Three-dimensional cerebrospinal fluid flow within the human ventricular system

Cerebrospinal fluid (CSF) is a Newtonian fluid and can, therefore, be modelled using computational fluid dynamics (CFD). Previous modelling of the CSF has been limited to simplified geometric models. This work describes a geometrically accurate three dimensional (3D) computational model of the human ventricular system (HVS) constructed from magnetic resonance images (MRI) of the human brain. It is an accurate and full representation of the HVS and includes appropriately positioned CSF production and drainage locations. It was used to investigate the pulsatile motion of CSF within the human brain. During this investigation CSF flow rate was set at a constant 500 ml/day, to mimic real life secretion of CSF into the system, and a pulsing velocity profile was added to the inlets to incorporate the effect of cardiac pulsations on the choroid plexus and their subsequent influence on CSF motion in the HVS. Boundary conditions for the CSF exits from the ventricles (foramina of Magendie and Lushka) were found using a “nesting” approach, in which a simplified model of the entire central nervous system (CNS) was used to examine the effects of the CSF surrounding the ventricular system (VS). This model provided time varying pressure data for the exits from the VS nested within it. The fastest flow was found in the cerebral aqueduct, where a maximum velocity of 11.38 mm/s was observed over five cycles. The maximum Reynolds number recorded during the simulation was 15 with an average Reynolds number of the order of 0.39, indicating that CSF motion is creeping flow in most of the computational domain and consequently will follow the geometry of the model. CSF pressure also varies with geometry with a maximum pressure drop of 1.14 Pa occurring through the cerebral aqueduct. CSF flow velocity is substantially slower in the areas that are furthest away from the inlets; in some areas flow is nearly stagnant.     

Three-dimensional cerebrospinal fluid flow within the human ventricular system

Cerebrospinal fluid (CSF) is a Newtonian fluid and can, therefore, be modelled using computational fluid dynamics (CFD). Previous modelling of the CSF has been limited to simplified geometric models. This work describes a geometrically accurate three dimensional (3D) computational model of the human ventricular system (HVS) constructed from magnetic resonance images (MRI) of the human brain. It is an accurate and full representation of the HVS and includes appropriately positioned CSF production and drainage locations. It was used to investigate the pulsatile motion of CSF within the human brain. During this investigation CSF flow rate was set at a constant 500 ml/day, to mimic real life secretion of CSF into the system, and a pulsing velocity profile was added to the inlets to incorporate the effect of cardiac pulsations on the choroid plexus and their subsequent influence on CSF motion in the HVS. Boundary conditions for the CSF exits from the ventricles (foramina of Magendie and Lushka) were found using a "nesting" approach, in which a simplified model of the entire central nervous system (CNS) was used to examine the effects of the CSF surrounding the ventricular system (VS). This model provided time varying pressure data for the exits from the VS nested within it. The fastest flow was found in the cerebral aqueduct, where a maximum velocity of 11.38 mm/s was observed over five cycles. The maximum Reynolds number recorded during the simulation was 15 with an average Reynolds number of the order of 0.39, indicating that CSF motion is creeping flow in most of the computational domain and consequently will follow the geometry of the model. CSF pressure also varies with geometry with a maximum pressure drop of 1.14 Pa occurring through the cerebral aqueduct. CSF flow velocity is substantially slower in the areas that are furthest away from the inlets; in some areas flow is nearly stagnant.     

The effects of the interthalamic adhesion position on cerebrospinal fluid dynamics in the cerebral ventricles

The interthalamic adhesion is a unique feature of the third ventricle in the brain. It differs in shape and size and its location varies between individuals. In this study, computational fluid dynamics was performed on 4 three-dimensional models of the cerebral ventricular system with the interthalamic adhesion modeled in different locations in the third ventricle. Cerebrospinal fluid (CSF) was modeled as incompressible Newtonian fluid and flow was assumed laminar. The periodic motion of CSF flow as a function of the cardiac cycle starting from diastole was prescribed as the inlet boundary condition at the foramen of Monroe. Results from this study show how the location of the interthalamic adhesion influences the pattern of pressure distribution in the cerebral ventricles. In addition, the highest CSF pressure in the third ventricle can vary by ～50% depending on the location of the interthalamic adhesion. We suggest that the interthalamic adhesion may have functional implications on the development of hydrocephalus and it is important to model this anatomical feature in future studies.     

