In-silico trial of intracranial flow diverters replicates and expands insights from conventional clinical trials.
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ABSTRACT:
SUBMITTER: Sarrami-Foroushani A
PROVIDER: S-EPMC8222326 | biostudies-literature | 2021 Jun
REPOSITORIES: biostudies-literature
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In-silico trial of intracranial flow diverters replicates and expands insights from conventional clinical trials.
Sarrami-Foroushani Ali A Lassila Toni T MacRaild Michael M Asquith Joshua J Roes Kit C B KCB Byrne James V JV Frangi Alejandro F AF
Nature communications 20210623 1
The cost of clinical trials is ever-increasing. In-silico trials rely on virtual populations and interventions simulated using patient-specific models and may offer a solution to lower these costs. We present the flow diverter performance assessment (FD-PASS) in-silico trial, which models the treatment of intracranial aneurysms in 164 virtual patients with 82 distinct anatomies with a flow-diverting stent, using computational fluid dynamics to quantify post-treatment flow reduction. The predicte ...[more]
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Project description:Flow diverters (pipeline embolization device, Silk flow diverter, and Surpass flow diverter) have been developed to treat intracranial aneurysms. These endovascular devices are placed within the parent artery rather than the aneurysm sac. They take advantage of altering hemodynamics at the aneurysm/parent vessel interface, resulting in gradual thrombosis of the aneurysm occurring over time. Subsequent inflammatory response, healing, and endothelial growth shrink the aneurysm and reconstruct the parent artery lumen while preserving perforators and side branches in most cases. Flow diverters have already allowed treatment of previously untreatable wide neck and giant aneurysms. There are risks with flow diverters including in-stent thrombosis, perianeurysmal edema, distant and delayed hemorrhages, and perforator occlusions. Comparative efficacy and safety against other therapies are being studied in ongoing trials. Antiplatelet therapy is mandatory with flow diverters, which has highlighted the need for better evidence for monitoring and tailoring antiplatelet therapy. In this paper we review the devices, their uses, associated complications, evidence base, and ongoing studies.
| S-EPMC4054970 | biostudies-other
Project description:OBJECTIVEFlow diverters (FDs) are designed to occlude intracranial aneurysms (IAs) while preserving flow to essential arteries. Incomplete occlusion exposes patients to risks of thromboembolic complications and rupture. A priori assessment of FD treatment outcome could enable treatment optimization leading to better outcomes. To that end, the authors applied image-based computational analysis to clinically FD-treated aneurysms to extract information regarding morphology, pre- and post-treatment hemodynamics, and FD-device characteristics and then used these parameters to train machine learning algorithms to predict 6-month clinical outcomes after FD treatment.METHODSData were retrospectively collected for 84 FD-treated sidewall aneurysms in 80 patients. Based on 6-month angiographic outcomes, IAs were classified as occluded (n = 63) or residual (incomplete occlusion, n = 21). For each case, the authors modeled FD deployment using a fast virtual stenting algorithm and hemodynamics using image-based computational fluid dynamics. Sixteen morphological, hemodynamic, and FD-based parameters were calculated for each aneurysm. Aneurysms were randomly assigned to a training or testing cohort in approximately a 3:1 ratio. The Student t-test and Mann-Whitney U-test were performed on data from the training cohort to identify significant parameters distinguishing the occluded from residual groups. Predictive models were trained using 4 types of supervised machine learning algorithms: logistic regression (LR), support vector machine (SVM; linear and Gaussian kernels), K-nearest neighbor, and neural network (NN). In the testing cohort, the authors compared outcome prediction by each model trained using all parameters versus only the significant parameters.RESULTSThe training cohort (n = 64) consisted of 48 occluded and 16 residual aneurysms and the testing cohort (n = 20) consisted of 15 occluded and 5 residual aneurysms. Significance tests yielded 2 morphological (ostium ratio and neck ratio) and 3 hemodynamic (pre-treatment inflow rate, post-treatment inflow rate, and post-treatment aneurysm averaged velocity) discriminants between the occluded (good-outcome) and the residual (bad-outcome) group. In both training and testing, all the models trained using all 16 parameters performed better than all the models trained using only the 5 significant parameters. Among the all-parameter models, NN (AUC = 0.967) performed the best during training, followed by LR and linear SVM (AUC = 0.941 and 0.914, respectively). During testing, NN and Gaussian-SVM models had the highest accuracy (90%) in predicting occlusion outcome.CONCLUSIONSNN and Gaussian-SVM models incorporating all 16 morphological, hemodynamic, and FD-related parameters predicted 6-month occlusion outcome of FD treatment with 90% accuracy. More robust models using the computational workflow and machine learning could be trained on larger patient databases toward clinical use in patient-specific treatment planning and optimization.
