The glymphatic system has in previous studies been shown as fundamental to clearance of waste metabolites from the brain interstitial space, and is proposed to be instrumental in normal ageing and brain pathology such as Alzheimer’s disease and brain trauma. Assessment of glymphatic function using magnetic resonance imaging with intrathecal contrast agent as a cerebrospinal fluid tracer has so far been limited to rodents. We aimed to image cerebrospinal fluid flow characteristics and glymphatic function in humans, and applied the methodology in a prospective study of 15 idiopathic normal pressure hydrocephalus patients (mean age 71.3 ± 8.1 years, three female and 12 male) and eight reference subjects (mean age 41.1 + 13.0 years, six female and two male) with suspected cerebrospinal fluid leakage (seven) and intracranial cyst (one). The imaging protocol included T₁-weighted magnetic resonance imaging with equal sequence parameters before and at multiple time points through 24 h after intrathecal injection of the contrast agent gadobutrol at the lumbar level. All study subjects were kept in the supine position between examinations during the first day. Gadobutrol enhancement was measured at all imaging time points from regions of interest placed at predefined locations in brain parenchyma, the subarachnoid and intraventricular space, and inside the sagittal sinus. Parameters demonstrating gadobutrol enhancement and clearance in different locations were compared between idiopathic normal pressure hydrocephalus and reference subjects. A characteristic flow pattern in idiopathic normal hydrocephalus was ventricular reflux of gadobutrol from the subarachnoid space followed by transependymal gadobutrol migration. At the brain surfaces, gadobutrol propagated antegradely along large leptomeningeal arteries in all study subjects, and preceded glymphatic enhancement in adjacent brain tissue, indicating a pivotal role of intracranial pulsations for glymphatic function. In idiopathic normal pressure hydrocephalus, we found delayed enhancement (P < 0.05) and decreased clearance of gadobutrol (P < 0.05) at the Sylvian fissure. Parenchymal (glymphatic) enhancement peaked overnight in both study groups, possibly indicating a crucial role of sleep, and was larger in normal pressure hydrocephalus patients (P < 0.05 at inferior frontal gyrus). We interpret decreased gadobutrol clearance from the subarachnoid space, along with persisting enhancement in brain parenchyma, as signs of reduced glymphatic clearance in idiopathic normal hydrocephalus, and hypothesize that reduced glymphatic function is instrumental for dementia in this disease. The study shows promise for glymphatic magnetic resonance imaging as a method to assess human brain metabolic function and renders a potential for contrast enhanced brain extravascular space imaging.

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特发性常压性脑积水的淋巴MRI检查

在先前的研究中，淋巴系统被证明是清除脑间质空间废物代谢产物的基础，并被提议在正常衰老和脑病理学（例如阿尔茨海默氏病和脑外伤）中发挥作用。迄今为止，使用鞘内造影剂作为脑脊髓液示踪剂的磁共振成像对淋巴功能的评估仅限于啮齿动物。我们旨在对人的脑脊液流动特征和淋巴功能进行成像，并将该方法应用于前瞻性研究中，对15例特发性正常压力脑积水患者（平均年龄71.3±8.1岁，3例女性和12例男性）和8例参考受试者（平均年龄） 41.1 + 13.0岁，女性6例，男性2例），疑似脑脊液漏（七例）和颅内囊肿（一例）。_1个鞘内注射造影剂加多布特罗在腰椎水平之前和之后的多个时间点之前和之后的24小时内，使用相等的序列参数进行加权磁共振成像。在第一天之间，所有研究对象在两次检查之间保持仰卧姿势。在所有成像时间点，从位于脑实质，蛛网膜下腔和脑室内空间以及矢状窦内的预定位置的感兴趣区域测量了Gadobutrol的增强作用。比较了特发性正常压力脑积水和参考对象在不同位置显示了gadobutrol增强和清除的参数。特发性正常脑积水的典型血流模式是ado从蛛网膜下腔向室性返流，然后经室间隔y移。在脑表面，加多布罗尔在所有研究对象中均沿大的软脑膜动脉前期传播，并在相邻脑组织内的淋巴管增强之前发生，这表明颅内搏动对淋巴管功能起着关键作用。在特发性正常压力脑积水中，我们发现延迟增强（P <0.05），降低了西多维亚裂隙中加多布特罗的清除率（P <0.05）。在两个研究组中，实质（淋巴）增强在夜间达到峰值，这可能表明睡眠至关重要，而在正常压力脑积水患者中则更大（P下额回小于0.05）。我们将蛛网膜下腔中gadobutrol清除率的降低以及脑实质的持续增强解释为特发性正常脑积水中淋巴清除率降低的迹象，并假设降低的淋巴管功能对这种疾病的痴呆症具有重要作用。这项研究显示了将淋巴核磁共振成像作为评估人脑代谢功能的一种方法的前景，并为对比增强脑血管外空间成像提供了潜力。