The effect of ventricular volume increase in the amplitude of intracranial pressure

We study the impact of vascular pulse in the cerebrospinal fluid (CSF) pressure measured on the lateral cerebral ventricles, as well as its sensitivity with respect to ventricular volume change. Recent studies have addressed the importance of the compliance capacity in the brain and its relation to arterial pulse abortion in communicating hydrocephalus. Nevertheless, this mechanism is not fully understood. We propose a fluid-structure interaction (FSI) model on a 3?D idealized geometry based on realistic physiological and morphological parameters. The computational model describes the pulsatile deformation of the third ventricle due to arterial pulse and the resulting CSF dynamics inside brain pathways. The results show that when the volume of lateral ventricles increases up to 3.5 times, the amplitudes of both average and maximum pressure values, computed on the lateral ventricles surface, substantially decrease. This indicates that the lateral ventricles expansion leads to a dumping effect on the pressure exerted on the walls of the ventricles. These results strengthen the possibility that communicant hydrocephalus may, in fact, be a natural response to reduce abnormal high intracranial pressure (ICP) amplitude. This conclusion is in accordance with recent hypotheses suggesting that communicant hydrocephalus is related to a disequilibrium in brain compliance capacity.     

Hydrodynamic modeling of cerebrospinal fluid motion within the spinal cavity

The fluid that resides within cranial and spinal cavities, cerebrospinal fluid (CSF), moves in a pulsatile fashion to and from the cranial cavity. This motion can be measured hy magnetic resonance imaging (MRI) and may he of clinical importance in the diagnosis of several brain and spinal cord disorders such as hydrocephalus, Chiari malformation, and syringomyelia. In the present work, a geometric and hydrodynamic characterization of an anatomically relevant spinal canal model is presented. We found that inertial effects dominate the flow field under normal physiological flow rates. Along the length of the spinal canal, hydraulic diameter was found to vary significantly from 5 to 15 mm. The instantaneous Reynolds number at peak flow rate ranged from 150 to 450, and the Womersle number ranged from 5 to 17. Pulsatile flow calculations are presented for an idealized geometric representation of the spinal cavity. A linearized Navier-Stokes model of the pulsatile CSF flow was constructed based on MRI flow rate measurements taken on a healthy volunteer. The numerical model was employed to investigate effects of cross-sectional geometry and spinal cord motion on unsteady velocity, shear stress, and pressure gradientfields. The velocity field was shown to be blunt, due to the inertial character of the flow, with velocity peaks located near the boundaries of the spinal canal rather than at the midpoint between boundaries. The pressure gradient waveform was found to be almost exclusively dependent on the flow waveform and cross-sectional area. Characterization of the CSF dynamics in normal and diseased states may be important in understanding the pathophysiology of CSF related disorders. Flow models coupled with MRI flow measurements mnay become a noninvasive tool to explain the abnormal dynamics of CSF in related brain disorders as well as to determine concentration and local distribution of drugs delivered into the CSF space.     

3D Modeling of the Lateral Ventricles and Histological Characterization of Periventricular Tissue in Humans and Mouse

The ventricular system carries and circulates cerebral spinal fluid (CSF) and facilitates clearance of solutes and toxins from the brain. The functional units of the ventricles are ciliated epithelial cells termed ependymal cells, which line the ventricles and through ciliary action are capable of generating laminar flow of CSF at the ventricle surface. This monolayer of ependymal cells also provides barrier and filtration functions that promote exchange between brain interstitial fluids (ISF) and circulating CSF. Biochemical changes in the brain are thereby reflected in the composition of the CSF and destruction of the ependyma can disrupt the delicate balance of CSF and ISF exchange. In humans there is a strong correlation between lateral ventricle expansion and aging. Age-associated ventriculomegaly can occur even in the absence of dementia or obstruction of CSF flow. The exact cause and progression of ventriculomegaly is often unknown; however, enlarged ventricles can show regional and, often, extensive loss of ependymal cell coverage with ventricle surface astrogliosis and associated periventricular edema replacing the functional ependymal cell monolayer. Using MRI scans together with postmortem human brain tissue, we describe how to prepare, image and compile 3D renderings of lateral ventricle volumes, calculate lateral ventricle volumes, and characterize periventricular tissue through immunohistochemical analysis of en face lateral ventricle wall tissue preparations. Corresponding analyses of mouse brain tissue are also presented supporting the use of mouse models as a means to evaluate changes to the lateral ventricles and periventricular tissue found in human aging and disease. Together, these protocols allow investigations into the cause and effect of ventriculomegaly and highlight techniques to study ventricular system health and its important barrier and filtration functions within the brain.     

