FIGURE 1.

Schematic outline of key steps in the magnetic resonance imaging (MRI) and histology processing and analysis. Top panel (A): matching ex vivo MRI with histology. Lesions of interest were identified on ex vivo MRI (A). Based on anatomical landmarks, each brain slab was then visually matched with the corresponding MRI slice (B), and tissue blocks were excised and embedded in paraffin. MRI slices were cropped and oriented to best match the corresponding histological section (C). Tissue samples were processed, stained for myelin (LFB‐PAS, Luxol fast blue–periodic acid Schiff) and axons (Bielschowsky's silver stain), digitized at 10× magnification, and then cropped in a similar fashion (D). Stained sections and MRI were coregistered using a 2D nonrigid thin‐plate spline approach (E). Scale bar: 1 cm. Bottom panel (B): in vivo workflow. Gadolinium‐enhancing lesions were identified on T1‐weighted images and confirmed on 3 T FLAIR images. Three tesla images were coregistered with 7 T MP2RAGE images. Hypointense lesions were manually segmented on 3 T T1‐weighted images. Finally, lesions were assessed visually for qualitative classification, and regions of interest were manually delineated for T1 time computation. [Color figure can be viewed at www.annalsofneurology.org]