Dreha-Kulaczewski Steffi, Joseph Arun A, Merboldt Klaus-Dietmar, Ludwig Hans-Christoph, Gärtner Jutta, Frahm Jens
Department of Pediatrics and Adolescent Medicine, Division of Pediatric Neurology, and
Biomedizinische NMR Forschungs GmbH am Max-Planck-Institut für biophysikalische Chemie, 37077 Göttingen, Germany, and.
J Neurosci. 2017 Mar 1;37(9):2395-2402. doi: 10.1523/JNEUROSCI.2754-16.2017. Epub 2017 Jan 30.
CSF flux is involved in the pathophysiology of neurodegenerative diseases and cognitive impairment after traumatic brain injury, all hallmarked by the accumulation of cellular metabolic waste. Its effective disposal via various CSF routes has been demonstrated in animal models. In contrast, the CSF dynamics in humans are still poorly understood. Using novel real-time MRI, forced inspiration has been identified recently as a main driving force of CSF flow in the human brain. Exploiting technical advances toward real-time phase-contrast MRI, the current work analyzed directions, velocities, and volumes of human CSF flow within the brain aqueduct as part of the internal ventricular system and in the spinal canal during respiratory cycles. A consistent upward CSF movement toward the brain in response to forced inspiration was seen in all subjects at the aqueduct, in 11/12 subjects at thoracic level 2, and in 4/12 subjects at thoracic level 5. Concomitant analyses of CSF dynamics and cerebral venous blood flow, that is, in epidural veins at cervical level 3, uniquely demonstrated CSF and venous flow to be closely communicating cerebral fluid systems in which inspiration-induced downward flow of venous blood due to reduced intrathoracic pressure is counterbalanced by an upward movement of CSF. The results extend our understanding of human CSF flux and open important clinical implications, including concepts for drug delivery and new classifications and therapeutic options for various forms of hydrocephalus and idiopathic intracranial hypertension. Effective disposal of brain cellular waste products via CSF has been demonstrated repeatedly in animal models. However, CSF dynamics in humans are still poorly understood. A novel quantitative real-time MRI technique yielded CSF flow directions, velocities, and volumes in the human brain and upper spinal canal. CSF moved upward toward the head in response to forced inspiration. Concomitant analysis of brain venous blood flow indicated that CSF and venous flux act as closely communicating systems. The finding of a human CSF-venous network with upward CSF net movement opens new clinical concepts for drug delivery and new classifications and therapeutic options for various forms of hydrocephalus and ideopathic intracranial hypertension.
脑脊液流动参与神经退行性疾病的病理生理学过程以及创伤性脑损伤后的认知障碍，这些均以细胞代谢废物的积累为特征。在动物模型中已证实通过各种脑脊液途径有效清除这些废物。相比之下，人类脑脊液动力学仍知之甚少。利用新型实时磁共振成像技术，最近已确定强制吸气是人类大脑中脑脊液流动的主要驱动力。借助实时相位对比磁共振成像技术的技术进步，当前研究分析了作为脑室系统一部分的中脑导水管以及呼吸周期中脊髓管内人类脑脊液流动的方向、速度和体积。在所有受试者的中脑导水管处、12名受试者中的11名在胸2水平以及12名受试者中的4名在胸5水平均观察到，强制吸气时脑脊液一致向上流向大脑。对脑脊液动力学和脑静脉血流（即颈3水平硬膜外静脉）的同步分析独特地表明，脑脊液和静脉血流是紧密相连的脑液系统，其中由于胸腔内压力降低导致的吸气诱导静脉血向下流动被脑脊液向上运动所抵消。这些结果扩展了我们对人类脑脊液流动的理解，并开启了重要的临床意义，包括药物递送概念以及各种形式脑积水和特发性颅内高压的新分类和治疗选择。在动物模型中已反复证明通过脑脊液有效清除脑细胞废物。然而，人类脑脊液动力学仍知之甚少。一种新型定量实时磁共振成像技术得出了人类大脑和上脊髓管中的脑脊液流动方向、速度和体积。强制吸气时脑脊液向上流向头部。对脑静脉血流的同步分析表明，脑脊液和静脉血流是紧密相连的系统。发现具有脑脊液净向上运动的人类脑脊液 - 静脉网络为药物递送开启了新的临床概念，并为各种形式的脑积水和特发性颅内高压提供了新的分类和治疗选择。
