Blood flow and emboli transport patterns during venoarterial extracorporeal membrane oxygenation: A computational fluid dynamics study.

PROBLEM: Despite advances in Venoarterial Extracorporeal Membrane Oxygenation (VA-ECMO), a significant mortality rate persists due to complications. The non-physiological blood flow dynamics of VA-ECMO may lead to neurological complications and organ ischemia. Continuous retrograde high-flow oxygenated blood enters through a return cannula placed in the femoral artery which opposes the pulsatile deoxygenated blood ejected by the left ventricle (LV), which impacts upper body oxygenation and subsequent hyperoxemia. The complications underscore the critical need to comprehend the impact of VA-ECMO support level and return cannula size, as mortality remains a significant concern. AIM: The aim of this study is to predict and provide insights into the complications associated with VA-ECMO using computational fluid dynamics (CFD) simulations. These complications will be assessed by characterising blood flow and emboli transport patterns through a comprehensive analysis of the influence of VA-ECMO support levels and arterial return cannula sizes. METHODS: Patient-specific 3D aortic and major branch models, derived from a male patient's CT scan during VA-ECMO undergoing respiratory dysfunction, were analyzed using CFD. The investigation employed species transport and discrete particle tracking models to study ECMO blood (oxygenated) mixing with LV blood (deoxygenated) and to trace emboli transport patterns from potential sources (circuit, LV, and aorta wall). Two cannula sizes (15 Fr and 19 Fr) were tested alongside varying ECMO pump flow rates (50%, 70%, and 90% of the total cardiac output). RESULTS: Cannula size did not significantly affect oxygen transport. At 90% VA-ECMO support, all arteries distal to the aortic arch achieved 100% oxygen saturation. As support level decreased, oxygen transport to the upper body also decreased to a minimum saturation of 73%. Emboli transport varied substantially between emboli origin and VAECMO support level, with the highest risk of cerebral emboli coming from the LV with a 15 Fr cannula at 90% support. CONCLUSION: Arterial return cannula sizing minimally impacted blood oxygen distribution; however, it did influence the distribution of emboli released from the circuit and aortic wall. Notably, it was the support level alone that significantly affected the mixing zone of VA-ECMO and cardiac blood, subsequently influencing the risk of embolization of the cardiogenic source and oxygenation levels across various arterial branches.

Scale resolving simulations of the effect of glottis motion and the laryngeal jet on flow dynamics during respiration.

BACKGROUND AND OBJECTIVE: The movement of the respiratory walls has a significant impact on airflow through the respiratory tract. The majority of computational fluid dynamics (CFD) studies assume a static geometry which may not provide a realistic flow field. Furthermore, many studies use Reynolds Averaged Navier-Stokes (RANS) turbulence models that do not resolve turbulence structure. Combining the application of advanced scale-resolving turbulence models with moving respiratory walls using CFD will provide detailed insights into respiratory flow structures. METHODS: This study simulated a complete breathing cycle involving inhalation and exhalation in a nasal cavity to trachea geometry that incorporated moving glottis walls. A second breathing cycle was simulated with static glottis walls for comparison. A recently developed hybrid RANS-LES turbulence model, the Stress-Blended Eddy Simulation (SBES), was incorporated to resolve turbulent flow structures in fine detail for both transient simulations. Transient results were compared with steady-state RANS simulations for the same respiratory geometry. RESULTS: Glottis motion caused substantial effects on flow structure through the complete breathing cycle. Significant flow structure and velocity variations were observed due to glottal motion, primarily in the larynx and trachea. Resolved turbulence structures using SBES showed an intense mixing section in the glottis region during inhalation and in the nasopharynx during expiration, which was not present in the RANS simulations. CONCLUSION: Transient simulations of a realistic breathing cycle uncovered flow structures absent in simulations with a constant flow rate. Furthermore, the incorporation of glottis motion impacted airflow characteristics that suggest rigid respiratory walls do not accurately describe respiratory flow. Future research in respiratory airflow should be conducted using transient scale-resolving models in conjunction with moving respiratory walls to capture flow structures in detail.

A counter-swirl design concept for dry powder inhalers.

