Imaging collaterals and tissue metabolism in patients with Moyamoya syndrome

烟雾病综合征患者的络脉和组织代谢成像

• 批准号: 9301056
• 负责人: Manus J Donahue
• 金额: $ 34.56万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2021-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9301056
• 关键词: Adult; Age; Angiography; Atherosclerosis; Blood; Blood Vessels; Brain; Caliber; Catheters; Characteristics; Child; Clinical; Clinical Trials; Core-Binding Factor; Data; Development; Disease; Down Syndrome; Endothelial Growth Factors; Etiology; Evaluation; Financial compensation; Functional disorder; Goals; Gold; Hypercapnia; Hyperoxia; Image; Impairment; Incidence; Infarction; Inflammatory; Internal carotid artery structure; Lipids; Longevity; Magnetic Resonance Imaging; Measures; Medical; Metabolic; Metabolism; Methods; Microvascular Dysfunction; Morphologic artifacts; Morphology; Moyamoya Disease; Multiparametric Analysis; Neurologic; Neurologic Symptoms; Operative Surgical Procedures; Oxygen; Patients; Perfusion; Pharmacologic Substance; Phenotype; Physiological Processes; Population; Procedures; Process; Proteins; Protocols documentation; Radiation therapy; Recording of previous events; Reporting; Rest; Risk; Scanning; Screening procedure; Secondary to; Severity of illness; Sickle Cell Anemia; Smooth Muscle; Specificity; Stenosis; Stroke; Structure; Surrogate Markers; Testing; Thick; Time; Tissues; Treatment Protocols; Variant; Vascular Diseases; Work; endothelial dysfunction; follow-up; hemodynamics; high risk; imaging modality; improved; intracranial artery; neuroimaging; novel; novel marker; patient stratification; pediatric patients; persistent symptom; personalized medicine; response; screening; symptomatology; tool

Abstract The goal of this work is to apply novel neuroimaging methods in patients with Moyamoya syndrome to test fundamental hypotheses regarding hemodynamic compensation, stroke history, and symptomatology. Moyamoya disease (MMD) has unknown etiology and is characterized by steno-occlusion of the supraclinoid internal carotid arteries and proximal branches, development of collateral vessels, and a high risk of stroke. Idiopathic MMD is relatively rare, however moyamoya syndrome (MMS), which can arise secondary to Down syndrome, sickle cell disease, atherosclerosis, and radiotherapy shares many phenotypical characteristics as idiopathic MMD, yet is observed much more frequently. Patients with MMS are at high risk for stroke, and compared with atherosclerotic disease where preferred treatment regimens are outlined by recent clinical trial results, optimal MMS therapies are less clear and may comprise medical management and/or surgical revascularization. Owing to the dynamic course of MMS, which includes a wide variation of progressive steno- occlusion, abnormal expression of endothelial growth factors and inflammatory proteins, hemo-metabolic disturbances, intimal vessel wall thickening, and neoangiogensis, there is a pressing clinical need to understand the pathophysiology of these processes, how they relate to symptomatology and stroke incidence, and ultimately may be used to stratify patients for therapy or guide development of novel pharmaceuticals. The critical barrier to achieving this rests with a lack of optimal methods that can be implemented for mapping and surveillance. Here, in adults and children with MMS, we propose to implement new MRI methods developed in our center to test focused hypotheses regarding (Aim 1) relationships between endothelial dysfunction, stroke incidence, and symptomatology; (Aim 2) changes in vessel wall morphology, disease chronicity, and neurological symptoms; and (Aim 3) oxygen extraction fraction response to surgical revascularization therapy. The short-term significance of this work is that it will improve our understanding of the physiological processes that underlie how tissue responds to proximal non-atherosclerotic steno-occlusion and revascularization, which will serve as a prerequisite for utilizing functional neuroimaging to stratify patients with MMS for appropriate therapy. The longer-term goal is to use this information to guide the development of novel pharmaceuticals or early screening procedures that may enable therapies to be titrated to patients prior to irreversible tissue damage. Finally, methods implemented are translatable to other vascular diseases, and findings should have broader relevance for discerning pathophysiological differences between atherosclerotic and non- atherosclerotic hemodynamic compensation mechanisms.

抽象的 这项工作的目的是在Moyamoya综合征患者中应用新颖的神经影像学方法进行测试 关于血液动力学补偿，中风病史和症状学的基本假设。 Moyamoya病（MMD）具有未知的病因，其特征是链霉素类固醇 内部颈动脉和近端分支，侧支船的发展以及中风的高风险。 特发性MMD相对较少，但是Moyamoya综合征（MMS），可能是继发于下降的 综合征，镰状细胞疾病，动脉粥样硬化和放射治疗具有许多表型特征 特发性MMD，但观察到更频繁的频率。 MMS患者中风的风险很高，并且 与动脉粥样硬化疾病相比，最近临床试验概述了首选治疗方案 结果，最佳MMS疗法不太清楚，可能包括医疗管理和/或手术 血运重建。由于MMS的动态过程，其中包括进行性促进性的广泛变化 闭塞，内皮生长因子的异常表达和炎症蛋白，血压代谢 干扰，内膜容器壁增厚和新血管生成，有紧迫的临床需求 了解这些过程的病理生理学，它们与症状学和中风发生率之间的关系， 最终可能用于对患者进行治疗或指导新药的开发。这 实现这一目标的关键障碍是缺乏最佳方法，这些方法可用于映射和 监视。在这里，在成人和具有MMS的儿童中，我们建议实施开发的新MRI方法 我们的中心测试有关（AIM 1）内皮功能障碍，中风之间关系的集中假设 发病率和症状； （AIM 2）容器壁形态的变化，疾病慢性和 神经症状； （AIM 3）提取氧气对手术血运重建疗法的反应。 这项工作的短期意义在于，它将提高我们对生理过程的理解 这是组织如何应对近端非动脉粥样硬化的狭窄和血运重建的基础 将作为利用功能性神经成像来对MMS进行分层的先决条件 治疗。长期目标是使用此信息来指导新型药物的开发或 早期筛查程序可能使治疗在不可逆组织之前滴定给患者 损害。最后，实施的方法可转换为其他血管疾病，发现应该具有 与动脉粥样硬化与非 - 非 - 动脉粥样硬化血液动力学补偿机制。