title: Identification of the Upward Movement of Human CSFIn Vivoand its Relation to the Brain Venous System.
abstract: 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.SIGNIFICANCE STATEMENTEffective 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 yieldedin vivoCSF 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.
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Division of Pediatric Neurology, and sdreha@gwdg.de.
authors.forename: Steffi
authors.initials: S
authors.lastname: Dreha-Kulaczewski
authors.affiliation: Biomedizinische NMR Forschungs GmbH am Max-Planck-Institut für biophysikalische Chemie, 37077 Göttingen, Germany, and.|German Center for Cardiovascular Research, Partner Site Göttingen, Germany.
authors.forename: Arun A
authors.initials: AA
authors.lastname: Joseph
authors.affiliation: Biomedizinische NMR Forschungs GmbH am Max-Planck-Institut für biophysikalische Chemie, 37077 Göttingen, Germany, and.
authors.forename: Klaus-Dietmar
authors.initials: KD
authors.lastname: Merboldt
authors.affiliation: Department of Neurosurgery, Division of Pediatric Neurosurgery, University Medical Center Göttingen, 37075 Göttingen, Germany.
authors.forename: Hans-Christoph
authors.identifier: 0000-0001-8744-9510
authors.initials: HC
authors.lastname: Ludwig
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Division of Pediatric Neurology, and.
authors.forename: Jutta
authors.initials: J
authors.lastname: Gärtner
authors.affiliation: Biomedizinische NMR Forschungs GmbH am Max-Planck-Institut für biophysikalische Chemie, 37077 Göttingen, Germany, and.|German Center for Cardiovascular Research, Partner Site Göttingen, Germany.
authors.forename: Jens
authors.identifier: 0000-0002-8279-884X
authors.initials: J
authors.lastname: Frahm
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000502:physiology*; D002552:Cerebral Ventricles / Q000502:physiology*; D002555:Cerebrospinal Fluid / Q000502:physiology*; D002560:Cerebrovascular Circulation / Q000502:physiology*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D013116:Spinal Cord / Q000000981:diagnostic imaging; D055815:Young Adult
keywords: CSF; human; in vivo flow; phase-contrast real-time MRI; respiration