A swirling airflow is incorporated in several dry powder inhalers (DPIs) for effective powder de-agglomeration. This commonly requires the use of a flow-straightening grid in the DPI to reduce drug deposition loss caused by large lateral spreading of the emerging aerosol. Here, we propose a novel grid-free DPI design concept that improves the aerosol flow characteristics and reduces the aforementioned drug loss. The basis of this design is the implementation of a secondary airflow that swirls in the opposite direction (counter-swirl) to that of a primary swirling airflow. In-vitro deposition, computational fluid dynamics simulations and particle image velocimetry measurements are used to evaluate the counter-swirl DPI aerosol performance and flow characteristics. In comparison with a baseline-DPI that has only a primary swirling airflow, the counter-swirl DPI has 20% less deposition of the emitted drug dose in the induction port and pre-separator of a next generation impactor (NGI). This occurs as a result of the lower flow-swirl generated from the counter-swirl DPI which eliminates the axial reverse flow outside of the mouthpiece and substantially reduces lateral spreading in the exiting aerosol. Modifications to the counter-swirl DPI design were made to prevent drug loss from the secondary airflow tangential inlets, which involved the addition of wall perforations in the tangential inlets and the separation of the primary and secondary swirling airflows by an annular channel. These modified DPI devices were successful in that aspect but had higher flow-swirl than that in the counter-swirl DPI and thus had higher drug mass retained in the device and deposited in the induction port and pre-separator of the NGI. The fine particle fraction in the aerosols generated from all the counter-swirl-based DPIs and the baseline-DPI are found to be statistically similar to each other.

Computational investigation of nasal surface coverage from squeeze bottle and Neti Pot saline irrigation flow.

BACKGROUND AND OBJECTIVE: Nasal saline irrigation is a common therapy for inflammatory nasal and paranasal disease or for managing post nasal and sinus surgery recovery. Two common irrigation devices include the netipot and squeeze bottles, where anecdotally, these devices alleviate congestion, facial pain, and pressure. However, a quantitative evaluation of these devices' performance and the fluid dynamics responsible for the irrigation distribution through the nose is lacking. This study tracked the liquid surface coverage and wall shear stresses during nasal saline irrigation produced from a Neti Pot and squeeze bottle. METHODS: This study used transient computational fluid dynamics (CFD) simulations to investigate the saline irrigation flow field in a subject-specific sinonasal model. The computational nasal cavity model was constructed from a high-resolution computed tomography scan (CT). The irrigation procedure applied a head position tilted at 90° forward using an 80 ml squeeze bottle and 120 ml Neti Pot. RESULTS: The results from a single sinonasal model demonstrated that the Neti Pot irrigation was more effective in delivering saline solution to the nasal cavity on the contralateral side of irrigation due to typically larger volumes but at the expense of reduced flow and shearing rates, as the flow entered under gravitational forces. The squeeze bottle irrigation provided greater surface coverage on the side of irrigation. CONCLUSIONS: The results from the single patient model, demonstrated the Neti Pot increased surface coverage in the paranasal sinuses. Reducing the jet diameter may aid the direct targeting of a specific region at the side of irrigation by preventing the impingement of the jet to the nasal passage surface and redirection of the flow. Evaluating this performance across a wider cohort of patients can strengthen the findings.

Nasal Irrigation Delivery in Three Post-FESS Models From a Squeeze-bottle Using CFD.

PURPOSE: Nasal saline irrigation is highly recommended in patients following functional endoscopic sinus surgery (FESS) to aid the postoperative recovery. Post-FESS patients have significantly altered anatomy leading to markedly different flow dynamics from those found in pre-op or non-diseased airways, resulting in unknown flow dynamics. METHODS: This work investigated how the liquid stream disperses through altered nasal cavities following surgery using Computational Fluid Dynamics (CFD). A realistic squeeze profile was determined from physical experiments with a 27-year-old male using a squeeze bottle with load sensors. The administration technique involved a head tilt of 45-degrees forward to represent a head position over a sink. After the irrigation event that lasted 4.5 s, the simulation continued for an additional 1.5 s, with the head orientation returning to an upright position. RESULTS: The results demonstrated that a large maxillary sinus ostium on the right side allows saline penetration into this sinus. The increased volume of saline entering the maxillary sinus limits the saline volume available to the rest of the sinonasal cavity and reduces the surface coverage of the other paranasal sinuses. The average wall shear stress was higher on the right side than on the other side for two patients. The results also revealed that head position alters the sinuses' saline residual, especially the frontal sinuses. CONCLUSION: While greater access to sinuses is achieved through FESS surgery, patients without a nasal septum limits posterior sinus penetration due to the liquid crossing over to the contralateral cavity and exiting the nasal cavity early.

