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

GATTO, RODOLFO G.; WEISSMANN, CARINA; AMIN, MANISH; FINKIELSZTEIN, ARIEL; SUMAGIN, RONEN; MARECI, THOMAS H.; UCHITEL, OSVALDO D.; MAGIN, RICHARD L.

Animal Models and Experimental Medicine

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Año: 2020 vol. 3 p. 117 - 129

2576-2095

Objective: Cell structural changes are one of the main features observed during thedevelopment of amyotrophic lateral sclerosis (ALS). In this work, we propose the useof diffusion tensor imaging (DTI) metrics to assess specific ultrastructural changes inthe 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, excisedmouse brains, and spinal cords from ALS (G93A-SOD1) mice.Results: Changes in fractional anisotropy (FA) and linear, planar, and spherical anisotropyratios (CL, CP, and CS, respectively) of the diffusion eigenvalues were measuredin white matter (WM) and gray matter (GM) areas associated with early axonaldegenerative processes (in both the brain and the spinal cord). Specifically, in WMstructures (corpus callosum, corticospinal tract, and spinal cord funiculi) as the diseaseprogressed, FA, CL, and CP values decreased, whereas CS values increased.In GM structures (prefrontal cortex, hippocampus, and central spinal cord) FA andCP d ecreased, w hereas t he C L a nd C S values were unchanged or slightly smaller.Histological studies of a fluorescent mice model (YFP, G93A-SOD1 mouse) corroboratedthe early alterations in neuronal morphology and axonal connectivity measuredby DTI.Conclusions: Changes in diffusion tensor shape were observed in this animal modelat the early, nonsymptomatic stages of ALS. Further studies of CL, CP, and CS as imagingbiomarkers should be undertaken to refine this ne