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

磁共振成像方法改善脑血管疾病患者氧提取分数的空间测量

• 批准号: 10394797
• 负责人: Spencer Leon Waddle
• 金额: $ 1.39万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10394797
• 关键词: 3-Dimensional; Address; Adult; Affect; Age; Angiography; Atherosclerosis; Biological Markers; Blood; Blood specimen; Brain; Carrying Capacities; Cause of Death; Cerebral Infarction; Cerebrovascular Circulation; Cerebrovascular Disorders; Cerebrum; Child; Clinical; Clinical Trials; Collaborations; Custom; Cyclotrons; Development; Disease; Financial compensation; Goals; Hematocrit procedure; Hemolytic Anemia; Imaging technology; Impairment; Inherited; Injury; Institutes; Ionizing radiation; Label; Longevity; Magnetic Resonance Imaging; Measurement; Measures; Medical; Medical center; Metabolic; Metabolic dysfunction; Metabolism; Methods; Monitor; Morbidity - disease rate; Operative Surgical Procedures; Oxygen; Participant; Patients; Physiologic pulse; Physiological; Positron-Emission Tomography; Prevalence; Preventive therapy; Procedures; Protocols documentation; Radiation exposure; Recording of previous events; Relaxation; Reporting; Research; Risk Assessment; Scanning; Sickle Cell Anemia; Site; Specificity; Spin Labels; Stenosis; Stroke; Stroke prevention; Techniques; Testing; Tissues; Transfusion; Treatment Protocols; United States; Universities; Validation; Variant; Vascular Diseases; Venous; Water; Work; anatomic imaging; base; clinical application; clinical practice; cohort; disability; efficacy evaluation; expectation; experience; hemodynamics; imaging modality; imaging science; improved; in vivo; intracranial artery; member; neuroimaging; novel; radio frequency; recruit; regional difference; screening; stroke risk; symptomatology; therapy design; tool

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.

项目概要 镰状细胞性贫血（SCA）患者的携氧能力降低，脑血流量增加 和氧提取分数（OEF），以及中风和血管病变的发生率增加。一半成年人患有 SCA 30岁时会出现脑梗塞；然而，尽管导致残疾的伤害普遍存在，但没有 成人 SCA 的初级卒中预防机制已经建立。设计难度 这些患者的治疗方案部分是由于与测量脑血流量相关的困难 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病史，但是广泛实施 OEF 措施 由于 15-O 正电子发射相关的技术困难，临床实践受到阻碍 断层扫描测量，历史上曾用于测量 OEF。 OEF可以测量非 使用 T2 松弛下自旋标记 (TRUST) 脉冲进行侵入式磁共振成像 (MRI) 序列，但是该方法不提供 OEF 的区域测量，因此不报告区域 损伤和中风风险，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，拟议的研究将侧重于改进 TRUST 脉冲序列，以 报告 OEF 的区域信任 (rTRUST) 措施。功能有限的 rTRUST 脉冲序列已经 在我们的实验室中可以使用，但是该方法仅限于 OEF 的单侧半球测量。在 这项工作的第一个目标，我们将完善 rTRUST 以提高标记效率并增加空间信息 内容进一步，使用定制的自旋标记方法和射频开发，允许 3D 体积因特异性的提高而令人兴奋。精炼后的 rTRUST 脉冲序列将在 ex 中进行验证 体内血液模型并在健康对照中进行了优化。在第二个目标中，rTRUST 将在 vivo 将从超过 91 名已知的、特征良好的 SCA 中招募参与者 患者参与本研究的转化部分。患有侧化血管病变的 SCA 队列将是 在 3 特斯拉 MRI 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，与已知的关系一致 CBF、OEF 和 CMRO2 之间。 rTRUST 的开发以及 MRI 采集方法的验证 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 设计积极的手术血运重建、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方法 导致血液代谢功能障碍和中风的疾病，特别是其他脑血管疾病，例如 如动脉粥样硬化，其中氧气输送因狭窄闭塞而受损。