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In vivo Diffusion MRI Detects Early Changes in Spinal Cord Axonal Pathology in a Mouse Model of Amyotrophic Lateral Sclerosis

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posted on 14.01.2019 by Rodolfo G. Gatto, Weiguo Li, Jin Gao, Richard L. Magin
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.

Funding

Expenses associated with the use of the Agilent 9.4T scanner at the UIC Research Resource Center at UIC were covered by the Postdoctoral research grant from the Chicago Biomedical Consortium (CBC) to RG [Award #085740].

History

Publisher Statement

This is the pre-peer reviewed version of the following article:Gatto, R. G., Li, W. G., Gao, J., & Magin, R. L. (2018). In vivo diffusion MRI detects early spinal cord axonal pathology in a mouse model of amyotrophic lateral sclerosis. NMR in Biomedicine, 31(8), which has been published in final form at 10.1002/nbm.3954.

Citation

Gatto, R. G., Li, W. G., Gao, J., & Magin, R. L. (2018). In vivo diffusion MRI detects early spinal cord axonal pathology in a mouse model of amyotrophic lateral sclerosis. NMR in Biomedicine, 31(8). doi:10.1002/nbm.3954

Publisher

Wiley

Language

en_US

issn

0952-3480

Issue date

31/08/2018

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