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MRI, a widespread non-invasive medical imaging modality, is highly sensitive to patient motion. Despite many attempts over the years, motion correction remains a difficult problem and there is no general method applicable to all situations. We propose a retrospective method for motion estimation and correction to tackle the problem of in-plane rigid-body motion, apt for classical 2D Spin-Echo scans of the brain, which are regularly used in clinical practice. Due to the sequential acquisition of k-space, motion artifacts are well localized. The method leverages the power of deep neural networks to estimate motion parameters in k-space and uses a model-based approach to restore degraded images to avoid "hallucinations". Notable advantages are its ability to estimate motion occurring in high spatial frequencies without the need of a motion-free reference. The proposed method operates on the whole k-space dynamic range and is moderately affected by the lower SNR of higher harmonics. As a proof of concept, we provide models trained using supervised learning on 600k motion simulations based on motion-free scans of 43 different subjects. Generalization performance was tested with simulations as well as in-vivo. Qualitative and quantitative evaluations are presented for motion parameter estimations and image reconstruction. Experimental results show that our approach is able to obtain good generalization performance on simulated data and in-vivo acquisitions. We provide a Python implementation at https://gitlab.unige.ch/Oscar.Dabrowski/sismik_mri/.
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One of the routine clinical treatments to eliminate ischemic stroke thrombi is injecting a biochemical product into the patient's bloodstream, which breaks down the thrombi's fibrin fibers: intravenous or intravascular thrombolysis. However, this procedure is not without risk for the patient; the worst circumstances can cause a brain hemorrhage or embolism that can be fatal. Improvement in patient management drastically reduced these risks, and patients who benefited from thrombolysis soon after the onset of the stroke have a significantly better 3-month prognosis, but treatment success is highly variable. The causes of this variability remain unclear, and it is likely that some fundamental aspects still require thorough investigations. For that reason, we conducted in vitro flow-driven fibrinolysis experiments to study pure fibrin thrombi breakdown in controlled conditions and observed that the lysis front evolved non-linearly in time. To understand these results, we developed an analytical 1D lysis model in which the thrombus is considered a porous medium. The lytic cascade is reduced to a second-order reaction involving fibrin and a surrogate pro-fibrinolytic agent. The model was able to reproduce the observed lysis evolution under the assumptions of constant fluid velocity and lysis occurring only at the front. For adding complexity, such as clot heterogeneity or complex flow conditions, we propose a 3-dimensional mesoscopic numerical model of blood flow and fibrinolysis, which validates the analytical model's results. Such a numerical model could help us better understand the spatial evolution of the thrombi breakdown, extract the most relevant physiological parameters to lysis efficiency, and possibly explain the failure of the clinical treatment. These findings suggest that even though real-world fibrinolysis is a complex biological process, a simplified model can recover the main features of lysis evolution.
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Fibrina , Fibrinólise , Humanos , Tempo de Lise do Coágulo de Fibrina , Fibrinolíticos/farmacologia , Administração IntravenosaRESUMO
From a complexity perspective on governance, multilateral diplomacy is based on interactions between people, ideas, norms, policies and institutions. This article uses a computer-assisted methodology to better understand governance systems as a network of norms. All World Health Assembly (WHA) resolutions that were available from 1948 to 2022 were collected from the WHO Institutional Repository for Information Sharing (IRIS) database. Regular expressions were used to identify how resolutions cite other resolutions and the resulting relationships were analysed as a normative network. The findings show that WHA resolutions constitute a complex network of interconnected global health issues. This network is characterised by several community patterns. While chain-like patterns are associated with specific diseases programmes, radial patterns are characteristic of highly important procedural decisions that member states reaffirm in similar situations. Finally, densely connected communities correspond to contested topics and emergencies. While these emergeng patterns suggest the relevance of using network analysis to understand global health norms in international organisations, we reflect on how this computational approach can be extended to provide new understandings of how multilateral governance systems work, and to address some important contemporary questions about the effects of regime complexity on global health diplomacy.
