Lessons learnt from the COVID-19 pandemic in selected countries to inform strengthening of public health systems: a qualitative study.

INTRODUCTION: The COVID-19 pandemic has prompted governments internationally to consider strengthening their public health systems. To support the work of Ireland's Public Health Reform Expert Advisory Group, the Health Information and Quality Authority, an independent governmental agency, was asked to describe the lessons learnt regarding the public health response to COVID-19 internationally and the applicability of this response for future pandemic preparedness. METHODS: Semi-structured interviews with key public health representatives from nine countries were conducted. Interviews were conducted in March and April 2022 remotely via Zoom and were recorded. Notes were taken by two researchers, and a thematic analysis undertaken. RESULTS: Lessons learnt from the COVID-19 pandemic related to three main themes: 1) setting policy; 2) delivering public health interventions; and 3) providing effective communication. Real-time surveillance, evidence synthesis, and cross-sectoral collaboration were reported as essential for policy setting; it was noted that having these functions established prior to the pandemic would lead to a more efficient implementation in a health emergency. Delivering public health interventions such as testing, contact tracing, and vaccination were key to limiting and or mitigating the spread of the SARS-CoV-2 virus. However, a number of challenges were highlighted such as staff capacity and burnout, delays in vaccination procurement, and reduced delivery of regular healthcare services. Clear, consistent, and regular communication of the scientific evidence was key to engaging citizens with mitigation strategies. However, these communication strategies had to compete with an infodemic of information being circulated, particularly through social media. CONCLUSIONS: Overall, functions relating to policy setting, public health interventions, and communication are key to pandemic response. Ideally, these should be established in the preparedness phase so that they can be rapidly scaled-up during a pandemic.

Biomedical doctoral students' research practices when facing dilemmas: two vignette-based randomized control trials.

Our aim was to describe the research practices of doctoral students facing a dilemma to research integrity and to assess the impact of inappropriate research environments, i.e. exposure to (a) a post-doctoral researcher who committed a Detrimental Research Practice (DRP) in a similar situation and (b) a supervisor who did not oppose the DRP. We conducted two 2-arm, parallel-group randomized controlled trials. We created 10 vignettes describing a realistic dilemma with two alternative courses of action (good practice versus DRP). 630 PhD students were randomized through an online system to a vignette (a) with (n = 151) or without (n = 164) exposure to a post-doctoral researcher; (b) with (n = 155) or without (n = 160) exposure to a supervisor. The primary outcome was a score from - 5 to + 5, where positive scores indicated the choice of DRP and negative scores indicated good practice. Overall, 37% of unexposed participants chose to commit DRP with important variation across vignettes (minimum 10%; maximum 66%). The mean difference [95%CI] was 0.17 [- 0.65 to 0.99;], p = 0.65 when exposed to the post-doctoral researcher, and 0.79 [- 0.38; 1.94], p = 0.16, when exposed to the supervisor. In conclusion, we did not find evidence of an impact of postdoctoral researchers and supervisors on student research practices.Trial registration: NCT04263805, NCT04263506 (registration date 11 February 2020).

Pulsatile cerebral paraarterial flow by peristalsis, pressure and directional resistance.