| S-EPMC6421840 | biostudies-literature
Project description:Background and purposeLocally compacting the mesh of a flow diverter by a dynamic push-pull technique can accelerate intracranial aneurysm healing. We asked how this deployment strategy compares with overlapping 2 flow diverters for aneurysmal flow reduction.Materials and methodsUsing a high-fidelity virtual stent placement method, we simulated 3 flow-diverter strategies (single noncompacted, 2 overlapped, and single compacted) in 3 aneurysms (fusiform, large saccular, and medium saccular). Computational fluid dynamics analysis provided posttreatment hemodynamic parameters, including time-averaged inflow rate, aneurysm-averaged velocity, wall shear stress, total absolute circulation, and turnover time. We examined the relationship between the achieved degree of compaction and aneurysm orifice area.ResultsFlow-diverter compaction resulted in a compaction coverage of 57%, 47%, and 22% over the orifice of the fusiform, large, and medium saccular aneurysm, respectively. Compaction coverage increased linearly with orifice area. In the fusiform aneurysm, the single compacted flow diverter accomplished more aneurysmal flow reduction than the other 2 strategies, as indicated by all 5 hemodynamic parameters. In the 2 saccular aneurysms, the overlapped flow diverters achieved the most flow reduction, followed by the single compacted and the noncompacted flow diverter.ConclusionsCompacting a single flow diverter can outperform overlapping 2 flow diverters in aneurysmal flow reduction, provided that the compaction produces a mesh denser than 2 overlapped flow diverters and this denser mesh covers a sufficient portion of the aneurysm orifice area, for which we suggest a minimum of 50%. This strategy is most effective for aneurysms with large orifices, especially fusiform aneurysms.
| S-EPMC5352494 | biostudies-literature
Project description:BACKGROUND AND PURPOSE:Incompletely occluded flow diverter treated aneurysms remain at risk of rupture and thromboembolic complications. Our aim was to identify the potential for incomplete occlusion of intracranial aneurysms treated by flow diverters. We investigated whether aneurysm ostium size in relation to parent artery size affects angiographic outcomes of flow diverter-treated sidewall aneurysms. MATERIALS AND METHODS:Flow diverter-treated sidewall aneurysms were divided into "occluded" and "residual" (incomplete occlusion) groups based on 6-month angiographic follow-up. We calculated the ostium ratio, a new parameter defined as the aneurysm ostium surface area versus the circumferential surface area of the parent artery. We also calculated the neck ratio, defined as clinical aneurysm neck diameter versus parent artery diameter from pretreatment 2D DSA, as a 2D surrogate. We compared the performance of these ratios with existing aneurysm morphometrics (size, neck diameter, volume, aspect ratio, size ratio, undulation index, nonsphericity index, ellipticity index, bottleneck factor, aneurysm angle, and parent vessel angle) and flow diverter-related parameters (metal coverage rate and pore density). Statistical tests and receiver operating characteristic analyses were performed to identify significantly different parameters between the 2 groups and test their predictive performances. RESULTS:We included 63 flow diverter-treated aneurysms, 46 occluded and 17 residual. The ostium ratio and neck ratio were significantly higher in the residual group than in the occluded group (P < .001 and P = .02, respectively), whereas all other parameters showed no statistical difference. As discriminating parameters for occlusion, ostium ratio and neck ratio achieved areas under the curve of 0.912 (95% CI, 0.838-0.985) and 0.707 (95% CI, 0.558-0.856), respectively. CONCLUSIONS:High ostium ratios and neck ratios could predict incomplete occlusion of flow diverter-treated sidewall aneurysms. Neck ratio can be easily calculated by interventionists to predict flow-diverter treatment outcomes.
