IMPORTANCE OF HEMODYNAMIC FACTORS IN THE PROGNOSIS OF STROKE IN PATIENT WITH SCD

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。该项目的目标是利用正电子发射断层扫描(PET)脑扫描，更好地确定输血治疗预防镰状细胞性贫血(SCA)中风的生理学基础。SCA最可怕的后果是脑梗塞，30%的儿童在18岁之前就会发生脑梗塞。在这些患者中，每月输血治疗是中风的唯一二级预防措施。然而，治疗益处的生理学基础尚不清楚，20%的患者将发生第二次中风的原因也不清楚。氧提取分数(OEF)的变化可以通过脑部的PET研究来测量，已被发现是没有SCA的成年人中风风险的强大独立预测因子。目前还没有对SCA患者进行系统的PET研究，以确定输血治疗的血流动力学益处，并评估OEF缺乏变化是否是中风的独立危险因素。在这个项目中，我们将检验基本假设：在SCA和中风患者中，输血治疗导致与患者基线相比OEF下降。共有6名SCA和中风患者将在输血治疗前后进行脑部PET扫描。我们还将确定6名无卒中的SCA患者，以比较这些基线生理测量结果。我们将使用磁共振成像(MRI)、磁共振血管成像(MRA)和经颅多普勒超声(TCD)来验证上述三个次级假设状态。这项计划完成后，我们将对输血疗法在预防中风方面的作用有更深入的了解，并将随后收集关于这一患者群体中进行性神经系统疾病的生理基础的初步数据。我们还将收集初步数据，使用MRA评估脑血流动力学对脑血管抑制控制和消退的影响。

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 infarction, 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 the brain before 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 states above by using magnetic resonance imaging (MRI), magnetic resonance angiography (MRA), and trascranial 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 preliminary 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.