PURPOSE:Helical flow in the ascending aorta (AAo) is recognized as beneficial to cardiovascular physiology. Previous in vivo studies of bicuspid aortic valve (BAV) disease have mainly relied on qualitative assessments or surrogate measures of helical flow, hampering its use as potential hemodynamic biomarker. Here, we leveraged a rigorous fluid mechanical framework for helical flow structures to (i) determine how aortic valve (AV) phenotype-tricuspid (TAV) versus bicuspid-influences AAo helical flow and (ii) identify its principal anatomical and hemodynamic determinants. METHODS:4D flow MRI data from sixty subjects (41 TAV, 19 BAV) were analyzed. Helicity-derived quantities were computed to quantify the intensity and topology of AAo helical flow. Conventional hemodynamic and anatomical parameters were also extracted and their association with helicity-based quantities was explored. RESULTS:Compared with TAV subjects, BAV patients exhibited lower helicity intensity and reduced predisposition to form coherent helical flow patterns. In TAV, helical flow topology was primarily influenced by flow pulsatility and vessel anatomy, whereas in BAV, eccentric systolic jets promoted the arrangement of blood flow into helical structures without enhancing helicity intensity. Helical flow topology emerged as highly sensitive to AV phenotype, with its discriminative power augmented by conventional anatomical or hemodynamic parameters. CONCLUSION:AV phenotype critically shapes helical flow in AAo through phenotype-specific anatomical and hemodynamic determinants. The eccentric jet associated with BAV disrupts helicity intensity, potentially diminishing the protective role of helical flow. Integrating conventional hemodynamic and anatomical parameters with helical flow topology yields a robust, in vivo measurable morpho-hemodynamic signature of BAV, offering diagnostic and prognostic potential.

Abstract Cerebral aneurysms are abnormal outpouchings of arteries within the brain and occur in ∼1 in 30 adults. Their initiation, growth, and rupture have been linked to focal blood flow abnormalities—often termed “disturbed” or “hostile” hemodynamics—but commonly-used hemodynamic metrics yield conflicting associations with pathology and lack a unifying mechanistic interpretation. Building on a theoretically-grounded link between wall shear stress and near-wall vorticity, we hypothesized that a topology-based description of near-wall flow can operationalize the concept of hostile hemodynamics in a reproducible way. Inspired by atmospheric tornadic phenomena, we sought a principled taxonomy of coherent near-wall fluid structures with potential mechanobiological and clinical implications. Using high-fidelity computational fluid dynamics simulations in anatomically realistic geometries, we identified coherent near-wall fluid structures whose organization mirrors well-studied atmospheric phenomena: tornado-like columnar rotating cores; downburst-like nonrotating wall-impinging jets with tangential outflow, roll-cloud-like tangential vortices; and mixed configurations. These tornadic events on the aneurysm luminal surface were identified from wall shear stress topology, consistent with its theoretical connection to near-wall vorticity kinematics. The presence of tornadic phenomena—and their imprints on the aneurysm wall—was independently observed in vivo using 4D flow magnetic resonance imaging. By translating concepts from atmospheric physics into vascular biomechanics, this topology-based framework yields a unified mechanistic language for describing near-wall hemodynamics, resolving blood flow complexity into interpretable and reproducible coherent fluid structures, enabling standardized hemodynamic phenotyping, and supporting hypothesis-driven studies of aneurysms and other cardiovascular diseases where greater fluid-mechanical specificity and interpretability may strengthen links between mechanobiology and clinical risk.

The role of local hemodynamics on atherosclerosis at the carotid bifurcation has been the subject of study by computational fluid-dynamics (CFD) simulations for over three decades. Nevertheless, questions still swirl about the inherent rigid-wall assumption, especially with the introduction of increasingly predictive—but also increasingly intricate—hemodynamic parameters. Two-way-coupled fluid–structure interaction (FSI) simulations were performed on a cohort of 10 carotid bifurcations with ostensibly normal lumen geometries, along with CFD simulations assuming rigid arterial walls. In FSI simulations, carotid wall mechanical properties were assumed to be anisotropic via a fiber-reinforced hyperelastic material model, also accounting for prestress and external tissue support. Three-element Windkessel models were used to impose pressure conditions consistent with patient-specific measured inflow rates and outflow divisions. Maximum cross-sectional area changes over the cardiac cycle were generally less than 21

