PIV-Measured Versus CFD-Predicted Flow Dynamics in Anatomically Realistic Cerebral Aneurysm Models

2008 ◽  
Vol 130 (2) ◽  
Author(s):  
Matthew D. Ford ◽  
Hristo N. Nikolov ◽  
Jaques S. Milner ◽  
Stephen P. Lownie ◽  
Edwin M. DeMont ◽  
...  

Computational fluid dynamics (CFD) modeling of nominally patient-specific cerebral aneurysms is increasingly being used as a research tool to further understand the development, prognosis, and treatment of brain aneurysms. We have previously developed virtual angiography to indirectly validate CFD-predicted gross flow dynamics against the routinely acquired digital subtraction angiograms. Toward a more direct validation, here we compare detailed, CFD-predicted velocity fields against those measured using particle imaging velocimetry (PIV). Two anatomically realistic flow-through phantoms, one a giant internal carotid artery (ICA) aneurysm and the other a basilar artery (BA) tip aneurysm, were constructed of a clear silicone elastomer. The phantoms were placed within a computer-controlled flow loop, programed with representative flow rate waveforms. PIV images were collected on several anterior-posterior (AP) and lateral (LAT) planes. CFD simulations were then carried out using a well-validated, in-house solver, based on micro-CT reconstructions of the geometries of the flow-through phantoms and inlet/outlet boundary conditions derived from flow rates measured during the PIV experiments. PIV and CFD results from the central AP plane of the ICA aneurysm showed a large stable vortex throughout the cardiac cycle. Complex vortex dynamics, captured by PIV and CFD, persisted throughout the cardiac cycle on the central LAT plane. Velocity vector fields showed good overall agreement. For the BA, aneurysm agreement was more compelling, with both PIV and CFD similarly resolving the dynamics of counter-rotating vortices on both AP and LAT planes. Despite the imposition of periodic flow boundary conditions for the CFD simulations, cycle-to-cycle fluctuations were evident in the BA aneurysm simulations, which agreed well, in terms of both amplitudes and spatial distributions, with cycle-to-cycle fluctuations measured by PIV in the same geometry. The overall good agreement between PIV and CFD suggests that CFD can reliably predict the details of the intra-aneurysmal flow dynamics observed in anatomically realistic in vitro models. Nevertheless, given the various modeling assumptions, this does not prove that they are mimicking the actual in vivo hemodynamics, and so validations against in vivo data are encouraged whenever possible.

2021 ◽  
Author(s):  
Xiaolong Liu ◽  
Seda Aslan ◽  
Byeol Kim ◽  
Linnea Warburton ◽  
Derrick Jackson ◽  
...  

Background: Post-operative outcomes of the Fontan operation have been linked to graft shape after implantation. Computational fluid dynamics (CFD) simulations are used to explore different surgical options. The objective of this study is to perform a systematic in vitro validation for investigating the accuracy and efficiency of CFD simulation to predict Fontan hemodynamics. Methods: CFD simulations were performed to measure indexed power loss (iPL) and hepatic flow distribution (HFD) in 10 patient-specific Fontan models, with varying mesh and numerical solvers. The results were compared with a novel in vitro flow loop setup with 3D printed Fontan models. A high-resolution differential pressure sensor was used to measure the pressure drop for validating iPL predictions. Microparticles with particle filtering system were used to measure HFD. The computational time was measured for a representative Fontan model with different mesh sizes and numerical solvers. Results: When compared to in vitro setup, variations in CFD mesh sizes had significant effect on HFD (p = 0.0002) but no significant impact on iPL (p = 0.069). Numerical solvers had no significant impact in both iPL (p = 0.50) and HFD (P = 0.55). A transient solver with 0.5 mm mesh size requires computational time 100 times more than a steady solver with 2.5 mm mesh size to generate similar results. Conclusions: The predictive value of CFD for Fontan planning can be validated against an in vitro flow loop. The prediction accuracy can be affected by the mesh size, model shape complexity and flow competition.


Author(s):  
Mohammadali Sharzehee ◽  
Yasamin Seddighi ◽  
Eugene A. Sprague ◽  
Ender A. Finol ◽  
Hai-Chao Han

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.


