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

Cardena et al., NeuroImage (2017) 15, 200-208.
In a collaborative study between the National Institute of Health, the University of Maryland and the
University of Michigan, researchers used a 7 tesla (high intensity) MRI to image the donated brains from
donors with ALS and compared the findings to those obtained from donors without ALS. Although the
motor symptoms in ALS patients are caused by pathology in the motor regions of the brain and spinal
cord, the nerve fibers connecting different regions in the two hemispheres of the brain (corpus callosum)
is consistently abnormal in many ALS imaging studies. The strength of the MRI magnet used in this
study was several times greater than what is typically used to image the brain in routine clinical practice.
Also, each brain was imaged continuously for 23 hours to obtain the extensive data needed for analysis.
The focus of this study were several fold: first, it was to establish that high resolution MRI on
postmortem ALS brain is feasible; second, it confirmed the previously described changes in the corpus
callosum using a high resolution MRI; and third, it allowed for an understanding of the microscopic
abnormalities that underlie the alterations observed on the MRI.
The greater detail of the MRI analysis provided data confirming that the nerve fibers connecting the
motor regions of the two hemispheres were more disorganized. When the tissue was analyzed
microscopically, there was increased microglia-macrophages, which are signs of inflammation, and a loss
of myelinated axons of neurons. The findings indicate that the MRI abnormalities are the result of
complex changes on a microscopic level. Future research will address the exact sequence of the
observed changes so that treatments can be developed to interact at the earliest point.
Dr. Justin Kwan who is a co-author of the paper discusses the importance of tissue donation with his
patients. Several of his patients were included in this study. The spinal cord, brain and muscle samples
are recovered by the University of Maryland Brain and Tissue Bank, which is supported by a grant from
the Blazeman Foundation. Both the Blazeman Foundation and the Brain and Tissue Bank are
acknowledged in the article.

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Comment by blazedad on July 16, 2017 at 3:49pm

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ALS Tissue Donation Program Impacts Research


In a collaborative study between the National Institute of Health, the University of Maryland and the University of Michigan, researchers used a 7 tesla (high intensity) MRI to image the donated brains from donors with ALS and compared the findings to those obtained from donors without ALS. The spinal cord, brain and muscle samples used in the study were recovered by the University of Maryland Brain and Tissue Bank, which is supported by a grant from the Blazeman Foundation. Dr. Kwan (co-author) provides a summary of the study. For a more in-depth analysis, read the journal article from NeuroImage: Clinical 15 (2017) 200-208.


Comment by blazedad on July 13, 2017 at 1:16pm

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-fi xed

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.

Comment by blazedad on July 12, 2017 at 1:39pm
Comment by blazedad on July 12, 2017 at 1:17pm

The spinal cord, brain and muscle samples

are recovered by the University of Maryland Brain and Tissue Bank, which is supported by a grant from
the Blazeman Foundation. Both the Blazeman Foundation and the Brain and Tissue Bank are
acknowledged in the article.

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