Figure 1. Iron accumulates in subacute and chronic (but not acute) marmoset EAE lesions, inside microglia/macrophages, and in human MS lesions.

(A) In vivo MRI shows that once lesions are 6–8 weeks old, as determined by serial proton density-weighted (PDw) MRI (top row), they present a punctate hypointense signal on iron-sensitive T2*-weighted (T2*w) MRI (bottom row). (B) Intralesional hypointense signal on ex vivo T2*w MRI of the same lesion colocalizes with iron (DAB-Turnbull stain), as well as accumulation of microglia/macrophages (Iba1 immunohistochemistry) and demyelination (PLP immunohistochemistry). Note that the MRI section integrates over 100 μm of tissue and overemphasizes the extent of iron due to the “blooming artifact,” whereas the histopathological section is 5-μm thick, potentially accounting for apparent detailed discrepancies between the 2 images. (C) In vivo T2*-weighted MRI detects punctate hypointensity, suggesting iron deposition, in a representative white matter lesion in MS (red box). (D) Ex vivo T2*w MRI also detects intralesional hypointense foci in MS (red box). Histopathology confirms the presence of demyelination (PLP), as well as perivascular iron deposition (DAB-Turnbull), in MS, in a similar spatial pattern as observed in the marmoset EAE lesions. Scale bars: 100 μm for B, 20 μm for D. Counterstain: hematoxylin. Representative lesion from marmoset 1. Red box indicates magnified view on interpolated MRI.