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: 9908181
• 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 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9908181
• 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; 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; 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; early screening; 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; stroke incidence; stroke risk; symptomatology

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 这项工作的目标是应用新颖的神经影像学方法对烟雾综合征患者进行测试 关于血流动力学补偿、中风病史和症状学的基本假设。 烟雾病 (MMD) 病因不明，特点是床突上狭窄闭塞 颈内动脉和近端分支、侧支血管发育以及中风的高风险。 特发性烟雾病相对罕见，但烟雾病综合征 (MMS) 可能继发于唐氏综合症 综合征、镰状细胞病、动脉粥样硬化和放射治疗具有许多共同的表型特征： 特发性 MMD，但观察到的频率要高得多。 MMS 患者发生中风的风险很高，并且 与动脉粥样硬化疾病相比，最近的临床试验概述了首选治疗方案 结果表明，最佳的 MMS 疗法不太明确，可能包括药物治疗和/或手术 血运重建。由于 MMS 的动态过程，其中包括各种渐进性狭窄的变化， 闭塞、内皮生长因子和炎症蛋白表达异常、血液代谢 紊乱、内血管壁增厚和新生血管生成，临床迫切需要 了解这些过程的病理生理学，它们与症状和中风发病率的关系， 最终可用于对患者进行治疗分层或指导新药物的开发。这 实现这一目标的关键障碍在于缺乏可用于绘图和绘制的最佳方法 监视。在这里，我们建议在患有 MMS 的成人和儿童中实施新的 MRI 方法 我们的中心测试有关（目标 1）内皮功能障碍与中风之间关系的集中假设 发病率和症状； （目标 2）血管壁形态、疾病慢性化和 神经系统症状； （目标 3）氧提取分数对手术血运重建治疗的反应。 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 这是组织如何响应近端非动脉粥样硬化性狭窄闭塞和血运重建的基础， 将作为利用功能性神经影像对 MMS 患者进行适当分层的先决条件 治疗。长期目标是利用这些信息来指导新型药物或药物的开发 早期筛查程序可以使治疗在不可逆组织出现之前对患者进行滴定 损害。最后，所实施的方法可以转化为其他血管疾病，并且研究结果应该具有 对于辨别动脉粥样硬化和非动脉粥样硬化之间的病理生理学差异具有更广泛的相关性 动脉粥样硬化血流动力学补偿机制。