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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: The FA body/FA splenium ratio was reduced in ALS patients compared to controls. Patchy areas of myelin pallor and cells immunostained for CD68, a microglial-macrophage marker, were only observed in the body of the callosum of ALS patients. Blinded ratings showed increased CD68 + microglial cells in the body of the corpus callosum in ALS patients, especially those with C9orf72 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.

Original publication

DOI

10.1016/j.nicl.2017.04.024

Type

Journal article

Journal

Neuroimage Clin

Publication Date

2017

Volume

15

Pages

200 - 208

Keywords

7 T MRI, AD, axial diffusivity, ALS, Amyotrophic lateral sclerosis, Amyotrophic lateral sclerosis, DTI, diffusion tensor imaging, DW-SSFP, Diffusion Weighted Steady State Free Precession, DWI, diffusion weighted imaging, FA, fractional anisotropy, GFAP, glial fibrillary acidic protein, MD, mean diffusivity, MRI, magnetic resonance imaging, Microglia, Motor neuron disease, PMI, post mortem interval, PSI, scan interval (death to scan), Pathology, RD, radial diffusivity, SNR, signal to noise ratio, Steady-state free precession, VOI, volume of interest