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Neurofluids is a term introduced to define all fluids in the brain and spine such as blood, cerebrospinal fluid, and interstitial fluid. Neuroscientists in the past millennium have steadily identified the several different fluid environments in the brain and spine that interact in a synchronized harmonious manner to assure a healthy microenvironment required for optimal neuroglial function. Neuroanatomists and biochemists have provided an incredible wealth of evidence revealing the anatomy of perivascular spaces, meninges and glia and their role in drainage of neuronal waste products. Human studies have been limited due to the restricted availability of noninvasive imaging modalities that can provide a high spatiotemporal depiction of the brain neurofluids. Therefore, animal studies have been key in advancing our knowledge of the temporal and spatial dynamics of fluids, for example, by injecting tracers with different molecular weights. Such studies have sparked interest to identify possible disruptions to neurofluids dynamics in human diseases such as small vessel disease, cerebral amyloid angiopathy, and dementia. However, key differences between rodent and human physiology should be considered when extrapolating these findings to understand the human brain. An increasing armamentarium of noninvasive MRI techniques is being built to identify markers of altered drainage pathways. During the three-day workshop organized by the International Society of Magnetic Resonance in Medicine that was held in Rome in September 2022, several of these concepts were discussed by a distinguished international faculty to lay the basis of what is known and where we still lack evidence. We envision that in the next decade, MRI will allow imaging of the physiology of neurofluid dynamics and drainage pathways in the human brain to identify true pathological processes underlying disease and to discover new avenues for early diagnoses and treatments including drug delivery. Evidence level: 1 Technical Efficacy: Stage 3., (© 2023 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Background: Detecting changes in pulsatile cerebrospinal fluid (CSF) flow may assist clinical management decisions, but spinal CSF flow is relatively understudied. Traumatic spinal cord injuries (SCI) often cause spinal cord swelling and subarachnoid space (SAS) obstruction, potentially causing pulsatile CSF flow changes. Pigs are emerging as a favoured large animal SCI model; therefore, the aim of this study was to characterise CSF flow along the healthy pig spine., Methods: Phase-contrast magnetic resonance images (PC-MRI), retrospectively cardiac gated, were acquired for fourteen laterally recumbent, anaesthetised and ventilated, female domestic pigs (22-29 kg). Axial images were obtained at C2/C3, T8/T9, T11/T12 and L1/L2. Dorsal and ventral SAS regions of interest (ROI) were manually segmented. CSF flow and velocity were determined throughout a cardiac cycle. Linear mixed-effects models, with post-hoc comparisons, were used to identify differences in peak systolic/diastolic flow, and maximum velocity (cranial/caudal), across spinal levels and dorsal/ventral SAS. Velocity wave speed from C2/C3 to L1/L2 was calculated., Results: PC-MRI data were obtained for 11/14 animals. Pulsatile CSF flow was observed at all spinal levels. Peak systolic flow was greater at C2/C3 (dorsal: - 0.32 ± 0.14 mL/s, ventral: - 0.15 ± 0.13 mL/s) than T8/T9 dorsally (- 0.04 ± 0.03 mL/s; p < 0.001), but not different ventrally (- 0.08 ± 0.08 mL/s; p = 0.275), and no difference between thoracolumbar levels (p > 0.05). Peak diastolic flow was greater at C2/C3 (0.29 ± 0.08 mL/s) compared to T8/T9 (0.03 ± 0.03 mL/s, p < 0.001) dorsally, but not different ventrally (p = 1.000). Cranial and caudal maximum velocity at C2/C3 were greater than thoracolumbar levels dorsally (p < 0.001), and T8/T9 and L1/L2 ventrally (p = 0.022). Diastolic velocity wave speed was 1.41 ± 0.39 m/s dorsally and 1.22 ± 0.21 m/s ventrally, and systolic velocity wave speed was 1.02 ± 0.25 m/s dorsally and 0.91 ± 0.22 m/s ventrally., Conclusions: In anaesthetised and ventilated domestic pigs, spinal CSF has lower pulsatile flow and slower velocity wave propagation, compared to humans. This study provides baseline CSF flow at spinal levels relevant for future SCI research in this animal model., (© 2023. The Author(s).)

