Pathology of callosal damage in ALS: An ex-vivo, 7 T diffusion tensor MRI study

OBJECTIVES: The goal of this study was to better understand the changes in tissue microstructure that underlie white matter diffusion changes in ALS patients. METHODS: Diffusion tensor imaging was carried out in postmortem brains of 4 ALS patients and two subjects without neurological disease on a 7 T MRI scanner using steady-state free precession sequences. Fractional anisotropy (FA) was measured in the genu, body, and splenium of the corpus callosum in formalin-fixed hemispheres. FA of the body and genu was expressed as ratio to FA of the splenium, a region unaffected in ALS. After imaging, tissue sections of the same segments of the callosum were stained for markers of different tissue components. Coded image fields were rated for pathological changes by blinded raters. RESULTS: mutations, and increased reactive astrocytes throughout the callosum. CONCLUSION: Reduced FA of the corpus callosum in ALS results from complex changes in tissue microstructure. Callosal segments with reduced FA had large numbers of microglia-macrophages in addition to loss of myelinated axons and astrogliosis. Microglial inflammation contributed to reduced FA in ALS, and may contribute to a pro-inflammatory state, but further work is needed to determine their role.