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Diplomacia , Saúde Global , Humanos , PolíticasRESUMO
The goal of this work is to advance the characteristics of existing lattice Boltzmann Dirichlet velocity boundary schemes in terms of the accuracy, locality, stability, and mass conservation for arbitrarily grid-inclined straight walls, curved surfaces, and narrow fluid gaps, for both creeping and inertial flow regimes. We reach this objective with two infinite-member boundary classes: (1) the single-node "Linear Plus" (LI^{+}) and (2) the two-node "Extended Multireflection" (EMR). The LI^{+} unifies all directional rules relying on the linear combinations of up to three pre- or postcollision populations, including their "ghost-node" interpolations and adjustable nonequilibrium approximations. On this basis, we propose three groups of LI^{+} nonequilibrium local corrections: (1) the LI_{1}^{+} is parametrized, meaning that its steady-state solution is physically consistent: the momentum accuracy is viscosity-independent in Stokes flow, and it is fixed by the Reynolds number (Re) in inertial flow; (2) the LI_{3}^{+} is parametrized, exact for arbitrary grid-rotated Poiseuille force-driven Stokes flow and thus most accurate in porous flow; and (3) the LI_{4}^{+} is parametrized, exact for pressure and inertial term gradients, and hence advantageous in very narrow porous gaps and at higher Reynolds range. The directional, two-relaxation-time collision operator plays a crucial role for all these features, but also for efficiency and robustness of the boundary schemes due to a proposed nonequilibrium linear stability criterion which reliably delineates their suitable coefficients and relaxation space. Our methodology allows one to improve any directional rule for Stokes or Navier-Stokes accuracy, but their parametrization is not guaranteed. In this context, the parametrized two-node EMR class enlarges the single-node schemes to match exactness in a grid-rotated linear Couette flow modeled with an equilibrium distribution designed for the Navier-Stokes equation (NSE). However, exactness of a grid-rotated Poiseuille NSE flow requires us to perform (1) the modification of the standard NSE term for exact bulk solvability and (2) the EMR extension towards the third neighbor node. A unique relaxation and equilibrium exact configuration for grid-rotated Poiseuille NSE flow allows us to classify the Galilean invariance characteristics of the boundary schemes without any bulk interference; in turn, its truncated solution suggests how, when increasing the Reynolds number, to avoid a deterioration of the mass-leakage rate and momentum accuracy due to a specific Reynolds scaling of the kinetic relaxation collision rate. The optimal schemes and strategies for creeping and inertial regimes are then singled out through a series of numerical tests, such as grid-rotated channels and rotated Couette flow with wall-normal injection, cylindrical porous array, and Couette flow between concentric cylinders, also comparing them against circular-shape fitted FEM solutions.
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Introduction: The flow diverter stent (FDS) has become a first-line treatment for numerous intra-cranial aneurysms (IAs) by promoting aneurysm thrombosis. However, the biological phenomena underlying its efficacy remain unknown. We proposed a method to collect in situ blood samples to explore the flow diversion effect within the aneurysm sac. In this feasibility study, we assessed the plasma levels of nucleotides within the aneurysm sac before and after flow diversion treatment. Materials and methods: In total, 14 patients with unruptured IAs who were selected for FDS implantation were prospectively recruited from February 2015 to November 2015. Two catheters dedicated to (1) FDS deployment and (2) the aneurysm sac were used to collect blood samples within the parent artery (P1) and the aneurysm sac before (P2) and after (P3) flow diversion treatment. The plasma levels of adenosine monophosphate (AMP), adenosine diphosphate (ADP), and adenosine triphosphate (ATP) at each collection point were quantified with liquid chromatography and tandem mass spectrometry. Results: The aneurysms were extradural in nine (64.3%) patients and intra-dural in five (35.7%) patients. They presented an average diameter of 15.5 ± 7.1 mm, height of 15.8 ± 4.6 mm, and volume of 2,549 ± 2,794 ml. In all patients (100%), 16 FDS implantations and 42 in situ blood collections were performed successfully without any complications associated with the procedure. The ATP, ADP, and AMP concentrations within the aneurysm sac were decreased after flow diversion (p = 0.005, p = 0.03, and p = 0.12, respectively). Only the ATP levels within the aneurysm sac after flow diversion were significantly correlated with aneurysm volume (adjusted R 2 = 0.43; p = 0.01). Conclusion: In situ blood collection within unruptured IAs during a flow diversion procedure is feasible and safe. Our results suggest that the flow diversion technique is associated with changes in the nucleotide plasma levels within the aneurysm sac.
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The transport of platelets in blood is commonly assumed to obey an advection-diffusion equation with a diffusion constant given by the so-called Zydney-Colton theory. Here we reconsider this hypothesis based on experimental observations and numerical simulations including a fully resolved suspension of red blood cells and platelets subject to a shear. We observe that the transport of platelets perpendicular to the flow can be characterized by a non-trivial distribution of velocities with and exponential decreasing bulk, followed by a power law tail. We conclude that such distribution of velocities leads to diffusion of platelets about two orders of magnitude higher than predicted by Zydney-Colton theory. We tested this distribution with a minimal stochastic model of platelets deposition to cover space and time scales similar to our experimental results, and confirm that the exponential-powerlaw distribution of velocities results in a coefficient of diffusion significantly larger than predicted by the Zydney-Colton theory.
