Magnetic Resonance Imaging Methods to Improve Spatial Measures of Oxygen Extraction Fraction in Cerebrovascular Disease Patients

项目摘要 镰状细胞性贫血（SCA）患者的携氧能力降低，脑血流量增加， 和氧摄取分数（OEF），并增加中风和血管病变的发生率。一半的SCA成年人 在30岁时会出现脑梗死;然而，尽管残疾诱导损伤的流行， 一级预防中风的机制已在SCA成人中建立。设计难度 这些患者的治疗方案部分是由于与测量脑血流相关的困难， 新陈代谢.最近的研究表明，OEF的升高与疾病的临床指标相关， 包括脑血管病和中风史，然而，广泛实施OEF措施， 由于与15-O正电子发射相关的技术困难， 断层扫描测量，其在历史上被用于测量OEF。OEF可以测量非- 在磁共振成像（MRI）中使用T2弛豫自旋标记（TRUST）脉冲进行侵入性检查 序列，但是该方法不提供OEF的区域测量，因此不报告区域 这在SCA相关脑血管病患者中很常见。到 为了解决治疗中的这些差距，拟议的研究将集中在改进TRUST脉冲序列， 报告OEF的区域TRUST（rTRUST）措施。功能有限的rTRUST脉冲序列已经 在我们的实验室中可操作的，然而这种方法仅限于OEF的单侧半球测量。在 本文的第一个目标是对rTRUST进行改进，提高标注效率，增加空间信息量 内容进一步，使用定制的自旋标记方法与射频发展，允许3D 体积以改进的特异性被激发。改进的rTRUST脉冲序列将在 在健康对照中进行体内血液模型和优化。在第二个目标中，rTRUST将在 参与者将从超过91个已知的、充分表征的SCA队列中招募 病人的翻译组成部分，这项研究。患有偏侧性血管病变的SCA队列将 在3特斯拉MRI扫描仪上扫描，并使用空间特异性rTRUST OEF测量，我们将验证 血管病变和CBF降低的区域OEF升高，与已知的关系一致 CBF、OEF和CMRO 2之间的关系。开发rTRUST，并验证MRI方法， 空间OEF信息将有助于将OEF测量引入临床实践，提高我们 设计积极的外科血运重建、输血或医疗管理的治疗方案， 脑血管病和镰状细胞性贫血患者。这些方法将推广到其他 引起血液代谢功能障碍和中风的疾病，特别是其他脑血管疾病， 如动脉粥样硬化，其中氧输送因狭窄闭塞而受损。

Project Summary Patients with sickle cell anemia (SCA) have reduced oxygen carrying capacity, elevated cerebral blood flow and oxygen extraction fraction (OEF), and increased rate of stroke and vasculopathy. Half of adults with SCA will display a cerebral infarct by age 30; however, despite the prevalence of disability-inducing injury, no mechanism for primary stroke prevention has been established in adults with SCA. Difficulty in designing treatment protocols in these patients is partially due to difficulties associated with measuring cerebral hemo- metabolism. Recent work suggests that elevation in OEF is correlated with clinical indicators of disease, including cerebral vasculopathy and stroke history, however widespread implementation of OEF measures to clinical practice has been impeded due to technical difficulties associated with 15-O positron emission tomography measurements, which have historically been used to measure OEF. OEF can be measured non- invasively in magnetic resonance imaging (MRI) with the T2-relaxation-under-spin-tagging (TRUST) pulse sequence, however this method does not provide regional measures of OEF, so does not report regional impairment and stroke risk, which is common in patients with SCA associated cerebral vasculopathy. To address these gaps in treatment, the proposed research will focus on improving the TRUST pulse sequence to report regional TRUST (rTRUST) measures of OEF. A limited-functionality rTRUST pulse sequence is already operational in our lab, however this method is limited to unilateral, hemispheric measurements of OEF. In the first aim of this work, we will refine rTRUST to improve labeling efficiency and increase spatial information content further, using customized spin labeling approaches with radiofrequency developments that allow for 3D volumes to be excited with improved specificity. The refined rTRUST pulse sequence will be validated in ex vivo blood phantoms and optimized in healthy controls. In the second aim, rTRUST will be demonstrated in vivo whereby participants will be recruited from a cohort of more than 91 known, well-characterized, SCA patients for a translational component of this research. The SCA cohort with lateralizing vasculopathy will be scanned at a 3 Tesla MRI scanner, and using spatially specific rTRUST OEF measurements, we will validate that regions with vasculopathy and reduced CBF have elevated OEF, consistent with known relationships between CBF, OEF, and CMRO2. Development of rTRUST, and validation of MRI methods for acquiring spatial OEF information will help to introduce OEF measurement into clinical practice, improving our ability to design treatment protocols for aggressive surgical revascularization, transfusion, or medical management for patients with cerebral vasculopathy and sickle cell anemia. These methods will be generalizable to other diseases that cause hemo-metabolic dysfunction and stroke, particularly other cerebrovascular disease, such as atherosclerosis in which oxygen delivery is impaired by steno-occlusion.