Lagrangian Trajectory Simulation of Platelets and Synchrotron Microtomography Augment Hemodynamic Analysis of Intracranial Aneurysms Treated With Embolic Coils

2021 ◽  
Vol 143 (7) ◽  
Author(s):  
Venkat Keshav Chivukula ◽  
Laurel Marsh ◽  
Fanette Chassagne ◽  
Michael C. Barbour ◽  
Cory M. Kelly ◽  
...  
Keyword(s):  
Shear Stress ◽  
Treatment Outcomes ◽  
Intracranial Aneurysms ◽  
Thrombus Formation ◽  
Vascular Wall ◽  
Cfd Modeling ◽  
Patient Specific ◽  
Embolic Coils ◽  
Endovascular Coils

Abstract As frequency of endovascular treatments for intracranial aneurysms increases, there is a growing need to understand the mechanisms for coil embolization failure. Computational fluid dynamics (CFD) modeling often simplifies modeling the endovascular coils as a homogeneous porous medium (PM), and focuses on the vascular wall endothelium, not considering the biomechanical environment of platelets. These assumptions limit the accuracy of computations for treatment predictions. We present a rigorous analysis using X-ray microtomographic imaging of the coils and a combination of Lagrangian (platelet) and Eulerian (endothelium) metrics. Four patient-specific, anatomically accurate in vitro flow phantoms of aneurysms are treated with the same patient-specific endovascular coils. Synchrotron tomography scans of the coil mass morphology are obtained. Aneurysmal hemodynamics are computationally simulated before and after coiling, using patient-specific velocity/pressure measurements. For each patient, we analyze the trajectories of thousands of platelets during several cardiac cycles, and calculate residence times (RTs) and shear exposure, relevant to thrombus formation. We quantify the inconsistencies of the PM approach, comparing them with coil-resolved (CR) simulations, showing the under- or overestimation of key hemodynamic metrics used to predict treatment outcomes. We fully characterize aneurysmal hemodynamics with converged statistics of platelet RT and shear stress history (SH), to augment the traditional wall shear stress (WSS) on the vascular endothelium. Incorporating microtomographic scans of coil morphology into hemodynamic analysis of coiled intracranial aneurysms, and augmenting traditional analysis with Lagrangian platelet metrics improves CFD predictions, and raises the potential for understanding and clinical translation of computational hemodynamics for intracranial aneurysm treatment outcomes.

Techniques for Virtual Stenting of Intracranial Aneurysms

2007 ◽  
Author(s):  
Sunil Appanaboyina ◽  
Fernando Mut ◽  
Rainald Löhner ◽  
Christopher M. Putman ◽  
Juan R. Cebral
Keyword(s):  
Intracranial Aneurysms ◽  
Numerical Models ◽  
Thrombus Formation ◽  
Endovascular Embolization ◽  
Computational Grids ◽  
Patient Specific ◽  
Parent Vessel ◽  
Invasive Approach ◽  
Aneurysm Neck

Intracranial aneurysms are pathological dilations of the arteries in the brain, whose rupture is often fatal. Surgery and endovascular embolization are the two most common methods of treatment. Surgery involves opening a portion of the skull and placing metallic clips at the aneurysm neck thereby preventing blood flow into the aneurysm. In the case of embolization, a catheter is used to pack platinum coils in the aneurysm reducing the inflow and promoting thrombus formation. Due to its less invasive approach endovascular embolization is preferred over surgery. Nevertheless this approach also has some serious aftereffects. Coil compaction followed by the re-growth or the formation of the secondary aneurysm is the most common problem. The endovascular embolization approach also has a serious shortcoming that the coils alone cannot be used to block every type of aneurysm. Wide neck or fusiform aneurysms are coiled with the help of stents. Recent studies show that stent, which is a hollow cylindrical mesh, can be successfully used to limit the flow of blood into the aneurysm. However these studies have been conducted using idealized in-vitro and numerical models. Studies conducted using patient-specific models generated from medical images will provide a more realistic approach to computationally investigate the effects of stents on intra-aneurysmal flow patterns. However generation of computational grids inside the parent vessel and around these stents is a challenging task. In this paper an algorithm to map the stent to a patient-specific vascular model and an adaptive unstructured embedded gridding technique to model flow around stents are presented. Finally these techniques are demonstrated on patient-specific cases to prove their feasibility.