| S-EPMC6375759 | biostudies-literature
Project description:BackgroundNotwithstanding the widespread implementation of flow diverters (FDs) in the treatment of intracranial aneurysms, the exact mechanism of action of these devices remains elusive. We aimed to advance the understanding of cellular responses to FD implantation using a 3D tissue-engineered in vitro aneurysm model.MethodsAneurysm-like blood vessel mimics (aBVMs) were constructed by electrospinning polycaprolactone nanofibers onto desired aneurysm-like geometries. aBVMs were seeded with human aortic smooth muscle cells (SMCs) followed by human aortic endothelial cells (ECs). FDs were then deployed in the parent vessel of aBVMs covering the aneurysm neck and were cultivated for 7, 14, or 28 days (n=3 for each time point). The EC and SMC coverage in the neck was measured semi-quantitatively.ResultsAt day 7, the device segment in contact with the parent vessel was partially endothelialized. Also, the majority of device struts, but not pores, at the parent vessel and neck interface were partially covered with ECs and SMCs, while device struts in the middle of the neck lacked cell coverage. At 14 days, histology verified a neointimal-like lining had formed, partially covering both the struts and pores in the center of the neck. At 28 days, the majority of the neck was covered with a translucent neointimal-like layer. A higher degree of cellular coverage was seen on the struts and pores at the neck at 28 days compared with both 7 and 14 days.ConclusionaBVMs can be a valuable alternative tool for evaluating the healing mechanisms of endovascular aneurysm devices.
| S-EPMC8351456 | biostudies-literature
Project description:PurposeThe implantation of flow diverters requires administration of dual anti-platelet therapy, posing the potential for complications. The p48MW HPC (phenox, Bochüm, Germany) hydrophilic-coated flow diverting stent is designed to be anti-thrombotic, thus opening the potential for single anti-platelet therapy. We deploy a novel intravascular high-resolution imaging technique, high-frequency optical coherence tomography (HF-OCT), to study in an animal model the acute thrombus formation on coated p48MW devices versus uncoated control devices.MethodsThree pigs were implanted with 4 flow diverters each, two test hydrophilic-coated devices, and two control uncoated devices (p48MW). Each pig was treated with a different anti-platelet regime: no anti-platelet therapy, aspirin only, aspirin and clopidogrel. Twenty minutes after the flow diverter was implanted, an HF-OCT data set was acquired. Acute clot formed on the flow diverter at each covered side branch was measured from the HF-OCT slices. Factors considered to be important were the device type (pHPC versus bare metal), aspirin, clopidogrel, and vessel location. A linear model was constructed from the significant factors.ResultsBoth coating (p < 0.001) and aspirin (p = 0.003) were significantly related to reduction in clot burden, leading to an approximate 100-fold and 50-fold reduction in clot, respectively.ConclusionsThis study shows the power of HF-OCT not only in the detection of clot but also the quantification of clot burden. In an animal model, the pHPC-coated p48MW significantly reduced acute thrombus formation over jailed side branches as compared to the bare metal p48MW that was nearly eliminated when combined with aspirin administration.
| S-EPMC8209672 | biostudies-literature
Project description:Background and purposeFlow diversion is a recent endovascular treatment for intracranial aneurysms. We compared the safety and efficacy of flow diversion with the alternative standard management options.Materials and methodsA parallel group, prerandomized, controlled, open-label pragmatic trial was conducted in 3 Canadian centers. The trial included all patients considered for flow diversion. A Web-based platform 1:1 randomly allocated patients to flow diversion or 1 of 4 alternative standard management options (coiling with/without stent placement, parent vessel occlusion, surgical clipping, or observation) as prespecified by clinical judgment. Patients ineligible for alternative standard management options were treated with flow diversion in a registry. The primary safety outcome was death or dependency (mRS > 2) at 3 months. The composite primary efficacy outcome included the core lab-determined angiographic presence of a residual aneurysm, aneurysm rupture, progressive mass effect during follow-up, or death or dependency (mRS > 2) at 3-12 months.ResultsBetween May 2011 and November 2020, three hundred twenty-three patients were recruited: Two hundred seventy-eight patients (86%) had treatment randomly allocated (139 to flow diversion and 139 to alternative standard management options), and 45 (14%) received flow diversion in the registry. Patients in the randomized trial frequently had unruptured (83%), large (52% ≥10 mm) carotid (64%) aneurysms. Death or dependency at 3 months occurred in 16/138 patients who underwent flow diversion and 12/137 patients receiving alternative standard management options (relative risk, 1.33; 95% CI, 0.65-2.69; P = .439). A poor primary efficacy outcome was found in 30.9% (43/139) with flow diversion and 45.6% (62/136) of patients receiving alternative standard management options, with an absolute risk difference of 14.7% (95% CI, 3.3%-26.0%; relative risk, 0.68; 95% CI, 0.50-0.92; P = .014).ConclusionsFor patients with mostly unruptured, large, anterior circulation (carotid) aneurysms, flow diversion was more effective than the alternative standard management option in terms of angiographic outcome.
