RT Journal Article SR Electronic T1 Identification of the Upward Movement of Human Cerebrospinal Fluid In Vivo and its Relation to the Brain Venous System JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 2754-16 DO 10.1523/JNEUROSCI.2754-16.2017 A1 Steffi Dreha-Kulaczewski A1 Arun A Joseph A1 Klaus-Dietmar Merboldt A1 Hans-Christoph Ludwig A1 Jutta Gärtner A1 Jens Frahm YR 2017 UL http://www.jneurosci.org/content/early/2017/01/30/JNEUROSCI.2754-16.2017.abstract AB Cerebrospinal fluid (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. Forced Inspiration has recently been identified as a main driving force of CSF flow in the human brain using novel real-time magnetic resonance imaging (MRI). Exploiting technical advances towards real-time phase-contrast MRI the current work quantitatively analyzed directions, velocities and volumes of human CSF flow within the brain aqueduct, as part of the internal ventricular system, and the spinal canal during respiration. A consistent upward CSF movement towards 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, i.e., in epidural veins at cervical level C3, uniquely demonstrated CSF and venous flow to be closely communicating cerebral fluid systems where 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 opens important clinical implications, namely concepts for drug delivery as well as new classifications and therapeutic options for various forms of hydrocephalus and idiopathic intracranial hypertension.SIGNIFICANCE STATEMENTEffective disposal of brain cellular waste products via cerebrospinal fluid (CSF) has repeatedly been demonstrated in animal models. CSF dynamics in humans however are still poorly understood. A novel quantitative real-time magnetic resonance imaging technique yielded in vivo CSF flow directions, velocities and volumes in the human brain and upper spinal canal. CSF moved upwards towards the head in response to forced inspiration. Concomitant analysis of brain venous blood flow indicated CSF and venous flux to 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 as well as new classifications and therapeutic options for various forms of hydrocephalus and ideopathic intracranial hypertension.