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.

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.

Reconciling PC-MRI and CFD: An in-vitro study.

Several well-resolved 4D Flow MRI acquisitions of an idealized rigid flow phantom featuring an aneurysm, a curved channel as well as a bifurcation were performed under pulsatile regime. The resulting hemodynamics were processed to remove MRI artifacts. Subsequently, they were compared with CFD predictions computed on the same flow domain, using an in-house high-order low dissipative flow solver. Results show that reaching a good agreement is not straightforward but requires proper treatments of both techniques. Several sources of discrepancies are highlighted and their impact on the final correlation evaluated. While a very poor correlation (r2 = 0.63) is found in the entire domain between raw MRI and CFD data, correlation as high as r2 = 0.97 is found when artifacts are removed by post-processing the MR data and down sampling the CFD results to match the MRI spatial and temporal resolutions. This work demonstrates that, in a well-controlled environment, both PC-MRI and CFD might bring reliable and correlated flow quantities when a proper methodology to reduce the errors is followed.

Red cells' dynamic morphologies govern blood shear thinning under microcirculatory flow conditions.

Blood viscosity decreases with shear stress, a property essential for an efficient perfusion of the vascular tree. Shear thinning is intimately related to the dynamics and mutual interactions of RBCs, the major component of blood. Because of the lack of knowledge about the behavior of RBCs under physiological conditions, the link between RBC dynamics and blood rheology remains unsettled. We performed experiments and simulations in microcirculatory flow conditions of viscosity, shear rates, and volume fractions, and our study reveals rich RBC dynamics that govern shear thinning. In contrast to the current paradigm, which assumes that RBCs align steadily around the flow direction while their membranes and cytoplasm circulate, we show that RBCs successively tumble, roll, deform into rolling stomatocytes, and, finally, adopt highly deformed polylobed shapes for increasing shear stresses, even for semidilute volume fractions of the microcirculation. Our results suggest that any pathological change in plasma composition, RBC cytosol viscosity, or membrane mechanical properties will affect the onset of these morphological transitions and should play a central role in pathological blood rheology and flow behavior.

Flow-Induced Transitions of Red Blood Cell Shapes under Shear.

A recent study of red blood cells (RBCs) in shear flow [Lanotte et al., Proc. Natl. Acad. Sci. U.S.A. 113, 13289 (2016)PNASA60027-842410.1073/pnas.1608074113] has demonstrated that RBCs first tumble, then roll, transit to a rolling and tumbling stomatocyte, and finally attain polylobed shapes with increasing shear rate, when the viscosity contrast between cytosol and blood plasma is large enough. Using two different simulation techniques, we construct a state diagram of RBC shapes and dynamics in shear flow as a function of shear rate and viscosity contrast, which is also supported by microfluidic experiments. Furthermore, we illustrate the importance of RBC shear elasticity for its dynamics in flow and show that two different kinds of membrane buckling trigger the transition between subsequent RBC states.

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.

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.

Physics-Guided Neural Networks for Intraventricular Vector Flow Mapping.

Intraventricular vector flow mapping (iVFM) seeks to enhance and quantify color Doppler in cardiac imaging. In this study, we propose novel alternatives to the traditional iVFM optimization scheme by utilizing physics-informed neural networks (PINNs) and a physics-guided nnU-Net-based supervised approach. When evaluated on simulated color Doppler images derived from a patient-specific computational fluid dynamics model and in vivo Doppler acquisitions, both approaches demonstrate comparable reconstruction performance to the original iVFM algorithm. The efficiency of PINNs is boosted through dual-stage optimization and pre-optimized weights. On the other hand, the nnU-Net method excels in generalizability and real-time capabilities. Notably, nnU-Net shows superior robustness on sparse and truncated Doppler data while maintaining independence from explicit boundary conditions. Overall, our results highlight the effectiveness of these methods in reconstructing intraventricular vector blood flow. The study also suggests potential applications of PINNs in ultrafast color Doppler imaging and the incorporation of fluid dynamics equations to derive biomarkers for cardiovascular diseases based on blood flow.

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.

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.

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.

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.

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.

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.

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.

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.

Haemodynamic imaging of thoracic stent-grafts by computational fluid dynamics (CFD): presentation of a patient-specific method combining magnetic resonance imaging and numerical simulations.

OBJECTIVES: In the last decade, there was been increasing interest in finding imaging techniques able to provide a functional vascular imaging of the thoracic aorta. The purpose of this paper is to present an imaging method combining magnetic resonance imaging (MRI) and computational fluid dynamics (CFD) to obtain a patient-specific haemodynamic analysis of patients treated by thoracic endovascular aortic repair (TEVAR). METHODS: MRI was used to obtain boundary conditions. MR angiography (MRA) was followed by cardiac-gated cine sequences which covered the whole thoracic aorta. Phase contrast imaging provided the inlet and outlet profiles. A CFD mesh generator was used to model the arterial morphology, and wall movements were imposed according to the cine imaging. CFD runs were processed using the finite volume (FV) method assuming blood as a homogeneous Newtonian fluid. RESULTS: Twenty patients (14 men; mean age 62.2 years) with different aortic lesions were evaluated. Four-dimensional mapping of velocity and wall shear stress were obtained, depicting different patterns of flow (laminar, turbulent, stenosis-like) and local alterations of parietal stress in-stent and along the native aorta. CONCLUSIONS: A computational method using a combined approach with MRI appears feasible and seems promising to provide detailed functional analysis of thoracic aorta after stent-graft implantation. KEY POINTS : • Functional vascular imaging of the thoracic aorta offers new diagnostic opportunities • CFD can model vascular haemodynamics for clinical aortic problems • Combining CFD with MRI offers patient specific method of aortic analysis • Haemodynamic analysis of stent-grafts could improve clinical management and follow-up.

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.

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.

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.