Age-related and regional variations in porcine brain white matter: an integrated biomechanical and ultrastructural investigation

Lei, Rujing 2025. Age-related and regional variations in porcine brain white matter: an integrated biomechanical and ultrastructural investigation. PhD Thesis, Cardiff University. Item availability restricted.

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Abstract

Traumatic brain injury (TBI) is a leading cause of mortality and morbidity in children, yet computational models of the paediatric head often lack biofidelity due to a scarcity of age-specific material properties. Current models typically rely on scaled adult data, failing to capture the complex, evolving mechanical anisotropy of developing white matter (WM). This thesis addresses this critical gap by generating a comprehensive, multi-modal dataset characterising the mechanical and microstructural evolution of porcine WM across three developmental stages: infancy (0.5 months), adolescence (7 months), and young adulthood (36 months). Using a combined experimental approach, this work integrated biaxial tensile test ing to quantify hyperelasticity and anisotropy, oscillatory shear rheometry to characterise compression-dependent viscoelasticity, and quantitative transmission electron microscopy (TEM) to determine the underlying ultrastructural architecture across the brainstem (BS), parietal lobe (PL), and temporal lobe (TL). The results demonstrate that brain maturation is asynchronous and region-specific. Me chanically, tissue stiffness did not increase linearly with age but often peaked during ado lescence. Persistent anisotropy was observed across all ages, with stiffness consistently higher along the mean fibre direction (MFD) compared to the cross-fibre direction (CFD). Viscoelastic characterisation revealed a profound, age-dependent non-linear stiffening under static compression, particularly in the mature TL. Structurally, the BS matured via radial growth (increased axon radius and myelin thickness), whereas the TL matured via densi fication (increased packing density). Integrating these datasets revealed distinct structure function relationships: tensile strength was primarily driven by the total neural area fraction, while viscoelastic shear stiffness was governed by the mean axon radius. These findings challenge simple scaling laws, establishing that the developing brain is a mechanically and structurally distinct material. The provided age-resolved, region-specific, and microstructure-informed dataset offers a rigorous foundation for the next generation of biofidelic paediatric TBI models.

Item Type:	Thesis (PhD)
Date Type:	Completion
Status:	Unpublished
Schools:	Schools > Engineering
Uncontrolled Keywords:	White matter, Brain biomechanics, Paediatric traumatic brain injury, Viscoelasticity, Transmission electron microscopy, Anisotropy
Date of First Compliant Deposit:	18 May 2026
Last Modified:	18 May 2026 13:44
URI:	https://orca.cardiff.ac.uk/id/eprint/187079

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