Sickle cell disease (SCD) is an inherited form of anaemia, affecting oxygen transport throughout the body. One quarter of patients with SCD suffer ischaemic stroke before age 45. In children with SCD the risk of stroke can be detected and prevented, however, there is no method available for screening stroke risk in adult patients. The aim of the research presented in this thesis was to study imaging biomarkers that may aid in the identification of patients at risk for developing stroke. In one of the clinical observational cohort studies that we conducted, macrovascular haemodynamics were studied with MRI in the large vessels of the circle of Willis. The observed increase in vessel diameters led us to hypothesise that there is a maximum level of dilation that can be reached, also called the cerebrovascular reserve. In a subsequent clinical study we observed markedly reduced cerebrovascular reserve in adults with SCD, which led us to hypothesise that blood flow may be insufficient to maintain oxygen metabolism in the brain. Indeed, in a following study we observed that patients with SCD had reduced cerebral oxygen metabolism, despite adequate oxygen delivery, which was suggestive of cerebral shunting whereby blood travels directly from the arterial to the venous system without delivering oxygen to the tissue. Ultimately, the studies described in these thesis may help us better understand the physiology of SCD. Haemodynamic MRI has a potential clinical role in the assessment of treatment outcomes in future clinical trials for therapies in sickle cell patients