Amyotrophic lateral sclerosis (ALS) is the most prevalent type of motor neuron disease (MND) and is diagnosed with a delay from the first appearance of symptoms. Surrogate markers that may be used to detect pathological changes before a significant neuronal loss occurs and allow for early intervention with disease-modifying therapy techniques are desperately needed. Using water molecules that diffuse within the tissue and experience displacement on the micron scale, diffusion magnetic resonance imaging (MRI) is a promising technique that can be used to infer microstructural characteristics of the brain, such as microstructural integrity and complexity, axonal density, order, and myelination. Diffusion tensor imaging (DTI) is the primary diffusion MRI technique used to evaluate the pathogenesis of ALS. Neurite orientation dispersion and density imaging (NODDI), diffusion kurtosis imaging (DKI), and free water elimination DTI (FWE-DTI) are only a few of the approaches that have been developed to overcome the shortcomings of the diffusion tensor technique. This article provides a summary of these methods and their potential as surrogate markers for detecting the onset of ALS at an early stage.
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