Multiscale characterisation of brain structure during development

Xu, Lanxi 2025. Multiscale characterisation of brain structure during development. PhD Thesis, Cardiff University. Item availability restricted.

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Abstract

Brain growth and remodelling are dynamic processes that involve macrostructural and microstructural variations, including volumetric expansion, fibre orientation, myelination, and glial proliferation. Understanding how these features evolve across development is critical for explaining neurodevelopmental mechanisms and regional specialisation. Using the porcine brain as a model, this study quantitatively characterised macro- and microstructural during brain development across six brain regions (1, 7, 14, 180/210, and 1460 days) by combining different methodologies, namely diffusion MRI, histology, image-based microscopy and computational modelling. Age-dependent tractography revealed progressive increases in white matter coherence, while volumetric analysis showed marked brain growth. Diffusion metrics exhibited region-specific trends: low fractional anisotropy (FA) and high orientation dispersion index (ODI) were observed in cerebral tracts, particularly occipital and parietal lobes, whereas the corpus callosum displayed high FA, low ODI, and high neurite density index (NDI), indicative of dense, coherent fibres. Histological analyses confirmed increased fibre organisation and amount with age, a decrease in neuronal nuclei density, and increased glial cell alignment along fibre tracts, reflecting active myelination. Fibre dispersion and amount increased with postnatal development age, showing strong positive non-linear correlations, while cross-modal analysis revealed negative correlations between FA and ODI, and between ODI and NDI. Machine learning analysis (Linear discriminant analysis (LDA) and Random Forest (RF)) identified fibre amount, orientation, and nuclei density as primary discriminators of age, and NDI, FA and fibre dispersion as key markers of regional differences. These findings provide an integrated view of macrostructural and microstructural brain maturation, linking diffusion MRI with histological evidence. The study establishes a multimodal network to understand the developmental trends in fibre and cellular architecture, offering different perspectives on mechanisms of brain growth, remodelling, and regional specialisation.

Item Type:	Thesis (PhD)
Date Type:	Completion
Status:	Unpublished
Schools:	Schools > Engineering
Uncontrolled Keywords:	1. Postnatal brain growth and remodelling 2. Diffusion MRI 3. White matter maturation 4. Myelination 5. Histology 6. NODDI
Date of First Compliant Deposit:	18 May 2026
Last Modified:	18 May 2026 13:23
URI:	https://orca.cardiff.ac.uk/id/eprint/187009

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