Syringomyelia hydrodynamics: an in vitro study based on in vivo measurements

A simplified in vitro model of the spinal canal, based on in vivo magnetic resonance imaging, was used to examine the hydrodynamics of the human spinal cord and subarachnoid space with syringomyelia. In vivo magnetic resonance imaging (MRI) measurements of subarachnoid (SAS) geometry and cerebrospinal fluid velocity were acquired in a patient with syringomyelia and used to aid in the in vitro model design and experiment. The in vitro model contained a fluid-filled coaxial elastic tube to represent a syrinx. A computer controlled pulsatile pump was used to subject the in vitro model to a CSF flow waveform representative of that measured in vivo. Fluid velocity was measured at three axial locations within the in vitro model using the same MRI scanner as the patient study. Pressure and syrinx wall motion measurements were conducted external to the MR scanner using the same model and flow input. Transducers measured unsteady pressure both in the SAS and intra-syrinx at four axial locations in the model A laser Doppler vibrometer recorded the syrinx wall motion at 18 axial locations and three polar positions. Results indicated that the peak-to-peak amplitude of the SAS flow waveform in vivo was approximately tenfold that of the syrinx and in phase (SAS approximately 5.2 +/- 0.6 ml/s, syrinx approximately 0.5 +/- 0.3 ml/s). The in vitro flow waveform approximated the in vivo peak-to-peak magnitude (SAS approximately 4.6 +/- 0.2 ml/s, syrinx approximately 0.4 +/- 0.3 ml/s). Peak-to-peak in vitro pressure variation in both the SAS and syrinx was approximately 6 mm Hg. Syrinx pressure waveform lead the SAS pressure waveform by approximately 40 ms. Syrinx pressure was found to be less than the SAS for approximately 200 ms during the 860-ms flow cycle. Unsteady pulse wave velocity in the syrinx was computed to be a maximum of approximately 25 m/s. LDV measurements indicated that spinal cord wall motion was nonaxisymmetric with a maximum displacement of approximately 140 microm, which is below the resolution limit of MRI. Agreement between in vivo and in vitro MR measurements demonstrates that the hydrodynamics in the fluid filled coaxial elastic tube system are similar to those present in a single patient with syringomyelia. The presented in vitro study of spinal cord wall motion, and complex unsteady pressure and flow environment within the syrinx and SAS, provides insight into the complex biomechanical forces present in syringomyelia.     

The system of cerebrospinal fluid-contacting neurons. Its supposed role in the nonsynaptic signal transmission of the brain

