subset of Patient1’s left CST (A) and of Patient2’s right IFOF (B) at different time-points.

<p><b>(A)</b> Detection of a new lesion (L1) at W6 and at W8, and a preexisting lesion at W7, evolving by contaminating the CST). <b>(B)</b> Detection of a preexisting lesion (L4) and a new lesion (L5) at W6, both evolving in size and degree of FA alteration at W7, and remaining unchanged at W8.</p

Longitudinal analyses of the FA values along the right CST of Patient1.

<p><b>(A)</b> The “mean” method analysis showed no changes in the fiber-bundle between time-point 1 (W1, blue) and the other 7 time-points (yellow). <b>(B)</b> The “histogram” method analysis showed significant FA changes (red) between the reference time-point W1 (blue) and the others 7 time-points (W2 to W8) in different cross-sections of the fiber-bundle. <b>(C)</b> The “histogram” method allowed the distinction of “unchanged” fiber-subset (green) from “changed” fiber-subset (red) compared to the reference (W1) fiber-bundle (blue) as shown on the cross-sectional view of the CST. <b>(D)</b> FLAIR images of Patient1 showing the corresponding lesions.</p