Peripheral nerve diffusion tensor imaging as a measure of disease progression in ALS

Area of Science:

• Neuroscience
• Radiology
• Biomarker Discovery

Background:

• Clinical trial design for amyotrophic lateral sclerosis (ALS) is challenged by the absence of reliable biomarkers for disease progression.
• Axonal degeneration is a key pathological feature in ALS, necessitating sensitive markers.

Purpose of the Study:

• To evaluate peripheral nerve diffusion tensor imaging (DTI) as a surrogate marker for axonal degeneration in ALS.
• To assess the correlation between DTI metrics and functional assessments in ALS patients.

Main Methods:

• Longitudinal diffusion tensor imaging (DTI) of peripheral nerves was performed in ALS patients and age-matched controls.
• Imaging metrics, including fractional anisotropy and axial diffusivity, were correlated with functional rating scales (ALSFRS-R), muscle strength (MRCSS-LL), and neurophysiological measures (MUNE).

Main Results:

• ALS patients exhibited reduced fractional anisotropy in tibial and peroneal nerves at baseline compared to controls.
• Fractional anisotropy and axial diffusivity in the tibial nerve showed significant decline over 6 months in ALS patients.
• DTI metrics, particularly fractional anisotropy, strongly correlated with ALSFRS-R scores, muscle strength, and MUNE, indicating sensitivity to disease progression and motor neuron loss.

Conclusions:

• Peripheral nerve DTI metrics are sensitive indicators of axonal degeneration in ALS.
• DTI shows potential as a non-invasive biomarker for tracking disease progression and evaluating therapeutic efficacy in ALS clinical trials.