White Matter Microstructure Development in Neuroimaging

White matter comprises the myelinated axonal pathways that connect discrete neuronal populations, underpinning efficient signal transmission across the brain. Throughout childhood and adolescence, white matter undergoes rapid microstructural maturation marked by increasing myelin deposition, axonal packing density and fibre coherence. Non-invasive neuroimaging techniques, chiefly diffusion magnetic resonance imaging (dMRI), have transformed our ability to chart these processes in vivo. Early work using diffusion tensor imaging (DTI) established that metrics such as fractional anisotropy and mean diffusivity evolve along a posterior-to-anterior gradient, reflecting protracted frontal lobe myelination. More recent multi-shell acquisitions and advanced modelling approaches—including neurite orientation dispersion and density imaging (NODDI) and fixel-based analysis—offer improved specificity by disentangling intra-axonal, extra-axonal and morphological contributions. These advances have illuminated normative trajectories, individual differences related to sex and environment, and deviations associated with neurodevelopmental and psychiatric conditions. The integration of longitudinal cohorts and high-field scanners has further refined our understanding of how white matter maturation supports cognitive and behavioural development and how it may be perturbed by genetic risk or injury.

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White Matter Microstructure Development in Neuroimaging publication trend

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Technical terms

White matter: Regions of the brain composed of myelinated nerve fibres that facilitate communication between grey matter areas.

Diffusion tensor imaging (DTI): A dMRI technique modelling water diffusion as a tensor to infer fibre orientation and integrity.

Fractional anisotropy (FA): A scalar index from DTI reflecting the directionality of water diffusion, often interpreted as fibre coherence and myelination.

Neurite orientation dispersion and density imaging (NODDI): A multi-compartment model that estimates neurite density and orientation dispersion, offering enhanced microstructural specificity.

Fixel: A fibre population within a voxel, allowing the separation of crossing or kissing fibres for targeted analysis.

Apparent fibre density (AFD): A fixel-based metric quantifying the intra-axonal volume fraction of a specific fibre population, sensitive to developmental and pathological changes.

References

1. In vivo evidence of microstructural hypo-connectivity of brain white matter in 22q11.2 deletion syndrome. Molecular Psychiatry (2023).
2. Longitudinal Associations Between White Matter Microstructure and Psychiatric Symptoms in Youth. Journal of the American Academy of Child & Adolescent Psychiatry (2023).
3. Investigating white matter fibre density and morphology using fixel-based analysis. NeuroImage (2016).
4. Diffusion MRI of white matter microstructure development in childhood and adolescence: Methods, challenges and progress. Developmental Cognitive Neuroscience (2017).
5. Detailing neuroanatomical development in late childhood and early adolescence using NODDI. PLOS ONE (2017).
6. Cerebral White Matter Myelination and Relations to Age, Gender, and Cognition: A Selective Review. Frontiers in Human Neuroscience (2021).