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Reference: Cardenas, AM, Sarlls, JE, Kwan, JY et al., (2017). Pathology of callosal damage in ALS: an ex-vivo , 7 T diffusion tensor MRI study. NeuroImage: Clinical, 15, 200-208.Citable link to this page:


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

Abstract: 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.

Publication status:PublishedPeer Review status:Peer reviewedVersion:Publisher's versionDate of acceptance:2017-04-25 Funder: National Institutes of Health   Notes:This is an open access article under the CC BY license (

Bibliographic Details

Publisher: Elsevier

Publisher Website:

Journal: NeuroImage: Clinicalsee more from them

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Volume: 15

Issue Date: 2017-04-30



Issn: 2213-1582

Uuid: uuid:549baf76-170a-46d6-b23d-1f1e58373888

Urn: uri:549baf76-170a-46d6-b23d-1f1e58373888

Pubs-id: pubs:697167 Item Description

Type: journal-article;

Version: Publisher's versionKeywords: 7 T MRI Amyotrophic lateral sclerosis Microglia Motor neuron disease Pathology Steady-state free precession


Autor: Cardenas, AM - - - Sarlls, JE - - - Kwan, JY - - - Bageac, D - - - Gala, ZS - - - Danielian, LE - - - Ray-Chaudhury, A - - - Wang



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