Ultra-High Field Diffusion MRI Reveals Early Axonal Pathology in Spinal Cord of ALS mice

Translational Neurodegeneration

Rodolfo G. Gatto¹  Matthew Hey²  Thomas H. Mareci³  Richard L. Magin⁴  Manish Y. Amin⁵  Daniel Deyoung⁵ 

[1] Department of Anatomy and Cell Biology, University of Illinois at Chicago;Department of Applied Physiology and Kinesiology, University of Florida;Department of Biochemistry and Molecular Biology, University of Florida;Department of Bioengineering, University of Illinois at Chicago;Department of Physics, University of Florida;

关键词: Amyotrophic Lateral Sclerosis;    Spinal Cord;    Ultra-high Field MRI;    Diffusion Tensor Imaging;    Yellow Fluorescent Protein;    G93A-SOD1 mice;   

DOI  :  10.1186/s40035-018-0122-z

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown