Non-invasive diffusion tensor imaging detects white matter degeneration in the spinal cord of a mouse model of amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is characterized by selective degeneration of motor neurons. Here we examine the ability of magnetic resonance imaging (MRI) to measure axonal degeneration in the lumbar spinal cord of the SOD1 mouse model of ALS. Diffusion tensor imaging (DTI) was successful in detecting axonal spinal cord damage in vivo. Fractional anisotropy (FA) values were reduced exclusively in the ventral white matter tracts of the lumbar spinal cord of ALS-affected SOD1 mice compared to wild-type littermates, with this effect becoming more pronounced with disease progression. The reduced FA values were therefore limited to white matter tracts arising from the motor neurons, whereas sensory white matter fibers were preserved. Significant decreases in water diffusion parallel to the white matter fibers or axial diffusivity were observed in the SOD1 mice, which can be attributed to the axonal degeneration observed by electron microscopy. At the same time, radial diffusivity perpendicular to the spinal column increased in the SOD1 mice, reflecting reduced myelination. These results demonstrate the usefulness of MRI in tracking disease progression in live animals and will aid in the assessment of treatment efficacy. This method could also potentially be adapted to aid the diagnosis and assessment of ALS progression in humans.

Research highlights►In vivo DTI can detect axonal spinal cord damage in SOD1 mice. ►A reduction of FA in SOD1 mice is observed in white matter tracts that originate from the motor neuron pool. ►In SOD1 mice sensory white matter fibers appeared unaffected. ►Decreasing FA values in aging SOD1 mice correlate with their disease progression.