The health digital twin to tackle cardiovascular disease-a review of an emerging interdisciplinary field.

Potential benefits of precision medicine in cardiovascular disease (CVD) include more accurate phenotyping of individual patients with the same condition or presentation, using multiple clinical, imaging, molecular and other variables to guide diagnosis and treatment. An approach to realising this potential is the digital twin concept, whereby a virtual representation of a patient is constructed and receives real-time updates of a range of data variables in order to predict disease and optimise treatment selection for the real-life patient. We explored the term digital twin, its defining concepts, the challenges as an emerging field, and potentially important applications in CVD. A mapping review was undertaken using a systematic search of peer-reviewed literature. Industry-based participants and patent applications were identified through web-based sources. Searches of Compendex, EMBASE, Medline, ProQuest and Scopus databases yielded 88 papers related to cardiovascular conditions (28%, n = 25), non-cardiovascular conditions (41%, n = 36), and general aspects of the health digital twin (31%, n = 27). Fifteen companies with a commercial interest in health digital twin or simulation modelling had products focused on CVD. The patent search identified 18 applications from 11 applicants, of which 73% were companies and 27% were universities. Three applicants had cardiac-related inventions. For CVD, digital twin research within industry and academia is recent, interdisciplinary, and established globally. Overall, the applications were numerical simulation models, although precursor models exist for the real-time cyber-physical system characteristic of a true digital twin. Implementation challenges include ethical constraints and clinical barriers to the adoption of decision tools derived from artificial intelligence systems.

Wet surface wall model for latent heat exchange during evaporation.

Air conditioning is a dual heat and mass transfer process, and the human nasal cavity achieves this through the mucosal wall surface, which is supplied with an energy source through the sub-epithelial network of capillaries. Computational studies of air conditioning in the nasal cavity have included temperature and humidity, but most studies solved these flow parameters separately, and in some cases, a constant mucosal surface temperature was used. Recent developments demonstrated that both heat and mass transfer need to be modeled. This work expands on existing modeling efforts in accounting for the nasal cavity's dual heat and mass transfer process by introducing a new subwall model, given in the Supplementary Materials. The model was applied to a pipe geometry, and a human nasal cavity was recreated from CT-scans, and six inhalation conditions were studied. The results showed that when the energy transfer from the latent heat of evaporation is included, there is a cooling effect on the mucosal surface temperature.

N95 respirator mask breathing leads to excessive carbon dioxide inhalation and reduced heat transfer in a human nasal cavity.

Face masks and respirators are used to filter inhaled air, which may contain airborne droplets and high particulate matter (PM) concentrations. The respirators act as a barrier to the inhaled and exhaled air, which may change the nasal airflow characteristics and air-conditioning function of the nose. This study aims to investigate the nasal airflow dynamics during respiration with and without an N95 respirator driven by airflow through the nasal cavity to assess the effect of the respirator on breathing conditions during respiration. To achieve the objective of this study, transient computational fluid dynamics simulations have been utilized. The nasal geometry was reconstructed from high-resolution Computed Tomography scans of a healthy 25-year-old female subject. The species transport method was used to analyze the airflow, temperature, carbon dioxide (CO2), moisture content (H2O), and temperature distribution within the nasal cavity with and without an N95 respirator during eight consecutive respiration cycles with a tidal volume of 500 ml. The results demonstrated that a respirator caused excessive CO2 inhalation by approximately 7 × greater per breath compared with normal breathing. Furthermore, heat and mass transfer in the nasal cavity was reduced, which influences the perception of nasal patency. It is suggested that wearers of high-efficiency masks that have minimal porosity and low air exchange for CO2 regulation should consider the amount of time they wear the mask.

Phase offset between arterial pulsations and subarachnoid space pressure fluctuations are unlikely to drive periarterial cerebrospinal fluid flow.

