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Carotid artery webs (CaW) are non-atherosclerotic projections into the vascular lumen and have been linked to up to one-third of cryptogenic strokes in younger patients. Determining how CaW affects local hemodynamics is essential for understanding clot formation and stroke risk. Computational fluid dynamics simulations were used to investigate patient-specific hemodynamics in carotid artery bifurcations with CaW, bifurcations with atherosclerotic lesions having a similar degree of lumen narrowing, and with healthy carotid bifurcations. Simulations were conducted using segmented computed tomography angiography geometries with inlet boundary conditions extracted from 2D phase contrast MRI scans. The study included carotid bifurcations with CaW (n = 13), mild atherosclerosis (n = 7), and healthy bifurcation geometries (n = 6). Hemodynamic parameters associated with vascular dysfunction and clot formation, including shear rate, oscillatory shear index (OSI), low velocity, and flow stasis were calculated and compared between the subject groups. Patients with CaW had significantly larger regions containing low shear rate, high OSI, low velocity, and flow stasis in comparison to subjects with mild atherosclerosis or normal bifurcations. These abnormal hemodynamic metrics in patients with CaW are associated with clot formation and vascular dysfunction and suggest that hemodynamic assessment may be a tool to assess stroke risk in these patients., (© 2024. The Author(s).)

Background: Three-dimensional, ECG-gated, time-resolved, three-directional, velocity-encoded phase-contrast MRI (4D flow MRI) has been applied extensively to measure blood velocity in great vessels but has been much less used in diseased carotid arteries. Carotid artery webs (CaW) are non-inflammatory intraluminal shelf-like projections into the internal carotid artery (ICA) bulb that are associated with complex flow and cryptogenic stroke., Purpose: Optimize 4D flow MRI for measuring the velocity field of complex flow in the carotid artery bifurcation model that contains a CaW., Methods: A 3D printed phantom model created from computed tomography angiography (CTA) of a subject with CaW was placed in a pulsatile flow loop within the MRI scanner. 4D Flow MRI images of the phantom were acquired with five different spatial resolutions (0.50-2.00  mm 3 ) and four different temporal resolutions (23-96 ms) and compared to a computational fluid dynamics (CFD) solution of the flow field as a reference. We examined four planes perpendicular to the vessel centerline, one in the common carotid artery (CCA) and three in the internal carotid artery (ICA) where complex flow was expected. At these four planes pixel-by-pixel velocity values, flow, and time average wall shear stress (TAWSS) were compared between 4D flow MRI and CFD., Hypothesis: An optimized 4D flow MRI protocol will provide a good correlation with CFD velocity and TAWSS values in areas of complex flow within a clinically feasible scan time (~ 10 min)., Results: Spatial resolution affected the velocity values, time average flow, and TAWSS measurements. Qualitatively, a spatial resolution of 0.50  mm 3 resulted in higher noise, while a lower spatial resolution of 1.50-2.00  mm 3 did not adequately resolve the velocity profile. Isotropic spatial resolutions of 0.50-1.00  mm 3 showed no significant difference in total flow compared to CFD. Pixel-by-pixel velocity correlation coefficients between 4D flow MRI and CFD were > 0.75 for 0.50-1.00  mm 3 but were < 0.5 for 1.50 and 2.00  mm 3 . Regional TAWSS values determined from 4D flow MRI were generally lower than CFD and decreased at lower spatial resolutions (larger pixel sizes). TAWSS differences between 4D flow and CFD were not statistically significant at spatial resolutions of 0.50-1.00  mm 3 but were different at 1.50 and 2.00 mm 3 . Differences in temporal resolution only affected the flow values when temporal resolution was > 48.4 ms; temporal resolution did not affect TAWSS values., Conclusion: A spatial resolution of 0.74-1.00  mm 3 and a temporal resolution of 23-48 ms (1-2 k-space segments) provides a 4D flow MRI protocol capable of imaging velocity and TAWSS in regions of complex flow within the carotid bifurcation at a clinically acceptable scan time., (© 2023. The Author(s) under exclusive licence to Biomedical Engineering Society.)

