Advanced MRI Section, Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States.
Advanced MRI Section, Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States.
Neuroimage. 2022 Sep;258:119362. doi: 10.1016/j.neuroimage.2022.119362. Epub 2022 Jun 8.
Cerebrospinal fluid (CSF) provides physical protection to the central nervous system as well as an essential homeostatic environment for the normal functioning of neurons. Additionally, it has been proposed that the pulsatile movement of CSF may assist in glymphatic clearance of brain metabolic waste products implicated in neurodegeneration. In awake humans, CSF flow dynamics are thought to be driven primarily by cerebral blood volume fluctuations resulting from a number of mechanisms, including a passive vascular response to blood pressure variations associated with cardiac and respiratory cycles. Recent research has shown that mechanisms that rely on the action of vascular smooth muscle cells ("cerebrovascular activity") such as neuronal activity, changes in intravascular CO, and autonomic activation from the brainstem, may lead to CSF pulsations as well. Nevertheless, the relative contribution of these mechanisms to CSF flow remains unclear. To investigate this further, we developed an MRI approach capable of disentangling and quantifying CSF flow components of different time scales associated with these mechanisms. This approach was evaluated on human control subjects (n = 12) performing intermittent voluntary deep inspirations, by determining peak flow velocities and displaced volumes between these mechanisms in the fourth ventricle. We found that peak flow velocities were similar between the different mechanisms, while displaced volumes per cycle were about a magnitude larger for deep inspirations. CSF flow velocity peaked at around 10.4 s (range 7.1-14.8 s, n = 12) following deep inspiration, consistent with known cerebrovascular activation delays for this autonomic challenge. These findings point to an important role of cerebrovascular activity in the genesis of CSF pulsations. Other regulatory triggers for cerebral blood flow such as autonomic arousal and orthostatic challenges may create major CSF pulsatile movement as well. Future quantitative comparison of these and possibly additional types of CSF pulsations with the proposed approach may help clarify the conditions that affect CSF flow dynamics.
脑脊液（CSF）不仅为中枢神经系统提供物理保护，还为神经元的正常功能提供重要的动态平衡环境。此外，有人提出，CSF 的脉动运动可能有助于清除与神经退行性变有关的脑代谢废物的糖质淋清除。在清醒的人类中，CSF 流动动力学被认为主要是由多种机制引起的脑血流体积波动驱动的，包括与心脏和呼吸周期相关的血压变化引起的被动血管反应。最近的研究表明，依赖血管平滑肌细胞（“脑血管活动”）作用的机制，如神经元活动、血管内 CO 变化和来自脑干的自主激活，也可能导致 CSF 脉动。然而，这些机制对 CSF 流动的相对贡献尚不清楚。为了进一步研究这个问题，我们开发了一种 MRI 方法，能够分离和量化与这些机制相关的不同时间尺度的 CSF 流动成分。该方法在进行间歇性自愿深呼吸的人类对照受试者（n=12）上进行了评估，通过确定第四脑室中这些机制之间的峰值流速和位移体积来评估。我们发现，不同机制之间的峰值流速相似，而深呼吸时每个周期的位移体积要大一个数量级。CSF 流速在深呼吸后约 10.4 秒（范围 7.1-14.8 秒，n=12）达到峰值，与这种自主挑战的已知脑血管激活延迟一致。这些发现表明脑血管活动在 CSF 脉动的产生中起着重要作用。其他调节脑血流的触发因素，如自主唤醒和直立挑战，也可能产生主要的 CSF 脉动运动。未来使用这种方法对这些和可能的其他类型的 CSF 脉动与提出的方法进行定量比较，可能有助于阐明影响 CSF 流动动力学的条件。