Thickening of the venous plexus surrounding the petrous ICA, known as Rektorzik venous plexus (RVP), is a marker of inward ICA remodeling from a substantial reduction in blood flow, but clinical application of its detection remains unexplored. We reviewed contrast-enhanced vessel wall MRI imaging (VWMRI) and CTA examinations of the head and neck acquired at our institutions to identify cases with asymmetric RVP thickening that influenced the diagnosis or medical management of neurovascular diseases. Five representative patients were included. Two patients with intracranial MRA or CTA interpreted as having normal findings had asymmetric RVP thickening, in one case leading to cervical imaging that identified high-grade carotid stenosis and in the other case drawing attention to a linear filling defect at the ipsilateral distal M1 branch of the MCA identified as a dissection on image reconstruction. The third patient had intracranial ICA stenosis not considered to be flow-limiting but the asymmetric RVP thickening suggested otherwise, which was supported by cervical ICA flow measurements by Doppler ultrasound. Two patients had resolution of asymmetric RVP thickening confirming flow restoration, one following treatment of intracranial vasospasm and the other after carotid revascularization. Asymmetric RVP thickening is a valuable biomarker that can identify flow-limiting stenosis, at times incidentally, and monitor changes in flow impairment, offering the potential for improved diagnostic accuracy and stroke-risk assessment.

Venous pulsatile tinnitus (PT) is sound associated with abnormal blood flow near auditory structures in the head, which can impact mental health and may be associated with intracranial hypertension. High-frequency flow instabilities, vortical flow, and regions of high time-averaged wall shear stress (TAWSS) have previously been associated with the sounds of PT, but do not identify potential mechanisms for sound production. In this study, the spectral power index of the wall pressure ( SPI_P ) was used to determine the locations where sound could be transmitted through the walls of cerebral venous sinuses. These locations were then analyzed using maximum dissipation maps, streamlines, spectrograms, and swirling strength to understand the underlying flow phenomena that induce sound production. The results show that regions of high SPI_P do not correspond with high TAWSS, vortical flow, or regions of highest dissipation. Rather, they appear to occur beyond regions of high dissipation where part of the post-stenotic flow splits off and interacts with obstructions, forming larger structures that beat against the wall, in addition to smaller flow structures. It is proposed that these structures are capable of producing the intermittency in pressure required to create sound that may be able to transmit to the ear.

OBJECTIVE:Abnormal hemodynamics is thought to play an essential role in the development of cardiovascular diseases. Mouse models are widely used for elucidating the underlying mechanisms; however, their small size and high heart rates make it difficult to perform quantitative flow velocity field mapping with sufficient temporal resolution. Our objective was to develop a noninvasive method for quantitative flow field mapping in mice based on speckle-tracking from high-frequency ultrasound B-mode imaging. METHODS:Ultrasound ECG-gated kilohertz visualization (EKV) was performed on a mouse-aorta-sized tubular flow phantom at frame rates up to 10,000 fps. Unexpected velocity underestimations were elucidated by simulating EKV reconstruction and performing ultrasound image velocimetry (UIV) in silico. A technique for error correction was developed and validated in vitro, and demonstrated in vivo. RESULTS:In flow phantoms, EKV-UIV underestimated velocity in the beam lateral direction by 50%-70%. This was attributed to loss of speckle contiguity owing to EKV's retrospective strip-based reconstruction of the two-dimensional B-mode image. The proposed correction technique reduced the errors to <10% by accounting only for speckle movement within each image strip. A preliminary in vivo study showed that vortex shapes and near-wall expansion movement inside a mouse left ventricle were more aligned with physical expectations after correction. CONCLUSION:A novel technique was developed to quantitatively map blood flow with high spatiotemporal resolution. Further optimization will enable longitudinal studies in mice to gain insights on the role of local hemodynamic forces in the development of cardiovascular diseases.

Topological features of time-dependent, three-dimensional (3D) vector flow fields, such as wall shear stress (WSS) fixed points, are considered surrogates of pathological blood flow dynamics in cardiovascular diseases. Fixed-point visualizations are typically constrained to two-dimensional (2D) spaces, yet they aim to display complex spatiotemporal (four-dimensional (4D)) dynamics. There is a need for visualization strategies to reduce occlusion and reliance on animations to allow the detection of holistic flow patterns. Using intracranial aneurysms as a use case, we present the fixed-point carousel, a novel approach to visually depicting the "4D" nature of WSS fixed points via (1) topographic mapping of the 3D aneurysm sac to overcome occlusion while preserving fixed-point distances and sac morphological features; and (2) arranging these into a carousel model to present with temporal dimension holistically. Examples are presented for image-based computational fluid dynamic (CFD) models of intracranial aneurysms, illuminating the intricate and distinct fixed-point trajectories and interactions, a necessary step toward understanding the volumetric flow manifolds that drive them for this and other cardiovascular-and potentially nonbiomedical-fluid dynamics applications.