Four-dimensional flow magnetic resonance imaging (i.e., 4D flow MRI) has become a valuable tool for the in vivo assessment of blood flow within large vessels and cardiac chambers. As wall shear stress (WSS) has been correlated with the development and progression of cardiovascular disease, focus has been directed at developing techniques to quantify WSS directly from 4D flow MRI data. The goal of this study was to compare the accuracy of two such techniques - termed the velocity and flow-based methods - in the setting of simplified and complex flow scenarios. Synthetic MR data were created from exact solutions to the Navier-Stokes equations for the steady and pulsatile flow of an incompressible, Newtonian fluid through a rigid cylinder. In addition, synthetic MR data were created from the predicted velocity fields derived from a fluid-structure interaction (FSI) model of pulsatile flow through a thick-walled, multi-layered model of the carotid bifurcation. Compared to the analytical solutions for steady and pulsatile flow, the flow-based method demonstrated greater accuracy than the velocity-based method in calculating WSS across all changes in fluid velocity/flow rate, tube radius, and image signal-to-noise (p < 0.001). Furthermore, the velocity-based method was more sensitive to boundary segmentation than the flow-based method. When compared to results from the FSI model, the flow-based method demonstrated greater accuracy than the velocity-based method with average differences in time-averaged WSS of 0.31 ± 1.03 Pa and 0.45 ± 1.03 Pa, respectively (p <0.005). These results have implications on the utility, accuracy, and clinical translational of methods to determine WSS from 4D flow MRI., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: Endovascular intervention in uncomplicated type B dissection has not been shown conclusively to confer benefit on patients. The hemodynamic effect of primary entry tear coverage is not known. Endovascular stent grafts were deployed in a model of aortic dissection with multiple fenestrations to study these effects. It is hypothesized that endograft deployment will lead to restoration of parabolic true lumen flow as well as elimination of false lumen flow and transluminal jets and vortices locally while maintaining distal false lumen canalization., Methods: Thoracic stent grafts were placed in silicone models of aortic dissection with a compliant and mobile intimal flap and installed in a flow loop. Pulsatile fluid flow was established with a custom positive displacement pump, and the models were imaged by four-dimensional flow magnetic resonance imaging. Full flow fields were acquired in the models, and velocities were extracted to calculate flow rates, reverse flow indices, and oscillatory shear index, the last two of which are measures of stagnant and disturbed flows., Results: Complete obliteration of the false lumen was achieved in grafted aorta, with normal parabolic flow profiles in the true lumen (maximal velocity, 30.4 ± 8.4 cm/s). A blind false lumen pouch was created distal to this with low-velocity (5.8 ± 2.7 cm/s) and highly reversed (27.9% ± 13.9% reverse flow index) flows. In distal free false lumen segments, flows were comparable to ungrafted conditions with maximal velocities on the order of 7.0 ± 2.1 cm/s. Visualization studies revealed forward flow in these regions with left-handed vortices from true to false lumen. Shear calculations in free false lumen regions demonstrated reduced oscillatory shear index., Conclusions: Per the initial hypothesis, endovascular grafting improved true lumen hemodynamics in the grafted region. Just distally, a prothrombotic flow regimen was noted in the false lumen, yet free false lumen distal to this remained canalized. Clinically, this suggests a need for advancing endovascular intervention beyond sole entry tear coverage to prevent further false lumen canalization through uncovered fenestrations., (Copyright © 2019 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Wall shear stress (WSS) has been investigated as a prognostic marker for the prospective identification of rapidly progressing coronary artery disease (CAD) and atherosclerotic lesions likely to gain high-risk (vulnerable) characteristics. The goal of this study was to compare biplane angiographic vs. intravascular ultrasound (IVUS) derived reconstructed coronary geometries to evaluate agreement in geometry, computed WSS, and association of WSS and CAD progression. Baseline and 6-month follow-up angiographic and IVUS imaging data were collected in patients with non-obstructive CAD (n = 5). Three-dimensional (3D) reconstructions of the coronary arteries were generated with each technique, and patient-specific computational fluid dynamics models were constructed to compute baseline WSS values. Geometric comparisons were evaluated in arterial segments (n = 9), and hemodynamic data were evaluated in circumferential sections (n = 468). CAD progression was quantified from serial IVUS imaging data (n = 277), and included virtual-histology IVUS (VH-IVUS) derived changes in plaque composition. There was no significant difference in reconstructed coronary segment lengths and cross-sectional areas (CSA), however, IVUS derived geometries exhibited a significantly larger left main CSA than the angiographic reconstructions. Computed absolute time-averaged WSS (TAWSS ABS ) values were significantly greater in the IVUS derived geometries, however, evaluations of relative TAWSS (TAWSS REL ) values revealed improved agreement and differences within defined zones of equivalence. Associations between VH-IVUS defined CAD progression and angiographic or IVUS derived WSS exhibited poor agreement when examining TAWSS ABS data, but improved when evaluating the association with TAWSS REL data. We present data from a small cohort of patients highlighting strong agreement between angiographic and IVUS derived coronary geometries, however, limited agreement is observed between computed WSS values and associations of WSS with CAD progression.

