Optimizing Patient Care: A Multicentric Study on the Clinical Impact of Sim&Size™ Simulation Software in Intracranial Aneurysm Treatment With Pipeline Embolization Devices.

BACKGROUND: To determine the clinical effects (stent size, and number of stents used) of the Sim&Size™ simulation software on the endovascular treatment of unruptured saccular intracranial aneurysms with Pipeline Embolization Devices (PED). METHODS: This study is a retrospective analytical multicenter study of patients treated with PED (Flex and Flex with SHIELD) for intracranial aneurysm in FOSCAL clinic and CHU de Montpellier. RESULTS: The study included 253 patients, of which 75 were treated in Colombia and 178 were treated in France. The majority of patients were women (83.8%), with a median age of 57.48 years, and had large vessel location (88.1%), with most aneurysms located in the ICA paraclinoid segment (56.8%). Patients in the group with Sim&Size™ simulation had shorter stents than those without simulation (15.62 mm versus 17.36 mm, P-value = 0.001). Also, a lower proportion of these patients required more than one stent (1.4% versus 7.3%, P-value = 0.022). There were 7 complications reported in the group that used the Sim&Size™ simulation software, compared to 9 complications in the group that did not use the software. CONCLUSIONS: Using Sim&Size™ simulation software for endovascular treatment of patients with intracranial aneurysms using PED reduces the stent length and decreasing the number of devices needed per treatment.

Venous Thromboembolism: Review of Clinical Challenges, Biology, Assessment, Treatment, and Modeling.

Venous thromboembolism (VTE) is a massive clinical challenge, annually affecting millions of patients globally. VTE is a particularly consequential pathology, as incidence is correlated with extremely common risk factors, and a large cohort of patients experience recurrent VTE after initial intervention. Altered hemodynamics, hypercoagulability, and damaged vascular tissue cause deep-vein thrombosis and pulmonary embolism, the two permutations of VTE. Venous valves have been identified as likely locations for initial blood clot formation, but the exact pathway by which thrombosis occurs in this environment is not entirely clear. Several risk factors are known to increase the likelihood of VTE, particularly those that increase inflammation and coagulability, increase venous resistance, and damage the endothelial lining. While these risk factors are useful as predictive tools, VTE diagnosis prior to presentation of outward symptoms is difficult, chiefly due to challenges in successfully imaging deep-vein thrombi. Clinically, VTE can be managed by anticoagulants or mechanical intervention. Recently, direct oral anticoagulants and catheter-directed thrombolysis have emerged as leading tools in resolution of venous thrombosis. While a satisfactory VTE model has yet to be developed, recent strides have been made in advancing in silico models of venous hemodynamics, hemorheology, fluid-structure interaction, and clot growth. These models are often guided by imaging-informed boundary conditions or inspired by benchtop animal models. These gaps in knowledge are critical targets to address necessary improvements in prediction and diagnosis, clinical management, and VTE experimental and computational models.

The Woven EndoBridge device, an effective and safe alternative endovascular treatment of intracranial aneurysm-systematic review.

PURPOSE: This study is a systematic review about the WEB device and addresses the efficacy and safety of this device for the endovascular treatment of ruptured and unruptured intracranial aneurysms. MATERIAL AND METHODS: This systematic literature review followed PRISMA-P guidelines and included studies published until 2010. PubMed and ScienceDirect databases were searched, resulting in 22 articles meeting the inclusion criteria. RESULTS: The studies involved 1705 patients and 1224 aneurysms, predominantly wide-neck aneurysms in the middle cerebral artery, internal carotid artery, and basilar artery. The treatment success rate was 28.1%, with the WEB-SL and WEB-SLS devices being commonly used. The immediate post-treatment adequate occlusion rate was 33.3%, increasing to 49.7% at follow-up. Thromboembolic complications occurred in 6.5% of cases, while other complications were observed in 3.1% of cases. The mortality rate associated with the WEB device was low, approximately 1%. CONCLUSION: The WEB device demonstrates favorable outcomes in treating patients with intracranial aneurysms, with adequate occlusion rates improving over time. Thromboembolic complications are the primary concern, but overall complication and mortality rates remain low. Further research is needed to optimize device selection, standardize classification systems, and enhance long-term evaluation and training protocols.

