skip to main content


This content will become publicly available on September 1, 2024

Title: Vortical Structures Promote Atheroprotective Wall Shear Stress Distributions in a Carotid Artery Bifurcation Model
Carotid artery diseases, such as atherosclerosis, are a major cause of death in the United States. Wall shear stresses are known to prompt plaque formation, but there is limited understanding of the complex flow structures underlying these stresses and how they differ in a pre-disposed high-risk patient cohort. A ‘healthy’ and a novel ‘pre-disposed’ carotid artery bifurcation model was determined based on patient-averaged clinical data, where the ‘pre-disposed’ model represents a pathological anatomy. Computational fluid dynamic simulations were performed using a physiological flow based on healthy human subjects. A main hairpin vortical structure in the internal carotid artery sinus was observed, which locally increased instantaneous wall shear stress. In the pre-disposed geometry, this vortical structure starts at an earlier instance in the cardiac flow cycle and persists over a much shorter period, where the second half of the cardiac cycle is dominated by perturbed secondary flow structures and vortices. This coincides with weaker favorable axial pressure gradient peaks over the sinus for the ‘pre-disposed’ geometry. The findings reveal a strong correlation between vortical structures and wall shear stress and imply that an intact internal carotid artery sinus hairpin vortical structure has a physiologically beneficial role by increasing local wall shear stresses. The deterioration of this beneficial vortical structure is expected to play a significant role in atherosclerotic plaque formation.  more » « less
Award ID(s):
1854415
NSF-PAR ID:
10454787
Author(s) / Creator(s):
; ;
Date Published:
Journal Name:
Bioengineering
Volume:
10
Issue:
9
ISSN:
2306-5354
Page Range / eLocation ID:
1036
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. Background

    Carotid webs (CaWs) are fibromuscular projections in the internal carotid artery (ICA) that cause mild luminal narrowing (<50%), but may be causative in up to one‐third of seemingly cryptogenic strokes. Understanding hemodynamic alterations caused by CaWs is imperative to assessing stroke risk. Time‐Average Wall Shear Stress (TAWSS) and Oscillatory Shear Index (OSI) are hemodynamic parameters linked to vascular dysfunction and thrombosis.

    Purpose

    To test the hypothesis: “CaWs are associated with lower TAWSS and higher OSI than mild atherosclerosis or healthy carotid bifurcation.”

    Study Type

    Prospective study.

    Population

    A total of 35 subjects (N = 14 bifurcations with CaW, 11F, age: 49 ± 10, 10 mild atherosclerosis 6F, age: 72 ± 9, 11 healthy 9F, age: 42 ± 13).

    Field Strength/Sequence

    4D flow/STAR‐MATCH/3D TOF/3T MRI, CTA.

    Assessment

    4D Flow velocity data were analyzed in two ways: 1) 3D ROI in the ICA bulbar segment (complex flow patterns are expected) was used to quantify the regions with low TAWSS and high OSI. 2) 2D planes were placed perpendicular to the centerline of the carotid bifurcation for detailed analysis of TAWSS and OSI.

    Statistical Tests

    Independent‐samples Kruskal–Wallis‐H test with 0.05 used for statistical significance.

    Results

    The percent surface area where low TAWSS was present in the ICA bulb was 12.3 ± 8.0% (95% CI: 7.6–16.9) in CaW subjects, 1.6 ± 1.9% (95% CI: 0.2–2.9) in atherosclerosis, and 8.5 ± 7.7% (95% CI: 3.6–13.4) in healthy subjects, all differences were statistically significant (ƞ2 = 0.3 [95% CI: 0.05–0.5],P‐value CaW vs. healthy = 0.2). OSI had similar values in the CCA between groups (ƞ2 = 0.07 [95% CI: 0.0–0.2],P‐value = 0.5), but OSI was significantly higher downstream of the bifurcation in CaW subjects compared to atherosclerosis and normal subjects. OSI returned to similar values between groups 1.5 diameters distal to the bifurcation (ƞ2 = 0.03 [95% CI: 0.0–0.2],P‐value = 0.7).

    Conclusion

    Lower TAWSS and higher OSI are present in the ICA bulb in patients with CaW when compared to patients with atherosclerotic or healthy subjects.