Recent investigations confirm the importance of nonsynaptic signal transmission in several functions of the nervous tissue. Present in various periventricular brain regions of vertebrates, the system of cerebrospinal fluid (CSF)-contacting neurons seems to have a special role in taking up, transforming and emitting nonsynaptic signals mediated by the internal and external CSF and intercellular fluid of the brain. Most of the CSF-contacting nerve cells send dendritic processes into the internal CSF of the brain ventricles or central canal where they form terminals bearing stereocilia and a 9+0-, or 9+2-type cilium. Some of these neurons resemble known sensory cells of chemoreceptor-type, others may be sensitive to the pressure or flow of the CSF, or to the illumination of the brain tissue. The axons of the CSF-contacting neurons transmit information taken up by dendrites and perikarya to synaptic zones of various brain areas. By forming neurohormonal terminals, axons also contact the external CSF space and release various bioactive substances there. Some perikarya send their axons into the internal CSF, and form free endings there, or synapses on intraventricular dendrites, perikarya and/or on the ventricular surface of ependymal cells. Contacting the intercellular space, sensory-type cilia were also demonstrated on nerve cells situated in the brain tissue subependymally or farther away from the ventricles. Among neuronal elements entering the internal CSF-space, the hypothalamic CSF-contacting neurons are present in the magnocellular and parvicellular nuclei and in some circumventricular organs like the paraventricular organ and the vascular sac. The CSF-contacting dendrites of all these areas bear a solitary 9 x 2+0-type cilium and resemble chemoreceptors cytologically. In electrophysiological experiments, the neurons of the paraventricular organ are highly sensitive to the composition of the ventricular CSF. The axons of the CSF-contacting neurons terminate not only in the hypothalamic synaptic zones but also in tel-, mes- and rhombencephalic nuclei and reach the spinal cord as well. The supposed chemical information taken up by the CSF-contacting neurons from the ventricular CSF may influence the function of these areas of the central nervous system. Some nerve cells of the photoreceptor areas form sensory terminals similar to those of the hypothalamic CSF-contacting neurons. Special secondary neurons of the retina and pineal organ contact the retinal photoreceptor space and pineal recess respectively, both cavities being embryologically derived from the 3rd ventricle. The composition of these photoreceptor spaces is important in the photochemical transduction and may modify the activity of the secondary neurons. Septal and preoptic CSF-contacting neurons contain various opsins and other compounds of the phototransduction cascade and represent deep encephalic photoreceptors detecting the illumination of the brain tissue and play a role in the regulation of circadian and reproductive responses to light. The medullo-spinal CSF-contacting neurons present in the oblongate medulla, spinal cord and terminal filum, send their dendrites into the fourth ventricle and central canal. Resembling mechanoreceptors of the lateral line organ, the spinal CSF-contacting neurons may be sensitive to the pressure or flow of the CSF. The axons of these neurons terminate at the external CSF-space of the oblongate medulla and spinal cord and form neurohormonal nerve endings. Based on information taken up from the CSF, a regulatory effect on the production or composition of CSF was supposed for bioactive materials released by these terminals. Most of the axons of the medullospinal CSF-contacting neurons and the magno- and parvicellular neurosecretory nuclei running to neurohemal areas (neurohypophysis, median eminence, terminal lamina, vascular sac and urophysis) do not terminate directly on vessels, instead they form neurohormonal nerve terminals attached by half-desmosomes on the basal lamina of the external and vascular surface of the brain tissue. Therefore, the bioactive materials released from these terminals primarily enter the external CSF and secondarily, by diffusion into vessels and the composition of the external CSF, may have a modulatory effect on the bioactive substances released by the neurohormonal terminals. Contacting the intercellular space, sensory-type cilia were also demonstrated on nerve cells situated subependymally or farther away from the ventricles, among others in the neurosecretory nuclei. Since tight-junctions are lacking between ependymal cells of the ventricular wall, not only CSF-contacting but also subependymal ciliated neurons may be influenced by the actual composition of the CSF besides that of the intercellular fluid of the brain tissue. According to the comparative histological data summarised in this review, the ventricular CSF-contacting neurons represent the phylogenetically oldest component detecting the internal fluid milieu of the brain. The neurohormonal terminals on the external surface of the brain equally represent an ancient form of nonsynaptic signal transmission.     

Transventricular and transpial absorption of cerebrospinal fluid into cerebral microvessels

It is generally accepted that volume of cerebrospinal fluid (CSF) is secreted in brain ventricles and flows to subarachnoid space to be absorbed into dural venous sinuses or/and into lymphatics via perineural sheats of cranial nerves. Since 99% of CSF volume is water, in experiments on cats 3H-water was slowly infused into lateral ventricle and found that it does not flow to subarachnoid space but that it is rapidly absorbed transventricularly into periventricular capillaries. When 3H-water was infused in cortical subarachnoid space, it was absorbed locally into cerebral capillaries via pia mater. On the contrary, when macromolecule 3H-inulin is applied in CSF it is very slowly eliminated in bloodstream, and, with time, is carried by systolic-diastolic pulsations and mixing of CSF bidirectionally along CSF system. Thus, CSF volume (water) is absorbed rapidly into adjacent cerebral capillaries while inulin is distributed bidirectionally due to its long residence time in CSF Previously, the macromolecules have been used to study CSF volume hydrodynamics and with this misconception of CSF physiology arose.     