Circulation of fluid through the central nervous system maintains fluid homeostasis and is involved in solute clearance. The glymphatic system is hypothesised to facilitate waste clearance in the brain, with inflow via periarterial spaces, bulk flow through the parenchyma, and outflow via perivenous spaces. The driving force for this mechanism is unknown. Previous modelling in the spinal cord suggests that timing offsets between arterial and subarachnoid space pressure pulses can enable net inflow in perivascular spaces (PVS). This study adapted the spinal pulse offset mechanism to the brain and simulated movement of tracer particles used in experiments. Both bulk flow and diffusive movement of tracer were simulated. Intracranial pressure pulses were applied to one end of a 300-µm-long perivascular space combined with a moving arterial wall simulating arterial pulsations. The simulations indicate the pulse offset mechanism can enable net inflow via PVS; however, it is unknown whether the temporal offset required is physiologically realistic. Increasing the positive component of the ICP (intracranial pressure) pulse increased net flow. Tracer particles driven by bulk flow reached the outlet of the PVS with a net speed of ~ 16 µm/s when the permeability was two orders of magnitude higher than values in the literature. These particles were unable to penetrate into the parenchyma in the absence of diffusion. Dispersion dominated tracer movement in the parenchyma. Further research is required to reconcile discrepancies between these results, and both experimental and computational studies.

On the Use of Computational Fluid Dynamics (CFD) Modelling to Design Improved Dry Powder Inhalers.

PURPOSE: Computational Fluid Dynamics (CFD) simulations are performed to investigate the impact of adding a grid to a two-inlet dry powder inhaler (DPI). The purpose of the paper is to show the importance of the correct choice of closure model and modeling approach, as well as to perform validation against particle dispersion data obtained from in-vitro studies and flow velocity data obtained from particle image velocimetry (PIV) experiments. METHODS: CFD simulations are performed using the Ansys Fluent 2020R1 software package. Two RANS turbulence models (realisable k - ε and k - ω SST) and the Stress Blended Eddy Simulation (SBES) models are considered. Lagrangian particle tracking for both carrier and fine particles is also performed. RESULTS: Excellent comparison with the PIV data is found for the SBES approach and the particle tracking data are consistent with the dispersion results, given the simplicity of the assumptions made. CONCLUSIONS: This work shows the importance of selecting the correct turbulence modelling approach and boundary conditions to obtain good agreement with PIV data for the flow-field exiting the device. With this validated, the model can be used with much higher confidence to explore the fluid and particle dynamics within the device.

In-vitro and particle image velocimetry studies of dry powder inhalers.

Inhalation drug delivery has seen a swift rise in the use of dry powder inhalers (DPIs) to treat chronic respiratory conditions. However, universal adoption of DPIs has been restrained due to their low efficiencies and significant drug losses in the mouth-throat region. Aerosol efficiency of DPIs is closely related to the fluid-dynamics characteristics of the inhalation flow generated from the devices, which in turn are influenced by the device design. In-vitro and particle image velocimetry (PIV) have been used in this study to assess the aerosol performance of a model carrier formulation delivered by DPI devices and to investigate their flow characteristics. Four DPI device models, with modification to their tangential inlets and addition of a grid, have been explored. Similar aerosol performances were observed for all four device models, with FPF larger than 50%, indicating desirable lung deposition. A high swirling and recirculating jet-flow emerging from the mouthpiece of the DPI models without the grid was observed, which contributed to particle deposition in the throat. DPI models where the grid was present showed a straightened outflow without undesired lateral spreading, that reduced particle deposition in the throat and mass retention in the device. These findings demonstrate that PIV measurements strengthen in-vitro evaluation and can be jointly used to develop high-performance DPIs.

Understanding gradients in industrial bioreactors.

Gradients in industrial bioreactors have attracted substantial research attention since exposure to fluctuating environmental conditions has been shown to lead to changes in the metabolome, transcriptome as well as population heterogeneity in industrially relevant microorganisms. Such changes have also been found to impact key process parameters like the yield on substrate and the productivity. Hence, understanding gradients is important from both the academic and industrial perspectives. In this review the causes of gradients are outlined, along with their impact on microbial physiology. Quantifying the impact of gradients requires a detailed understanding of both fluid flow inside industrial equipment and microbial physiology. This review critically examines approaches used to investigate gradients including large-scale experimental work, computational methods and scale-down approaches. Avenues for future work have been highlighted, particularly the need for further coordinated development of both in silico and experimental tools which can be used to further the current understanding of gradients in industrial equipment.

Evaluation of personalized right ventricle to pulmonary artery conduits using in silico design and computational analysis of flow.

