Imaging collaterals and tissue metabolism in patients with Moyamoya syndrome

摘要 这项工作的目标是将新的神经成像方法应用于烟雾综合征患者进行测试 有关血流动力学代偿、卒中病史和症状学的基本假设。 Moyamoya病(MMD)病因不明，以床上骨狭窄闭塞为特征。 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，但可继发于Down的烟雾综合征(MMS) 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，如 特发性MMD，但更常被观察到。患有MMS的患者中风的风险很高， 与动脉粥样硬化性疾病相比，最近的临床试验列出了首选治疗方案 结果，最佳的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，包括渐进性狭窄的广泛变化。 血管闭塞、内皮生长因子和炎性蛋白异常表达、血液代谢 紊乱、内膜血管壁增厚和新血管生成，临床上迫切需要 了解这些过程的病理生理学，以及它们与症状和中风发病率的关系， 并最终可用于对患者进行分层治疗或指导新药物的开发。这个 实现这一目标的关键障碍在于缺乏可以实施的最佳方法来绘制和 监视系统。在这里，在患有MMS的成人和儿童中，我们建议实施在 我们的中心测试关于(目标1)内皮功能障碍和中风之间关系的有重点的假设 发病率和症状学；(目标2)血管壁形态、疾病慢性化和 神经症状；和(目标3)氧提取分数对手术血管重建治疗的反应。 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 心理治疗。更长期的目标是使用这些信息来指导新药或 早期筛查程序，可使治疗在不可逆转组织之前滴定到患者身上 损坏。最后，实施的方法可以移植到其他血管疾病，结果应该有 区分动脉粥样硬化和非动脉粥样硬化性心脏病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代偿机制。

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.