Using Multi-Modal Quantitative MRI to Investigate the Mechanisms of Brain Injury in Sickle Cell Disease

This thesis aimed to investigate cerebral injury in Sickle Cell anaemia (SCA), a complex disease with interdependent mechanisms underpinning acute injury and cognitive difficulties in adults and children. Quantitative Magnetic Resonance Imaging (MRI) allows exploration of various aspects of SCA pathophysiology. Haemodynamic compromise occurs when the compensatory mechanisms of oxygen-delivery to tissue fail. Imaging of cerebral haemodynamics is difficult in clinical settings as reference standard 15O PET requires on-site radionuclide production, rarely feasible and unethical in children and vulnerable adults. MRI methods offer a non-invasive option to explore the difference in haemodynamic parameters between SCA participants and healthy controls of all ages as well as monitoring disease progression. QQ (Quantitative Susceptibility Mapping + quantitative Blood Oxygenation Level Dependent MRI; QSM + qBOLD) is an MRI analysis method validated against PET in adults offering analysis of regional changes in cerebral haemodynamics. Oxygen extraction fraction estimated via QQ was increased in both adults and children with SCA compared to healthy controls. Cerebral blood flow, estimated via pseudo-continuous Arterial Spin Labelling, was elevated in children not adults with SCA compared to healthy controls. Estimation of Cerebral metabolic rate of oxygen utilisation (CMRO2) was possible with the addition of arterial oxygen content, which was stable across both SCA and controls. Studies of the connection between white ma[er (WM) integrity and cognition have been limited to diffusion-based MRI methods invalid in brain regions with complex fibre geometry. In this thesis I explored the use of a novel method modelling the individual fibre bundles within a voxel, Fixel-based analysis. Although there was no widespread significant difference in WM between SCA participants and controls, or correlation with cognition, fixel-based metrics detected a change in fibre-cross section with age. Measurement of cerebral haemodynamics and WM integrity in SCA may allow understanding of mechanisms, potentially enabling new treatments.