Imaging collaterals and tissue metabolism in patients with Moyamoya syndrome

摘要 这项工作的目标是应用新的神经影像学方法在烟雾综合征患者，以测试 关于血流动力学代偿、卒中史和脑血管病的基本假设。 烟雾病（MMD）的病因不明，其特征是床突上的狭窄闭塞 颈内动脉和近端分支，侧支血管的发展，以及中风的高风险。 特发性MMD相对罕见，但烟雾综合征（MMS），可继发于唐氏症 综合征、镰状细胞病、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。MMS患者中风的风险很高， 与动脉粥样硬化疾病相比，最近的临床试验概述了首选的治疗方案 结果，最佳MMS治疗不太清楚，可能包括医疗管理和/或手术治疗。 血运重建由于MMS的动态过程，包括广泛的渐进式速记变化， 闭塞，内皮生长因子和炎性蛋白的异常表达，血液代谢 由于血管内膜紊乱、内膜血管壁增厚和新生血管生成，临床上迫切需要 了解这些过程的病理生理学，它们与脑血管病和中风发病率的关系， 并最终可用于对患者进行分层以进行治疗或指导新药物的开发。的 实现这一目标的关键障碍在于缺乏可用于映射的最佳方法， 监视在这里，在成人和儿童与MMS，我们建议实施新的MRI方法， 我们的中心旨在测试关于（目标1）内皮功能障碍、卒中 （目的2）血管壁形态学、疾病慢性化和 神经系统症状;和（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 这是组织如何对近端非动脉粥样硬化性狭窄闭塞和血运重建做出反应的基础， 将作为利用功能神经成像对MMS患者进行分层的先决条件， 疗法长期目标是利用这些信息来指导新药物的开发， 早期筛查程序，可使患者在出现不可逆组织损伤之前接受滴定治疗 损害最后，所实施的方法可用于其他血管疾病，并且研究结果应具有 更广泛的相关性，以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， 动脉粥样硬化血流动力学补偿机制。

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.