Author(s):  
M. D. de Tullio ◽  
G. Pascazio ◽  
L. Weltert ◽  
R. De Paulis ◽  
R. Verzicco

The in vivo evaluation of prosthetic device performance is often difficult, if not impossible. In particular, in order to deal with potential problems such as thrombosis, haemolysis, etc., which could arise when a patient undergoes heart valve replacement, a thorough understanding of the blood flow dynamics inside the devices interacting with natural or composite tissues is required. Numerical simulation, combining both computational fluid and structure dynamics, could provide detailed information on such complex problems. In this work, a numerical investigation of the mechanics of two composite aortic prostheses during a cardiac cycle is presented. The numerical tool presented is able to reproduce accurately the flow and structure dynamics of the prostheses. The analysis shows that the vortical structures forming inside the two different grafts do not influence the kinematics of a bileaflet valve or the main coronary flow, whereas major differences are present for the stress status near the suture line of the coronaries to the prostheses. The results are in agreement with in vitro and in vivo observations found in literature.


Author(s):  
D. Keith Walters ◽  
Greg W. Burgreen ◽  
Robert L. Hester ◽  
David S. Thompson ◽  
David M. Lavallee ◽  
...  

Computational fluid dynamics (CFD) simulations were performed for unsteady periodic breathing conditions, using large-scale models of the human lung airway. The computational domain included fully coupled representations of the orotracheal region and large conducting zone up to generation four (G4) obtained from patient-specific CT data, and the small conducting zone (to G16) obtained from a stochastically generated airway tree with statistically realistic geometrical characteristics. A reduced-order geometry was used, in which several airway branches in each generation were truncated, and only select flow paths were retained to G16. The inlet and outlet flow boundaries corresponded to the oronasal opening (superior), the inlet/outlet planes in terminal bronchioles (distal), and the unresolved airway boundaries arising from the truncation procedure (intermediate). The cyclic flow was specified according to the predicted ventilation patterns for a healthy adult male at three different activity levels, supplied by the whole-body modeling software HumMod. The CFD simulations were performed using Ansys FLUENT. The mass flow distribution at the distal boundaries was prescribed using a previously documented methodology, in which the percentage of the total flow for each boundary was first determined from a steady-state simulation with an applied flow rate equal to the average during the inhalation phase of the breathing cycle. The distal pressure boundary conditions for the steady-state simulation were set using a stochastic coupling procedure to ensure physiologically realistic flow conditions. The results show that: 1) physiologically realistic flow is obtained in the model, in terms of cyclic mass conservation and approximately uniform pressure distribution in the distal airways; 2) the predicted alveolar pressure is in good agreement with previously documented values; and 3) the use of reduced-order geometry modeling allows accurate and efficient simulation of large-scale breathing lung flow, provided care is taken to use a physiologically realistic geometry and to properly address the unsteady boundary conditions.


2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Cynthia St. Hilaire ◽  
Hui Jin ◽  
Yuting Huang ◽  
Dan Yang ◽  
Alejandra Negro ◽  
...  

