Journal
AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION
Volume 20, Issue 7-8, Pages 549-561Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/21678421.2019.1620285
Keywords
Amyotrophic lateral sclerosis; diffusion tensor imaging; neurite orientation dispersion and density imaging; diffusion kurtosis imaging; transgenic animals; yellow fluorescence protein; G93A-SOD1 mice; neuronal degeneration
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Funding
- High Magnetic Field Laboratory (NHMFL) under Magnetic Laboratory Visiting Scientist Program [278]
- Advanced Magnetic Resonance Imaging and Spectroscopy (AMRIS) under Magnetic Laboratory Visiting Scientist Program [278]
- National Science Foundation (NSF) [DMR-1644779]
- State of Florida
- National Institutes of Health (NIH) [DK101675]
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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.
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