Topological features of time-dependent, three-dimensional vector flow fields, such as wall shear stress (WSS) fixed points, are considered surrogates of pathological blood flow dynamics in cardiovascular diseases. Fixed-point visualizations are typically constrained to two-dimensional spaces, yet they aim to display complex spatio-temporal (four-dimensional) dynamics. There is a need for visualization strategies to reduce occlusion and reliance on animations to allow the detection of holistic flow patterns. Using intracranial aneurysms as a use case, we present the fixed point carousel, a novel approach to visually depicting the ?4D? nature of WSS fixed points via 1) topographic mapping of the 3D aneurysm sac to overcome occlusion while preserving fixed point distances and sac morphological features; and 2) arranging these into a carousel model to present with temporal dimension holistically. Examples are presented for image-based computational fluid dynamic (CFD) models of intracranial aneurysms, illuminating the intricate and distinct fixed point trajectories and interactions, a necessary step towards understanding the volumetric flow manifolds that drive them for this and other cardiovascular?and potentially non-biomedical?fluid dynamics applications.

Deciphering the complex interactions at the blood vessel–wall interface remains a key challenge in hemodynamics research. Wall shear stress (WSS) is recognized as a signature for near-wall velocity dynamics, while vorticity represents a fundamental structure of fluid motion. In this work, we revise and extend a recently proposed unifying theoretical approach that sought to connect the topological features of surface vorticity (SV) and WSS [Mazzi, Gallo, Calò, Steinman, and Morbiducci, “Linking wall shear stress and vorticity topologies: Toward a unified theory of cardiovascular flow disturbances,” Phys. Fluids 36(6), 61905 (2024)], the latter recently gaining momentum as a predictor of vascular disease. By revising a partially erroneous interpretation of the link between WSS and SV fixed points (focal points on the luminal surface where these fields vanish), we demonstrate here that every WSS fixed point is also a SV fixed point, and vice versa, though their nature and stability may differ. Building upon the previous study, we establish a robust theoretical classification of the possible combinations of WSS and SV fixed points, based on their nature and stability, and mechanistically connect them to near-wall fluid structures. These structures can further be distinguished by the presence or absence of vorticity diffusion flux normal to the wall, depending on local vorticity kinematics. High-resolution computational fluid dynamics simulations on intracranial aneurysm models validate these theoretical insights. This unifying framework offers a clear taxonomy describing the mechanistic relationship between near-wall flow disturbances and intravascular hemodynamics, providing a deeper understanding of how local shear forces are influenced by near-wall fluid structures, while also paving the way for a clearer interpretation of the role of near-wall hemodynamics in vascular pathophysiology.

Recent high-fidelity fluid-structure interaction (FSI) simulations of cerebral aneurysms have revealed flow-induced wall vibrations. However, those simulations were conducted under simplified conditions, and the robustness of the predicted vibrations remains unknown. This study aimed to advance the physiological accuracy of previous models and to investigate the sensitivity to parameter uncertainty. We compared the previously used near-linear St. Venant-Kirchhoff wall model with a three-term hyperelastic Mooney-Rivlin (MR3) model fitted to experimental data and also modeled effects of surrounding cerebrospinal fluid (CSF). We then varied flow rate (1.83 mL/s  ± $$ \pm $$  25%), wall stiffness (soft, medium, stiff), and wall thickness (0.25  ± $$ \pm $$  0.1 mm). Our main findings for the four aneurysms considered were as follows: the MR3 model led to an average increase of 35% in pulsation and 240% in vibration amplitude, along with an 18% decrease in frequency. Viscous damping by the CSF reduced the vibration amplitude by 68% but did not affect the frequency or pulsation. Changes in flow rate had no effect on pulsation but increased vibration amplitude by 246%. Wall stiffness and thickness had a comparatively smaller impact on vibration, altering amplitude by 36% and 82% and frequency by 20% and 8%. In conclusion, the more advanced models led to a decrease of vibration amplitude and frequency during the cardiac cycle, consistent with clinical observations. Like computational fluid dynamics, FSI simulations can be sensitive to flow rates but are otherwise robust and can provide a fundamental understanding of aneurysm wall vibration without precise knowledge of wall properties.