Objective: The objective of this study was to develop a patient-specific induced pluripotent stem cell (iPSC)-based disease model to understand the process by which CD73-deficiency leads to vascular calcification in the disease, Arterial Calcification due to Deficiency of CD73 (ACDC). Approach & Results: ACDC is an autosomal recessive disease resulting from mutations in the gene encoding for CD73, which converts extracellular AMP to adenosine. CD73-deficiency manifests with tortuosity and vascular calcification of the medial layer of lower-extremity arteries, a pathology associated with diabetes and chronic kidney disease. We previously identified that dermal fibroblasts isolated from ACDC patients calcify in vitro, however in vivo studies of the vasculature are limited, as murine models of CD73 deficiency do not recapitulate the human disease phenotype. Thus, we created iPSCs from ACDC patients and control fibroblasts. ACDC and Control iPSCs form teratomas when injected in immune-compromised mice, however ACDC iPSC teratomas exhibit extensive calcifications. Control and ACDC iPSCs were differentiated down the mesenchymal lineage (MSC) and while there was no difference in chondrogenesis and adipogenesis, ACDC iMSCs underwent osteogenesis sooner than control iPSC, have higher activity of tissue-nonspecific alkaline phosphatase (TNAP), and lower levels of extracellular adenosine. During osteogenic simulation, TNAP activity in ACDC cells significantly increased adenosine levels, however, not to levels needed for functional compensatory stimulation of the adenosine receptors. Inhibition of TNAP with levimisole ablates this increase in adenosine. Treatment with an A2b adenosine receptor (AR) agonist drastically reduced TNAP activity in vitro, and calcification in ACDC teratomas, as did treatment with etidronate, which is currently being tested in a clinical trial on ACDC patients. Conclusions: These results illustrate a pro-osteogenic phenotype in CD73-deficient cells whereby TNAP activity attempts to compensate for CD73 deficiency, but subsequently induces calcification that can be reversed by activation of the A2bAR. The iPSC teratoma model may be used to screen other potential therapeutics for calcification disorders.


2019 ◽  
Author(s):  
Jordan F. Hastings ◽  
Alvaro Gonzalez-Rajal ◽  
Jeremy Z.R. Han ◽  
Rachael A. McCloy ◽  
Yolande E.I. O’Donnell ◽  
...  

AbstractIdentification of clinically viable strategies for overcoming resistance to platinum chemotherapy in lung adenocarcinoma has been hampered by inappropriately tailored in vitro assays of drug response. Therefore, using a pulse model that closely recapitulates the in vivo pharmacokinetics of platinum therapy, we profiled cisplatin-induced signalling, DNA damage and apoptotic responses across a panel of lung adenocarcinoma cell lines. By coupling this data with real-time, single cell imaging of cell cycle and apoptosis, we show that TP53 mutation status influenced the mode of cisplatin induced cell cycle arrest, but could not predict cisplatin sensitivity. In contrast, P70S6K-mediated signalling promoted resistance by increasing p53/p63 and p21 expression, reducing double-stranded DNA breaks and apoptosis. Targeting P70S6K sensitised both TP53 wildtype and null lines to cisplatin, but not TP53 mutant lines. In summary, using in vitro assays that mimic in vivo pharmacokinetics identified P70S6K as a robust mediator of cisplatin resistance and highlighted the importance of considering somatic mutation status when designing patient-specific combination therapies.


2019 ◽  
Author(s):  
Teresa G Krieger ◽  
Stephan M Tirier ◽  
Jeongbin Park ◽  
Tanja Eisemann ◽  
Heike Peterziel ◽  
...  

AbstractGlioblastoma multiforme (GBM) are devastating neoplasms with high invasive capacity. GBM has been difficult to study in vitro. Therapeutic progress is also limited by cellular heterogeneity within and between tumors. To address these challenges, we present an experimental model using human cerebral organoids as a scaffold for patient-derived glioblastoma cell invasion. By tissue clearing and confocal microscopy, we show that tumor cells within organoids extend a network of long microtubes, recapitulating the in vivo behavior of GBM. Single-cell RNA-seq of GBM cells before and after co-culture with organoid cells reveals transcriptional changes implicated in the invasion process that are coherent across patient samples, indicating that GBM cells reactively upregulate genes required for their dispersion. Functional therapeutic targets are identified by an in silico receptor-ligand pairing screen detecting potential interactions between GBM and organoid cells. Taken together, our model has proven useful for studying GBM invasion and transcriptional heterogeneity in vitro, with applications for both pharmacological screens and patient-specific treatment selection at a time scale amenable to clinical practice.


2021 ◽  
Vol 143 (7) ◽  
Author(s):  
Venkat Keshav Chivukula ◽  
Laurel Marsh ◽  
Fanette Chassagne ◽  
Michael C. Barbour ◽  
Cory M. Kelly ◽  
...  

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.


2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Vahid Serpooshan ◽  
Martin L Tomov ◽  
Akaash Kumar ◽  
Bowen Jing ◽  
Sai Raviteja Bhamidipati ◽  
...  

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.


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