In-Silico Trials for Treatment of Acute Ischemic Stroke

Frontiers in Neurology, Journal Year: 2020, Volume and Issue: 11

Published: Sept. 16, 2020

Despite improved treatment, a large portion of patients with acute ischemic stroke due to vessel occlusion have poor functional outcome. Further research exploring novel treatments and better patient selection has therefore been initiated. The feasibility new optimized are commonly tested in extensive expensive randomized clinical trials. As an alternative, in-silico trials, computer-based simulation proposed. In this white paper, we present our vision approach set up trials focusing on treatment stroke. INSIST project (IN-Silico for Ischemic STroke; www.insist-h2020.eu) is collaboration multiple experts computational science, cardiovascular biology, biophysics, biomedical engineering, epidemiology, radiology neurology. will generate virtual populations based data from the recent build existing emerging models stroke, its (thrombolysis thrombectomy) resulting perfusion changes. These be used design platform that validated provide proof concept potential efficacy technology. evaluate effectiveness safety medication, thrombectomy device configurations subpopulations In-silico allow rapid hypothesis testing while supporting trial hence, can benefit next generation

Language: Английский

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A porous circulation model of the human brain for in silico clinical trials in ischaemic stroke

Interface Focus, Journal Year: 2020, Volume and Issue: 11(1), P. 20190127 - 20190127

Published: Dec. 11, 2020

The advancement of ischaemic stroke treatment relies on resource-intensive experiments and clinical trials. In order to improve treatments, such as thrombolysis thrombectomy, we target the development computational tools for in silico trials which can partially replace these animal human with fast simulations. This study proposes a model that will serve part predictive unit within an trial estimating patient outcome function treatment. particular, present work aims at evaluation organ-scale microcirculation brain perfusion prediction. three-compartment porous continuum approach. Firstly, robust method is established compute anisotropic permeability tensors representing arterioles venules. Secondly, vessel encoded arterial spin labelling magnetic resonance imaging clustering are employed create anatomically accurate mapping between large arteries by identifying superficial territories. Thirdly, parameter space problem reduced analysing governing equations experimental data. Fourthly, optimization conducted. Finally, simulations performed tuned obtain maps corresponding open occluded (ischaemic stroke) scenario. map scenario shows promising qualitative agreement computed tomography images caused occlusion. results highlight case occlusion (i) territories essential capture location extent underperfused regions (ii) required give quantitatively realistic estimation change. future, be thoroughly validated against experiments.

Language: Английский

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A network-based model of dynamic cerebral autoregulation

Microvascular Research, Journal Year: 2023, Volume and Issue: 147, P. 104503 - 104503

Published: Feb. 9, 2023

Cerebrovascular diseases continue to be one of the leading causes morbidity and mortality in humans. Abnormalities dynamic cerebral autoregulation (dCA) have been implicated many these disease conditions. Accurate models are therefore needed better understand complex pathophysiology behind impaired dCA. We thus present here a simple framework for modelling vessel-driven network model dCA microvasculature, as opposed conventional compartmental approach. Network incorporate actual connectivity anatomy vasculature, thereby allowing us include trace changes calibre morphology individual vessels, investigate spatial specificity heterogeneity various control mechanisms help disentangle their contributions, link parameters physiology. The proposed feedback incorporated at level vessel, pressure flow fields solved within vessel network. In response an upstream drop, is found able recover blood (CBF) while exhibiting characteristic autoregulatory behaviour terms biphasic response. assess feasibility our formulation larger networks by comparing simulation results those obtained using one-dimensional (1D) CBF applied same microvasculature find that very good agreement with 1D solution, significantly reducing computational cost, enabling more detailed adopted future. computationally feasible representative vasculature can increase translatability haemodynamic into clinical environment, which would develop informed treatment guidelines patients cerebrovascular diseases.