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MRI is a non-invasive medical imaging modality that is sensitive to patient motion, which constitutes a major limitation in most clinical applications. Solutions may arise from the reduction of acquisition times or from motion-correction techniques, either prospective or retrospective. Benchmarking the latter methods requires labeled motion-corrupted datasets, which are uncommon. Up to our best knowledge, no protocol for generating labeled datasets of MRI images corrupted by controlled motion has yet been proposed. Hence, we present a methodology allowing the acquisition of reproducible motion-corrupted MRI images as well as validation of the system's performance by motion estimation through rigid-body volume registration of fast 3D echo-planar imaging (EPI) time series. A proof-of-concept is presented, to show how the protocol can be implemented to provide qualitative and quantitative results. An MRI-compatible video system displays a moving target that volunteers equipped with customized plastic glasses must follow to perform predefined head choreographies. Motion estimation using rigid-body EPI time series registration demonstrated that head position can be accurately determined (with an average standard deviation of about 0.39 degrees). A spatio-temporal upsampling and interpolation method to cope with fast motion is also proposed in order to improve motion estimation. The proposed protocol is versatile and straightforward. It is compatible with all MRI systems and may provide insights on the origins of specific motion artifacts. The MRI and artificial intelligence research communities could benefit from this work to build in-vivo labeled datasets of motion-corrupted MRI images suitable for training/testing any retrospective motion correction or machine learning algorithm.
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Artefatos , Inteligência Artificial , Encéfalo/diagnóstico por imagem , Humanos , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Movimento (Física) , Plásticos , Estudos Prospectivos , Estudos RetrospectivosRESUMO
Cardio/cerebrovascular diseases (CVD) have become one of the major health issue in our societies. But recent studies show that the present pathology tests to detect CVD are ineffectual as they do not consider different stages of platelet activation or the molecular dynamics involved in platelet interactions and are incapable to consider inter-individual variability. Here we propose a stochastic platelet deposition model and an inferential scheme to estimate the biologically meaningful model parameters using approximate Bayesian computation with a summary statistic that maximally discriminates between different types of patients. Inferred parameters from data collected on healthy volunteers and different patient types help us to identify specific biological parameters and hence biological reasoning behind the dysfunction for each type of patients. This work opens up an unprecedented opportunity of personalized pathology test for CVD detection and medical treatment.
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Doenças Cardiovasculares , Doenças Vasculares , Teorema de Bayes , Doenças Cardiovasculares/diagnóstico , HumanosRESUMO
In cardiovascular disorders, the study of thrombocytes, commonly known as platelets, is highly important since they are involved in blood clotting, essential in hemostasis, and they can in pathological situations affect the blood circulation. In this paper, single deposited platelets are measured using interferometric digital holographic microscopy. We have shown that the average optical height of platelets is significantly lower in healthy volunteers than in dialyzed patients, meaning a better spreading. It demonstrates the great interest for assessing this parameter in any patients, and therefore the high potential of analyzing single spread platelets using digital holographic microscopy in fundamental research as well as a diagnostic tool in routine laboratories, for usual blood tests.
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This perspective paper considers thrombolysis in the context of ischemic strokes, intending to build eventually a numerical model capable of simulating the thrombolytic treatment and predicting patient outcomes. Numerical modeling is a scientific methodology based on an abstraction of a system but requires understanding their spatio-temporal interactions. However, although important, the current knowledge on thrombolysis is fragmented in contributions from which it is difficult to obtain a complete picture of the process, especially in a clinically relevant setup. This paper discusses, from a general point of view, how to develop a numerical model to describe the evolution of a patient clot under the action of a thrombolytic drug. We will present critical, yet fundamental, open questions that have emerged during this elaboration and discuss original experimental observations that challenge some of our current knowledge of thrombolysis.
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Acidente Vascular Cerebral , Terapia Trombolítica , Fibrinolíticos/uso terapêutico , Humanos , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica/métodos , Resultado do TratamentoRESUMO
â¢A detailed, practical description of a 2D lattice Boltzmann (LB) free-surface model and its coupling with a 1D LB shallow water model is provided.â¢A Python code is provided, that implements the Gaussian droplet benchmark of the research article (Thorimbert et al., 2019) corresponding to this method article.â¢Particular attention is given to the details of the free-surface implementation which, in the literature, vary among authors. These ambiguities must be addressed in order to build a reproducible scheme, as well as the exact implementation and parameters of the coupling model proposed in the associated research article.
