Person:

Khalid, Fariha

Background: The reliable and efficient measurement of spinal cord atrophy is of growing interest in monitoring disease progression in multiple sclerosis (MS). Methods: We compared T1- and T2-weighted MRI for measuring cervical spinal cord volume in 31 patients with MS and 18 age-matched controls (NC) from T1-weighted gradient recalled echo and T2-weighted fast spin-echo 1.5 T axial acquisitions. The two sequences were matched on slice thickness, signal averages and voxel size. An active surface software tool determined the normalized mean cervical cord cross-sectional area. Results: T1-derived cord areas were higher than T2 areas in the whole cohort (estimated mean difference = 7.03 mm2 (8.89 %); 95 % Confidence Interval (CI): 5.91, 8.14; p < 0.0001) and in both groups separately. There were trends for lower spinal cord areas in MS vs. NC with both sequences. For the T1 cord area, the mean difference was 3.7 mm2 (4.55 %) (95 % CI: −1.36, 8.78; p = 0.15). For the T2 cord area, the difference was larger [mean difference 4.9 mm2 (6.52 %) (95 % CI: −0.83, 10.67); p = 0.091]. The T1 and T2 cord areas showed similar weak to moderate correlations with measures of clinical status and T2 spinal cord lesion volume in the MS group. Superficial spinal cord T2 lesions had no apparent confounding effect on the outlining tool. The mean intra-rater and inter-rater coefficients of variation ranged from 0.27 to 0.91 % for T1- and 0.66 to 0.99 % for T2-derived cord areas. Conclusion: T2-weighted images may prove efficient for measuring cervical spinal cord atrophy in MS, with the added advantage of lesion detectability.

Assess the sensitivity of the Magnetic Resonance Disease Severity Scale (MRDSS), based on cerebral lesions and atrophy, for treatment monitoring of glatiramer acetate (GA) in relapsing-remitting multiple sclerosis (MS). This retrospective non-randomized pilot study included patients who started daily GA [n = 23, age (median, range) 41 (26.2, 53.1) years, Expanded Disability Status Scale (EDSS) score 1.0 (0, 3.5)], or received no disease-modifying therapy (noDMT) [n = 21, age 44.8 (28.2, 55.4), EDSS 0 (0, 2.5)] for 2 years. MRDSS was the sum of z-scores (normalized to a reference sample) of T2 hyperintense lesion volume (T2LV), the ratio of T1 hypointense LV to T2LV (T1/T2), and brain parenchymal fraction (BPF) multiplied by negative 1. The two groups were compared by Wilcoxon rank sum tests; within group change was assessed by Wilcoxon signed rank tests. Glatiramer acetate subjects had less progression than noDMT on T1/T2 [(median z-score change (range), 0 (−1.07, 1.20) vs. 0.41 (−0.30, 2.51), p = 0.003)] and MRDSS [0.01 (−1.33, 1.28) vs. 0.46 (−1.57, 2.46), p = 0.01]; however, not on BPF [0.12 (−0.18, 0.58) vs. 0.10 (−1.47,0.50), p = 0.59] and T2LV [−0.03 (−0.90, 0.57) vs. 0.01 (−1.69, 0.34), p = 0.40]. While GA subjects worsened only on BPF [0.12 (−0.18, 0.58), p = 0.001], noDMT worsened on BPF [0.10 (−1.47, 0.50), p = 0.002], T1/T2 [0.41 (−0.30, 2.51), p = 0.0002], and MRDSS [0.46 (−1.57, 2.46), p = 0.0006]. These preliminary findings show the potential of two new cerebral MRI metrics to track MS therapeutic response. The T1/T2, an index of the destructive potential of lesions, may provide particular sensitivity to treatment effects.

Background: Spinal cord atrophy occurs early in multiple sclerosis (MS) and impacts disability. The therapeutic effect of interferon beta-1a (IFNβ-1a) on spinal cord atrophy in patients with relapsing-remitting (RR) MS has not been explored. Methods: We retrospectively identified 16 consecutive patients receiving weekly intramuscular IFNβ-1a for 2 years [baseline age (mean ± SD) 47.7 ± 7.5 years, Expanded Disability Status Scale score median (range) 1.5 (0–2.5), timed 25-foot walk 4.6 ± 0.7 seconds; time on treatment 68.3 ± 59.9 months] and 11 sex- and age-matched normal controls (NC). The spinal cord was imaged at baseline, 1 and 2 years later with 3T MRI. C1-C5 spinal cord volume was measured by an active surface method, from which normalized spinal cord area (SCA) was calculated. Results: SCA showed no change in the MS or NC group over 2 years [mean annualized difference (95 % CI) MS: −0.604 mm2 (−1.352, 0.144), p = 0.106; NC: −0.360 mm2 (−1.576, 0.855), p = 0.524]. Between group analysis indicated no differences in on-study SCA change [MS vs. NC; year 1 vs. baseline, mean annualized difference (95 % CI) 0.400 mm2 (−3.350, 2.549), p = 0.780; year 2 vs. year 1: −1.196 mm2 (−0.875, 3.266), p = 0.245; year 2 vs. baseline −0.243 mm2 (−1.120, 1.607), p = 0.712]. Conclusion: Established IFNβ-1a therapy was not associated with ongoing spinal cord atrophy or any difference in the rate of spinal cord volume change in RRMS compared to NC over 2 years. These results may reflect a treatment effect. However, due to sample size and study design, these results should be considered preliminary and await confirmation.

Background: Whole brain atrophy is a putative outcome measure in monitoring relapsing-remitting multiple sclerosis (RRMS). With the ongoing MRI transformation from 1.5T to 3T, there is an unmet need to calibrate this change. We evaluated brain parenchymal volumes (BPVs) from 1.5T versus 3T in MS and normal controls (NC). Methods: We studied MS [n = 26, age (mean, range) 43 (21-55), 22 (85%) RRMS, Expanded Disability Status Scale (EDSS) 1.98 (0-6.5), timed 25 foot walk (T25FW) 5.95 (3.2-33.0 seconds)] and NC [n = 9, age 45 (31-53)]. Subjects underwent 1.5T (Phillips) and 3T (GE) 3-dimensional T1-weighted scans to derive normalized BPV from an automated SIENAX pipeline. Neuropsychological testing was according to consensus panel recommendations. Results: BPV-1.5T was higher than BPV-3T [mean (95% CI) + 45.7 mL (+35.3, +56.1), P < .00001], most likely due to improved tissue-CSF contrast at 3T. BPV-3T showed a larger volume decrease and larger effect size in detecting brain atrophy in MS versus NC [-74.5 mL (-126.5, -22.5), P = .006, d = .92] when compared to BPV-1.5T [-51.3.1 mL (-99.8, -2.8), P = .04, d = .67]. Correlations between BPV-1.5T and EDSS (r = -.43, P = .027) and BPV-3T and EDSS (r = -.49, P = .011) and between BPV-1.5T and T25FW (r = -.46, P = .018) and BPV-3T and T25FW (r = -.56, P = .003) slightly favored 3T. BPV-cognition correlations were significant (P < .05) for 6 of 11 subscales to a similar degree at 1.5T (r range = .44-.58) and 3T (r range = .43-.53). Conclusions: Field strength may impact whole brain volume measurements in patients with MS though the differences are not too divergent between 1.5T and 3T.