Language: Английский

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Representing unsegmented vessels using available vascular data for bioheat transfer simulation

Frontiers in Thermal Engineering, Journal Year: 2025, Volume and Issue: 5

Published: Feb. 6, 2025

Introduction A primary challenge with voxel domains generated from imaging data is associated resolution. Due to the dimensional scale of blood vessels, not all vessels are captured in a given resolution, leading discontinuous segmentation. Pre-capillary like arterioles, which provide highest resistance flow, often modeled tissue as porous domain due resolution limitations. This results loss information that could have been if these were segmented and distinctly capillary bed. Methods paper focuses on developing mathematical equations calculate flow unsegmented vasculature reference available vascular data. 3D 32 terminal five generations bifurcation simulated. Each generation successively removed substituted new analyze error heat transfer lack segmentation Results The effect using bioheat analyzed. Two methods proposed demonstrated show considerable reduction transfer. Discussion Very high image allow modeling pre-capillary increases computational cost entire simulation domain. Instead, representation pressure drop induced used. potential reducing resulting data, improving accuracy simulations.

Language: Английский

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On the Sensitivity Analysis of Porous Finite Element Models for Cerebral Perfusion Estimation

Annals of Biomedical Engineering, Journal Year: 2021, Volume and Issue: 49(12), P. 3647 - 3665

Published: June 21, 2021

Computational physiological models are promising tools to enhance the design of clinical trials and assist in decision making. Organ-scale haemodynamic gaining popularity evaluate perfusion a virtual environment both healthy diseased patients. Recently, principles verification, validation, uncertainty quantification such have been laid down ensure safe applications engineering software medical device industry. The present study sets out establish guidelines for usage three-dimensional steady state porous cerebral model human brain following detailed verification validation (V&V 40) standard American Society Mechanical Engineers. relies on finite element method has developed specifically estimate how is altered ischaemic stroke patients before, during, after treatments. Simulations compared with exact analytical solutions thorough sensitivity analysis presented covering every numerical parameter. results suggest that can approximate blood pressure distributions reliably even coarse grid first order elements. On other hand, higher elements essential mitigate errors volumetric flow rate estimation through cortical surface regions. Matching corresponding major arteries identified as milestone. It found inlet velocity boundary conditions hard obtain constant feasible alternatives. A one-dimensional which serve computationally inexpensive replacement ease parameter optimisation, analyses quantification. findings be generalised organ-scale models. increase applicability computational regarding treatment development cerebrovascular conditions.

Language: Английский

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In silico trials for treatment of acute ischemic stroke: Design and implementation

Computers in Biology and Medicine, Journal Year: 2021, Volume and Issue: 137, P. 104802 - 104802

Published: Aug. 26, 2021

An in silico trial simulates a disease and its corresponding therapies on cohort of virtual patients to support the development evaluation medical devices, drugs, treatment. In trials have potential refine, reduce cost, partially replace current vivo studies, namely clinical animal testing. We present design implementation an for treatment acute ischemic stroke. propose event-based modelling approach simulation injury, where changes state system (the events) are assumed be instantaneous. Using this we able combine diverse set models, spanning multiple time scales, model stroke, treatment, resulting brain tissue injury. The is designed modular aid reproducibility. It provides comprehensive framework application any trial. A statistical population used generate cohorts patients. Patient functional outcomes also predicted with model, using injury results patient's parameters. demonstrate functionality by running proof concept trials. simulate same twice: once successful (successful recanalisation) unsuccessful (unsuccessful treatment). Ways overcome some challenges difficulties setting up such discussed, as validation computational limitations.

Language: Английский

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Modelling the impact of clot fragmentation on the microcirculation after thrombectomy

PLoS Computational Biology, Journal Year: 2021, Volume and Issue: 17(3), P. e1008515 - e1008515

Published: March 12, 2021

Many ischaemic stroke patients who have a mechanical removal of their clot (thrombectomy) do not get reperfusion tissue despite the thrombus being removed. One hypothesis for this ‘no-reperfusion’ phenomenon is micro-emboli fragmenting off large during thrombectomy and occluding smaller blood vessels downstream location. This impossible to observe in-vivo so we here develop an in-silico model based on in-vitro experiments effect brain tissue. Through obtain, under variety consistencies techniques, distributions post-thrombectomy. Blood flow through microcirculation modelled statistically accurate voxels microvasculature including penetrating arterioles capillary beds. A novel algorithm, informed by experimental data, used simulate impact successively entering bed. Scaled-up parameters–permeability coupling coefficients–are calculated various conditions. We find that beds are more susceptible occlusions than with 4x greater drop in permeability per volume vessel occluded. Individual microvascular geometries determine robustness micro-emboli. Hard fragmentation leads larger drops given number Thrombectomy technique has hence microvasculature. As such, modelling predicts specific factors, interventional technique, geometry strongly influence brain. Micro-emboli likely contributory no-reperfusion following successful major clot.