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It has been observed in vitro that complete clot lysis is generally preceded by a slow phase of lysis during which the degradation seems to be inefficient. However, this slow regime was merely noticed, but not yet quantitatively discussed. In our experiments, we observed that the lysis ubiquitously occurred in two distinct regimes, a slow and a fast lysis regime. We quantified extensively the duration of these regimes for a wide spectrum of experimental conditions and found that on average, the slow regime lasts longer than the fast one, meaning that during most of the process, the lysis is ineffective. We proposed a computational model in which the properties of the binding of the proteins change during the lysis: first, the biochemical reactions take place at the surface of the fibrin fibers, then in the bulk, resulting in the observed fast lysis regime. This simple hypothesis appeared to be sufficient to reproduce with a great accuracy the lysis profiles obtained experimentally.
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Fibrina , Trombose , Fibrinólise , HumanosRESUMO
We propose a procedure to implement Dirichlet velocity boundary conditions for complex shapes that use data from a single node only, in the context of the lattice Boltzmann method. Two ideas are at the base of this approach. The first is to generalize the geometrical description of boundary conditions combining bounce-back rule with interpolations. The second is to enhance them by limiting the interpolation extension to the proximity of the boundary. Despite its local nature, the resulting method exhibits second-order convergence for the velocity field and shows similar or better accuracy than the well-established Bouzidi's scheme for curved walls [M. Bouzidi, M. Firdaouss, and P. Lallemand, Phys. Fluids 13, 3452 (2001)]PHFLE61070-663110.1063/1.1399290. Among the infinite number of possibilities, we identify several meaningful variants of the method, discerned by their approximation of the second-order nonequilibrium terms and their interpolation coefficients. For each one, we provide two parametrized versions that produce viscosity independent accuracy at steady state. The method proves to be suitable to simulate moving rigid objects or surfaces moving following either the rigid body dynamics or a prescribed kinematic. Also, it applies uniformly and without modifications in the whole domain for any shape, including corners, narrow gaps, or any other singular geometry.
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Red blood cells (RBCs) in pathological situations undergo biochemical and conformational changes, leading to alterations in rheology involved in cardiovascular events. The shape of RBCs in volunteers and stable and exacerbated chronic obstructive pulmonary disease (COPD) patients was analyzed. The effects of RBC spherization on platelet transport (displacement in the flow field caused by their interaction with RBCs) were studied in vitro and by numerical simulations. RBC spherization was observed in COPD patients compared with volunteers. In in vitro experiments at a shear rate of 100 s-1 , treatment of RBCs with neuraminidase induced greater sphericity, which mainly affected platelet aggregates without changing aggregate size. At 400 s-1 , neuraminidase treatment changes both the size of the aggregates and the number of platelet aggregates. Numerical simulations indicated that RBC spherization induces an increase of the platelet mean square displacement, which is traditionally linked to the platelet diffusion coefficient. RBCs of COPD patients are more spherical than healthy volunteers. Experimentally, RBC spherization induces increased platelet transport to the wall. Additional studies are needed to understand the link between the effect of RBCs on platelet transport and the increased cardiovascular events observed in COPD patients.
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Plaquetas/patologia , Eritrócitos/patologia , Doença Pulmonar Obstrutiva Crônica/sangue , Idoso , Estudos Transversais , Índices de Eritrócitos , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
We propose a highly versatile computational framework for the simulation of cellular blood flow focusing on extreme performance without compromising accuracy or complexity. The tool couples the lattice Boltzmann solver Palabos for the simulation of blood plasma, a novel finite-element method (FEM) solver for the resolution of deformable blood cells, and an immersed boundary method for the coupling of the two phases. The design of the tool supports hybrid CPU-GPU executions (fluid, fluid-solid interaction on CPUs, deformable bodies on GPUs), and is non-intrusive, as each of the three components can be replaced in a modular way. The FEM-based kernel for solid dynamics outperforms other FEM solvers and its performance is comparable to state-of-the-art mass-spring systems. We perform an exhaustive performance analysis on Piz Daint at the Swiss National Supercomputing Centre and provide case studies focused on platelet transport, implicitly validating the accuracy of our tool. The tests show that this versatile framework combines unprecedented accuracy with massive performance, rendering it suitable for upcoming exascale architectures.
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Many organs are formed through folding of an epithelium. This change in shape is usually attributed to tissue heterogeneities, for example, local apical contraction. In contrast, compressive stresses have been proposed to fold a homogeneous epithelium by buckling. While buckling is an appealing mechanism, demonstrating that it underlies folding requires measurement of the stress field and the material properties of the tissue, which are currently inaccessible in vivo. Here, we show that monolayers of identical cells proliferating on the inner surface of elastic spherical shells can spontaneously fold. By measuring the elastic deformation of the shell, we infer the forces acting within the monolayer and its elastic modulus. Using analytical and numerical theories linking forces to shape, we find that buckling quantitatively accounts for the shape changes of our monolayers. Our study shows that forces arising from epithelial growth in three-dimensional confinement are sufficient to drive folding by buckling.
