Age-Dependence of Cerebral Oxygen Metabolism and Stroke Risk in Pediatric Sickle Cell Disease

小儿中风可能发生，因为氧气供应不足，以满足高能量 大脑发育的需求。大脑经历了巨大的成长和发育 整个童年。脑组织消耗血液输送的氧气，提供能量 for cellular细胞processes处理.大脑对氧气的需求似乎在5-9岁之间达到顶峰。 如果大脑的某些区域得不到足够的氧气， 如果没有足够的氧气，或者因为血液不能到达组织，就可能发生中风。脑 氧利用代谢率（CMRO 2），反映了大脑的能量需求，是一个 血液中可用的氧气量、血液输送速率（脑血流量， 或CBF）和由脑组织吸收的递送的氧的百分比（氧提取 分数或OEF）。CBF和OEF是动态过程，能够补偿微小的 扰动或增加的需求，以保持稳定的能源消耗率。在 在成年人中，OEF增加表明高代谢补偿，并意味着高 中风风险。因为儿童的需氧量比成人高， 在整个儿童期，尚不清楚OEF和CBF的增加是否也意味着 高中风风险。一个原因是未知的，因为以前OEF需要辐射 用于组织水平测量;因此使OEF测量不符合儿科伦理 research.我们的团队开发了新的MR序列来测量组织水平的OEF。儿童 患有镰状细胞病（SCD）的人血液中的氧气含量较低， 贫血SCD儿童的中风发病率也很高，3个孩子中就有1个 在成年前就出现了中风本项目旨在了解 OEF和CBF的年龄依赖性增加是否可预测SCD儿童的卒中。我 假设年龄和氧代谢可预测SCD儿童卒中风险很长的- 本项目的长期目标是开发这些方法来评估中风风险和机制 在儿童中风人群中。目标1：确定年龄和SCD对氧气的影响 新陈代谢.我将研究年龄、血细胞计数和SCD对CBF和OEF的影响。 目的2：确定年龄和氧代谢是否可预测个体卒中风险， SCD。我将随访SCD受试者4年，以确定总体和 年龄和氧代谢的区域测量，计算血细胞计数和疾病 严重性。目的3：确定氧代谢对治疗干预的反应是否与年龄有关。 依赖。我将研究如何全球和区域代谢的变化与输血。

Pediatric stroke may occur because of an inadequate oxygen supply to meet the high energy demands of a developing brain. The brain undergoes tremendous growth and development throughout childhood. Brain tissues consume oxygen delivered by the blood, providing energy for cellular processes. The brain’s demand for oxygen appears to peak between ages 5-9. If regions of the brain do not get enough oxygen, either because the blood does not carry enough oxygen, or because blood does not reach the tissue, a stroke can occur. The cerebral metabolic rate of oxygen utilization (CMRO2), reflecting the energy demands of the brain, is a product of amount of oxygen available in the blood, rate of blood delivery (cerebral blood flow, or CBF) and the percentage of oxygen delivered taken up by the brain tissue (oxygen extraction fraction, or OEF). CBF and OEF are dynamic processes, able to compensate for minor perturbations or increased demand as needed to maintain a steady energy consumption rate. In adults, an increased OEF demonstrates high metabolic compensation and signifies a high stroke risk. Because the oxygen demand is higher in children than adults and changes throughout childhood, it is unclear whether increased OEF and increased CBF also denote a high stroke risk. One reason this is unknown is because previously OEF has required radiation for tissue-level measurements; thus rendering OEF measurements unethical for pediatric research. Our team has developed novel MR sequences to measure tissue-level OEF. Children with sickle cell disease (SCD) have lower amounts of oxygen available in their blood due to anemia. Children with SCD also have a high incidence of stroke, with 1 of 3 children demonstrating stroke on MRI before reaching adulthood. This project seeks to understand whether or not age-dependent increases in OEF and CBF predict stroke in children with SCD. I hypothesize that age and oxygen metabolism predict stroke risk in children with SCD. The long- term goal of this project is to develop these methods to assess stroke risk and mechanism across pediatric stroke populations. Aim 1: To determine effects of age and SCD on oxygen metabolism. I will examine the contribution of age, blood counts, and SCD on CBF and OEF. Aim 2: To determine if age and oxygen metabolism predict individual stroke risk in subjects with SCD. I will follow subjects with SCD for 4 years to determine the predictive value of global and regional measures of age and oxygen metabolism, accounting blood counts, and disease severity. Aim 3: To determine if oxygen metabolism response to therapeutic intervention is age- dependent. I will examine how global and regional metabolism changes with transfusion.