Objectives: Right ventricle to pulmonary artery (RV-PA) conduits are required for the surgical management of pulmonary atresia with ventricular septal defect and truncus arteriosus. Bioengineered RV-PA connections may address some of the shortcomings of homografts and xenografts, such as lack of growth potential and structural deterioration and may be manufactured to accommodate patient-specific anatomy. The aim of this study was to develop a methodology for in silico patient-specific design and analysis of RV-PA conduits. Methods: Cross-sectional imaging was obtained from patients with truncus arteriosus (n = 5) and pulmonary atresia with ventricular septal defect (n = 5) who underwent complete repair with a RV-PA conduit. Three-dimensional models of the heart were constructed by segmentation of the right ventricle, existing conduit, branch pulmonary arteries, and surrounding structures. A customized conduit design for each patient was proposed. Computational fluid dynamics analysis was performed and outputs, including wall shear stress and energy loss, were used to compare the performance of the existing conduits and the customized geometries. Results: In this study, a methodology for patient-specific analysis of RV-PA conduit in silico was developed. The results of simulations for 10 patients showed between 23% and 56% decrease in the average wall shear stress and between 24% and 87% reduction in average power requirements in customized designs compared with the stenosed conduits, translating into better hemodynamic performance. Conclusions: Creation of an optimal conduit for an individual patient can be achieved using surgeon-guided design and computational fluid dynamics analysis. Manufacture of personalized RV-PA conduits may obviate the need for surgical customization to accommodate existing materials and provide superior long-term outcomes.

An automated segmentation framework for nasal computational fluid dynamics analysis in computed tomography.

The use of computational fluid dynamics (CFD) to model and predict surgical outcomes in the nasal cavity is becoming increasingly popular. Despite a number of well-known nasal segmentation methods being available, there is currently a lack of an automated, CFD targeted segmentation framework to reliably compute accurate patient-specific nasal models. This paper demonstrates the potential of a robust nasal cavity segmentation framework to automatically segment and produce nasal models for CFD. The framework was evaluated on a clinical dataset of 30 head Computer Tomography (CT) scans, and the outputs of the segmented nasal models were further compared with ground truth models in CFD simulations on pressure drop and particle deposition efficiency. The developed framework achieved a segmentation accuracy of 90.9 DSC, and an average distance error of 0.3 mm. Preliminary CFD simulations revealed similar outcomes between using ground truth and segmented models. Additional analysis still needs to be conducted to verify the accuracy of using segmented models for CFD purposes.

The effects of variation in the arterial pulse waveform on perivascular flow.

Cerebrospinal fluid (CSF) enters nervous tissues through perivascular spaces. Flow through these pathways is important for solute transport and to prevent fluid accumulation. Syringomyelia is commonly associated with subarachnoid space obstructions such as Chiari I malformation. However, the mechanism of development of these fluid-filled cavities is unclear. Studies have suggested that changes in the arterial and CSF pressures could alter normal perivascular flow. This study uses an idealised model of the perivascular space to investigate how variation in the arterial pulse influences fluid flow. The model used simulated subarachnoid pressures from healthy controls (N = 9), Chiari patients with (N = 7) and without (N = 8) syringomyelia. A parametric analysis was conducted to determine how features of the arterial pulse altered flow. The features of interest included: the timing and magnitude of the peak displacement, and the area under the curve in the phases of uptake and decline. A secondary aim was to determine if the previously observed differences between subject groups were sensitive to variation in the arterial pulse wave. The study demonstrated that the Chiari patients without a syrinx maintained a significantly higher level of perivascular inflow over a physiologically likely range of pulse wave shapes. The analysis also suggested that age-related changes in the arterial pulse (i.e. increased late systolic pulse amplitude and faster diastolic decay), could increase resistance to perivascular inflow affecting solute transport.

Current Challenges and Emergent Technologies for Manufacturing Artificial Right Ventricle to Pulmonary Artery (RV-PA) Cardiac Conduits.

Despite advances in modern surgery, congenital heart disease remains a medical challenge and major cause of infant mortality. Valved conduits are routinely used to surgically correct blood flow in hearts with congenital malformations by connecting the right ventricle to the pulmonary artery (RV-PA). This review explores the current range of RV-PA conduits and describes their strengths and disadvantages. Homografts and xenografts are currently the primary treatment modalities, however both graft types have limited biocompatibility and durability, and present a disease transmission risk. Structural deterioration of a replaced valve can lead to pulmonary valve stenosis and/or regurgitation. Moreover, as current RV-PA conduits are of a fixed size, multiple subsequent operations are required to upsize a valved conduit over a patient's lifetime. We assess emerging biomaterials and tissue engineering techniques with a view to replicating the features of native tissues, including matching the durability and elasticity required for normal fluid flow dynamics. The benefits and limitations of incorporating cellular elements within the biomaterial are also discussed. Present review demonstrates that an alignment of medical and engineering disciplines will be ultimately required to produce a biocompatible and high-functioning artificial conduit.