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Fenômenos Biomecânicos/fisiologia , Módulo de Elasticidade/fisiologia , Epitélio/crescimento & desenvolvimento , Adesão Celular/fisiologia , Proliferação de Células/fisiologia , Simulação por Computador , Humanos , Modelos BiológicosRESUMO
The fibrin clot is gelatinous matter formed upon injury to stop blood loss and is later destroyed by fibrinolysis, an enzymatic cascade with feedback. Pharmacological fibrinolysis stimulation is also used to destroy pathological, life-threatening clots and thrombi (thrombolysis). The regulation of the nonlinear spatially nonuniform fibrinolytic process in thrombolysis is not currently well understood. We developed a reaction-diffusion-advection model of thrombolysis by tissue plasminogen activator (TPA) in an occluded vessel with a pressure gradient. Sensitivity-analysis-based model reduction was used to reveal the critical processes controlling different steps of thrombolysis. The propagation of thrombolysis in the system without flow was predominantly controlled by TPA diffusion, whereas transport of other active components was rendered nonessential either by their high fibrin-binding parameters and short lifetimes or their initial uniform distribution. The concentration of the main TPA inhibitor plasminogen activator inhibitor 1 (PAI-1) controlled both the extent of lysis propagation and the shape of fibrin spatial distribution during lysis. Interestingly, PAI-1 remained important even when its concentration was an order of magnitude below that of TPA because of its role at the edge of the diffusing TPA front. The system was robust to reaction rate constant perturbations. Using these data, a reduced model of thrombolysis was proposed. In the presence of flow, convection of TPA was the critical controlling process; although the role of PAI-1 concentration was much less in the presence of flow, its influence became greater in the presence of collateral bypassing vessels, which sufficiently reduced TPA flux through the thrombus. Flow bypass through the collateral vessel caused a decrease in TPA flux in the clotted vessel, which increased the PAI-1/TPA ratio, thus making PAI-1-induced inhibition relevant for the regulation of spatial lysis up to its arrest.
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Fibrinólise , Ativador de Plasminogênio Tecidual , Fibrina , Inibidor 1 de Ativador de Plasminogênio , Terapia TrombolíticaRESUMO
Over the last decades, several types of collision models have been proposed to extend the validity domain of the lattice Boltzmann method (LBM), each of them being introduced in its own formalism. This article proposes a formalism that describes all these methods within a common mathematical framework, and in this way allows us to draw direct links between them. Here, the focus is put on single and multirelaxation time collision models in either their raw moment, central moment, cumulant, or regularized form. In parallel with that, several bases (nonorthogonal, orthogonal, Hermite) are considered for the polynomial expansion of populations. General relationships between moments are first derived to understand how moment spaces are related to each other. In addition, a review of collision models further sheds light on collision models that can be rewritten in a linear matrix form. More quantitative mathematical studies are then carried out by comparing explicit expressions for the post-collision populations. Thanks to this, it is possible to deduce the impact of both the polynomial basis (raw, Hermite, central, central Hermite, cumulant) and the inclusion of regularization steps on isothermal LBMs. Extensive results are provided for the D1Q3, D2Q9, and D3Q27 lattices, the latter being further extended to the D3Q19 velocity discretization. Links with the most common two and multirelaxation time collision models are also provided for the sake of completeness. This work ends by emphasizing the importance of an accurate representation of the equilibrium state, independently of the choice of moment space. As an addition to the theoretical purpose of this article, general instructions are provided to help the reader with the implementation of the most complicated collision models.
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In this position paper, we discuss two relevant topics: (i) generic multiscale computing on emerging exascale high-performing computing environments, and (ii) the scaling of such applications towards the exascale. We will introduce the different phases when developing a multiscale model and simulating it on available computing infrastructure, and argue that we could rely on it both on the conceptual modelling level and also when actually executing the multiscale simulation, and maybe should further develop generic frameworks and software tools to facilitate multiscale computing. Next, we focus on simulating multiscale models on high-end computing resources in the face of emerging exascale performance levels. We will argue that although applications could scale to exascale performance relying on weak scaling and maybe even on strong scaling, there are also clear arguments that such scaling may no longer apply for many applications on these emerging exascale machines and that we need to resort to what we would call multi-scaling. This article is part of the theme issue 'Multiscale modelling, simulation and computing: from the desktop to the exascale'.