BACKGROUND: A glymphatic system has been proposed that comprises flow that enters along cerebral paraarterial channels between the artery wall and the surrounding glial layer, continues through the parenchyma, and then exits along similar paravenous channels. The mechanism driving flow through this system is unclear. The pulsatile (oscillatory plus mean) flow measured in the space surrounding the middle cerebral artery (MCA) suggests that peristalsis created by intravascular blood pressure pulses is a candidate for the paraarterial flow in the subarachnoid spaces. However, peristalsis is ineffective in driving significant mean flow when the amplitude of channel wall motion is small, as has been observed in the MCA artery wall. In this paper, peristalsis in combination with two additional mechanisms, a longitudinal pressure gradient and directional flow resistance, is evaluated to match the measured MCA paraarterial oscillatory and mean flows. METHODS: Two analytical models are used that simplify the paraarterial branched network to a long continuous channel with a traveling wave in order to maximize the potential effect of peristalsis on the mean flow. The two models have parallel-plate and annulus geometries, respectively, with and without an added longitudinal pressure gradient. The effect of directional flow resistors was also evaluated for the parallel-plate geometry. RESULTS: For these models, the measured amplitude of arterial wall motion is too large to cause the small measured amplitude of oscillatory velocity, indicating that the outer wall must also move. At a combined motion matching the measured oscillatory velocity, peristalsis is incapable of driving enough mean flow. Directional flow resistance elements augment the mean flow, but not enough to provide a match. With a steady longitudinal pressure gradient, both oscillatory and mean flows can be matched to the measurements. CONCLUSIONS: These results suggest that peristalsis drives the oscillatory flow in the subarachnoid paraarterial space, but is incapable of driving the mean flow. The effect of directional flow resistors is insufficient to produce a match, but a small longitudinal pressure gradient is capable of creating the mean flow. Additional experiments are needed to confirm whether the outer wall also moves, as well as to validate the pressure gradient.

Practical implications of the erroneous treatment of exposure time in the Eulerian hemolysis power law model.

BACKGROUND: Eulerian and Lagrangian power-law formulations are both widely used for computational fluid dynamics (CFD) to predict flow-induced hemolysis in blood-contacting medical devices. Both are based on the same empirical power-law correlation between hemolysis and the shear stress and exposure time. In the Lagrangian approach, blood damage is predicted by tracking both the stress and exposure time along a finite number of pathlines in the domain. In the Eulerian approach, a scalar transport equation is solved for a time-linearized damage index within the entire domain. Previous analytical work has demonstrated that there is a fundamental problem with the treatment of exposure time in the Eulerian model formulation such that the only condition under which the model correctly represents the true exposure time is in a flow field with no streamwise velocity variation. However, the practical implications of this limitation have yet to be thoroughly investigated. METHODS: In this study, we demonstrate the inaccuracy of Eulerian hemolysis power-law model predictions due to the erroneous treatment of exposure time by systematically considering four benchmark test cases with increasing degrees of flow acceleration: Poiseuille flow through a straight tube, inclined Couette flow, and flow through a converging tube with two different convergence ratios. RESULTS: Compared with Lagrangian predictions, we show that, as flow acceleration becomes more pronounced, the resultant inaccuracy in the Eulerian predictions increases. For the inclined Couette flow case, there is a small degree of flow acceleration that yields a discrepancy in the range of 10% between Lagrangian and Eulerian predictions. For flows with a larger degree of acceleration, as occurs in the converging tube flow cases, the discrepancy is considerably larger (up to 257%). CONCLUSION: The inaccuracy of hemolysis predictions due to the erroneous treatment of exposure time in the Eulerian power-law model can be significant when there is streamwise velocity variation in the flow field. These results may partially explain the extremely large variability in CFD hemolysis predictions reported in the literature between Lagrangian and Eulerian models.

Functional brain plasticity following childhood maltreatment: A longitudinal fMRI investigation of autobiographical memory processing.

Altered autobiographical memory (ABM) processing characterizes some individuals with experiences of childhood maltreatment. This fMRI study of ABM processing evaluated potential developmental plasticity in neural functioning following maltreatment. Adolescents with (N = 19; MT group) and without (N = 18; Non-MT group) documented childhood maltreatment recalled specific ABMs in response to emotionally valenced cue words during fMRI at baseline (age 12.71 ± 1.48) and follow-up (14.88 ± 1.53 years). Psychological assessments were collected at both timepoints. Longitudinal analyses were carried out with BOLD signal changes during ABM recall and psychopathology to investigate change over time. In both groups there was relative stability of the ABM brain network, with some developmental maturational changes observed in cortical midline structures (ventromedial PFC (vmPFC), posterior cingulate cortex (pCC), and retrosplenial cortex (rSC). Significantly increased activation of the right rSC was observed only in the MT group, which was associated with improved psychological functioning. Baseline group differences in relation to hippocampal functioning, were not detected at follow-up. This study provides preliminary empirical evidence of functional developmental plasticity in children with documented maltreatment experience using fMRI. This suggests that altered patterns of brain function, associated with maltreatment experience, are not fixed and may reflect the potential to track a neural basis of resilience.

