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Ultra-High Field Diffusion MRI Reveals Early Axonal Pathology in Spinal Cord of ALS mice.
Transl Neurodegener. 2018; 7:20.TN

Abstract

Background

Amyotrophic lateral sclerosis (ALS) is a disease characterized by a progressive degeneration of motor neurons leading to paralysis. Our previous MRI diffusion tensor imaging studies detected early white matter changes in the spinal cords of mice carrying the G93A-SOD1 mutation. Here, we extend those studies using ultra-high field MRI (17.6 T) and fluorescent microscopy to investigate the appearance of early structural and connectivity changes in the spinal cords of ALS mice.

Methods

The spinal cords from presymptomatic and symptomatic mice (80 to 120 days of age) were scanned (ex-vivo) using diffusion-weighted MRI. The fractional anisotropy (FA), axial (AD) and radial (RD) diffusivities were calculated for axial slices from the thoracic, cervical and lumbar regions of the spinal cords. The diffusion parameters were compared with fluorescence microscopy and membrane cellular markers from the same tissue regions.

Results

At early stages of the disease (day 80) in the lumbar region, we found, a 19% decrease in FA, a 9% decrease in AD and a 35% increase in RD. Similar changes were observed in cervical and thoracic spinal cord regions. Differences between control and ALS mice groups at the symptomatic stages (day 120) were larger. Quantitative fluorescence microscopy at 80 days, demonstrated a 22% reduction in axonal area and a 22% increase in axonal density. Tractography and quantitative connectome analyses measured by edge weights showed a 52% decrease in the lumbar regions of the spinal cords of this ALS mice group. A significant increase in ADC (23.3%) in the ALS mice group was related to an increase in aquaporin markers.

Conclusions

These findings suggest that the combination of ultra-high field diffusion MRI with fluorescent ALS mice reporters is a useful approach to detect and characterize presymptomatic white matter micro-ultrastructural changes and axonal connectivity anomalies in ALS.

Authors+Show Affiliations

1Department of Anatomy and Cell Biology, University of Illinois at Chicago, 808 S. Wood St. Rm 578 M/C 512, Chicago, IL 60612 USA.2Department of Physics, University of Florida, Gainesville, FL USA.2Department of Physics, University of Florida, Gainesville, FL USA.3Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL USA.4Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL USA.5Department of Bioengineering, University of Illinois at Chicago, Chicago, IL USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30128146

Citation

Gatto, Rodolfo G., et al. "Ultra-High Field Diffusion MRI Reveals Early Axonal Pathology in Spinal Cord of ALS Mice." Translational Neurodegeneration, vol. 7, 2018, p. 20.
Gatto RG, Amin MY, Deyoung D, et al. Ultra-High Field Diffusion MRI Reveals Early Axonal Pathology in Spinal Cord of ALS mice. Transl Neurodegener. 2018;7:20.
Gatto, R. G., Amin, M. Y., Deyoung, D., Hey, M., Mareci, T. H., & Magin, R. L. (2018). Ultra-High Field Diffusion MRI Reveals Early Axonal Pathology in Spinal Cord of ALS mice. Translational Neurodegeneration, 7, 20. https://doi.org/10.1186/s40035-018-0122-z
Gatto RG, et al. Ultra-High Field Diffusion MRI Reveals Early Axonal Pathology in Spinal Cord of ALS Mice. Transl Neurodegener. 2018;7:20. PubMed PMID: 30128146.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ultra-High Field Diffusion MRI Reveals Early Axonal Pathology in Spinal Cord of ALS mice. AU - Gatto,Rodolfo G, AU - Amin,Manish Y, AU - Deyoung,Daniel, AU - Hey,Matthew, AU - Mareci,Thomas H, AU - Magin,Richard L, Y1 - 2018/08/08/ PY - 2018/03/12/received PY - 2018/07/02/accepted PY - 2018/8/22/entrez PY - 2018/8/22/pubmed PY - 2018/8/22/medline KW - Amyotrophic Lateral Sclerosis KW - Axonal Degeneration KW - Connectomics KW - Diffusion Tensor Imaging KW - G93A-SOD1 mice KW - Spinal Cord KW - Tractography KW - Ultra-high Field MRI KW - Yellow Fluorescent Protein SP - 20 EP - 20 JF - Translational neurodegeneration JO - Transl Neurodegener VL - 7 N2 - Background: Amyotrophic lateral sclerosis (ALS) is a disease characterized by a progressive degeneration of motor neurons leading to paralysis. Our previous MRI diffusion tensor imaging studies detected early white matter changes in the spinal cords of mice carrying the G93A-SOD1 mutation. Here, we extend those studies using ultra-high field MRI (17.6 T) and fluorescent microscopy to investigate the appearance of early structural and connectivity changes in the spinal cords of ALS mice. Methods: The spinal cords from presymptomatic and symptomatic mice (80 to 120 days of age) were scanned (ex-vivo) using diffusion-weighted MRI. The fractional anisotropy (FA), axial (AD) and radial (RD) diffusivities were calculated for axial slices from the thoracic, cervical and lumbar regions of the spinal cords. The diffusion parameters were compared with fluorescence microscopy and membrane cellular markers from the same tissue regions. Results: At early stages of the disease (day 80) in the lumbar region, we found, a 19% decrease in FA, a 9% decrease in AD and a 35% increase in RD. Similar changes were observed in cervical and thoracic spinal cord regions. Differences between control and ALS mice groups at the symptomatic stages (day 120) were larger. Quantitative fluorescence microscopy at 80 days, demonstrated a 22% reduction in axonal area and a 22% increase in axonal density. Tractography and quantitative connectome analyses measured by edge weights showed a 52% decrease in the lumbar regions of the spinal cords of this ALS mice group. A significant increase in ADC (23.3%) in the ALS mice group was related to an increase in aquaporin markers. Conclusions: These findings suggest that the combination of ultra-high field diffusion MRI with fluorescent ALS mice reporters is a useful approach to detect and characterize presymptomatic white matter micro-ultrastructural changes and axonal connectivity anomalies in ALS. SN - 2047-9158 UR - https://www.unboundmedicine.com/medline/citation/30128146/Ultra_High_Field_Diffusion_MRI_Reveals_Early_Axonal_Pathology_in_Spinal_Cord_of_ALS_mice_ L2 - https://translationalneurodegeneration.biomedcentral.com/articles/10.1186/s40035-018-0122-z DB - PRIME DP - Unbound Medicine ER -
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