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），也称为Virchow-Robin间隙，已被广泛应用于临床。 研究，其定义为蛛网膜下腔的软脑膜内衬延伸，其中 蛛网膜下脑脊液进入大脑PVS围绕穿通动脉并继续沿沿着 从穿通动脉进入白色物质。扩大的PVS常见于 磁共振成像在一些神经系统疾病。正常PVS通常不可见，因为 他们的体型很小，尤其是年轻人。因此，生理和 PVS的病理生理学意义仍不清楚。最近，几条证据表明， 表明PVS作为脑“淋巴”系统的一部分， 溶质从脑中清除。具体地说，已经证明动脉搏动 驱动蛛网膜下CSF流入PVS， 淀粉样蛋白β（Aβ）从大脑中清除; PVS通路功能障碍因此可能导致 PVS扩大，Aβ沉积增加，以及随后的神经元功能障碍和丧失， 这显然对阿尔茨海默病有着深远的影响。虽然这些最近的研究 为PVS清洁间质溶质的功能提供了宝贵的见解， 侵入性方法，如双光子显微镜或注入荧光和放射性， 使用不适用于人的标记示踪剂。因此有 开发能够显示PVS的非侵入性方法的需求日益增加 形态学（直径、长度等）和血流动力学（速度和动脉搏动） 功能，以便直接评估PVS的功能状态。我们最近 结果表明，健康青年PVS的形态学和血流动力学特征 成年人可以使用7 T进行评估。虽然我们的初步结果表明， 成像PVS，在本申请中，我们建议采取进一步措施，通过开发成像 能够分别评价CSF的形态学特征和穿透性的方法 血管（目标1）。在PVS中单独评估这两个隔室的能力将揭示 如果患病人群的CSF、穿通血管或两者均发生改变。而且 将在Aim中测量PVS中穿透性小动脉的流速和动脉搏动 2，这可能有助于评价间质溶质如何从组织中清除。 个脑袋最后，还将在目标1中评估这些参数如何随老化进行修改 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.