| S-EPMC9451626 | biostudies-literature
Project description:Endovascular treatment of intracranial aneurysms with endoluminal flow diverters (single or multiple) has proven to be clinically safe and effective, but is associated with a risk of thromboembolic complications. Recently, a novel biomimetic surface modification with covalently bound phosphorylcholine (Shield Technology™) has shown to reduce the material thrombogenicity of the Pipeline flow diverter. Thrombogenicity of Pipeline Flex, Pipeline Shield, and Flow Redirection Endoluminal Device (FRED) in the presence of human blood under physiological flow conditions-in addition to relative increase in thrombogenicity with multiple devices-remains unknown and was investigated here. Thrombin generation (mean ± SD; ?g/mL; thrombin-antithrombin complex or TAT) was measured as FRED (30.3 ± 2.9), Pipeline (13.9 ± 4.4), Pipeline Shield (0.4 ± 0.3), and negative control (no device; 0.1 ± 0.0). Platelet activation (mean ± SD; IU/?L; beta-thromboglobulin or ?TG) was measured as FRED (148 ± 45), Pipeline (92.8 ± 41), Pipeline Shield (16.2 ± 3.5), and negative control (2.70 ± 0.16). FRED was significantly more thrombogenic than Pipeline and Pipeline Shield (p < 0.05) for TAT. Additionally, Pipeline Shield had significantly lower TAT and ?TG than the other devices tested (p < 0.05) and these were comparable to the negative control (p > 0.05). TAT and ?TG scaled proportionately with multiple Pipeline devices (N = 6) but was unaffected by multiple Pipeline Shield (N = 6) devices-the latter being statistically similar to negative control (p > 0.05). © 2018 The Authors. Journal Of Biomedical Materials Research Part A Published By Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 3195-3202, 2018.
| S-EPMC6282594 | biostudies-literature
Project description:Background and purposePatients with fusiform basilar trunk aneurysms have a poor prognosis. Reconstructive endovascular therapy is possible with modern devices. We describe the clinical presentation, radiologic features, and clinical outcome of 13 patients with fusiform basilar trunk aneurysms treated with flow diverters, stents, and coils.Materials and methodsOf the 13 patients, 7 were men and 6 were women with a mean age of 59.7 years. Clinical presentation was SAH in 3 patients, mass effect on the brain stem in 4 patients, vertebral artery dissection in 1 patient, and the aneurysm was an incidental finding in 5 patients. Mean aneurysm size was 21 mm. All except 1 were large or giant aneurysms. Nine aneurysms were partially thrombosed.ResultsStents were used in all 13 patients, in 2 patients with additional flow diverters and in 11 patients with additional coils. In 4 patients, 1 vertebral artery was subsequently occluded with coils to decrease flow into the aneurysm. Of 13 patients, 9 had a good outcome with adequate aneurysm occlusion and stable size on follow-up of 6-72 months. One of 3 patients who presented with SAH died of a rebleed 1 month later. One other patient died soon after treatment of in-stent thrombosis, and another patient became mute after treatment. In 2 of 3 patients who presented with symptoms of mass effect, there was improvement at a follow-up of 6-24 months.ConclusionsReconstructive endovascular therapy of fusiform and dissecting basilar trunk aneurysms is feasible but carries substantial risks. The safety and effectiveness in relation to natural history has not yet been elucidated.
| S-EPMC7964923 | biostudies-literature
Project description:Prior studies have shown that in a healthy heart, there exist a large asymmetric vortex structure that aids in establishing a steady flow field in the left ventricle. However, the implantation of existing artificial heart valves at the mitral position is found to have a negative effect on this physiological flow pattern. In light of this, a novel D-shaped bileaflet porcine bioprosthesis (GD valve) has been designed based on the native geometry mitral valve, with the hypothesis that biomimicry in valve design can restore physiological left ventricle flow patterns after valve implantation. An in-vitro experiment using two dimensional particle velocimetry imaging was carried out to determine the hemodynamic performance of the new bileaflet design and then compared to that of the well-established St. Jude Epic valve which functioned as a control in the experiment. Although both valves were found to have similar Reynolds shear stress and Turbulent Kinetic Energy levels, the novel D-shape valve was found to have lower turbulence intensity and greater mean kinetic energy conservation.
| S-EPMC4892640 | biostudies-literature