Purpose: To measure arterial, venous, and cerebrospinal fluid (CSF) velocities simultaneously by using Bayesian multipoint velocity-encoded magnetic resonance (MR) imaging and to compare interacquisition reproducibility relative to that of standard phase-contrast MR imaging for sequential measurements of arterial, venous, and CSF velocities., Materials and Methods: This study was approved by the local ethics committee, and informed consent was obtained from all subjects. Simultaneous measurement of blood and CSF flow was performed at the C1-C2 level in 10 healthy subjects (mean age, 24.4 years ± 2.7; five men, five women) by using accelerated Bayesian multipoint velocity-encoded MR imaging. Data were compared with those obtained from two separate conventional phase-contrast MR imaging acquisitions, one optimized for arterial and venous blood flow (velocity encoding range, ±50 cm/sec) and the other optimized for CSF flow (velocity encoding range, ±10 cm/sec), with an imaging time of approximately 2 minutes each. Data acquisition was repeated six times. Intraclass correlation coefficient (ICC) and linear regression were used to quantify interacquisition reproducibility., Results: There was no significant difference in arterial blood flow measured with Bayesian multipoint velocity-encoded MR imaging and that measured with phase-contrast MR imaging (mean ICC, 0.96 ± 0.03 vs 0.97 ± 0.02, respectively). Likewise, there was no significant difference between CSF flow measured with Bayesian multipoint velocity-encoded MR imaging and that measured with phase-contrast MR imaging (mean ICC, 0.97 ± 0.02 vs 0.96 ± 0.05, respectively). For venous blood flow, the ICC with Bayesian multipoint MR imaging was significantly larger than that with conventional phase-contrast MR imaging (mean, 0.75 ± 0.23 vs 0.65 ± 0.26, respectively; P = .016)., Conclusion: Bayesian multipoint velocity-encoded MR imaging allows for simultaneous assessment of fast and slow flows in arterial, venous, and CSF lumina in a single acquisition. It eliminates the need for vessel-dependent adjustment of the velocity-encoding range, as required for conventional sequential phase-contrast MR imaging measurements., (© RSNA, 2013.)

We describe herein a novel life-size phantom model of the intracranial cavity and its validation. The cerebrospinal fluid (CSF) domains including ventricular, cysternal, and subarachnoid spaces were derived via magnetic resonance imaging. Brain mechanical properties and cranio-spinal compliance were set based on published data. Both bulk and pulsatile physiologic CSF flow were modeled. Model validation was carried out by comparisons of flow and pressure measurements in the phantom with published in vivo data of healthy subjects. Physiologic intracranial pressure with 10 mmHg mean and 0.4 mmHg peak pulse amplitude was recorded in the ventricles. Peak CSF flow rates of 0.2 and 2 ml/s were measured in the cerebral aqueduct and subarachnoid space, respectively. The phantom constitutes a first-of-its-kind approach to modeling physiologic intracranial dynamics in vitro. Herein, we describe the phantom design and manufacturing, definition and implementation of its operating parameters, as well as the validation of the modeled dynamics.

The arachnoid membrane (AM) and granulations (AGs) are important in cerebrospinal fluid (CSF) homeostasis, regulating intracranial pressure in health and disease. We offer a functional perspective of the human AM's transport mechanism to clarify the role of AM in the movement of CSF and metabolites. Using cultures of human AG cells and a specialized perfusion system, we have shown that this in vitro model mimics the in vivo characteristics of unidirectional fluid transport and we present the first report of serum-free permeability values (92.5 microl min(-1) mm Hg(-1) cm(-2)), which in turn are in agreement with the CSF outflow rates derived from a dynamic, in vivo magnetic resonance imaging-based computational model of the subarachnoid cranial space (130.9 microl min(-1) mm Hg(-1) cm(-2)). Lucifer yellow permeability experiments have verified the maintenance of tight junctions by the arachnoidal cells with a peak occurring around 21 days post-seeding, which is when all perfusion experiments were conducted. Addition of ruthenium red to the perfusate, and subsequent analysis of its distribution post-perfusion, has verified the passage of perfusate via both paracellular and transcellular mechanisms with intracellular vacuoles of approximately 1 microm in diameter being the predominant transport mechanism. The comparison of the computational and in vitro models is the first report to measure human CSF dynamics functionally and structurally, enabling the development of innovative approaches to modify CSF outflow and will change concepts and management of neurodegenerative diseases resulting from CSF stagnation.

