Assessing neuraxial microstructural changes in a transgenic mouse model of early stage Amyotrophic Lateral Sclerosis by ultra-high field MRI and diffusion tensor metrics

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Objective: Cell structural changes are one of the main features observed during the development of amyotrophic lateral sclerosis (ALS). In this work, we propose the use of diffusion tensor imaging (DTI) metrics to assess specific ultrastructural changes in the central nervous system during the early neurodegenerative stages of ALS. Methods: Ultra-high field MRI and DTI data at 17.6T were obtained from fixed, excised mouse brains, and spinal cords from ALS (G93A-SOD1) mice. Results: Changes in fractional anisotropy (FA) and linear, planar, and spherical anisotropy ratios (CL, CP, and CS, respectively) of the diffusion eigenvalues were measured in white matter (WM) and gray matter (GM) areas associated with early axonal degenerative processes (in both the brain and the spinal cord). Specifically, in WM structures (corpus callosum, corticospinal tract, and spinal cord funiculi) as the disease progressed, FA, CL, and CP values decreased, whereas CS values increased. In GM structures (prefrontal cortex, hippocampus, and central spinal cord) FA and CP decreased, whereas the CL and CS values were unchanged or slightly smaller. Histological studies of a fluorescent mice model (YFP, G93A-SOD1 mouse) corroborated the early alterations in neuronal morphology and axonal connectivity measured by DTI. Conclusions: Changes in diffusion tensor shape were observed in this animal model at the early, nonsymptomatic stages of ALS. Further studies of CL, CP, and CS as imaging biomarkers should be undertaken to refine this neuroimaging tool for future clinical use in the detection of the early stages of ALS.

Original languageEnglish (US)
Pages (from-to)117-129
Number of pages13
JournalAnimal Models and Experimental Medicine
Volume3
Issue number2
DOIs
StatePublished - Jun 2020

Keywords

  • G93A-SOD1 mice
  • amyotrophic lateral sclerosis
  • animal models
  • diffusion tensor imaging
  • ultra-high field MRI

ASJC Scopus subject areas

  • Medical Laboratory Technology
  • General Medicine
  • Molecular Biology
  • Biochemistry
  • veterinary (miscalleneous)
  • Medicine (miscellaneous)

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