Critical evaluation of kinetic schemes for coagulation.

Two well-established numerical representations of the coagulation cascade either initiated by the intrinsic system (Chatterjee et al., PLOS Computational Biology 2010) or the extrinsic system (Butenas et al., Journal of Biological Chemistry, 2004) were compared with thrombin generation assays under realistic pathological conditions. Biochemical modifications such as the omission of reactions not relevant to the case studied, the modification of reactions related to factor XI activation and auto-activation, the adaptation of initial conditions to the thrombin assay system, and the adjustment of some of the model parameters were necessary to align in vitro and in silico data. The modified models are able to reproduce thrombin generation for a range of factor XII, XI, and VIII deficiencies, with the coagulation cascade initiated either extrinsically or intrinsically. The results emphasize that when existing models are extrapolated to experimental parameters for which they have not been calibrated, careful adjustments are required.

Assessing a heterogeneous model for accounting for endovascular devices in hemodynamic simulations of cerebral aneurysms.

The heterogeneous model developed by Berod et al [Int J Numer Method Biomed Eng 38, 2021] for representing the hemodynamic effects of endovascular prostheses is applied to a series of 10 patient specific cerebral aneurysms, 6 being treated by flow diverters, 4 being equipped with WEBs. Two markers correlated with the medical outcome of the treatment are used to assess the potential of the model, namely the saccular mean velocity and the inflow rate at the neck of the aneurysm. The comparison with the corresponding wire-resolved simulations is very favorable in both cases, and the model-based simulations also retrieve the jetting-type flows generated downstream of the struts. Noteworthy, the very same model was used for representing the flow diverters and the WEBs, showing the versatility and robustness of the heterogeneous modeling of the devices.

An adjoint-based method for the computation of gradients in coagulation schemes.

An adjoint-based methodology is proposed to compute the gradient of the outcomes of mathematical models for the coagulation cascade. The method is first exposed and validated by considering a simple, analytically tractable case involving only 3 species. Its potential is further illustrated by considering a detailed model for the extrinsic pathway involving 34 chemical species interacting through 45 chemical reactions and for which the gradient of Endogeneous Thrombin Potential, clotting time, maximum rate and peak value of thrombin with respect to the initial concentrations and reactions rates are computed. It is shown that the method produces gradients estimates that are fully consistent with the finite differences approximation used so far in the literature, but at a much lower computational cost.

Heterogeneous model to evaluate CFD in intracranial bifurcation aneurysms treated with the WEB device to predict angiographic outcome.

INTRODUCTION: The Woven EndoBridge device (WEB) was developed as an alternative to treat Wide-Necked bifurcation aneurysms. It has proven to be effective and safe, however, cases of recanalization have been reported. The purpose of this study was to evaluate and quantify hemodynamic parameters and indexes with CFD of the intracranial aneurysms before and after WEB simulation and to establish their relationship to complete occlusion. MATERIALS AND METHODS: Using the heterogeneous model based on the marching cubes algorithm, we created 3D representations of 27 bifurcated intracranial aneurysms treated with the single-layer WEB device to evaluate hemodynamics parameters with CFD, calculated with and without the WEB. RESULTS: We observed a lower treatment entry concentration indices (ICI) (2.12 ± 1.31 versus 3.14 ± 0.93, p-value: 0.029) previous to placement of WEB and higher pre-treatment FN (7.56 ± 5.92 versus 3.35 ± 1.51, p-value: 0.018) and post-treatment FN (5.34 ± 5.89 versus 1.99 ± 0.83, p-value: 0.021) for cases with successful occlusions. Lower post-treatment SRa (197.81 ± 221.29 versus 80.02 ± 45.25, p-value: 0.044) and higher pre (0.11 ± 0.07 versus 0.25 ± 0.19, p-value: 0.011) and post-treatment MATT (0.69 ± 1.23 versus 1.02 ± 0.46, p-value: 0.006) were observed in non-occluded cases. CONCLUSIONS: In our CFD analysis of the hemodynamic parameters of IA, we found lower ICI before the placement of the WEB device and higher FN pre- and post-treatment for cases with successful occlusions. Non-occluded cases had lower post-treatment SRa and higher pre-treatment and post-treatment MATT.