Comparison of Papile versus Laterality-Based Al-Abdi System to Predict Neurodevelopmental Impairment in Extreme Preterm Infants after Severe Germinal Matrix Hemorrhage-Intraventricular Hemorrhage: A Retrospective Comparative Observational Study.

BACKGROUND AND PURPOSE: The traditional Papile classification system for severe germinal matrix hemorrhage-intraventricular hemorrhage is limited in objectivity and interrater variability for accurate prediction of neurodevelopmental impairment in extremely preterm infants. Many extremely preterm infants with severe germinal matrix hemorrhage-intraventricular hemorrhage are still offered "redirection of care" in spite of the recent evidence suggesting that many of these infants can have normal outcomes. Therefore, it is important to consider the laterality and extent of brain hemisphere involvement while classifying severe germinal matrix hemorrhage-intraventricular hemorrhage to predict neurodevelopmental impairment. The aim of the present study was to compare the Al-Abdi system with the Papile system for their accuracy in predicting neurodevelopmental impairment in extremely preterm infants with severe germinal matrix hemorrhage-intraventricular hemorrhage. MATERIALS AND METHODS: This is a retrospective study of extremely preterm infants with severe germinal matrix hemorrhage-intraventricular hemorrhage admitted to a tertiary neonatal intensive care unit (2006-2016). Cranial sonograms were independently re-reviewed by 2 radiologists as per the Al-Abdi system. The prognostic statistical indices for both systems to predict neurodevelopmental impairment were calculated. RESULTS: A total of 91 infants with severe germinal matrix hemorrhage-intraventricular hemorrhage survived, and 83 (median gestational age, 26.3 weeks; and median birth weight, 890 g) completed developmental assessment. The receiver operating characteristic areas under the curve to predict neurodevelopmental impairment by the Papile versus Al-Abdi systems were 0.702 versus 0.723, respectively (P = .474). Corresponding Al-Abdi cutoff scores of 19, 20, 21, and 22 demonstrated increased specificity (76.36%-85.45%) and correct classification (69.88%-72.29%) to predict moderate-to-severe neurodevelopmental impairment. CONCLUSIONS: The Al-Abdi system is comparable with the Papile system for predicting neurodevelopmental impairment for extremely preterm infants with severe germinal matrix hemorrhage-intraventricular hemorrhage, with higher Al-Abdi scores being more specific. This finding may prove useful for neonatal health care providers and parents in their decision regarding "continuation of care." Future multicentric studies are warranted to ascertain the validity of individual Al-Abdi scores.

Defining requirements for integrating information between design, manufacturing, and inspection.

Industry desires a digital thread of information that aligns as-designed, as-planned, as-executed, and as-inspected viewpoints. An experiment was conducted to test selected open data standards' ability to integrate the lifecycle stages of engineering design, manufacturing, and quality assurance through a thorough implementation of a small scale model-based enterprise. The research team set out to answer: from design, through production, and final inspections, what are the hurdles that a manufacturer would face during the development of a fully linked and integrated information chain? The research team was not able to fully link all the required information, but value for industry was still identified. This paper presents the results of the experiment, provides guidance on how to overcome or mitigate identified challenges, and discusses the benefits or incentives to be gained from tracing or linking information through multiple stages a product lifecycle.

Mechanisms of tracer transport in cerebral perivascular spaces.

