Project Abstract: SCD is a genetic blood disorder characterized by abnormal hemoglobin S (HbS) synthesis with sickle cell anemia (SCA) as the most common subtype. Stroke is the most frequent cause of death and long-term disability in both children and adults with SCD. Studies of patients with focal neurologic deficits have revealed abnormalities of both large and small vessels in SCD. Currently, the main clinical screening test is the use of transcranial Doppler (TCD) for neurologically asymptomatic children with SCD. The TCD test is not effective to screen stroke risk in adult SCD patients. Cerebral oxygen extraction fraction (OEF), the ratio between oxygen consumption and delivery, has been recognized as a potentially more sensitive and specific indicator of cerebrovascular impairment in SCD. OEF measurement based on T2-oximetry MRI is promising as it does not require a contrast agent and is free of radiation. The existing T2-oximetry MRI techniques are not yet able to reliably measure the blood oxygenation in small veins. However, the blood oxygenation in these small veins is more sensitive to local neurological vasopathology. Using our recently developed velocity-selective MR angiography technique (that preserves high blood signal while suppressing tissue signal), we aim to fill this gap by developing a fast and reliable protocol for quantitative OEF venography including the small veins. This will help to establish the role of OEF for stroke prevention among adult SCD patients. The overall objectives of this projects are: 1) to develop and validate a robust T2-oximetry MRI protocol and demonstrated its reliability, reproducibility and accuracy in healthy volunteers. 2) to build a SCD specific T2 calibration model that can reliably translate the measured MRI parameter (blood T2) to blood oxygenation. 3) to measure the whole brain and regional cerebral OEF before and after transfusion in SCD patients with a history of stroke to have a pilot study on the relationship between between OEF and the brain injury (silent cerebral infarction and stroke).