Endothelial albumin permeability is shear dependent, time dependent, and reversible

1991 ◽  
Vol 260 (6) ◽  
pp. H1992-H1996 ◽  
Author(s):  
H. Jo ◽  
R. O. Dull ◽  
T. M. Hollis ◽  
J. M. Tarbell
Keyword(s):  
Shear Stress ◽  
Endothelial Cell ◽  
Fluorescein Isothiocyanate ◽  
Vascular Wall ◽  
Laminar Shear Stress ◽  
Aortic Endothelial Cells ◽  
Transendothelial Permeability ◽  
Steady Laminar Shear Stress ◽  
Laminar Shear

Altered permeability of vascular endothelium to macromolecules may play a role in vascular disease as well as vascular homeostasis. Because the shear stress of flowing blood on the vascular wall is known to influence many endothelial cell properties, an in vitro system to measure transendothelial permeability (Pe) to fluorescein isothiocyanate conjugated bovine serum albumin under defined physiological levels of steady laminar shear stress was developed. Bovine aortic endothelial cells grown on polycarbonate filters pretreated with gelatin and fibronectin constituted the model system. Onset of 1 dyn/cm2 shear stress resulted in a Pe rise from 5.1 +/- 1.3 x 10(-6) cm/s to 21.9 +/- 4.6 X 10(-6) cm/s at 60 min (n = 6); while 10 dyn/cm2 shear stress increased Pe from 4.8 +/- 1.5 X 10(-6) cm/s to 50.2 +/- 6.8 X 10(-6) cm/s at 30 min and 49.6 +/- 8.9 X 10(-6) cm/s at 60 (n = 9). Pe returned to preshear values within 120 and 60 min after removal of 1 and 10 dyn/cm2 shear stress, respectively. The data show that endothelial cell Pe in vitro is acutely sensitive to shear stress.

Abstract 427: A Patient-Specific 3D Bioprinted Platform for in vitro Disease Modeling and Treatment Planning in Pulmonary Vein Stenosis

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Vahid Serpooshan ◽  
Martin L Tomov ◽  
Akaash Kumar ◽  
Bowen Jing ◽  
Sai Raviteja Bhamidipati ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Pulmonary Vein ◽  
Disease Modeling ◽  
Unmet Need ◽  
Cfd Modeling ◽  
Pulmonary Vein Stenosis ◽  
Patient Specific ◽  
Clinical Interventions ◽  
Vein Stenosis

Pulmonary vein stenosis (PVS) is an acute pediatric cardiovascular disease that is always lethal if not treated early. While current clinical interventions (stenting and angioplasties) have shown promising results in treating PVS, they require multiple re-interventions that can lead to re-stenosis and diminished long-term efficacy. Thus, there is an unmet need to develop functional in vitro models of PVS that can serve as a platform to study clinical interventions. Patient-inspired 3D bioprinted tissue models provide a unique model to recapitulate and analyze the complex tissue microenvironment impacted by PVS. Here, we developed perfusable in vitro models of healthy and stenotic pulmonary vein by 3D reconstruction and bioprinting inspired by patient CT data ( Figure 1 ). Models were seeded with human endothelial (ECs) and smooth muscle cells (SMCs) to form a bilayer structure and perfused using a bioreactor to study cell response to stenotic geometry, and to the stent-based treatment. Flow hemodynamics through printed veins were quantified via Computational Fluid Dynamics (CFD) modeling, 4D MRI and 3D Ultrasound Particle Imaging Velocimetry (echo PIV). Cell growth and endothelialization were analyzed. Our work demonstrates the feasibility of bioprinting various cardiovascular cells, to create perfusable, patient-specific vascular constructs that mimic complex in vivo geometries. Deeper understanding of EC-SMC crosstalk mechanisms in in vitro biomimetic models that incorporate tissue-like geometrical, chemical, and biomechanical ques could offer substantial insights for prevention and treatment of PVS, as well as other cardiovascular disease.

