Diffusion Imaging Techniques in Multiple Sclerosis

Diffusion imaging has emerged as a pivotal tool for probing the microstructural alterations that underpin multiple sclerosis. Conventional magnetic resonance imaging remains indispensable for lesion detection, but diffusion techniques provide unique insights into tissue integrity at a microscopic level. Measures such as fractional anisotropy and mean diffusivity quantify the directional coherence and overall mobility of water molecules, revealing demyelination, axonal injury and extracellular changes that often precede overt lesion formation. Advanced protocols employ multicompartment modelling to disentangle intra‐axonal, myelin and extracellular water fractions, enabling estimation of axonal diameter distributions and free-water content. These approaches have broadened our understanding of disease evolution, linking subtle changes in normal-appearing white matter to clinical disability and neuropsychiatric outcomes. Together, diffusion imaging techniques offer sensitive biomarkers for early diagnosis, prognosis and treatment monitoring, and are increasingly applied in both brain and spinal cord studies.

Research from Nature Portfolio

Recent studies have shown that longitudinal estimation of extracellular water content can predict later neuropsychiatric symptoms in relapsing–remitting multiple sclerosis. Annual diffusion MRI assessments over three years demonstrated that elevated free-water fraction in subcortical regions at baseline correlates with depressive symptom scores two years later. Structural equation modelling pinpointed the thalamus as a region where early microstructural changes carry the greatest predictive weight. This work emphasises the capacity of diffusion metrics not only to characterise demyelination and axonal loss but also to serve as early indicators of mood disturbances in multiple sclerosis.

Research from all publishers

A translational framework has validated axonal diameter mapping as a sensitive marker of acute axonal damage. In an animal model of neurotoxin-induced pathology, multicompartment diffusion modelling revealed significant enlargement of mean axonal calibre that correlated with histological staining; the same protocol applied to patients uncovered diffuse increases in axon diameter across normal-appearing white matter, particularly in early disease stages. Complementary work combining sodium MRI with diffusion basis spectrum imaging and neurite orientation dispersion and density imaging has delineated relationships between total and extracellular sodium concentrations and microstructural disruption. These studies confirm that shifts in ionic homeostasis accompany microstructural changes, underscoring the metabolic dimension of tissue injury in multiple sclerosis.

Diffusion Imaging Techniques in Multiple Sclerosis publication trend

The graph below shows the total number of articles in diffusion imaging techniques in multiple sclerosis across all publications each year (not limited to Nature Index journals).

Technical terms

Free-water fraction: The proportion of extracellular water within a voxel, indicative of oedema or tissue loss.

Fractional anisotropy (FA): A scalar measure of the directional preference of water diffusion, reflecting fibre tract integrity.

Mean diffusivity (MD): The average rate of water diffusion within tissue, sensitive to cellular density and extracellular expansion.

Axonal diameter mapping: A technique that models diffusion signals to estimate the distribution of axon calibres in vivo.

Multicompartment modelling: An analytical approach that separates diffusion signals into distinct tissue compartments such as intra-axonal, myelin and extracellular spaces.

References

1. Microstructural changes precede depression in patients with relapsing-remitting Multiple Sclerosis. Communications Medicine (2023).
2. A translational MRI approach to validate acute axonal damage detection as an early event in multiple sclerosis. eLife (2024).
3. Relationship between sodium and diffusion MRI metrics in multiple sclerosis. Brain Communications (2024).