.. .. Methods,

.. .. Results, 84 6.4.1 Inter-subject and intra-subject variability

, {C6,C7} have SLE on 4 metrics, pp.8-74

M. D. Fa, R. Fa, and M. D. , This patient has a special case with a decrease EDSS score Subjects have SLE on, C5 Patient08-16-C6 Patient08-10-C3 Patient08-10-C4 Patient08-10-C5 Patient08-10-C6 Patient08-35-C5 Patient08-35-C6 Patient08-35-C7 Patient08-71-C7 Patient08-71-C6 Patient08-74-C7 Patient08-79-C5 Patient08-79-C6 Patient08-79-C7 Subjects have SLE on [FWW, Stick-AD, MD,RD] Any Patient Subjects have SLE on 4 metrics from FWW, pp.8-35

, 94 7.1.2 Characterization of Multiple Sclerosis Abnormalities within the Cervical Spinal Cord, Contents 7.1 Contributions summary

, Reproducibility and Evolution of Diffusion MRI Measurements within the Cervical Spinal Cord in Multiple Sclerosis

.. .. Perspectives,

. Tang, A spline model (a) and its Frenet frame (b), p.39, 2018.

, 2 (left) T1 image with segmented spinal cord for reference; (right) barycenters of the spline mask (red dots), fitted centerline (black line) and the Frenet frame (blue arrows)

, Distribution of mean angle directions (MAD) and angular concentration of directions (ACD) per vertebral level for cervical part (estimated with kernel density estimation).s is the smoothing factor

, Gradient directions of diffusion MRI acquisition

, Manual identification of two vertebral levels. (3) Registration to the PAM50 template. (4) Motion and distortion correction of dMRI data. (5) Segmentation of the cord using DWI mean data. (6) Registration of PAM50-T1 registered to DWI mean data using the inverse warping field from previous registration as an initial warping field. (7) Computing MAD and ACD by vertebral level of the cervical part, p.45

, Examples of discarded data due to a problem during the acquisition related to motion or ghosting

, Examples of failures in segmentation (red box) and the result after changes (green box) for T 2 -weighted images (first line), and for T 1 -weighted images, p.47

. .. Checking-of-labeling, 47 4.10 Examples of b = 0 volume corrected by various methods; the mask of the spinal cord computed using T 2 -weighted and registered to diffusion image is overlaid. Failed and effective registration are in red and green box respectively, p.48

M. Mean, This way of representation shows that extreme vertebral level of the acquisition window are more affected by distortion, degree) and mean ACD (× 100) by vertebral level

, Boxplots graphics of cross-correlation (left) and mutual information (right) between T2 and corrected b=0 diffusion images

. .. Regions, Distribution of lesion's volume in, p.60

, Manual identification of two vertebral levels. (3) Registration to the PAM50 template. (4) Motion and distortion correction of dMRI data. (5) Segmentation of the cord using DWI mean data. (6) Registration of PAM50-T1 registered to DWI mean data using the inverse warping field from previous registration as an initial warping field

, Estimated marginal means (x axis) for each metric in cervical vertebral levels (y axis) for healthy volunteers data. The blue bars are confidence intervals for the EMMs, and the red arrows are for the comparisons among them. If an arrow from one level overlaps an arrow from another level, the difference is not significant (p-value > 0.05). Else, the difference is significant, p.64

, ROC AUC for scalar and geometric metrics between MS patients and healthy volunteers. Lesion volume is the part of the vertebral volume occupied by a lesion, p.68

, Distribution of lesion's volume in [C2-C4] region in 10 thresholds, p.69

, M S(10%) (2nd line right). Dark blue square shows strong correlation between the two metrics and white square indicates no relationship between them, NAWM (1st line right), M S(5%)

, ROC AUC for various combinations of 2 metrics between MS patients and healthy volunteers

, ROC AUC for various combinations of 3 and 4 metrics between MS patients and healthy volunteers

, Overlays of ROC AUC mean for the best combinations

. .. Metrics, 75 5.11 Variation of ROC AUC score of PCA using various number of components for volume lesion > to 6%, ROC AUC mean for PCA components trained on 9

, First two components [64%-67%] of PCA trained on 9 metrics, p.76

, An illustrative example of the Receiver operating characteristic (ROC) curve. (adapted from commons.wikimedia.org)

, Registration to the PAM50 template. (4) Motion and distortion correction of dMRI data. (5) Segmentation of the cord using DWI mean data. (6) Registration of PAM50-T1 registered to DWI mean data using the inverse warping field from previous registration as an initial warping field

, Distribution of FWW, Stick-AD, FA, MD and RD for MS patients at M0 and M12, vol.87

, Associated confidence interval is represented by the dashed lines. Red: overlaid metrics difference Scan(M12)-Scan(M0) for MS patients; data points falling outside the 95% confidence interval correspond to significant evolution between M0 and M12, Blue: Bland-Altman plot for healthy volunteers (scan and re-scan) for chosen metrics

, Summary of clinical imaging studies of multiple sclerosis using diffusion MRI parameters. AD: axial diffusivity; FA: fractional anisotropy; MD: mean diffusivity

. .. , RD: radial diffusivity; NASC: normal-appearing spinal cord, vol.21

, The fibre orientation n is defined by the angles ?

