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

• Published in: NeuroImage clinical Vol. 15; pp. 200 - 208
• Main Authors: Cardenas, Agustin M, Sarlls, Joelle E, Kwan, Justin Y, Bageac, Devin, Gala, Zachary S, Danielian, Laura E, Ray-Chaudhury, Abhik, Wang, Hao-Wei, Miller, Karla L, Foxley, Sean, Jbabdi, Saad, Welsh, Robert C, Floeter, Mary Kay
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier 01.01.2017
• Subjects: Adult; Aged; Amyotrophic Lateral Sclerosis - diagnostic imaging; Amyotrophic Lateral Sclerosis - pathology; Corpus Callosum - diagnostic imaging; Corpus Callosum - pathology; Diffusion Tensor Imaging - methods; Female; Humans; Male; Middle Aged; Radiology; Regular; magnetic resonance imaging; Diffusion Weighted Steady State Free Precession; MRI; Motor neuron disease; ALS; volume of interest; diffusion weighted imaging; 7 T MRI; scan interval (death to scan); SNR; DWI; MD; DW-SSFP; axial diffusivity; mean diffusivity; AD; radial diffusivity; PSI; Amyotrophic lateral sclerosis; PMI; GFAP; Microglia; VOI; Pathology; Steady-state free precession; RD; DTI; diffusion tensor imaging; fractional anisotropy; FA; glial fibrillary acidic protein; signal to noise ratio; post mortem interval; 7 T MRI; FA, fractional anisotropy; GFAP, glial fibrillary acidic protein; PSI, scan interval (death to scan); DWI, diffusion weighted imaging; ALS, Amyotrophic lateral sclerosis; PMI, post mortem interval; RD, radial diffusivity; MRI, magnetic resonance imaging; DW-SSFP, Diffusion Weighted Steady State Free Precession; MD, mean diffusivity; AD, axial diffusivity; SNR, signal to noise ratio; DTI, diffusion tensor imaging; VOI, volume of interest
• ISSN: 2213-1582; 2213-1582
• DOI: 10.1016/j.nicl.2017.04.024

AbstractObjectivesThe goal of this study was to better understand the changes in tissue microstructure that underlie white matter diffusion changes in ALS patients. MethodsDiffusion 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. ResultsThe 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. ConclusionReduced 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.