Geometry of intracranial aneurysms and of intrasaccular devices may influence aneurysmal occlusion rates after endovascular treatment.

INTRODUCTION: The Woven EndoBridge device (WEB) is used to treat wide-neck bifurcation aneurysms. These devices are deployed inside the sac. Therefore, the mesh structure provides apposition with the aneurysm wall and induces aneurysmal thrombosis. The objective of our study was to evaluate the anatomic and device-related parameters and indexes with Computational Fluid Dynamics (CFD) of the intracranial aneurysms before and after WEB simulation and find their relationship to complete occlusion. MATERIALS AND METHODS: Using the heterogeneous model based on the marching cubes algorithm, we created 3D representations of 27 bifurcated intracranial aneurysms treated with the single-layer WEB device to evaluate anatomic and device-related parameters with CFD. RESULTS: In our CFD analysis, we observed higher large volumes (Va) (0.25 ± 0.18 versus 0.39 ± 0.09, p-value= 0.025) and higher volume to neck surface ratio (Ra) (1.32 ± 0.17 versus 1.54 ± 0.14, p-value= 0.021) in cases with occlusion failure. CONCLUSIONS: Large aneurysm volumes (Va) and higher volume to neck surface ratio (Ra) could be associated with occlusion failure in aneurysms treated with the WEB device.

Red blood cell rheology during a complete blood count: A proof of concept.

Counting and sizing blood cells in hematological analyzers is achieved using the Coulter principle. The cells flow in a micro-aperture in which a strong electrical field is imposed, so that an electrical perturbation, called pulse, is measured each time a cell crosses the orifice. The pulses are expected to contain information on the shape and deformability of Red Blood Cells (RBCs), since recent studies state that RBCs rotate and deform in the micro-orifice. By implementing a dedicated numerical model, the present study sheds light on a variety of cells dynamics, which leads to different associated pulse signatures. Furthermore, simulations provide new insights on how RBCs shapes and mechanical properties affect the measured signals. Those numerical observations are confirmed by experimental assays. Finally, specific features are introduced for assessing the most relevant characteristics from the various pulse signatures and shown to highlight RBCs alterations induced by drugs. In summary, this study paves the way to a characterization of RBC rheology by routine hematological instruments.

Clinical impact of Sim & Size® simulation software in the treatment of patients with cerebral aneurysms with flow-diverter Pipeline stents.

OBJECTIVES: This study evaluated the clinical impact of the Sim&Size® simulation software on the endovascular treatment with flow-diverter stents of patients with unruptured saccular intracranial aneurysms. METHODS: This monocentric retrospective study evaluated a cohort of patients treated with flow-divert stents between June 1, 2014, and December 31, 2019, for cerebral aneurysms. Patients belonged to two groups, patients treated with and without the Sim&Size® simulation software. Univariate, bivariate, and multivariate analyses were used to evaluate the clinical impact of simulation software. RESULTS: Out of the 73 interventions involving 68 patients analyzed by the study, 76.7% were simulated using the Sim&Size® simulation software, and 23.3% were not. Patients treated with the simulation software had shorter stent lengths (16.00 mm vs. 20.00 mm p-value = 0.001) and surgical time (100.00 min vs. 118.00 min p-value = 0.496). Also, fewer of them required more than one stent (3.6% vs. 17.6% p-value = 0.079). Three patients belonging to the non-stimulated group presented hemorrhagic complications. CONCLUSIONS: Using the Sim&Size® simulation software for the endovascular treatment of intracranial aneurysms with pipeline flow-diverter stents reduces the stent length.

Validation of three-dimensional printed models of intracranial aneurysms.

