Characterizing morphological and hemodynamic characteristics of human brain perivascular spaces with aging using 7T MRI

项目摘要 血管周围间隙(PVS)，也被称为Virchow-Robin间隙，已经被广泛地 定义为蛛网膜下腔的软脑膜延长线，其中 蛛网膜下腔脑脊液进入大脑。PVS环绕穿透动脉并继续沿着 在穿透动脉的外面进入白质。增大的PVS常见于 磁共振成像在一些神经系统疾病中。由于以下原因，正常PVS通常不可见 它们的体型很小，尤其是年轻人。因此，生理学和 PVS的病理生理学意义仍不清楚。最近，有几条证据表明 提示PVS是大脑“淋巴”系统的一部分，通过间质 溶质从大脑中清除。具体地说，已经证明动脉搏动 推动蛛网膜下腔脑脊液流入PVS，并通过该系统 淀粉样β蛋白(Aβ)从脑中清除；PVS通路功能障碍可能导致 PVS增大，Aβ沉积增加，继而出现神经元功能障碍和丢失， 这显然对阿尔茨海默氏症有着深远的影响。虽然最近的这些研究 为PVS清洁间隙溶质的功能提供了宝贵的见解， 侵入性方法，如双光子显微镜或荧光和放射性输注- 使用了标记示踪剂，这不适用于人类。因此，有以下几种 开发能够显示PVS的非侵入性方法的需求日益增长 形态(直径、长度等)和血流动力学(速度和动脉搏动) 功能，以便能够直接评估PVS的功能状态。我们最近做了 证实了健康青年PVS的形态和血流动力学特征。 成人可以使用7T进行评估。虽然我们的初步结果证明了 成像PVS，在本应用程序中，我们建议通过开发成像进一步采取步骤 可分别评价脑脊液形态特征和穿透性的方法 船只(目标1)。在PVS中分别评估这两个隔间的能力将揭示 在患病人群中，如果脑脊液、穿透血管或两者都改变了。此外， AIM将测量PVS中穿透小动脉的血流速度和动脉搏动 2，潜在地能够评估间隙溶质是如何从 大脑。最后，这些参数如何随着老化而修改，也将在AIMS 1中进行评估 和2.

Project Summary Perivascular spaces (PVS), also known as the Virchow-Robin spaces, have been widely studied, which are defined as the pia-lined extensions of the subarachnoid space where subarachnoid CSF enters the brain. PVS surround penetrating arteries and continue along the outside of the penetrating arteries into white matter. Enlarged PVS are commonly observed in MR images in a number of neurological disorders. Normal PVS are typically not visible due to their small sizes, particularly in young adults. As a result, the physiological and pathophysiological significance of PVS remain elusive. Recently, several lines of evidence have suggested that PVS serve as part of the brain “lymphatic” system through which interstitial solutes are cleared from the brain. Specifically, it has been demonstrated that arterial pulsation drives subarachnoid CSF flowing into the PVS and through which soluble proteins such as amyloid beta (Aβ) are cleared from the brain; dysfunction of PVS pathway thus may lead to enlarged PVS, an increased Aβ deposition, and subsequent neuronal dysfunction and loss, which clearly has profound implications in Alzheimer's diseases. While these recent studies have provided invaluable insights into the functions of PVS for cleaning interstitial solutes, invasive approaches such as two-photon microscopy or infusion of fluorescent and radio- labeled tracers were employed, which are not applicable to humans. Therefore, there are increasing needs of developing non-invasive approaches capable of revealing the PVS morphological (diameters, lengths and so on) and hemodynamic (velocity and arterial pulsation) features so as to allow direct assessments of the functional status of PVS. We have recently demonstrated that both the morphological and hemodynamic features of PVS in healthy young adults can be assessed using 7T. While our preliminary results demonstrate the feasibility of imaging PVS, in this application we propose to take steps further by developing imaging approaches capable of separately evaluating the morphological features of CSF and penetrating vessels (Aim 1). The ability of separately evaluating these two compartments in PVS will reveal if the CSF, penetrating vessels or both are altered in diseased populations. Furthermore, the flow velocity and arterial pulsatility of the penetrating arterioles in PVS will be measured in Aim 2 which could, potentially, enable the evaluation of how interstitial solutes are cleared from the brain. Finally, how these parameters are modified with aging will also be evaluated in Aims 1 and 2.