Polypeptide-affined interpenetrating hydrogels with tunable physical and mechanical properties.

Novel hydrogels with tunable mechanical properties similar to human soft tissue have increasing applications in biomedicine, soft robotics, and biocompatible electronics. However, most of these materials require multiple-step fabrication, are not robust, and compromise bioactivity. Thus, aiming to address these shortfalls, herein, we report a versatile hydrogel system with tunable properties and a facile one-pot fabrication process. The hydrogel system is comprised of a hydrogen-bonded hydrophilic polyurethane (HPU) network and a loosely crosslinked copolymer crosslinked with long chain crosslinkers and decorated with succinimide groups. The active succinimide sites conjugate to proteins, such as bovine serum albumin as a model protein, providing additional biocompatibility and controlled release of growth factors and peptides. The interpenetrating nature of this hydrogel system provides a high degree of freedom over mechanical and physical properties by adjusting the ratio of networks and the composition of the second network. Through this process, a library of biocompatible hydrogels with stiffness ranging from 1 to more than 200 kPa was developed. Moreover, it was found that the succinimide groups impact the degree of crosslinking and contribute to the controlled release of peptides.

Tough and Processable Hydrogels Based on Lignin and Hydrophilic Polyurethane.

Lignin is a low-cost, natural polymer with abundant polar sites on its backbone that can be utilized for physical cross-linking of polymers. Here, we use lignin for additional cross-linking of hydrophilic polyether-based polyurethane (HPU) hydrogels, aiming to improve their mechanical properties and processability. Without reducing the swelling, simple addition of 2.5 wt % lignin increases the fracture energy and Young's modulus of HPU hydrogels from, respectively, 1540 ± 40 to 2050 ± 50 J m-2 and 1.29 ± 0.06 to 2.62 ± 0.84 MPa. Lignin also increases the lap shear adhesiveness of hydrogels and induces an immediate load recovery of 95%. We further confirm that hydrogen bonding is the dominant toughening mechanism and elucidate the toughening mechanism by applying the Lake-Thomas and a recently developed sequential debonding theory. We show that unlike the Lake-Thomas theory, the latter model is able to capture the impact of lignin on toughening of hydrogels. Moreover, the lignin-loaded HPU hydrogels are easily processable by various techniques, such as fiber spinning, casting, and 3D printing and are biocompatible with primary human dermal fibroblasts.

Chiari malformation may increase perivascular cerebrospinal fluid flow into the spinal cord: A subject-specific computational modelling study.

Syringomyelia is associated with Chiari I malformation, although the mechanistic link is unclear. Studies have suggested that cerebrospinal fluid enters the spinal cord via the perivascular spaces, and that changes in the timing of the subarachnoid pressures may increase flow into the spinal cord. This study aims to determine how Chiari malformation and syringomyelia alter the subarachnoid space pressures and hence perivascular flow. Subject-specific models of healthy controls (N = 9), Chiari patients with (N = 7) and without (N = 8) syringomyelia, were developed from magnetic resonance imaging (MRI), to simulate the subarachnoid pressures. These pressures were input to an idealised model of the perivascular space to evaluate potential differences in perivascular flow. Peak pressures in Chiari patients without a syrinx were higher than in controls (46% increase; p = .029) and arrived earlier in the cardiac cycle than both controls (2.58% earlier; p = .045) and syrinx patients (2.85% earlier; p = .045). The perivascular model predicted Chiari patients without a syrinx would have the greatest flow into the cord (p < .05) if the arterial pulse delay was between 4 and 10% of the cardiac cycle. Using phase-contrast MRI the mean arterial delay for all subjects was similar, and was estimated as 4.7 ±â€¯0.2%. The perivascular pumping rate showed a strong positive correlation (RAdj2=0.85; p < .0001) with extended periods of high pressure that arrived earlier in the cardiac cycle, suggesting these pressure characteristics may play a role in syrinx development.