Dysfunctional cilia lead to altered ependyma and choroid plexus function, and result in the formation of hydrocephalus

Cilia are complex organelles involved in sensory perception and fluid or cell movement. They are constructed through a highly conserved process called intraflagellar transport (IFT). Mutations in IFT genes, such as Tg737, result in severe developmental defects and disease. In the case of the Tg737orpk mutants, these pathological alterations include cystic kidney disease, biliary and pancreatic duct abnormalities, skeletal patterning defects, and hydrocephalus. Here, we explore the connection between cilia dysfunction and the development of hydrocephalus by using the Tg737orpk mutants. Our analysis indicates that cilia on cells of the brain ventricles of Tg737orpk mutant mice are severely malformed. On the ependymal cells, these defects lead to disorganized beating and impaired cerebrospinal fluid (CSF) movement. However, the loss of the cilia beat and CSF flow is not the initiating factor, as the pathology is present prior to the development of motile cilia on these cells and CSF flow is not impaired at early stages of the disease. Rather, our results suggest that loss of cilia leads to altered function of the choroid plexus epithelium, as evidenced by elevated intracellular cAMP levels and increased chloride concentration in the CSF. These data suggest that cilia function is necessary for regulating ion transport and CSF production, as well as for CSF flow through the ventricles.     

Totally tubular: the mystery behind function and origin of the brain ventricular system

A unique feature of the vertebrate brain is the ventricular system, a series of connected cavities which are filled with cerebrospinal fluid (CSF) and surrounded by neuroepithelium. While CSF is critical for both adult brain function and embryonic brain development, neither development nor function of the brain ventricular system is fully understood. In this review, we discuss the mystery of why vertebrate brains have ventricles, and whence they originate. The brain ventricular system develops from the lumen of the neural tube, as the neuroepithelium undergoes morphogenesis. The molecular mechanisms underlying this ontogeny are described. We discuss possible functions of both adult and embryonic brain ventricles, as well as major brain defects that are associated with CSF and brain ventricular abnormalities. We conclude that vertebrates have taken advantage of their neural tube to form the essential brain ventricular system.     

Multiple Primary Cilia Modulate the Fluid Transcytosis in Choroid Plexus Epithelium

Functional defects in cilia are associated with various human diseases including congenital hydrocephalus. Previous studies suggested that defects in cilia not only disrupt the flow of cerebrospinal fluid (CSF) generated by motile cilia in ependyma lining the brain ventricles, but also cause increased CSF production at the choroid plexus. However, the molecular mechanisms of CSF overproduction by ciliary dysfunction remain elusive. To dissect the molecular mechanisms, choroid plexus epithelial cells (CPECs) were isolated from porcine brain. These cells expressed clusters of primary cilia on the apical surface. Deciliation of CPECs elevated the intracellular cyclic AMP (cAMP) levels and stimulated basolateral‐to‐apical fluid transcytosis, without detrimental effects on other morphological and physiological features. The primary cilia possessed neuropeptide FF (NPFF) receptor 2. In deciliated cells, the responsiveness to NPFF was reduced at nanomolar concentrations. Furthermore, CPECs expressed NPFF precursor along with NPFFR2. An NPFFR antagonist, BIBP3226, increased the fluid transcytosis, suggesting the presence of autocrine NPFF signaling in CPECs for a tonic inhibition of fluid transcytosis. These results suggest that the clusters of primary cilia in CPECs act as a sensitive chemosensor to regulate CSF production.     

Modélisation des flux cérébraux par une analogie électrique : validation par vélocimétrie IRM

The cine Phase-Contrast Magnetic Resonance (PCMR) sequence is the only noninvasive technique for the study of cerebrospinal fluid (CSF) oscillations. It can provide CSF and blood flow measurements throughout the cardiac cycle. To study cerebral hydro-hemodynamic, models have been developed; nevertheless the majority of these models did not take into account the CSF oscillations. The objective of this study was to establish reference values for cerebral hydro-hemodynamic and propose a new electrical model of the brain dynamics.Material and methodsCSF and blood flows were measured in 19 control subjects by PCMR imaging. Dynamic flow images were analyzed on dedicated software to reconstruct the flow curves during the cardiac cycle. An electrical analogue was realized. The inputs of the model were fed by PCMR arterial and venous flows to simulate CSF oscillations. The simulated CSF oscillations were compared to the measured CSF oscillations to validate the model.ResultsThe key parameters of the CSF and blood flow curves were obtained, e.g. total cerebral blood flow was 688 ± 115 mL/min, ventricular CSF oscillatory volume was 0.05 ± 0.02 mL/cardiac cycle, and the subarachnoid CSF oscillatory volume was 0.55 ± 0.15 mL/cardiac cycle. A close agreement was found between measured and simulated cerebral CSF oscillations.ConclusionThis study established the main values characterizing cerebral hydrodynamics in a control population. It provided a better understanding of the mechanisms of intracranial volumes regulation during the cardiac cycle. Our results are now used in clinical practice and the model proposed is effective to study cerebral hydro-hemodynamic.     