. .. , 41 4.2 Mean and standard deviation for Mean Angle Direction (MAD) metric for data corrected by Block-Matching, HySCO, TOPUP and Voss and uncorrected data. Weak green means that p-value shows significant improvement with 10 ?3 < p-value < 5.10 ?2 , weak red means that p-value shows significant deterioration, BS: brain stem, p.48

, Dark green means that p-value shows significant improvement with p-value < 10 ?3 , weak green means that p-value shows also significant improvement but 10 ?3 < p-value < 5.10 ?2 . BS: brain stem, Mean and standard deviation multiplied by 10 2 for ACD metric for data corrected by Block-Matching, HySCO, TOPUP and Voss and uncorrected data

P. Tukey, . Block-matching, and . Hysco, Voss for Cross-correlation for the whole of the spinal cord region. Dark green means that p-value shows significant improvement and inferior to 10 ?3 , weak green means that p-value shows significant improvement but 10 ?3 < p-value < 5.10 ?2

P. Tukey, . Block-matching, and . Hysco, Voss for Mutual information for the whole of the spinal cord region. Dark green means that p-value shows significant improvement and inferior to 10 ?3 , weak green means that pvalue shows significant improvement but 10 ?3 < p-value < 5.10 ?2, p.50

, mm 3 ) of spinal cord, segmented mask, corrected by Block-Matching, HySCO, TOPUP, Voss and uncorrected. Dark red means that p-value shows significant difference and inferior to 10 ?3 , weak red means that p-value shows significant difference, vol.of every vertebral level

, Quantification of dMRI metrics approaches. PVE: Partial volume effect

, Demographic and clinical information for all participating subjects, healthy volunteers and MS patients in the EMISEP cohort

, Computed scalar and geometric metrics using both diffusion reconstruction models: 10 metrics

, Summary of the pairwise comparisons for each metric between all vertebrae levels for healthy volunteers data

C. For and . Levels, mean and STD of each metric for healthy volunteers, for MS patients with or without lesions and for MS patients with lesion >5%. Dark green means that there is a significant difference between healthy volunteers and MS patients and p-value is inferior to 10 ?2 , weak green means that p-value shows significant difference but 10 ?2 < p-value < 5.10 ?2 . n represents the number of vertebral level data available in [C2,C4] region.The unit of FWW, p.66

. .. , Proposed combinations of 2, 3 and 4 metrics to be studied, p.70

, The cumulative sum for percentage of variance explained by the 9 components of PCA fitted in [C2-C4] region. V is data of healthy volunteers, M S(thr) is data of MS patients patients possess lesion > thr% and ALL is data of all MS patients with/without lesion

, The 4th column presents the number of new lesions in spinal cord at M12. The 5th column presents the number of lesions in brain at baseline M0. Boxcolors mean MS patients with EDSS increase , with New lesion in SC at M12 and with EDSS increase + New lesion in SC at M12, EDSS score between baseline M0 and 12-months M12 follow-up

, Standard Deviation of difference between scan and re-scan, and Standard Deviation of scan and re-scan (multiplied by 1000) of DTI and Ball-and-Stick metrics averaged on each vertebral level. Diffusivities are measured in mm 2 /s, p.85

, MS patients with significant longitudinal evolution (SLE) for several metrics conjointly. Boxcolors means MS patients with EDSS increase , with New lesion in M12 and with EDSS increase + New lesion in M12

, Evolution of EDSS score between baseline M0 and 12-months M12 follow-up. The 4th column presents the number of new lesions in spinal cord at M12. The 5th column presents the number of lesions in brain at baseline M0, p.90

. .. Roc, 67 2 ROC AUC for a combination of metric

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, He got his baccalaureate degree from Abou ElKacem Chebbi school in Sfax in 2009, his engineering degree from École nationale d'ingénieurs de Sfax and École Centrale de Nantes in 2014 and his master degree from Pierre and Marie Curie University in co-habilitation with Télécom ParisTech in 2015, he joined Inria Rennes -Bretagne Atlantique research center as a PhD student, collaborating with Empenn (ex. VisAGeS) research Unit. This, 2015.