Abstract
Objective markers of disease sensitive to the clinical activity, symptomatic progression, and underlying substrates of neurodegeneration are highly coveted in amyotrophic lateral sclerosis in order to more eloquently stratify the highly heterogeneous phenotype and facilitate the discovery of effective disease modifying treatments for patients. Magnetic resonance imaging (MRI) is a promising, non-invasive biomarker candidate whose acquisition techniques and analysis methods are undergoing constant evolution in the pursuit of parameters which more closely represent biologically-applicable tissue changes. Neurite Orientation Dispersion and Density Imaging (NODDI; a form of diffusion imaging), and quantitative Magnetization Transfer Imaging (qMTi) are two such emerging modalities which have each broadened the understanding of other neurological disorders and have the potential to provide new insights into structural alterations initiated by the disease process in ALS. Furthermore, novel neuroimaging data analysis approaches such as Event-Based Modeling (EBM) may be able to circumvent the requirement for longitudinal scanning as a means to comprehend the dynamic stages of neurodegeneration in vivo. Combining these and other innovative imaging protocols with more sophisticated techniques to analyse ever-increasing datasets holds the exciting prospect of transforming understanding of the biological processes and temporal evolution of the ALS syndrome, and can only benefit from multicentre collaboration across the entire ALS research community.
Highlights
Specialty section: This article was submitted to Neurodegeneration, a section of the journal Frontiers in Neurology
Neurite Orientation Dispersion and Density Imaging (NODDI; a form of diffusion imaging), and quantitative Magnetization Transfer Imaging are two such emerging modalities which have each broadened the understanding of other neurological disorders and have the potential to provide new insights into structural alterations initiated by the disease process in amyotrophic lateral sclerosis (ALS)
diffusion tensor imaging (DTI) assumes that water movement will obey Gaussian properties and is widely accepted to lose consistency when neuronal fibers bend or fan out within a voxel, or where otherwise aligned fiber tracts are crossing each other [5] which is common to areas such as the centrum semiovale and even regions of the foliated corpus callosum [27, 28]
Summary
Diffusion MRI is sensitive to the motion of water molecules at microscopic level. the signal it measures is averaged across volumes of 1–2 mm (the so-called “voxel”). Compared to DTI, NODDI indices, ODI, have been shown to correlate with histological measures of orientation dispersion in the spinal cord and might display more inter-subject variability with implications for the sample sizes required for group analyses [33, 34]. This may not necessarily be an inaccuracy in modeling rather a more accurate depiction of tissue composition [31]. NODDI is considered non-inferior to other MRI modalities of high-angular resolution in this regard [48], it may be that acquisition protocols or MRI data modeling methods undertaken in NODDI, such as spherical (rather than linear) tensor encoding [49] along with tract-based [50], gray matter based [37], and gray matter surface based [51] spatial statistics are further refined in due course to overcome its own recognized limitations
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