Abnormal cerebrospinal fluid (CSF) flow is suspected to be a contributor to the pathogenesis of neurodegenerative diseases such as Alzheimer's through the accumulation of toxic metabolites, and to the malfunction of intracranial pressure regulation, possibly through disruption of neuroendocrine communication. For the understanding of transport processes involved in either, knowledge of in vivo CSF dynamics is important. We present a three-dimensional, transient, subject-specific computational analysis of CSF flow in the human cranial subarachnoid space (SAS) based on in vivo magnetic resonance imaging. We observed large variations in the spatial distribution of flow velocities with a temporal peak of 5 cm s(-1) in the anterior SAS and less than 4 mm s(-1) in the superior part. This could reflect dissimilar flushing requirements of brain areas that may show differences in susceptibility to pathological CSF flow. Our methods can be used to compare the transport of metabolites and neuroendocrine substances in healthy and diseased brains.

The cerebrospinal fluid flow in the third ventricle of the brain and the aqueduct of Sylvius was studied using computational fluid dynamics (CFD) based on subject-specific boundary conditions derived from magnetic resonance imaging (MRI) scans. The flow domain geometry was reconstructed from anatomical MRI scans by manual image segmentation. The movement of the domain boundary was derived from MRI brain motion scans. Velocimetric MRI scans were used to reconstruct the velocity field at the inferior end of the aqueduct of Sylvius based on the theory of pulsatile flow in pipes. A constant pressure boundary condition was assigned at the foramina of Monro. Three main flow features were observed: a fluid jet emerging from the aqueduct of Sylvius, a moderately mobile recirculation zone above the jet and a mobile recirculation below the jet. The flow in the entire domain was laminar with a maximum Reynolds number of 340 in the aqueduct. The findings demonstrate that by combining MRI scans and CFD simulations, subject-specific detailed quantitative information of the flow field in the third ventricle and the aqueduct of Sylvius can be obtained.

This animal study investigates the hypothesis of an immature liver growth following ALPPS (associating liver partition and portal vein ligation for staged hepatectomy) by measuring liver volume and function using gadoxetic acid avidity in magnetic resonance imaging (MRI) in models of ALPPS, major liver resection (LR) and portal vein ligation (PVL). Wistar rats were randomly allocated to ALPPS, LR or PVL. In contrast-enhanced MRI scans with gadoxetic acid (Primovist®), liver volume and function of the right median lobe (=future liver remnant, FLR) and the deportalized lobes (DPL) were assessed until post-operative day (POD) 5. Liver function FLR/DPL was defined as the inverse value of time from injection of gadoxetic acid to the blood pool-corrected maximum signal intensity FLR/DPL multiplied by the volume FLR/DPL. In ALPPS (n = 6), LR (n = 6) and PVL (n = 6), volume FLR and function FLR increased proportionally, except on POD 1. Thereafter, function FLR exceeded volume FLR increase in LR and ALPPS, but not in PVL. Total liver function was significantly reduced after LR until POD 3, but never undercuts 60% of its pre-operative value following ALPPS and PVL. This study shows for the first time that functional increase is proportional to volume increase in ALPPS using gadoxetic acid avidity in MRI. [ABSTRACT FROM AUTHOR]

The objective of this work is to quantify age-related differences in the characteristics and coupling of cerebral arterial inflow and cerebrospinal fluid (CSF) dynamics. To this end, 3T phase-contrast magnetic resonance imaging blood and CSF flow data of eleven young (24±3 years) and eleven elderly subjects (70±5 years) with a comparable sex-ratio were acquired. Flow waveforms and their frequency composition, transfer functions from blood to CSF flows and cross-correlations were analyzed. The magnitudes of the frequency components of CSF flow in the aqueduct differ significantly between the two age groups, as do the frequency components of the cervical spinal CSF and the arterial flows. The males' aqueductal CSF stroke volumes and average flow rates are significantly higher than those of the females. Transfer functions and crosscorrelations between arterial blood and CSF flow reveal significant age-dependence of phase-shift between these, as do the waveforms of arterial blood, as well as cervical-spinal and aqueductal CSF flows. These findings accentuate the need for ageand sex-matched control groups for the evaluation of cerebral pathologies such as hydrocephalus. [ABSTRACT FROM AUTHOR]