The prevalence of abdominal aortic aneurysms differs greatly between men and women across the spectrum of ages. The reason for this discrepancy is not clear and likely involves several factors including the impact of sex hormones. We hypothesize that the unique spatial localization of abdominal aortic aneurysms is dictated in part by local hemodynamic forces on the vascular wall. Specifically, we propose that oscillatory shear stress is a specific signal to the endothelium that initiates the events ultimately leading to abdominal aortic aneurysm formation. We are proposing that sex-dependent differences in oscillatory shear stress in the infra-renal aorta may explain the observed differences between men and women. Initial observations suggest that, indeed, men and women have different degrees of oscillatory blood flow in the infra-renal abdominal aorta. The challenge is to extend these observations to show a causal relationship between oscillatory flow and aneurysm formation., Competing Interests: Potential Conflicts of Interest: None disclosed.

Background: The development of clinically applicable fluid-structure interaction (FSI) models of the left heart is inherently challenging when using in vivo cardiovascular magnetic resonance (CMR) data for validation, due to the lack of a well-controlled system where detailed measurements of the ventricular wall motion and flow field are available a priori. The purpose of this study was to (a) develop a clinically relevant, CMR-compatible left heart physical model; and (b) compare the left ventricular (LV) volume reconstructions and hemodynamic data obtained using CMR to laboratory-based experimental modalities., Methods: The LV was constructed from optically clear flexible silicone rubber. The geometry was based off a healthy patient's LV geometry during peak systole. The LV phantom was attached to a left heart simulator consisting of an aorta, atrium, and systemic resistance and compliance elements. Experiments were conducted for heart rate of 70 bpm. Wall motion measurements were obtained using high speed stereo-photogrammetry (SP) and cine-CMR, while flow field measurements were obtained using digital particle image velocimetry (DPIV) and phase-contrast magnetic resonance (PC-CMR)., Results: The model reproduced physiologically accurate hemodynamics (aortic pressure = 120/80 mmHg; cardiac output = 3.5 L/min). DPIV and PC-CMR results of the center plane flow within the ventricle matched, both qualitatively and quantitatively, with flow from the atrium into the LV having a velocity of about 1.15 m/s for both modalities. The normalized LV volume through the cardiac cycle computed from CMR data matched closely to that from SP. The mean difference between CMR and SP was 5.5 ± 3.7%., Conclusions: The model presented here can thus be used for the purposes of: (a) acquiring CMR data for validation of FSI simulations, (b) determining accuracy of cine-CMR reconstruction methods, and, ((c) conducting investigations of the effects of altering anatomical variables on LV function under normal and disease conditions.)

Cardiac allograft vasculopathy (CAV) is one of the leading causes of morbidity and morality in orthotopic heart transplant (HTx) patients. While disturbed flow patterns have been linked to the spatial localization of atherosclerosis, the role of hemodynamics in CAV development has not been examined. HTx patients (n = 5) requiring percutaneous coronary intervention (PCI) for a focal, epicardial lesion were studied. Angiographic images were retrospectively obtained from baseline (i.e., in the presence of no observed disease) and follow-up catheterizations (i.e., at the time of PCI; 12.4 ± 2.6 years post-HTx). Patient-specific computational models were created from baseline images. Computational fluid dynamic techniques were employed to quantify the hemodynamic environment, which was expressed as normalized time-averaged WSS (TAWSSnorm; measure of temporal WSS magnitude) and normalized WSS angle deviation (WSSADnorm; measure of instantaneous WSS vector oscillation) values. Baseline hemodynamic and follow-up angiographic data were co-registered to investigate the association between WSS and subsequent occlusive CAV lesion location. Results indicate a high degree of co-localization between baseline low WSS data and follow-up occlusive CAV lesion. Local minima in TAWSSnorm were located 2.5 ± 0.6 mm from the site of PCI. Furthermore, local maxima in WSSADnorm were located 3.9 ± 0.7 mm from the site of PCI. In 3 patients, the occlusive lesion formed in a region that was subjected to both low and oscillatory WSS at baseline. There was discernable spatial co-localization between baseline disturbed flow patterns and follow-up CAV lesions requiring PCI. These results suggest a role of fluid mechanics in the development of focal, flow-limiting CAV lesions.