Tracers infused into the brain appear to be transported along channels surrounding cerebral blood vessels. Bulk fluid flow has been hypothesized in paravascular "glymphatic" channels (outer space between the pial membrane and astrocyte endfeet), as well as in the periarterial space (inner space between smooth muscle cells). The plausibility of net flow in these channels due to steady and oscillatory pressures is reviewed, as is that of transport by oscillatory shear-enhanced dispersion in the absence of net flow. Models including 1D branching networks of annular channels and an expanded compartmental model for humans both predict that flow driven by physiologic steady pressure differences is unlikely in both periarterial and paraarterial spaces, whether the spaces are open or filled with porous media. One exception is that a small additional steady pressure difference could drive paraarterial flow if the space is open. The potential that the tracer injection itself could present such a pressure difference is outlined. Oscillatory (peristaltic) wall motion alone has been found to be insufficient to drive significant forward flow. However, a number of hypothesized mechanisms that have yet to be experimentally verified in the brain may create directional flow in combination with wall motion. Shear-augmented dispersion due to oscillatory pressure in channels with a range of porosity has been modeled analytically. Enhancement of axial dispersion is small for periarterial channels. In open paraarterial channels, dispersion enhancement with optimal lateral mixing is large enough that it may explain observed tracer transport without net forward fluid flow.

Feasibility Study for an Automated Engineering Change Process.

Engineering change is a significant cost sink in many projects. While avoiding and mitigating the risk of change is the ideal approach, mistakes and improvements are recognized inevitably as more is learned over time about the quality of the decisions made in a product's design. This paper presents a feasibility and performance analysis of automating engineering change requests to demonstrate the promise for increasing speed, efficiency, and effectiveness of product-lifecycle-wide engineering-change-request processes. To explore this idea, a comparatively simple case study is examined both to mimic the reduced set of alterable aspects of a typical change request and to highlight the need of appropriate search algorithms as brute force methods quickly prohibitively resource intensive. Although such cases may seem trivial for human agents, with the volume of expected change requests in a typical facility, the potential opportunity gain by eliminating or reducing the amount of human effort in low level change requests accumulate into significant returns for industry on time and money. Within this work, the genetic algorithm is selected to demonstrate feasibility due to its broad scope of applicability and low barriers to deployment. Future refinement of this or other sophisticated algorithms leveraging the nature of the standard representations and qualities of alterable design features could produce tools with strong implications for process efficiency and industry competitiveness in the execution of its projects.

On the Discretization of the Power-Law Hemolysis Model.

Flow-induced hemolysis remains a concern for blood-contacting devices, and computer-based prediction of hemolysis could facilitate faster and more economical refinement of such devices. While evaluation of convergence of velocity fields obtained by computational fluid dynamics (CFD) simulations has become conventional, convergence of hemolysis calculations is also essential. In this paper, convergence of the power-law hemolysis model is compared for simple flows, including pathlines with exponentially increasing and decreasing stress, in gradually expanding and contracting Couette flows, in a sudden radial expansion and in the Food and Drug Administration (FDA) channel. In the exponential cases, convergence along a pathline required from one to tens of thousands of timesteps, depending on the exponent. Greater timesteps were required for rapidly increasing (large exponent) stress and for rapidly decreasing (small exponent) stress. Example pathlines in the Couette flows could be fit with exponential curves, and convergence behavior followed the trends identified from the exponential cases. More complex flows, such as in the radial expansion and the FDA channel, increase the likelihood of encountering problematic pathlines. For the exponential cases, comparison of converged hemolysis values with analytical solutions demonstrated that the error of the converged solution may exceed 10% for both rapidly decreasing and rapidly increasing stress.

Psychological interventions for acute psychiatric inpatients with schizophrenia-spectrum disorders: A systematic review and meta-analysis.