The pathogenesis of normal pressure hydrocephalus: A theoretical analysis

Hydrocephalus is an abnormal accumulation of cerebrospinal fluid (CSF) in the cerebral ventricles, usually caused by impaired absorption of the fluid into the bloodstream. Despite obstructed absorption and continued secretion of CSF into the ventricles at a near normal rate, the ventricular CSF pressure (VCSFP) is often normal. We attempt to understand how hydrocephalus can exist with normal VCSFP by exploring the role of the brain parenchyma in absorbing CSF in hydrocephalus. We test three theories: (1) the ventricular wall is impermeable to CSF; (2) ventricular CSF seeps into the parenchyma, from which it is efficiently absorbed; and (3) ventricular CSF seeps into the parenchyma but is absorbed inefficiently. We model the brain as a thick spherical shell consisting of a porous, elastic, solid matrix, containing interstitial fluid and blood. We modify the equations of poroelasticity, which describe flow of fluid through porous solids, to allow for parenchymal absorption. For each of the three theories we calculate the steady state changes in VCSFP and in parenchymal fluid pressure caused by an incremental defect in CSF absorption. We also calculate the steady state changes in fluid content, tissue volume, tissue displacement, and stresses caused by a small increment of VCSFP. We conclude that only the second theory—seepage of CSF with efficient parenchymal absorption—accounts for the clinical features of normal pressure hydrocephalus. These features include sustained ventricular dilatation despite normal VCSFP, increased periventricular fluid content, and localized periventricular white matter damage.     

Choroid plexus trophic factors in the developing and adult brain

The choroid plexus (CP), localized in brain ventricles, is the major source of cerebrospinal fluid (CSF) and participates in the blood-CSF barrier. It is essential for brain immunosurveillance and the clearance of toxics, and for brain development and activity. Indeed, the CP secretes a large variety of trophic factors in the CSF that impact the entire brain. These factors are mainly implicated in neurogenesis, but also in the maintenance of brain functions and the vasculature. In this mini-review, we provide an overview of the various trophic factors secreted by the CP in the CSF, and describe their roles in the developing, adult and diseased brain.     

The Choroid Plexuses and the Barriers Between the Blood and the Cerebrospinal Fluid

1. The fluid homeostasis of the brain depends both on the endothelial blood–brain barrier and on the epithelial blood–cerebrospinal fluid (CSF) barrier located at the choroid plexuses and the outer arachnoid membrane.2. The brain has two fluid environments: the brain interstitial fluid, which surrounds the neurons and glia, and the CSF, which fills the ventricles and external surfaces of the central nervous system.3. CSF acts as a fluid cushion for the brain and as a drainage route for the waste products of cerebral metabolism.4. Recent findings suggest that CSF may also act as a third circulation conveying substances secreted into the CSF rapidly to many brain regions.     

Comparison of 4D Phase-Contrast MRI Flow Measurements to Computational Fluid Dynamics Simulations of Cerebrospinal Fluid Motion in the Cervical Spine

Cerebrospinal fluid (CSF) dynamics in the cervical spinal subarachnoid space (SSS) have been thought to be important to help diagnose and assess craniospinal disorders such as Chiari I malformation (CM). In this study we obtained time-resolved three directional velocity encoded phase-contrast MRI (4D PC MRI) in three healthy volunteers and four CM patients and compared the 4D PC MRI measurements to subject-specific 3D computational fluid dynamics (CFD) simulations. The CFD simulations considered the geometry to be rigid-walled and did not include small anatomical structures such as nerve roots, denticulate ligaments and arachnoid trabeculae. Results were compared at nine axial planes along the cervical SSS in terms of peak CSF velocities in both the cranial and caudal direction and visual interpretation of thru-plane velocity profiles. 4D PC MRI peak CSF velocities were consistently greater than the CFD peak velocities and these differences were more pronounced in CM patients than in healthy subjects. In the upper cervical SSS of CM patients the 4D PC MRI quantified stronger fluid jets than the CFD. Visual interpretation of the 4D PC MRI thru-plane velocity profiles showed greater pulsatile movement of CSF in the anterior SSS in comparison to the posterior and reduction in local CSF velocities near nerve roots. CFD velocity profiles were relatively uniform around the spinal cord for all subjects. This study represents the first comparison of 4D PC MRI measurements to CFD of CSF flow in the cervical SSS. The results highlight the utility of 4D PC MRI for evaluation of complex CSF dynamics and the need for improvement of CFD methodology. Future studies are needed to investigate whether integration of fine anatomical structures and gross motion of the brain and/or spinal cord into the computational model will lead to a better agreement between the two techniques.     

