Fig. 2

MRI techniques detect progression of corpus callosum (CC) pathology during acute through chronic cuprizone (CPZ). a: Experimental timeline for longitudinal in vivo magnetic resonance imaging (MRI) of the same mice scanned three times: at baseline (BL, 8 weeks of age prior to the start of CPZ), again after acute CPZ (6 weeks) and finally after chronic CPZ (12 weeks). Naïve mice were scanned at matched time points but continuously fed normal chow pellets without CPZ. CC region-of-interest (ROI) for quantification shown in yellow with DAPI nuclear staining of cytoarchitecture. b: Representative T2-weighted images with corresponding direction encoded (DEC) color images below for each set. T2 panels show increased signal intensity in the CC during acute and chronic CPZ while DEC maps show altered CC microstructure, as compared to naïve mice (age-matched to the 12 week CPZ time point). Arrows indicate medial CC regions that show CPZ effect. Colors represent fiber directions as red (medial-lateral), blue (anterior-posterior), and green (superior-inferior). c-h: Quantitative analysis of the CC shows significant differences between naïve and CPZ mice at both 6 weeks and 12 weeks after the start of CPZ using values from T2-weighted imaging (c), magnetization transfer ratio (MTR, d), and diffusion tensor imaging parameters of trace (e), fractional anisotropy (FA; f), and radial diffusivity (RD; h). Axial diffusivity (AD, g) remained unchanged. Bar color reflects the treatment condition. The naïve cohort (white; no cuprizone shown as “-“under bars) was scanned along with the CPZ cohort at each of the three time points. The CPZ cohort was scanned at baseline (gray; “-“before starting CPZ) and during demyelination (black; at 6 and 12 weeks of CPZ). Data are mean values ± sem. Two-way ANOVA with repeated measures and Bonferroni multiple comparisons test for naïve (n = 6) versus CPZ (n = 6) mice