Image Based CFD Modeling of Coronary Artery Wall Shear Stress and Importance of Patient-Specific Velocity Boundary Conditions

2007 ◽  
Author(s):  
Kevin R. Johnson ◽  
John N. Oshinski
Keyword(s):  
Shear Stress ◽  
Wall Shear Stress ◽  
Spatial Resolution ◽  
Multidetector Ct ◽  
Atherosclerotic Lesion ◽  
Cfd Modeling ◽  
Patient Specific ◽  
Lesion Development ◽  
Wall Shear ◽  
Atherosclerotic Lesion Development

Low and oscillatory arterial wall shear stress (WSS) have been shown to have an effect on many factors implicated in atherosclerotic lesion development. The majority of studies on the relationship between low or oscillating WSS and sites of intimal thickening and early atherosclerotic lesion development are based on in-vitro model studies of flow and WSS distribution. These models are based on average vessel geometries with average flow conditions and compared to average pathology distribution of lesions that may obscure the true relationship between WSS and lesion distribution[1]. Recent techniques have been developed using coronary MR angiography to create patient-specific 3D models along with velocity measurements of blood flow using phase contrast magnetic resonance (PCMR). However, these models may lack adequate spatial resolution for accurate, localized calculation of WSS[2]. Current, state-of-art multidetector CT scanners offer improvements in spatial resolution over MRI for creation of 3D vessel models.

scholarly journals In vitro and in vivo Studies of the Extent of Electrothrombotic Deposition of Blood Elements on the Surface of Electrolytically Detachable Coils

2004 ◽  
Vol 10 (3) ◽  
pp. 189-201 ◽  
Author(s):  
H. Henkes ◽  
S. Brew ◽  
S. Felber ◽  
E. Miloslavski ◽  
G. Mogilevski ◽  
...  
Keyword(s):  
Endovascular Treatment ◽  
Intravenous Administration ◽  
Direct Current ◽  
Intracranial Aneurysms ◽  
Thrombus Formation ◽  
Applied Current ◽  
Detachable Coils ◽  
Platinum Coils

Endovascular treatment of intracranial aneurysms with electrolytically detachable coils is often claimed to be based on electrothrombosis, i.e. intra-aneurysmal thrombus formation through applied direct current. Despite the fact that this concept was described more than a century ago, the significance of electrothrombosis in the endovascular treatment of aneurysms remains debatable. Apart from electrothrombosis, mechanical obliteration of the aneurysmal lumen might be one of the many possible mechanisms to explain why and how detachable coils are effective in preventing aneurysms from (re-)rupture. The purpose of this experimental study was to investigate to what extent direct current comparable to that used for coil detachment would influence the adhesion of cellular and liquid blood components to the surface of electrolytically detachable platinum coils. For the in vitro study, electrolytically detachable platinum coils of various types were exposed to stagnant heparinised blood for a total of 16 h, without or with applied direct current for 30 or 90 s (1 mA, 4–6 V, coil as anode). For the in vivo study, electrolytically detachable platinum coils were exposed to flowing blood for 180 s, without or with applied direct current (2 mA, 4–6 V, coil as either anode or cathode), without anti-coagulation and after intravenous administration of 5000 U Heparin and again after the intravenous administration of 500 mg Aspisol in addition to Heparin. After exposure to blood according to these different experimental protocols, the coils were fixed in formalin solution, gold coated and examined by scanning electron microscopy. Thrombus formation on the surface of all unfibred coils was thin and highly variable both from coil to coil, and on different areas of any given coil. The application of direct current minimally enhanced thrombus formation in stagnant blood in vitro, but not in vivo. The cellular and fibrin adhesions on the coil surfaces without and with applied current did not effectively increase the diameter or volume of unfibred coils. Coils with attached nylon fibres, however, proved to be highly thrombogenic without or with application of current. In fibred coils, surface adhesions without and with applied current were voluminous enough to effectively increase the diameter of the coil, potentially important for the process of endosaccular aneurysm occlusion. Electrothrombosis plays no role in the endovascular treatment of intracranial aneurysms with electrolytically detachable coils. This explains why platinum coils with non-electrolytic detachment mechanisms show a similar efficiency and recurrence rate.

