IMPORTANCE OF HEMODYNAMIC FACTORS IN THE PROGNOSIS OF STROKE IN SICKLE CELL

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。该项目的目标是更好地定义输血治疗的生理基础，以预防镰状细胞性贫血（SCA）中风，使用正电子发射断层扫描（PET）扫描大脑。SCA最可怕的后果是脑梗死，30%的儿童在18岁之前发生。每月输血治疗是该患者人群中卒中的唯一二级预防。然而，治疗获益的生理学基础尚不清楚，也不清楚为什么20%的患者会发生二次卒中。氧摄取分数（OEF）的变化，可以使用PET研究的大脑，已被发现是一个强大的独立预测中风风险的成年人没有SCA。尚未在SCA患者中进行系统的PET研究，以确定输血治疗的血流动力学获益，并评估OEF缺乏变化是否是卒中的独立风险因素。在本项目中，我们将检验以下主要假设：在SCA和卒中患者中，与患者基线相比，输血治疗导致OEF降低。共有6名SCA和中风患者将在输血治疗后进行脑部PET扫描。我们还将确定6例无卒中的SCA患者，以比较这些基线生理测量值。我们将使用磁共振成像（MRI）、磁共振血管造影（MRA）和经颅多普勒超声（TCD）来检验上述三个次要假设。完成本项目后，我们将更好地了解输血治疗在预防卒中中的作用，并随后收集该患者人群进行性神经系统疾病生理基础的初步数据。我们还将收集初步数据，以评估脑血流动力学的影响，抑制控制和解决脑血管使用MRA。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The goal of this project is to better define the physiologic basis for blood transfusion therapy to prevent strokes in sickle cell anemia (SCA) using Positron Emission Tomography (PET) scan of the brain. The most feared consequence of SCA is cerebral infraction, which occurs in 30% of children before their 18th birthday. Monthly blood transfusion therapy is the only secondary prevention for strokes in this patient population. However, the physiologic basis for the therapeutic benefit is not known, nor is the reason why 20% of the patients will have a second stroke. Changes in oxygen extraction fraction (OEF), which can be measured using PET studies of the brain, have been found to be a strong independent predictor of stroke risk in adults without SCA. PET studies have not been systematically performed in patients with SCA to determine the hemodynamic benefit of blood transfusion therapy and to assess whether a lack of change in OEF is an independent risk factor for strokes. In this project, we will test the primary hypothesis that: In patients with SCA and strokes, blood transfusion therapy results in a decrease in the OEF when compared to the patient's baseline. A total of six patients with SCA and strokes will have a PET scan of he brain and after blood transfusion therapy. We will also identify six patients with SCA without strokes to compare these baseline physiologic measurements. We will test the three secondary hypotheses stated above by using magnetic resonance imaging (MRI), magnetic resonance angiography (MRA), and transcranial doppler ultrasonography (TCD). After completion of this project, we will have a better understanding of the role of blood transfusion therapy in preventing strokes and will subsequently collect primary data on the physiologic basis for progressive neurological disease in this patient population. We will also gather preliminary data to assess the influence of cerebral hemodynamic on inhibitory control and resolution of cerebral vasculature using MRA.