Cerebrospinal fluid (CSF) circulation has recently been shown to be important in nutrient distribution, waste removal, and neurogenesis. Increased CSF volumes are frequently observed in congenital heart disease (CHD) and are associated with neurodevelopmental deficits. This suggests prolonged perturbation to the CSF system and possible interference to its homeostatic function, which may contribute to the neurodevelopmental deficits in CHD. CSF flow has yet to be studied in CHD patients, but the pulsatile flow of CSF throughout the brain is driven mainly by cardiopulmonary circulation. Given the underlying heart defects in CHD, the cardiopulmonary circulatory mechanisms in CHD might be impaired with resultant perturbation on the CSF circulation. In this study, we determine whether CSF flow, using MRI measurements of static and dynamic pulsatile flow, is abnormal in youths with CHD compared to healthy controls in relation to executive cognitive function. CSF flow measurements were obtained on a total of 58 child and young adult participants (CHD=20, healthy controls = 38). The CSF flow was measured across the lumen of the Aqueduct of Sylvius using cardiac-gated phase-contrast MRI at 3.0T. Static pulsatility was characterized as anterograde and retrograde peak velocities, mean velocity, velocity variance measurements, and dynamic pulsatility calculated as each participant’s CSF flow deviation from the study cohort’s consensus flow measured with root mean squared deviation (RMSD) were obtained. The participants had neurocognitive assessments for executive function with focus on inhibition, cognitive flexibility, and working memory domains. The CHD group demonstrated greater dynamic pulsatility (higher overall flow RMSD over the entire CSF flow cycle) compared to controls (p=0.0353), with no difference detected in static pulsatility measures. However, lower static CSF flow pulsatility (anterograde peak velocity: p=0.0323) and lower dynamic CSF flow pulsatility (RMSD: p=0.0181) predicted poor inhibitory executive function outcome. Taken together, while the whole CHD group exhibited higher dynamic CSF flow pulsatility compared to controls, the subset of CHD subjects with relatively reduced static and dynamic CSF flow pulsatility had the worst executive functioning, specifically the inhibition domain. These findings suggest that altered CSF flow pulsatility may be central to not only brain compensatory mechanisms but can also drive cognitive impairment in CHD. Further studies are needed to investigate possible mechanistic etiologies of aberrant CSF pulsatility (i.e. primary cardiac hemodynamic disturbances, intrinsic brain vascular stiffness, altered visco-elastic properties of tissue, or glial-lymphatic disturbances), which can result in acquired small vessel brain injury (including microbleeds and white matter hyperintensities).

中文翻译：

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先天性心脏病的定量磁共振脑脊液流动特性和执行功能认知结果

最近被证明脑脊液（CSF）循环对于营养分配、废物清除和神经发生很重要。脑脊液体积增加常见于先天性心脏病 (CHD)，并且与神经发育缺陷相关。这表明脑脊液系统受到长期干扰，并可能干扰其稳态功能，这可能导致先心病的神经发育缺陷。 CSF 流量尚未在 CHD 患者中进行研究，但整个大脑的 CSF 脉动流量主要由心肺循环驱动。鉴于冠心病潜在的心脏缺陷，冠心病的心肺循环机制可能会受到损害，从而扰乱脑脊液循环。在这项研究中，我们通过静态和动态脉动流的 MRI 测量，确定与健康对照相比，患有 CHD 的青少年的脑脊液流在执行认知功能方面是否异常。总共 58 名儿童和青少年参与者（CHD=20，健康对照=38）获得了脑脊液流量测量结果。使用 3.0T 的心脏门控相位对比 MRI 测量穿过西尔维乌斯导水管管腔的脑脊液流量。静态搏动的特征是顺行和逆行峰值速度、平均速度、速度方差测量值，以及动态搏动，计算为每个参与者的脑脊液流量与使用均方根偏差（RMSD）测量的研究队列一致流量的偏差。参与者对执行功能进行了神经认知评估，重点关注抑制、认知灵活性和工作记忆领域。与对照组相比，CHD 组表现出更大的动态搏动性（整个 CSF 血流周期的总血流 RMSD 更高）（p=0.0353），而静态搏动性测量结果没有检测到差异。然而，较低的静态脑脊液流量脉动（顺行峰值速度：p=0.0323）和较低的动态脑脊液流量脉动（RMSD：p=0.0181）预示着较差的抑制执行功能结果。总而言之，虽然与对照组相比，整个 CHD 组表现出更高的动态 CSF 血流脉动，但静态和动态 CSF 血流脉动相对降低的 CHD 受试者子集的执行功能最差，特别是抑制域。这些发现表明，脑脊液流量脉动的改变可能不仅是大脑代偿机制的核心，而且还可能导致冠心病的认知障碍。需要进一步的研究来调查异常脑脊液搏动的可能机制（即原发性心脏血流动力学紊乱、固有脑血管僵硬、组织粘弹性特性改变或神经胶质淋巴紊乱），这可能导致获得性小血管脑损伤。包括微出血和白质高信号）。