Spontaneous internal carotid artery (ICA) dissection (sICAD) results from an intimal tear located around the distal carotid sinus. The mechanisms causing the tear are unknown. This case-control study tested the hypotheses that head movements increase the wall stress in the cervical ICA and that the stress increase is greater in patients with sICAD than in controls. Five patients with unilateral, recanalized, left sICAD and five matched controls were investigated before and after maximal head rotation to the left and neck hyperextension after 45° head rotation to the left. The anatomy of the extracranial carotid arteries was assessed by magnetic resonance imaging and used to create finite element models of the right ICA. Wall stress increased after head movements. Increases above the 80th and 90th percentile were located at the intimal side of the artery wall from 7.4 mm below to 10 mm above the cranial edge of the carotid sinus, i.e., at the same location as histologically confirmed tears in patients with sICAD. Wall stress increase did not differ between patients and controls. The present findings suggest that wall stress increases at the intimal side of the artery wall surrounding the distal edge of the carotid bulb after head movements may be important for the development of carotid dissection. The lack of wall stress difference between the two groups indicates that the carotid arteries of patients with carotid dissection have either distinct functional or anatomical properties or endured unusually heavy wall stresses to initiate dissection. [ABSTRACT FROM AUTHOR]

Anatomic, velocimetric, and brain motion MRI scans were combined with a computational fluid dynamics model to investigate cerebrospinal fluid (CSF) mixing in the third cerebral ventricle of a healthy male adult. It was found that advection dominates over diffusion in most of the third ventricle. Three zones where diffusion plays an important role in the mixing process were identified. One of these zones, consisting of recessus infundibulus, recessus opticus and the adjacent regions up to commissura anterior, is likely to exist in the general population. We hypothesize that this zone may act as a buffer to flatten concentration peaks of pituitary gland hormones released into the CSF of the third ventricle. We further hypothesize that this zone may facilitate the communication between hypothalamus and the pituitary gland through the third ventricle cerebrospinal fluid by prolonging residence times of the communicated hormones. [ABSTRACT FROM AUTHOR]

Summary: Transport of biochemical substances and other species in the cerebrospinal fluid is influenced by the latter’s pulsatile flow. By combining magnetic resonance imaging and computational fluid dynamics, the cerebrospinal fluid flow field can be reconstructed in a subject-specific manner. Here we describe the general flow features in the cranial subarachnoid space as observed in a healthy volunteer. [Copyright &y& Elsevier]

This study aims at investigating three-dimensional subject-specific cerebrospinal fluid (CSF) dynamics in the inferior cranial space, the superior spinal subarachnoid space (SAS), and the fourth cerebral ventricle using a combination of a finite-volume computational fluid dynamics (CFD) approach and magnetic resonance imaging (MRI) experiments. An anatomically accurate 3D model of the entire SAS of a healthy volunteer was reconstructed from high resolution T2 weighted MRI data. Subject-specific pulsatile velocity boundary conditions were imposed at planes in the pontine cistern, cerebellomedullary cistern, and in the spinal subarachnoid space. Velocimetric MRI was used to measure the velocity field at these boundaries. A constant pressure boundary condition was imposed at the interface between the aqueduct of Sylvius and the fourth ventricle. The morphology of the SAS with its complex trabecula structures was taken into account through a novel porous media model with anisotropic permeability. The governing equations were solved using finite-volume CFD. We observed a total pressure variation from -42 Pa to 40 Pa within one cardiac cycle in the investigated domain. Maximum CSF velocities of about 15 cm/s occurred in the inferior section of the aqueduct, 14 cm/s in the left foramen of Luschka, and 9 cm/s in the foramen of Magendie. Flow velocities in the right foramen of Luschka were found to be significantly lower than in the left, indicating three-dimensional brain asymmetries. The flow in the cerebellomedullary cistern was found to be relatively diffusive with a peak Reynolds number (Re)=72, while the flow in the pontine cistern was primarily convective with a peak Re=386. The net volumetric flow rate in the spinal canal was found to be negligible despite CSF oscillation with substantial amplitude with a maximum volumetric flow rate of 109 ml/min. The observed transient flow patterns indicate a compliant behavior of the cranial subarachnoid space. Still, the estimated deformations were small owing to the large parenchymal surface. We have integrated anatomic and velocimetric MRI data with computational fluid dynamics incorporating the porous SAS morphology for the subject-specific reconstruction of cerebrospinal fluid flow in the subarachnoid space. This model can be used as a basis for the development of computational tools, e.g., for the optimization of intrathecal drug delivery and computer-aided evaluation of cerebral pathologies such as syrinx development in syringomelia. [ABSTRACT FROM AUTHOR]