Unveiling early cortical and subcortical neuronal degeneration in ALS mice by ultra-high field diffusion MRI

Rodolfo G. Gatto*, Manish Amin, Ariel Finkielsztein, Carina Weissmann, Thomas Barrett, Caroline Lamoutte, Osvaldo Uchitel, Ronen Sumagin, Thomas H. Mareci, Richard L. Magin

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease primarily characterized by the progressive impairment of motor functions. However, a significant portion of affected patients develops severe cognitive dysfunction, developing a widespread white (WM) and gray matter (GM) microstructural impairment. The objective of this study is to determine if Gaussian and non-Gaussian diffusion models gathered by ultra-high field diffusion MRI (UHFD-MRI) are an appropriate tool to detect early structural changes in brain white and gray matter in a preclinical model of ALS. ALS brains (G93A-SOD1mice) were scanned in a 16.7 T magnet. Diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) have shown presymptomatic decrease in axonal organization by Fractional Anisotropy (FA) and neurite content by Intracellular Volume Fraction (ICVF) across deep WM (corpus callosum) as well as superficial (cortex) and deep (hippocampus) GM. Additional diffusion kurtosis imaging (DKI) analysis demonstrated broader and earlier GM reductions in mean kurtosis (MK), possibly related to the decrease in neuronal complexity. Histological validation was obtained by an ALS fluorescent mice reporter (YFP, G93A-SOD1 mice). The combination of DTI, NODDI, and DKI models have proved to provide a more complete assessment of the early microstructural changes in the ALS brain, particularly in areas associated with high cognitive functions. This comprehensive approach should be considered as a valuable tool for the early detection of neuroimaging markers.

Original languageEnglish (US)
Pages (from-to)549-561
Number of pages13
JournalAmyotrophic Lateral Sclerosis and Frontotemporal Degeneration
Issue number7-8
StatePublished - Oct 2 2019


  • Amyotrophic lateral sclerosis
  • G93A-SOD1 mice
  • diffusion kurtosis imaging
  • diffusion tensor imaging
  • neurite orientation dispersion and density imaging
  • neuronal degeneration
  • transgenic animals
  • yellow fluorescence protein

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology


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