Macrovascular thrombosis is driven by tissue factor derived primarily from the blood vessel wall

Blood ◽  
2005 ◽  
Vol 105 (1) ◽  
pp. 192-198 ◽  
Author(s):  
Sharlene M. Day ◽  
Jennifer L. Reeve ◽  
Brian Pedersen ◽  
Diana M Farris ◽  
Daniel D. Myers ◽  
...  
Keyword(s):  
Blood Vessel ◽  
Tissue Factor ◽  
Vessel Wall ◽  
Thrombus Formation ◽  
Vena Cava ◽  
Vascular Wall ◽  
Blood Vessel Wall ◽  
Wild Type

Abstract Leukocytes and leukocyte-derived microparticles contain low levels of tissue factor (TF) and incorporate into forming thrombi. Although this circulating pool of TF has been proposed to play a key role in thrombosis, its functional significance relative to that of vascular wall TF is poorly defined. We tested the hypothesis that leukocyte-derived TF contributes to thrombus formation in vivo. Compared to wild-type mice, mice with severe TF deficiency (ie, TF–/–, hTF-Tg+, or “low-TF”) demonstrated markedly impaired thrombus formation after carotid artery injury or inferior vena cava ligation. A bone marrow transplantation strategy was used to modulate levels of leukocyte-derived TF. Transplantation of low-TF marrow into wild-type mice did not suppress arterial or venous thrombus formation. Similarly, transplantation of wild-type marrow into low-TF mice did not accelerate thrombosis. In vitro analyses revealed that TF activity in the blood was very low and was markedly exceeded by that present in the vessel wall. Therefore, our results suggest that thrombus formation in the arterial and venous macrovasculature is driven primarily by TF derived from the blood vessel wall as opposed to leukocytes.

scholarly journals Vascular Gas6 contributes to thrombogenesis and promotes tissue factor up-regulation after vessel injury in mice

Blood ◽  
2013 ◽  
Vol 121 (4) ◽  
pp. 692-699 ◽  
Author(s):  
Richard S. Robins ◽  
Catherine A. Lemarié ◽  
Sandrine Laurance ◽  
Meghedi N. Aghourian ◽  
Jianqiu Wu ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Thrombus Formation ◽  
Vascular Wall ◽  
Specific Gene ◽  
Tissue Factor Expression ◽  
Vessel Injury ◽  
Factor Expression ◽  
Platelet Signaling

Abstract Gas6 (growth-arrest specific gene 6) plays a role in thrombus stabilization. Gas6 null (−/−) mice are protected from lethal venous and arterial thromboembolism through platelet signaling defects induced only by 5μM ADP and 10μM of the thromboxane analog, U46619. This subtle platelet defect, despite a dramatic clinical phenotype, raises the possibility that Gas6 from a source other than platelets contributes to thrombus formation. Thus, we hypothesize that Gas6 derived from the vascular wall plays a role in venous thrombus formation. Bone marrow transplantation and platelet depletion/reconstitution experiments generating mice with selective ablations of Gas6 from either the hematopoietic or nonhematopoietic compartments demonstrate an approximately equal contribution by Gas6 from both compartments to thrombus formation. Tissue factor expression was significantly reduced in the vascular wall of Gas6−/− mice compared with WT. In vitro, thrombin-induced tissue factor expression was reduced in Gas6−/− endothelial cells compared with wild-type endothelium. Taken together, these results demonstrate that vascular Gas6 contributes to thrombus formation in vivo and can be explained by the ability of Gas6 to promote tissue factor expression and activity. These findings support the notion that vascular wall-derived Gas6 may play a pathophysiologic role in venous thromboembolism.

scholarly journals Combined In Silico and In Vitro Approach Predicts Low Wall Shear Stress Regions in a Hemofilter that Correlate with Thrombus Formation In Vivo

ASAIO Journal ◽  
2018 ◽  
Vol 64 (2) ◽  
pp. 211-217 ◽  
Author(s):  
Amanda K. W. Buck ◽  
Joseph J. Groszek ◽  
Daniel C. Colvin ◽  
Sara B. Keller ◽  
Clark Kensinger ◽  
...  
Keyword(s):  
Shear Stress ◽  
Wall Shear Stress ◽  
In Silico ◽  
Thrombus Formation ◽  
Wall Shear

scholarly journals High Wall Shear Stress can Predict Wall Degradation in Ascending Aortic Aneurysms: An Integrated Biomechanics Study

