In vivo diffusion MRI detects early spinal cord axonal pathology in a mouse model of amyotrophic lateral sclerosis

Area of Science:

• Neuroimaging
• Neurodegenerative Diseases
• Biomedical Engineering

Background:

• Diffusion magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) are sensitive to microstructural changes in neurodegenerative diseases.
• Previous research has utilized DTI to identify spinal cord white matter alterations in symptomatic amyotrophic lateral sclerosis (ALS) patients and animal models.

Purpose of the Study:

• To evaluate the sensitivity of DTI in detecting preclinical signs of tissue damage in an animal model of ALS.
• To investigate DTI metrics for early pathological changes in the spinal cord before symptom manifestation.

Main Methods:

• High-field (9.4-T) MRI was employed to acquire diffusion-weighted imaging (DWI) data from the spinal cords of an ALS mouse model at pre-symptomatic (day 80) and symptomatic (day 120) stages.
• DTI metrics including mean diffusivity (MD), fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) were calculated for the lumbar spinal cord.
• MRI findings were correlated with optical microscopy data of spinal cord tissue, including yellow fluorescent protein (YFP) expression and cellular markers.

Main Results:

• Significant alterations in DTI metrics were observed at postnatal day 80 (pre-symptomatic stage): FA decreased by 6.7% (p < 0.01), AD decreased by 19.5% (p < 0.01), and RD increased by 16.1% (p < 0.001).
• These diffusion changes correlated with reduced axonal fluorescence intensity and modifications in cellular membrane markers.
• The observed DTI changes indicate early pathological progression in the spinal cord prior to the onset of clinical symptoms.

Conclusions:

• Diffusion tensor imaging (DTI) shows promise as a sensitive tool for detecting early, subclinical pathological changes in the spinal cord associated with amyotrophic lateral sclerosis (ALS).
• This preclinical validation supports the potential of DTI for monitoring disease progression and evaluating therapeutic interventions in ALS.
• Early detection using DTI could accelerate the development of effective treatments for ALS patients.