BACKGROUND: Acute inpatient psychiatric wards are important yet challenging environments in which to implement psychological interventions for people with schizophrenia-spectrum disorders. No meta-analysis to date has evaluated whether psychological interventions are effective in this context. METHODS: We systematically searched Embase, Medline and PsycInfo databases for randomised controlled trials (RCTs) of psychological interventions implemented in acute inpatient psychiatric settings with individuals with schizophrenia-spectrum disorders. We conducted random effects meta-analyses of between-groups outcomes at post-intervention and relapse/re-hospitalisation rates by follow-up. RESULTS: Twenty-nine trials were suitable for meta-analysis. Psychological interventions improved post-intervention positive symptoms, social functioning and treatment compliance and reduced the risk of relapse/ re-hospitalisation, relative to control conditions. Analyses of specific intervention effects found positive effects of psychoeducation on several key outcomes (power > 80%) and preliminary evidence for positive effects of acceptance and commitment therapy (ACT), cognitive behaviour therapy (CBT) and metacognitive training (MCT) on some outcomes (power < 80%). CONCLUSION: Psychological interventions can be helpful for acute inpatients with schizophrenia-spectrum disorders. However, risk of bias was often high or unclear, and some analyses were underpowered. Further research should use more rigorous RCT designs and publish meta-analysable data on positive symptoms, general psychopathology, relapse/ re-hospitalisation, social functioning and treatment compliance.

In vitro and numerical simulation of blood removal from cerebrospinal fluid: comparison of lumbar drain to Neurapheresis therapy.

BACKGROUND: Blood removal from cerebrospinal fluid (CSF) in post-subarachnoid hemorrhage patients may reduce the risk of related secondary brain injury. We formulated a computational fluid dynamics (CFD) model to investigate the impact of a dual-lumen catheter-based CSF filtration system, called Neurapheresis™ therapy, on blood removal from CSF compared to lumbar drain. METHODS: A subject-specific multiphase CFD model of CSF system-wide solute transport was constructed based on MRI measurements. The Neurapheresis catheter geometry was added to the model within the spinal subarachnoid space (SAS). Neurapheresis flow aspiration and return rate was 2.0 and 1.8 mL/min, versus 0.2 mL/min drainage for lumbar drain. Blood was modeled as a bulk fluid phase within CSF with a 10% initial tracer concentration and identical viscosity and density as CSF. Subject-specific oscillatory CSF flow was applied at the model inlet. The dura and spinal cord geometry were considered to be stationary. Spatial-temporal tracer concentration was quantified based on time-average steady-streaming velocities throughout the domain under Neurapheresis therapy and lumbar drain. To help verify CFD results, an optically clear in vitro CSF model was constructed with fluorescein used as a blood surrogate. Quantitative comparison of numerical and in vitro results was performed by linear regression of spatial-temporal tracer concentration over 24-h. RESULTS: After 24-h, tracer concentration was reduced to 4.9% under Neurapheresis therapy compared to 6.5% under lumbar drain. Tracer clearance was most rapid between the catheter aspiration and return ports. Neurapheresis therapy was found to have a greater impact on steady-streaming compared to lumbar drain. Steady-streaming in the cranial SAS was ~ 50× smaller than in the spinal SAS for both cases. CFD results were strongly correlated with the in vitro spatial-temporal tracer concentration under Neurapheresis therapy (R2 = 0.89 with + 2.13% and - 1.93% tracer concentration confidence interval). CONCLUSION: A subject-specific CFD model of CSF system-wide solute transport was used to investigate the impact of Neurapheresis therapy on tracer removal from CSF compared to lumbar drain over a 24-h period. Neurapheresis therapy was found to substantially increase tracer clearance compared to lumbar drain. The multiphase CFD results were verified by in vitro fluorescein tracer experiments.

Deformation of human red blood cells in extensional flow through a hyperbolic contraction.

Flow-induced damage to red blood cells has been an issue of considerable importance since the introduction of the first cardiovascular devices. Early blood damage prediction models were based on measurements of damage by shear stress only. Subsequently, these models were extrapolated to include other components of the fluid stress tensor. However, the expanded models were not validated by measurements of damage in response to the added types of stress. Recent investigations have proposed that extensional stress might be more damaging to red cells than shear stress. In this study, experiments were conducted to compare human red cell deformation under laminar extensional stress versus laminar shear stress. It was found that the deformation caused by shear stress is matched by that produced by an extensional stress that is approximately 34 times smaller. Assuming that blood damage scales directly with cell deformation, this result indicates that mechanistic blood damage prediction models should weigh extensional stress more than shear stress.

