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. 2016 Jun 6;126(7):2597–2609. doi: 10.1172/JCI86198

Figure 6. MRI/pathology of demyelinated lesions with persistent phase rim.

Figure 6

Images shown are from lesions 2 and 3 in Figure 8. (A) In vivo and postmortem 7T MRI shows 2 periventricular lesions with persistent phase rims that become partially confluent over time as the lesion expands (between 2006 and 2013). The rims were visible on an in vivo 7T MRI in 2013 (not shown), as well as postmortem (red arrows). On the in vivo 7T 3D T1-MPRAGE (2013), these lesions appear strongly hypointense (mean lesion T1 intensity values, respectively: –25.1 and –21.2 in units of SD of normal-appearing white matter signal; mean cerebrospinal fluid T1 intensity: –29.9). Scale bar: 5 mm. (B) In vivo and postmortem MRI-guided histopathology allowed precise localization of the target area. MRI-matched thumbnails of representative serial sections (10-μm-thick sections) show the Luxol fast blue/periodic acid–Schiff (LFB-PAS) stain for myelin, myelin proteolipid protein (PLP) immunohistochemistry, and Bielschowsky staining for axons. Insets i–v are indicated as red squares on the thumbnails to facilitate their localization and the interpretation of the pathological data. Both lesions were completely demyelinated. (i–iii) The lesion edge, where the phase rim was detected on MRI, is characterized by the presence of an extensive CD68-positive cellular infiltrate, corresponding to macrophages/activated microglia (inflammatory infiltrate thickness ~200–400 μm). Luxol fast blue–positive myelin debris (cyan, black arrows) and late myelin degradation products (lipofuscin, purple) can be seen within macrophages at the lesion edge, suggesting ongoing demyelination (ii). The majority of CD68-positive cells also stained positive by the DAB-Turnbull method, indicating the intracellular accumulation of iron (iii). (iv and v) Extensive axonal loss with transection and dystrophy of the remaining axons is seen throughout the lesion center (v). At the lesion edge, some axons were better preserved, and fiber bundles could be discerned (iv). Scale bars: 200 μm (i); 10 μm (ii); 50 μm (iii–v).