Effects of fluid structure interaction in a three dimensional model of the spinal subarachnoid space

It is unknown whether spinal cord motion has a significant effect on cerebrospinal fluid (CSF) pressure and therefore the importance of including fluid structure interaction (FSI) in computational fluid dynamics models (CFD) of the spinal subarachnoid space (SAS) is unclear. This study aims to determine the effects of FSI on CSF pressure and spinal cord motion in a normal and in a stenosis model of the SAS. A three-dimensional patient specific model of the SAS and spinal cord were constructed from MR anatomical images and CSF flow rate measurements obtained from a healthy human being. The area of SAS at spinal level T4 was constricted by 20% to represent the stenosis model. FSI simulations in both models were performed by running ANSYS CFX and ANSYS Mechanical in tandem. Results from this study show that the effect of FSI on CSF pressure is only about 1% in both the normal and stenosis models and therefore show that FSI has a negligible effect on CSF pressure.     

Cerebrospinal fluid flow increases from newborn to adult stages

Solute transport through the brain is of major importance for the clearance of toxic molecules and metabolites, and it plays key roles in the pathophysiology of the central nervous system. This solute transport notably depends on the cerebrospinal fluid (CSF) flow, which circulates in the subarachnoid spaces, the ventricles and the perivascular spaces. We hypothesized that the CSF flow may be different in the perinatal period compared to the adult period. Using in vivo magnetic resonance imaging (MRI) and near‐infrared fluorescence imaging (NIRF), we assessed the dynamic of the CSF flow in rodents at different ages. By injecting a contrast agent into the CSF, we first used MRI to demonstrate that CSF flow gradually increases with age, with the adult pattern observed at P90. This observation was confirmed by NIRF, which revealed an increased CSF flow in P90 rats when compared with P4 rats not only at the surface of the brain but also deep in the brain structures. Lastly, we evaluated the exit routes of the CSF from the brain. We demonstrated that indocyanine green injected directly into the striatum spread throughout the parenchyma in adult rats, whereas it stayed at the injection point in P4 rats. Moreover, the ability of CSF to exit through the nasal mucosa was increased in the adult rodents. Our results provide evidence that the perinatal brain has nonoptimal CSF flow and exit and, thus, may have impaired clean‐up capacity. © 2018 Wiley Periodicals, Inc. Develop Neurobiol, 2018     

Development of the brain: a vital role for cerebrospinal fluid

There has been considerable recent progress in understanding the processes involved in brain development. An analysis of a number of neurological conditions, together with our studies of the hydrocephalic Texas (H-Tx) rat, presents an important role for cerebrospinal fluid (CSF) in the developmental process. The fluid flow is essentially one-way and the location of the choroid plexuses in the lateral, third, and fourth ventricles allows for the possibility of new components being added to the fluid at these points. The role of the fourth ventricular CSF is particularly interesting since this is added to the fluid downstream of the cerebral hemisphere germinal epithelium (the main site of cortical cell proliferation and differentiation) and is destined for the basal cisterns and subarachnoid space suggesting different target cells to those within the ventricular system. Moreover, other sources of additions to the CSF exist, notably the subcommissural organ, which sits at the opening of the third ventricle into the cerebral aqueduct and is the source of Reisner's fibre, glycoproteins, and unknown soluble proteins. In this paper a model for the role of CSF is developed from studies of the development of the cortex of the H-Tx rat. We propose that CSF is vital in controlling development of the nervous system along the whole length of the neural tube and that the externalisation of CSF during development is essential for the formation of the layers of neurones in the cerebral cortex.