The effect of white matter microstructure on transverse relaxation rates

Dell'Acqua, Veronica 2024. The effect of white matter microstructure on transverse relaxation rates. PhD Thesis, Cardiff University. Item availability restricted.

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Abstract

Magnetic Resonance Imaging (MRI) is widely used clinically with unquestionable utility in many neurological disorders. Quantitative MRI (qMRI), as the name suggests, estimates quantifiable parameters, providing specific and comparable information about changes in tissue, for example, across scans or over time. However, due to the tissue complexity, it still remains a major challenge to achieve biological specificity by accurately identifying the biological sources of the estimated parameters and quantifying the contribution of each microenvironment to the MRI signal. In this respect, this thesis focuses on enhancing the specificity and interpretability of transverse relaxation times (T2 and T∗ 2). This is made possible by employing the latest ultra-strong gradient technology and the newly proposed biophysical models that combine diffusion and relaxation measures to simultaneously resolve multiple metrics for different tissue compartments, such as intra-axonal and extra-axonal spaces. First, compartmental T2 and T∗ 2 anisotropy is characterised in relation to myelin development, comparing children and young adults. Orientation dependence of these metrics, potentially linked to myelin-induced susceptibility effects, was observed in both groups, suggesting possible confounding sources of variance in clinical studies. The second major focus of the thesis is the estimation of the inner axon radius. Specifically, the generalizability and robustness of the relationship between the intra-axonal T2 and axon radius is assessed both in vivo and in a pre-clinical contex. We present the first direct validation experiment of the surface-based relaxation model in ex vivo tissue, estimating submicrometer axon radii. Lastly, the above measurements of axon radius are compared to those obtained with a recently introduced diffusion MRI approach. The results highlighted variability in the axon radii estimates and further work is needed towards the validation of such approaches. Overall, the outcomes of this thesis contribute to the ongoing efforts in the field to enhance the interpretability and reliability of qMRI metrics. They also help to uncover how variations in white matter microstructure, such as axon diameter and myelin, influence MRI-based estimates of compartmental T2 and T∗2,paving the way for novel biomarkers that provide deeper insights into brain development and disease.

Item Type:	Thesis (PhD)
Date Type:	Completion
Status:	Unpublished
Schools:	Schools > Psychology
Date of First Compliant Deposit:	21 February 2025
Last Modified:	21 Feb 2025 12:07
URI:	https://orca.cardiff.ac.uk/id/eprint/176371

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