Recent computational and experimental studies of intracranial aneurysms have revealed potential mechanisms of aneurysm bruits and murmurs, driven by flow instabilities rather than by stable pulsatile flow. Some of these studies have been conducted under the assumption of constant flow rate (steady flow); however the validity of this assumption has not been evaluated for high-frequency flow instability, or vibrations from fluid-structure interaction (FSI) simulations. We evaluated the time-averaged wall shear stress, flow instability and vibration amplitude of steady flow simulations, performed at both cycle-averaged and peak-systolic flow rates, and compared these to recent pulsatile FSI simulations. Wall shear stress fields of pulsatile flow (time-averaged and peak values) were well-approximated by the respective steady-flow FSI simulations, and the spatial distribution and frequency content of flow instability and vibrations were reasonably approximated by the steady flow simulations at peak-systolic flow rates. However, the level of flow instability and vibration was generally overpredicted by the steady flow simulations at peak-systolic flow rates as flow remained unstable for longer than in the pulsatile simulation, while no flow instability was detected for steady flow at cycle-averaged flow rates. Additionally, the amplitude of flow instability and vibration fluctuated considerably in the steady flow simulations, while the pulsatile simulations exhibited consistent vibration amplitudes (less than 10 % variation at peak systole between cycles). Finally, steady flow simulations at peak-systolic conditions required 2-3x more compute time than the pulsatile simulations for the same time duration. Therefore, we recommend using pulsatile flow simulations when investigating vibrations and flow instabilities.

Background Venous sinus stenosis can be associated with cerebrovascular disorders. Understanding the role of blood flow disturbances in these disorders is often hampered by the lack of patient-specific flow rates. Our goal was to demonstrate the impact of this by predicting individual flow rates retrospectively from routine manometry and angiography.Methods Ten cases, spanning a range of stenosis severities and pressure gradients, were selected from a cohort of patients who had undergone venous stenting for pulsatile tinnitus. Lumen geometries were digitally segmented from CT venograms. A simplified Bernoulli formula was derived to estimate individual cycle-average flow rates from clinical pressure gradients and minimum lumen cross-section areas. High-fidelity pulsatile computational fluid dynamics (CFD) simulations were performed to compare predictions of flow disturbances using generic versus individual flow rates, and to validate the Bernoulli formula.Results Individual flow rates derived from the Bernoulli formula deviated by up to 47% from the assumed generic flow rate, resulting in substantial differences in CFD predictions of post-stenotic flow instabilities. Pressure gradients estimated by the simplified Bernoulli formula were, however, highly predictive of pressure gradients from the full CFD simulations (R2=0.95; slope=0.98, 95% CI 0.88 to 1.09).Conclusions A simple Bernoulli formula can predict CFD-estimated trans-stenotic pressure gradients in realistic venous geometries. As demonstrated here, this may be used to recover individual flow rates from routine-but-invasive clinical measurements; however, it also suggests a simpler path towards non-invasive estimation of trans-stenotic pressure gradients that may avoid some of the challenges associated with 4D flow MRI approaches.

Broadening current knowledge about the complex relationship at the blood-vessel wall interface is a main challenge in hemodynamics research. Moving from the consideration that wall shear stress (WSS) provides a signature for the near-wall velocity dynamics and vorticity is considered the skeleton of fluid motion, here we present a unified theory demonstrating the existing link between surface vorticity (SV) and WSS topological skeletons, the latter recently emerged as a predictor of vascular disease. The analysis focused on WSS and SV fixed points, i.e., points where the fields vanish, as they play a major role in shaping the main vector field features. The theoretical analysis proves that: (i) all SV fixed points on the surface must necessarily be WSS fixed points, although with differences in nature and stability and (ii) a WSS fixed point is not necessarily a SV fixed point. In the former case, WSS fixed points are the consequence of flow patterns where only shear contributes to vorticity; in the latter case, WSS fixed points are the consequence of flow impingement to/emanation from the vessel wall. Moreover, fluid structures interacting with the wall characterized by zero or non-zero rotational momentum generate WSS fixed points of different nature/stability. High-fidelity computational fluid dynamics simulations in intracranial aneurysm models confirmed the applicability of the theoretical considerations. The presented unified theory unambiguously explains the mechanistic link between near-wall flow disturbances and the underlying intravascular flow features expressed in terms of vorticity, ultimately facilitating a clearer interpretation of the role of local hemodynamics in vascular pathophysiology.