2021 ◽  
Vol 9 ◽  
Author(s):  
M. Yousuf Salmasi ◽  
Selene Pirola ◽  
Sumesh Sasidharan ◽  
Serena M. Fisichella ◽  
Alberto Redaelli ◽  
...  
Keyword(s):  
Shear Stress ◽  
Wall Shear Stress ◽  
Computational Modelling ◽  
Vascular Wall ◽  
Aortic Aneurysms ◽  
Patient Specific ◽  
Segmental Analysis ◽  
4D Mri ◽  
Wall Shear ◽  
Mechanical And Microstructural Properties

Background: Blood flow patterns can alter material properties of ascending thoracic aortic aneurysms (ATAA) via vascular wall remodeling. This study examines the relationship between wall shear stress (WSS) obtained from image-based computational modelling with tissue-derived mechanical and microstructural properties of the ATAA wall using segmental analysis.Methods: Ten patients undergoing surgery for ATAA were recruited. Exclusions: bicuspid aortopathy, connective tissue disease. All patients had pre-operative 4-dimensional flow magnetic resonance imaging (4D-MRI), allowing for patient-specific computational fluid dynamics (CFD) analysis and anatomically precise WSS mapping of ATAA regions (6–12 segments per patient). ATAA samples were obtained from surgery and subjected to region-specific tensile and peel testing (matched to WSS segments). Computational pathology was used to characterize elastin/collagen abundance and smooth muscle cell (SMC) count.Results: Elevated values of WSS were predictive of: reduced wall thickness [coef −0.0489, 95% CI (−0.0905, −0.00727), p = 0.022] and dissection energy function (longitudinal) [−15,0, 95% CI (−33.00, −2.98), p = 0.048]. High WSS values also predicted higher ultimate tensile strength [coef 0.136, 95% CI (0 0.001, 0.270), p = 0.048]. Additionally, elevated WSS also predicted a reduction in elastin levels [coef −0.276, 95% (CI −0.531, −0.020), p = 0.035] and lower SMC count ([oef −6.19, 95% CI (−11.41, −0.98), p = 0.021]. WSS was found to have no effect on collagen abundance or circumferential mechanical properties.Conclusions: Our study suggests an association between elevated WSS values and aortic wall degradation in ATAA disease. Further studies might help identify threshold values to predict acute aortic events.

A Hemodynamic Comparison of Myocardial Bridging and Coronary Atherosclerotic Stenosis: A Computational Model with Experimental Evaluation

2020 ◽  
Author(s):  
Mohammadali Sharzehee ◽  
Yasamin Seddighi ◽  
Eugene A. Sprague ◽  
Ender A. Finol ◽  
Hai-Chao Han
Keyword(s):  
Pressure Drop ◽  
Experimental Results ◽  
Cfd Modeling ◽  
Patient Specific ◽  
Flow Loop ◽  
Myocardial Bridging ◽  
Atherosclerotic Stenosis ◽  
Stenosis Severity ◽  
The Difference

Abstract Myocardial bridging (MB) and coronary atherosclerotic stenosis can impair coronary blood flow and may cause myocardial ischemia or even stoke. It remains unclear how MB and stenosis are similar or different regarding their impacts on coronary hemodynamics. The purpose of this study was to compare the hemodynamic effects of MB and stenosis using experimental and computational fluid dynamics (CFD) approaches. For CFD modeling, three MB patients with different levels of lumen obstruction such as mild, moderate, and severe were selected. Patient-specific left anterior descending coronary artery models were reconstructed from biplane angiograms. For each MB patient, the virtually healthy and stenotic models were also simulated for comparison. In addition, an in vitro flow-loop was developed to evaluate the model-predicted pressure drop. The CFD modeling results demonstrated that the difference between MB and stenosis increased with increasing MB/stenosis severity and flow rate. Experimental results showed that increasing the MB length (by 140%) only had significant impact on the pressure drop in the severe MB (39% increase at the exercise). However, increasing the stenosis length dramatically increased the pressure drop in both moderate and severe stenoses at all flow rates (31% and 93% increase at the exercise, respectively). Both CFD and experimental results confirmed that the MB had a higher maximum and a lower mean pressure drop in comparison with the stenosis, regardless of MB/stenosis severity. A better understanding of MB and stenosis may improve the therapeutic strategies in coronary disease patients and prevent acute coronary syndromes.

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