Fig. 5: Detection of rBRLs using TSPO PET.
a, Detection of rBRLs versus non-BRLs using TSPO PET. Examples of rBRL, non-rBRL rim-active and inactive lesions are shown (labeled as HH, HL and LL, respectively). The color bar shows the dynamic range of DVR in the images. b, Patients with no, one or more than one rBRL. c, Violin plot of the proportion of rBRLs in patients with at least one rBRL. d, Total lesion numbers were higher in patients with at least one rBRL (P = 1.1 × 10−6; Mann–Whitney U-test). e,f, Proportion of rBRLs correlated with the proportion of TSPO PET rim-active lesions (e) (P = 0.0005) and inversely with the proportion of TSPO PET inactive lesions (f) (P = 1.1 × 10−8) (Spearman correlation). g–i, Proportions of rBRL correlated with T1 (g) (P = 4.5 × 10−7) and T2 (h) lesion loads (P = 4.9 × 10−8) in MRI and with NAWM DVR (i) (P = 4.5 × 10−7) in TSPO PET (Spearman correlation). j–m, FA in NAWM (j,k) correlated negatively and MD in NAWM (l) correlated positively with rBRL proportions (Spearman correlation); rBRL patients had lower FA (k) P = 0.006) and higher MD values (m) (P = 0.039) in NAWM (Welch’s t-test). n, Patients (n = 41) with at least one rBRL had slightly higher numbers of QSM+ rim lesions (P = 0.087; Mann–Whitney U-test). o, Violin plot of age at disease onset in patients with and without rBRLs. An unpaired t-test was used. p,q, Proportions of patients treated with DMTs (Fisher’s exact test) (p) and annual relapse rate (q) in patients with and without rBRLs (Mann–Whitney U-test). r, Proportion of SPMS in patients with and without rBRL (P = 0.075; Fisher’s exact test). s, Disease duration in patients with and without rBRL (P = 0.044; Mann–Whitney U-test). t,u, EDSS milestones (EDSS 4 or 6 within 12 years) in patients with rBRL, non-rBRL rim-active lesion or neither (t, P = 0.028; u, P = 0.006). A Fisher’s exact test was used. v, Higher EDSS in patients with rBRL (P = 0.005; Dunn’s test) but not non-rBRL rim-active lesions compared to those without these lesion types (Kruskal–Wallis test, P = 0.006). w,x, Changes in rBRL numbers in natalizumab-treated (w) (n = 9) and untreated (x) MS patients (n = 9). y, Natalizumab and untreated cohorts in w,x had a significant difference in the change in rBRL numbers (P = 0.021; Mann–Whitney U-test). All tests used in this figure are two-tailed. *P ≤ 0.05; **P ≤ 0.01; ****P < 0.0001.