Part I – IntroductIon It has been two decades since the first ‘patientspecific’ 3D computational fluid dynamics (CFD) models of intracranial aneurysms were published in the American Journal of Neuroradiology (AJNR). 2 Thousands of cases have since been simulated, 4 primarily towards identifying hemodynamic factors associated with aneurysm wall degradation as proxies for rupture risk, and secondarily for planning treatments and/or predicting their outcomes. It has also been nearly a decade since the Food and Drug Administration's approval of the first clinical CFD application: calculating pressure drops and fractional flow reserve (FFR) noninvasively for coronary artery disease. Nevertheless, clinical utility of CFD for cerebral artery diseases still seems like fusion energy—always at least a couple of decades away. It is therefore understandable that journal readers may view with some skepticism recent work in the Journal of NeuroInterventional Surgery (JNIS) and other journals applying CFD to cerebral veins. As we outline here, CFD modeling in venous diseases, while not without its own challenges, might have a more straightforward path to the clinic. This is because, as for FFR, it is the pathophysiology of the blood flow itself, rather than the impact of disturbed flow on the pathobiology of the blood or wall, that is of central interest. It is perhaps fitting that the first computational models for cerebral venous diseases began to emerge during the heyday of promising but controversial neurointerventions for multiple sclerosis. These models were primarily onedimensional networks, aimed at understanding the upstream effects of chronic cerebrospinal venous insufficiency (CCSVI) on permeability of the blood–brain barrier. As the promise of the CCSVI hypothesis faded, so too did interest in CFD modeling of cerebral venous diseases. There is, however, now a growing recognition of the contribution of venous disease—and associated disturbed venous blood flow— to a subset of patients, notably those with idiopathic intracranial hypertension (IIH) or pulsatile tinnitus (PT). As extensively reported in the pages of this Journal, there has been an explosion of interest in cerebral venous sinus stenting as a primary treatment modality for IIH, due to the perceived benefits over traditional surgical methods, 15 and stenting or coiling has shown promise in patients with refractory PT.

INTRODUCTION:Overestimation of intracranial aneurysm neck width by 3D angiography is a recognized clinical problem, and has long been a concern for image-based computational fluid dynamics (CFD). Recently, it was demonstrated that neck overestimation in 3D rotational angiography (3DRA) could be corrected via segmentation with upsampled resolution and gradient enhancement (SURGE). Our aim was to leverage this approach to determine whether and how neck overestimation actually impacts CFD-derived hemodynamics. MATERIALS AND METHODS:A subset of 17 cases having the largest neck errors from a consecutive clinical sample of 60 was segmented from 3DRA using both standard watershed and SURGE methods. High-fidelity, pulsatile CFD was performed, and a variety of scalar hemodynamic parameters that have been associated with aneurysm growth and/or rupture status were derived. RESULTS:With a few exceptions, flow and wall shear stress (WSS) patterns were qualitatively similar between neck-overestimated and corrected models. Sac-averaged WSS values were significantly lower after neck correction (p = 0.0005) but were highly correlated with their neck-overestimated counterparts (R2 = 0.98). Jet impingement was significantly more concentrated in the neck-corrected vs. -uncorrected models (p = 0.0011), and only moderately correlated (R2 = 0.61). Parameters quantifying velocity or WSS fluctuations were not significantly different after neck correction, but this reflected their poorer correlations (R2 < 0.4). Nevertheless, for all hemodynamic parameters, median absolute differences were < 26%, and no parameter had more than 5/17 cases with absolute differences > 50%. CONCLUSION:Differences in hemodynamics due to neck width overestimation were found to be at most equal to, and often less than, those reported for other sources of error/uncertainty in intracranial aneurysm CFD, such as solver settings or assumed inflow rates.

Clinical, experimental, and recent computational studies have demonstrated the presence of wall vibrations in cerebral aneurysms, thought to be induced by blood flow instability. These vibrations could induce irregular, high-rate deformation of the aneurysm wall, and potentially disrupt regular cell behavior and promote deleterious wall remodeling. In order to elucidate, for the first time, the onset and nature of such flow-induced vibrations, in this study we imposed a linearly increasing flow rate on high-fidelity fluid–structure interaction models of three anatomically realistic aneurysm geometries. Prominent narrow-band vibrations in the range of 100–500 Hz were found in two out of the three aneurysm geometries tested, while the case that did not exhibit flow instability did not vibrate. Aneurysm vibrations consisted mostly of fundamental modes of the entire aneurysm sac, with the vibrations exhibiting more frequency content at higher frequencies than the flow instabilities driving those vibrations. The largest vibrations occurred in the case which exhibited strongly banded fluid frequency content, and the vibration amplitude was highest when the strongest fluid frequency band was an integer multiple of one of the natural frequencies of the aneurysm sac. Lower levels of vibration occurred in the case which exhibited turbulent-like flow with no distinct frequency bands. The current study provides a plausible mechanistic explanation for the high-frequency sounds observed in cerebral aneurysms, and suggests that narrow-band (vortex-shedding type) flow might stimulate the wall more, or at least at lower flow rates, than broad-band, turbulent-like flow.