In vivo diffusion MRI detects early spinal cord axonal pathology in a mouse model of amyotrophic lateral sclerosis. (26th June 2018)

• Record Type: Journal Article
• Authors: Gatto, Rodolfo G.; Li, Weiguo; Gao, Jin; Magin, Richard L.
• Is Part Of: NMR in biomedicine. Volume 31:Number 8(2018)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2018-06-26
• Subjects: amyotrophic lateral sclerosis -- axonal degeneration -- diffusion tensor imaging -- G93A‐SOD1 mice -- MRI -- spinal cord; Nuclear magnetic resonance -- Periodicals; Magnetic Resonance Spectroscopy -- Periodicals; 574
• DOI: 10.1002/nbm.3954
• Languages: English
• ISSNs: 0952-3480

Abstract

Abstract : Diffusion magnetic resonance imaging (MRI) exhibits contrast that identifies macro‐ and microstructural changes in neurodegenerative diseases. Previous studies have shown that MR diffusion tensor imaging (DTI) can observe changes in spinal cord white matter in animals and humans affected with symptomatic amyotrophic lateral sclerosis (ALS). The goal of this preclinical work was to investigate the sensitivity of DTI for the detection of signs of tissue damage before symptoms appear. High‐field MRI data were acquired using a 9.4‐T animal scanner to examine the spinal cord of an ALS mouse model at pre‐ and post‐symptomatic stages (days 80 and 120, respectively). The MRI results were validated using yellow fluorescent protein (YFP) via optical microscopy of spinal cord tissue slices collected from the YFP, G93A‐SOD1 mouse strain. DTI maps of diffusion‐weighted imaging (DWI) signal intensity, mean diffusivity (MD), fractional anisotropy (FA), axial diffusivity (AD) and radial diffusivity (RD) were computed for axial slices of the lumbar region of the spinal cord. Significant changes were observed in FA (6.7% decrease, p < 0.01), AD (19.5% decrease, p < 0.01) and RD (16.1% increase, p < 0.001) at postnatal day 80 (P80). These differences were correlated with changes in axonal fluorescence intensity and membrane cellular markers. This study demonstrates the value of DTI as a potential tool to detect the underlying pathological progression associated with ALS, and may accelerate the discovery of therapeutic strategies for patients with this disease. Abstract : Magnetic resonance imaging (MRI) and diffusion tensor imaging can detect presymptomatic in vivo changes in amyotrophic lateral sclerosis (ALS) mouse spinal cord (G93A‐SOD1). A progressive distal to proximal axonal degeneration represents one of the key pathological features of the disease. Diffusion anomalies are associated with early histological alterations.