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)患者携氧能力降低，脑血流量增加 和氧摄取分数(OEF)，卒中和血管病变的发生率增加。一半患有SCA的成年人 将在30岁时表现为脑梗塞；然而，尽管致残损伤盛行，没有 已经在患有SCA的成年人中建立了一级卒中预防机制。设计中的难点 这些患者的治疗方案部分是由于与测量脑血流有关的困难。 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， 包括脑血管疾病和中风病史，但广泛实施OEF措施以 由于与15-O正电子发射相关的技术困难，临床实践受到阻碍 体层摄影术测量，历史上一直用于测量OEF。OEF可以非测量 T2弛豫下自旋标记(TRUST)脉冲在磁共振成像(MRI)中的侵入性 序列，但此方法不提供OEF的区域度量，因此不报告区域 损害和中风风险，这在SCA相关性脑血管病患者中很常见。至 针对治疗中的这些差距，拟议的研究将侧重于改进信任脉冲序列，以 报告OEF的地区信任(RTRUST)衡量标准。功能有限的rTRUST脉冲序列已经 然而，这种方法仅限于对OEF的单侧、半球测量。在 这项工作的第一个目标是对rTRUST进行细化，以提高标注效率和增加空间信息 内容进一步，使用定制的自旋标记方法和允许3D的射频开发 以更好的特异性激发的体积。细化的rTRUST脉冲序列将在EX中进行验证 活体血液模体，并在健康对照组中进行优化。在第二个目标中，rTRUST将在 VIVO，参与者将从91多名知名的、特征明确的SCA队列中招募 患者对这项研究的翻译部分。有偏侧性血管病变的SCA队列将是 在3特斯拉核磁共振扫描仪上扫描，并使用空间特定的rTRUST OEF测量，我们将验证 血管病变和CBF减少的区域OEF升高，这与已知的关系一致 在CBF、OEF和CMRO2之间。RTRUST的发展和磁共振成像方法的验证 空间OEF信息将有助于将OEF测量引入临床实践，提高我们的能力 设计积极的外科血运重建、输血或医疗管理治疗方案 脑血管病和镰状细胞性贫血患者。这些方法将可推广到其他 引起血液代谢障碍和中风的疾病，尤指其他脑血管疾病，如 动脉粥样硬化是指由于狭窄闭塞而导致的氧气输送障碍。

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.