Impact of Neurapheresis System on Intrathecal Cerebrospinal Fluid Dynamics: A Computational Fluid Dynamics Study.

It has been hypothesized that early and rapid filtration of blood from cerebrospinal fluid (CSF) in postsubarachnoid hemorrhage patients may reduce hospital stay and related adverse events. In this study, we formulated a subject-specific computational fluid dynamics (CFD) model to parametrically investigate the impact of a novel dual-lumen catheter-based CSF filtration system, the Neurapheresis™ system (Minnetronix Neuro, Inc., St. Paul, MN), on intrathecal CSF dynamics. The operating principle of this system is to remove CSF from one location along the spine (aspiration port), externally filter the CSF routing the retentate to a waste bag, and return permeate (uncontaminated CSF) to another location along the spine (return port). The CFD model allowed parametric simulation of how the Neurapheresis system impacts intrathecal CSF velocities and steady-steady streaming under various Neurapheresis flow settings ranging from 0.5 to 2.0 ml/min and with a constant retentate removal rate of 0.2 ml/min simulation of the Neurapheresis system were compared to a lumbar drain simulation with a typical CSF removal rate setting of 0.2 ml/min. Results showed that the Neurapheresis system at a maximum flow of 2.0 ml/min increased average steady streaming CSF velocity 2× in comparison to lumbar drain (0.190 ± 0.133 versus 0.093 ± 0.107 mm/s, respectively). This affect was localized to the region within the Neurapheresis flow loop. The mean velocities introduced by the flow loop were relatively small in comparison to normal cardiac-induced CSF velocities.

Dispersion in porous media in oscillatory flow between flat plates: applications to intrathecal, periarterial and paraarterial solute transport in the central nervous system.

BACKGROUND: As an alternative to advection, solute transport by shear-augmented dispersion within oscillatory cerebrospinal fluid flow was investigated in small channels representing the basement membranes located between cerebral arterial smooth muscle cells, the paraarterial space surrounding the vessel wall and in large channels modeling the spinal subarachnoid space (SSS). METHODS: Geometries were modeled as two-dimensional. Fully developed flows in the channels were modeled by the Darcy-Brinkman momentum equation and dispersion by the passive transport equation. Scaling of the enhancement of axial dispersion relative to molecular diffusion was developed for regimes of flow including quasi-steady, porous and unsteady, and for regimes of dispersion including diffusive and unsteady. RESULTS: Maximum enhancement occurs when the characteristic time for lateral dispersion is matched to the cycle period. The Darcy-Brinkman model represents the porous media as a continuous flow resistance, and also imposes no-slip boundary conditions at the walls of the channel. Consequently, predicted dispersion is always reduced relative to that of a channel without porous media, except when the flow and dispersion are both unsteady. DISCUSSION/CONCLUSIONS: In the basement membranes, flow and dispersion are both quasi-steady and enhancement of dispersion is small even if lateral dispersion is reduced by the porous media to achieve maximum enhancement. In the paraarterial space, maximum enhancement Rmax = 73,200 has the potential to be significant. In the SSS, the dispersion is unsteady and the flow is in the transition zone between porous and unsteady. Enhancement is 5.8 times that of molecular diffusion, and grows to a maximum of 1.6E+6 when lateral dispersion is increased. The maximum enhancement produces rostral transport time in agreement with experiments.

Modeling and prediction of flow-induced hemolysis: a review.

Despite decades of research related to hemolysis, the accuracy of prediction algorithms for complex flows leaves much to be desired. Fundamental questions remain about how different types of fluid stresses translate to red cell membrane failure. While cellular- and molecular-level simulations hold promise, spatial resolution to such small scales is computationally intensive. This review summarizes approaches to continuum-level modeling of hemolysis, a method that is likely to be useful well into the future for design of typical cardiovascular devices. Weaknesses are revealed for the Eulerian method of hemolysis prediction and for the linearized damage function. Wide variations in scaling of red cell membrane tension are demonstrated with different types of fluid stresses when the scalar fluid stress is the same, as well as when the energy dissipation rate is the same. New experimental data are needed for red cell damage in simple flows with controlled levels of different types of stresses, including laminar shear, laminar extension (normal), turbulent shear, and turbulent extension. Such data can be curve-fit to create more universal continuum-level models and can serve to validate numerical simulations.