INTRODUCTION: Three-dimensional (3D) printing has evolved for medical applications as it can produce customized 3D models of devices and implants that can improve patient care. In this study, we aimed to validate the geometrical accuracy of the 3D models of intracranial aneurysms printed using Stereolithography 3D printing technology. MATERIALS AND METHODS: To compare the unruptured intracranial aneurysm mesh between the five patients and 3D printed models, we opened the DICOM files in the Sim&Size® simulation software, selected the region of interest, and performed the threshold check. We juxtaposed the 3D reconstructions and manually rotated the images to get the same orientation when needed and measured deviations at different nodes of the patient and 3D printed model meshes. RESULTS: In the first patient, 80% of the nodes were separated by <0.56 mm and 0.17 mm. In the second patient, the deviations were below 0.17 mm for 80% of the meshes' nodes. In the next three patients, the deviations were below 0.21, 0.23, and 0.11 mm for 80% of the meshes' nodes. Finally, the overall deviation was below 0.21 mm for 80% of the mesh nodes of the five aneurysms. CONCLUSIONS: 3D printed models of intracranial aneurysms are accurate, having surfaces that resemble that of patients' angiographies with an 80% cumulative deviation below 0.21 mm.

Accelerated sequences of 4D flow MRI using GRAPPA and compressed sensing: A comparison against conventional MRI and computational fluid dynamics.

PURPOSE: To evaluate hemodynamic markers obtained by accelerated GRAPPA (R = 2, 3, 4) and compressed sensing (R = 7.6) 4D flow MRI sequences under complex flow conditions. METHODS: The accelerated 4D flow MRI scans were performed on a pulsatile flow phantom, along with a nonaccelerated fully sampled k-space acquisition. Computational fluid dynamics simulations based on the experimentally measured flow fields were conducted for additional comparison. Voxel-wise comparisons (Bland-Altman analysis, L 2 $$ {L}_2 $$ -norm metric), as well as nonderived quantities (velocity profiles, flow rates, and peak velocities), were used to compare the velocity fields obtained from the different modalities. RESULTS: 4D flow acquisitions and computational fluid dynamics depicted similar hemodynamic patterns. Voxel-wise comparisons between the MRI scans highlighted larger discrepancies at the voxels located near the phantom's boundary walls. A trend for all MR scans to overestimate velocity profiles and peak velocities as compared to computational fluid dynamics was noticed in regions associated with high velocity or acceleration. However, good agreement for the flow rates was observed, and eddy-current correction appeared essential for consistency of the flow rates measurements with respect to the principle of mass conservation. CONCLUSION: GRAPPA (R = 2, 3) and highly accelerated compressed sensing showed good agreement with the fully sampled acquisition. Yet, all 4D flow MRI scans were hampered by artifacts inherent to the phase-contrast acquisition procedure. Computational fluid dynamics simulations are an interesting tool to assess these differences but are sensitive to modeling parameters.

Full-volume three-component intraventricular vector flow mapping by triplane color Doppler.

Objective. Intraventricular vector flow mapping (iVFM) is a velocimetric technique for retrieving two-dimensional velocity vector fields of blood flow in the left ventricular cavity. This method is based on conventional color Doppler imaging, which makesiVFM compatible with the clinical setting. We have generalized theiVFM for a three-dimensional reconstruction (3D-iVFM).Approach.3D-iVFM is able to recover three-component velocity vector fields in a full intraventricular volume by using a clinical echocardiographic triplane mode. The 3D-iVFM problem was written in the spherical (radial, polar, azimuthal) coordinate system associated to the six half-planes produced by the triplane mode. As with the 2D version, the method is based on the mass conservation, and free-slip boundary conditions on the endocardial wall. These mechanical constraints were imposed in a least-squares minimization problem that was solved through the method of Lagrange multipliers. We validated 3D-iVFMin silicoin a patient-specific CFD (computational fluid dynamics) model of cardiac flow and tested its clinical feasibilityin vivoin patients and in one volunteer.Main results.The radial and polar components of the velocity were recovered satisfactorily in the CFD setup (correlation coefficients,r = 0.99 and 0.78). The azimuthal components were estimated with larger errors (r = 0.57) as only six samples were available in this direction. In bothin silicoandin vivoinvestigations, the dynamics of the intraventricular vortex that forms during diastole was deciphered by 3D-iVFM. In particular, the CFD results showed that the mean vorticity can be estimated accurately by 3D-iVFM.Significance. Our results tend to indicate that 3D-iVFM could provide full-volume echocardiographic information on left intraventricular hemodynamics from the clinical modality of triplane color Doppler.