Language: Английский

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MRI-based parameter inference for cerebral perfusion modelling in health and ischaemic stroke

Computers in Biology and Medicine, Journal Year: 2023, Volume and Issue: 166, P. 107543 - 107543

Published: Sept. 30, 2023

Cerebral perfusion modelling is a promising tool to predict the impact of acute ischaemic stroke treatments on spatial distribution cerebral blood flow (CBF) in human brain. To estimate treatment efficacy based CBF, simulations need become suitable for group-level investigations and thus account physiological variability between individuals. However, computational date has been restricted few patient-specific cases. This study set out establish automated parameter inference neuroimaging data enable CBF groups. Magnetic resonance imaging (MRI) from 75 healthy senior adults were utilised. Brain geometries computed reference subjects' T1-weighted MRI. Haemodynamic model parameters determined maps measured by arterial spin labelling (ASL) Thereafter, conducted cases followed 150 representing an occlusion cessation left right middle arteries. The anatomical fitness brain was evaluated comparing simulated grey (GM) white matter (WM) volumes measurements subjects. Strong positive correlations found both tissue types (GM: Pearson's r 0.74, P<0.001; WM: 0.84, P<0.001). tuning verified total volumetric rate subjects (Pearson's 0.89, In cases, infarct volume using perfusion-based 197±25 ml. Computational predictions agreement with haemodynamic values literature concerning T1-weighted, T2-weighted, phase-contrast MRI scenarios did not capture small infarcts (left tail distribution), which could be explained neglected compensatory mechanisms, e.g. collaterals. proposed method provides foundation silico clinical trials assist medical device drug development.

Language: Английский

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A1D–0D–3Dcoupled model for simulating blood flow and transport processes in breast tissue

International Journal for Numerical Methods in Biomedical Engineering, Journal Year: 2022, Volume and Issue: 38(7)

Published: May 6, 2022

In this work, we present mixed dimensional models for simulating blood flow and transport processes in breast tissue the vascular tree supplying it. These are considered, to start from aortic inlet capillaries of breast. Large variations biophysical properties conditions exist system necessitating use different geometries regimes. total, consider four model types. First, a 1D nonlinear hyperbolic PDEs is considered simulate larger arteries with highly elastic vessel walls. Second, assign linearized smaller stiffer The third type consists ODE systems (0D models). It used arterioles peripheral circulation. Finally, homogenized 3D porous media within volume. Sink terms account influence venous lymphatic systems. Combining types, obtain two 1D-0D-3D coupled processes: first covers whole path aorta breast, while second sub-model obtained by restriction vasculature making possible significant reduction computational cost. Several numerical experiments conducted that demonstrate realistic simulations compared existing data on human system.

Language: Английский

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A dynamic multiscale model of cerebral blood flow and autoregulation in the microvasculature

Applied Mathematical Modelling, Journal Year: 2023, Volume and Issue: 123, P. 213 - 240

Published: July 3, 2023

Models of the micro-circulatory blood flow in brain can play a key role understanding variety cerebrovascular diseases that occur microvasculature. These conditions are often linked to structural modifications vessel network, alterations patterns, as well impairment autoregulatory response, all which pathological changes model should be able address if it were have any clinical value. Furthermore, results validated against MRI data, simulations need computationally feasible when used on networks scale an voxel. This requires some form upscaling approach bypasses for explicit architectural representation whole network while maintaining relevant anatomical connections. To this end, we developed hybrid multiscale and autoregulation traces dynamic flow, volume, pressure cortical microvasculature, where discrete topology penetrating vessels is preserved, these then appropriately coupled homogenised capillary bed by spatially distributing support function terminal endings. In contrast other models, here accounts physiological phenomena processes microvessels. We show how adaptive meshing scheme study employed ensure scale-invariant coupling formulation numerically accurate simulations, without compromising computational feasibility model. A statistically voxel generated, parameter values calibrated using Monte Carlo Filtering analysis physiologically informed. The found capture steep gradients been reported at interfaces. response upstream drop, recover cerebral exhibiting characteristic behaviour terms calibre biphasic response. Overall, offers high-quality characterisation microvasculature improved efficiency lays ground whole-brain simulations.

Language: Английский

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