    Evidence Level

    2

    Technical Efficacy

    Stage 2

     
    more » « less
  2. Abstract  
    more » « less
  3. Abstract

    In this study, we develop a physiologic internal pressure and wall stress analysis procedure and apply it to a patient‐specific abdominal aortic aneurysm model. Time‐dependent pressure loading of the inner vessel wall was experimentally measured in a 3D printed aneurysm phantom. The results were used as boundary conditions for finite element calculations of von Mises stresses throughout the AAA model over the cardiac cycle. A nonlinear hyperelastic constitutive law with parameters based on biaxial stress‐deformation data from aneurysmal tissue samples was used to describe the mechanical behavior of the aneurysm wall. The internal pressure was found to be fairly spatially uniform (within 10%) over most of the cardiac cycle, but average internal pressure varied by more than a factor of two between systole and diastole. The aneurysm wall stress was highly spatially nonuniform. The highest value of von Mises stress was localized in a small area within the aneurysm bulge and remained in the same place throughout the cardiac cycle, suggesting that this area was the most likely point of rupture. Large variations in wall stress over the cardiac cycle suggest calculations that assume steady flow are a poor approximation for physiological stresses.

     
    more » « less
  4. Proper heart morphogenesis requires a delicate balance between hemodynamic forces, myocardial activity, morphogen gradients, and epigenetic signaling, all of which are coupled with genetic regulatory networks. Recently both in vivo and in silico studies have tried to better understand hemodynamics at varying stages of veretebrate cardiogenesis. In particular, the intracardial hemodynamics during the onset of trabeculation is notably complex—the inertial and viscous fluid forces are approximately equal at this stage and small perturbations in morphology, scale, and steadiness of the flow can lead to significant changes in bulk flow structures, shear stress distributions, and chemical morphogen gradients. The immersed boundary method was used to numerically simulate fluid flow through simplified two-dimensional and stationary trabeculated ventricles of 72, 80, and 120 h post fertilization wild type zebrafish embryos and ErbB2-inhibited embryos at seven days post fertilization. A 2D idealized trabeculated ventricular model was also used to map the bifurcations in flow structure that occur as a result of the unsteadiness of flow, trabeculae height, and fluid scale ( R e ). Vortex formation occurred in intertrabecular regions for biologically relevant parameter spaces, wherein flow velocities increased. This indicates that trabecular morphology may alter intracardial flow patterns and hence ventricular shear stresses and morphogen gradients. A potential implication of this work is that the onset of vortical (disturbed) flows can upregulate Notch1 expression in endothelial cells in vivo and hence impacts chamber morphogenesis, valvulogenesis, and the formation of the trabeculae themselves. Our results also highlight the sensitivity of cardiac flow patterns to changes in morphology and blood rheology, motivating efforts to obtain spatially and temporally resolved chamber geometries and kinematics as well as the careful measurement of the embryonic blood rheology. The results also suggest that there may be significant changes in shear signalling due to morphological and mechanical variation across individuals and species. 
    more » « less
  5. Abstract

    Previous in vitro studies interrogating the endothelial response to physiologically relevant flow regimes require specialized pumps to deliver time‐dependent waveforms that imitate in vivo blood flow. The aim of this study is to create a low‐cost and broadly adaptable approach to mimic physiological flow, and then use this system to characterize the effect of flow separation on velocity and shear stress profiles in a three‐dimensional (3D) topology. The flow apparatus incorporates a programmable linear actuator that superposes oscillations on a constant mean flow driven by a peristaltic pump to emulate flow in the carotid artery. The flow is perfused through a 3D in vitro model of the blood–brain barrier designed to induce separated flow. Experimental flow patterns measured by microparticle image velocimetry and modeled by computational fluid dynamics reveal periodic changes in the instantaneous shear stress along the channel wall. Moreover, the time‐dependent flow causes periodic flow separation zones, resulting in variable reattachment points during the cycle. The effects of these complex flow regimes are assessed by evaluating the integrity of the in vitro blood–brain barrier model. Permeability assays and immunostaining for proteins associated with tight junctions reveal barrier breakdown in the region of disturbed flow. In conclusion, the flow system described here creates complex, physiologically relevant flow profiles that provide deeper insight into the fluid dynamics of separated flow and pave the way for future studies interrogating the cellular response to complex flow regimes.

     
    more » « less