A Pipeline for the Generation of Synthetic Cardiac Color Doppler.

Color Doppler imaging (CDI) is the modality of choice for simultaneous visualization of myocardium and intracavitary flow over a wide scan area. This visualization modality is subject to several sources of error, the main ones being aliasing and clutter. Mitigation of these artifacts is a major concern for better analysis of intracardiac flow. One option to address these issues is through simulations. In this article, we present a numerical framework for generating clinical-like CDI. Synthetic blood vector fields were obtained from a patient-specific computational fluid dynamics CFD model. Realistic texture and clutter artifacts were simulated from real clinical ultrasound cineloops. We simulated several scenarios highlighting the effects of 1) flow acceleration; 2) wall clutter; and 3) transmit wavefronts, on Doppler velocities. As a comparison, an "ideal" color Doppler was also simulated, without these harmful effects. This synthetic dataset is made publicly available and can be used to evaluate the quality of Doppler estimation techniques. Besides, this approach can be seen as a first step toward the generation of comprehensive datasets for training neural networks to improve the quality of Doppler imaging.

A heterogeneous model of endovascular devices for the treatment of intracranial aneurysms.

Numerical computations of hemodynamics inside intracranial aneurysms treated by endovascular braided devices such as flow-diverters contribute to understanding and improving such treatment procedures. Nevertheless, these simulations yield high computational and meshing costs due to the heterogeneity of length scales between the dense weave of the fine struts of the device and the arterial volume. Homogeneous strategies developed over the last decade to circumvent this issue substitute local dissipations due to the wires with a global effect in the form of a pressure-drop across the device surface. However, these methods cannot accurately reproduce the flow-patterns encountered near the struts, the latter strongly dictating the intra-saccular flow environment. In this work, a versatile theoretical framework which aims at correctly reproducing the local flow heterogeneities due to the wires while keeping memory consumption, meshing and computational times as low as possible is introduced. This model reproduces the drag forces exerted by the device struts onto the fluid, thus producing local and heterogeneous effects on the flow. Extensive validation for various flow and geometric configurations using an idealized device is performed. To further illustrate the method capabilities, a real patient-specific aneurysm endovascularly treated with a flow-diverter is used, enabling quantitative comparisons with classical approaches for both intra-saccular velocities and computational costs reduction. The proposed heterogeneous model endeavors to bridge the gap between computational fluid dynamics and clinical applications and ushers in a new era of numerical treatment planning with minimally costing computational tools.

Physics-constrained intraventricular vector flow mapping by color Doppler.

Color Doppler by transthoracic echocardiography creates two-dimensional fan-shaped maps of blood velocities in the cardiac cavities. It is a one-component velocimetric technique since it only returns the velocity components parallel to the ultrasound beams. Intraventricular vector flow mapping (iVFM) is a method to recover the blood velocity vectors from the Doppler scalar fields in an echocardiographic three-chamber view. We improved ouriVFM numerical scheme by imposing physical constraints. TheiVFM consisted in minimizing regularized Doppler residuals subject to the condition that two fluid-dynamics constraints were satisfied, namely planar mass conservation, and free-slip boundary conditions. The optimization problem was solved by using the Lagrange multiplier method. A finite-difference discretization of the optimization problem, written in the polar coordinate system centered on the cardiac ultrasound probe, led to a sparse linear system. The single regularization parameter was determined automatically for non-supervision considerations. The physics-constrained method was validated using realistic intracardiac flow data from a patient-specific computational fluid dynamics (CFD) model. The numerical evaluations showed that theiVFM-derived velocity vectors were in very good agreement with the CFD-based original velocities, with relative errors ranged between 0.3% and 12%. We calculated two macroscopic measures of flow in the cardiac region of interest, the mean vorticity and mean stream function, and observed an excellent concordance between physics-constrainediVFM and CFD. The capability of physics-constrainediVFM was finally tested within vivocolor Doppler data acquired in patients routinely examined in the echocardiographic laboratory. The vortex that forms during the rapid filling was deciphered. The physics-constrainediVFM algorithm is ready for pilot clinical studies and is expected to have a significant clinical impact on the assessment of diastolic function.

