Cerebrovascular reserve and white matter disease in patients with chronic anemia

Low haemoglobin levels raise resting cerebral blood flow (CBF) and leave patients with inadequate cerebrovascular reserve (CVR). As a result , impaired CVR represents the strongest risk factor for white matter injury, volume loss, and stroke. The main goal of this project is to identify CVR predictors including CBF, age, sex and vascular stressors in anaemic and control subject using several MRI techniques. While anaemia is correlated with other cerebrovascular risk factors in the general population (hypertension, kidney disease, chronic inflammation, heart failure), we assume that anaemia, by decreasing CVR, created and increased vulnerability to white matter damage in patients with Sickle Cell Disease (SCD). Through the use of simple and exchange transfusions in selected patients with SCD and thalassemia, we will study the relative importance of haemoglobin S% and total haemoglobin level on regional CVR. We will identify other modifiable risk factors (iron overload, vascular inflammation) that may impair CVR. By comparing CVR and white matter damage across a broad spectrum of SCD and thalassemia syndromes, we will be able to separate the damaging effects of haemolytic anaemias in general froom damage specifi to sickle haemoglobin.

relationship between CVR, CB, and vascular/inflammatory markers
Co-localization of white matter damage and regions of low CVR
Global and regional rsponse of CVR to simple trnasfusions, exchange transfusions and hydroxyurea.

2 MRIs

Blood draw, Neurocognitive tests, infusion placed. ECG leads or pulse unit placed, 15 minutes structural MRI, 15 min Functional MRI pre-ACZ, administration of ACZ, 15 min ASL assesses time course, 15 min functional MRI post ACZ.