On Eulerian versus Lagrangian models of mechanical blood damage and the linearized damage function.

Two limitations have been discovered in the derivation of the Eulerian method of hemolysis prediction using a linearized blood damage function. First is that in the transformation from the Lagrangian material volume of the original power-law model to a fixed Eulerian control volume, the spatial dependence of duration of exposure to fluid stress was neglected. This omission has the implication that the Eulerian method as reported is valid only for steady, uniaxial flow in which velocity is constant along streamlines. The second issue is related to linearization, which involves distributing an exponent across an integral. This operation is valid only for limited conditions that include the exponent being unity (which is not the case for any power-law hemolysis models) or the blood damage function being constant throughout the flow regime. These constraints severely restrict the applicability of the Eulerian method. An example problem is presented that demonstrates that the source term of the Eulerian method as reported does not account for differences in velocity between 2 similar flows. Correcting the source term to match the hemolysis prediction to that of the original, unlinearized method requires an analytical description of the flow field that may not be easily obtained for the complex flows in some cardiovascular devices.

Anthropomorphic Model of Intrathecal Cerebrospinal Fluid Dynamics Within the Spinal Subarachnoid Space: Spinal Cord Nerve Roots Increase Steady-Streaming.

Cerebrospinal fluid (CSF) dynamics are thought to play a vital role in central nervous system (CNS) physiology. The objective of this study was to investigate the impact of spinal cord (SC) nerve roots (NR) on CSF dynamics. A subject-specific computational fluid dynamics (CFD) model of the complete spinal subarachnoid space (SSS) with and without anatomically realistic NR and nonuniform moving dura wall deformation was constructed. This CFD model allowed detailed investigation of the impact of NR on CSF velocities that is not possible in vivo using magnetic resonance imaging (MRI) or other noninvasive imaging methods. Results showed that NR altered CSF dynamics in terms of velocity field, steady-streaming, and vortical structures. Vortices occurred in the cervical spine around NR during CSF flow reversal. The magnitude of steady-streaming CSF flow increased with NR, in particular within the cervical spine. This increase was located axially upstream and downstream of NR due to the interface of adjacent vortices that formed around NR.

Is bulk flow plausible in perivascular, paravascular and paravenous channels?

BACKGROUND: Transport of solutes has been observed in the spaces surrounding cerebral arteries and veins. Indeed, transport has been found in opposite directions in two different spaces around arteries. These findings have motivated hypotheses of bulk flow within these spaces. The glymphatic circulation hypothesis involves flow of cerebrospinal fluid from the cortical subarachnoid space to the parenchyma along the paraarterial (extramural, Virchow-Robin) space around arteries, and return flow to the cerebrospinal fluid (CSF) space via paravenous channels. The second hypothesis involves flow of interstitial fluid from the parenchyma to lymphatic vessels along basement membranes between arterial smooth muscle cells. METHODS: This article evaluates the plausibility of steady, pressure-driven flow in these channels with one-dimensional branching models. RESULTS: According to the models, the hydraulic resistance of arterial basement membranes is too large to accommodate estimated interstitial perfusion of the brain, unless the flow empties to lymphatic ducts after only several generations (still within the parenchyma). The estimated pressure drops required to drive paraarterial and paravenous flows of the same magnitude are not large, but paravenous flow back to the CSF space means that the total pressure difference driving both flows is limited to local pressure differences among the different CSF compartments, which are estimated to be small. CONCLUSIONS: Periarterial flow and glymphatic circulation driven by steady pressure are both found to be implausible, given current estimates of anatomical and fluid dynamic parameters.