Detecting cells rotations for increasing the robustness of cell sizing by impedance measurements, with or without machine learning.

The Coulter principle is a widespread technique for sizing red blood cells (RBCs) in hematological analyzers. It is based on the monitoring of the electrical perturbations generated by cells passing through a micro-orifice, in which a concentrated electrical field is imposed by two electrodes. However, artifacts associated with near-wall passages in the sensing region are known to skew the statistics for RBCs sizing. This study presents numerical results that emphasize the link between the cell flow-induced rotation in the detection area and the error in its measured volume. Based on these observations, two methods are developed to identify and reject pulses impaired by cell rotation. In the first strategy, the filtering is allowed by a metric computed directly from the waveform. In the second, a numerical database is employed to train a neural network capable of detecting if the cell has experienced a rotation, given its electrical pulse. Detecting and rejecting rotation-associated pulses are shown to provide results comparable to hydrodynamical focusing, which enforces cells to flow in the center of the orifice, the gold standard implementation of the Coulter principle.

Numerical simulation of time-resolved 3D phase-contrast magnetic resonance imaging.

A numerical approach is presented to efficiently simulate time-resolved 3D phase-contrast Magnetic resonance Imaging (or 4D Flow MRI) acquisitions under realistic flow conditions. The Navier-Stokes and Bloch equations are simultaneously solved with an Eulerian-Lagrangian formalism. A semi-analytic solution for the Bloch equations as well as a periodic particle seeding strategy are developed to reduce the computational cost. The velocity reconstruction pipeline is first validated by considering a Poiseuille flow configuration. The 4D Flow MRI simulation procedure is then applied to the flow within an in vitro flow phantom typical of the cardiovascular system. The simulated MR velocity images compare favorably to both the flow computed by solving the Navier-Stokes equations and experimental 4D Flow MRI measurements. A practical application is finally presented in which the MRI simulation framework is used to identify the origins of the MRI measurement errors.

Mathematical and Computational Modeling of Device-Induced Thrombosis.

Given the extensive and routine use of cardiovascular devices, a major limiting factor to their success is the thrombotic rate that occurs. This both poses direct risk to the patient and requires counterbalancing with anticoagulation and other treatment strategies, contributing additional risks. Developing a better understanding of the mechanisms of device-induced thrombosis to aid in device design and medical management of patients is critical to advance the ubiquitous use and durability. Thus, mathematical and computational modelling of device-induced thrombosis has received significant attention recently, but challenges remain. Additional areas that need to be explored include microscopic/macroscopic approaches, reconciling physical and numerical timescales, immune/inflammatory responses, experimental validation, and incorporating pathologies and blood conditions. Addressing these areas will provide engineers and clinicians the tools to provide safe and effective cardiovascular devices.

Augmented patient-specific functional medical imaging by implicit manifold learning.

This paper uses machine learning to enrich magnetic resonance angiography and magnetic resonance imaging acquisitions. A convolutional neural network is built and trained over a synthetic database linking geometrical parameters and mechanical characteristics of the arteries to blood flow rates and pressures in an arterial network. Once properly trained, the resulting neural network can be used in order to predict blood pressure in cerebral arteries noninvasively in nearly real-time. One challenge here is that not all input variables present in the synthetic database are known from patient-specific medical data. To overcome this challenge, a learning technique, which we refer to as implicit manifold learning, is employed: in this view, the input and output data of the neural network are selected based on their availability from medical measurements rather than being defined from the mechanical description of the arterial system. The results show the potential of the method and that machine learning is an alternative to costly ensemble based inversion involving sophisticated fluid structure models.