Patient-specific computational fluid dynamics (CFD) is a powerful tool for researching the role of blood flow in disease processes. Modern clinical imaging technology such as MRI and CT can provide high resolution information about vessel geometry, but in many situations, patient-specific inlet velocity information is not available. In these situations, a simplified velocity profile must be selected. We studied how idealized inlet velocity profiles (blunt, parabolic, and Womersley flow) affect patient-specific CFD results when compared to simulations employing a "reference standard" of the patient's own measured velocity profile in the carotid bifurcation. To place the magnitude of these effects in context, we also investigated the effect of geometry and the use of subject-specific flow waveform on the CFD results. We quantified these differences by examining the pointwise percent error of the mean wall shear stress (WSS) and the oscillatory shear index (OSI) and by computing the intra-class correlation coefficient (ICC) between axial profiles of the mean WSS and OSI in the internal carotid artery bulb. The parabolic inlet velocity profile produced the most similar mean WSS and OSI to simulations employing the real patient-specific inlet velocity profile. However, anatomic variation in vessel geometry and the use of a nonpatient-specific flow waveform both affected the WSS and OSI results more than did the choice of inlet velocity profile. Although careful selection of boundary conditions is essential for all CFD analysis, accurate patient-specific geometry reconstruction and measurement of vessel flow rate waveform are more important than the choice of velocity profile. A parabolic velocity profile provided results most similar to the patient-specific velocity profile.

Accurate fluid mechanics models are important tools for predicting the flow field in the carotid artery bifurcation and for understanding the relationship between hemodynamics and the initiation and progression of atherosclerosis. Clinical imaging modalities can be used to obtain geometry and blood flow data for developing subject-specific human carotid artery bifurcation models. We developed subject-specific computational fluid dynamics models of the human carotid bifurcation from magnetic resonance (MR) geometry data and phase contrast MR velocity data measured in vivo. Two simulations were conducted with identical geometry, flow rates, and fluid parameters: (1) Simulation 1 used in vivo measured velocity distributions as time-varying boundary conditions and (2) Simulation 2 used idealized fully-developed velocity profiles as boundary conditions. The position and extent of negative axial velocity regions (NAVRs) vary between the two simulations at any given point in time, and these regions vary temporally within each simulation. The combination of inlet velocity boundary conditions, geometry, and flow waveforms influences NAVRs. In particular, the combination of flow division and the location of the velocity peak with respect to individual carotid geometry landmarks (bifurcation apex position and the departure angle of the internal carotid) influences the size and location of these reversed flow zones. Average axial wall shear stress (WSS) distributions are qualitatively similar for the two simulations; however, instantaneous WSS values vary with the choice of velocity boundary conditions. By developing subject-specific simulations from in vivo measured geometry and flow data and varying the velocity boundary conditions in otherwise identical models, we isolated the effects of measured versus idealized velocity distributions on blood flow patterns. Choice of velocity distributions at boundary conditions is shown to influence pathophysiologically relevant flow patterns in the human carotid bifurcation. Although mean WSS distributions are qualitatively similar for measured and idealized inlet boundary conditions, instantaneous NAVRs differ and warrant imposing in vivo velocity boundary conditions in computational simulations. A simulation based on in vivo measured velocity distributions is preferred for modeling hemodynamics in subject-specific carotid artery bifurcation models when studying atherosclerosis initiation and development.

MR phase velocity mapping was used to calculate wall shear stress (WSS) in the suprarenal and infrarenal abdominal aorta, two sites with very different proclivities for development of a atherosclerosis. For the eight subjects studied, the average value of the mean (time averaged over the cardiac cycle) WSS in the suprarenal aorta was 10.4 dynes/cm2 at the posterior wall and 8.6 at the anterior wall. In the infrarenal aorta, WSS values were 4.7 at the posterior wall and 6.1 at the anterior wall. Peak WSS over the cardiac cycle was 48 and 54 at the anterior and posterior walls of the suprarenal aorta, respectively, and 33 and 30 at the anterior and posterior walls of the infrarenal aorta, respectively. Wide variation was found in both mean and peak WSS values among subjects. However, for 28 of 32 locations examined, mean and peak WSS were higher in the suprarenal aorta than in the infrarenal aorta. Because atherosclerosis is more likely to form in the infrarenal aorta than in the suprarenal aorta, this study supports the hypothesis that low WSS is a localizing factor for atherosclerosis, and high WSS may act as a deterrent against formation of atherosclerosis.