On the sensitivity analysis of porous finite element models for cerebral perfusion estimation

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

Analytical solutions of incompressible laminar channel and pipe flows driven by in-plane wall oscillations

Emerging flow control strategies have been proposed to tackle long-lasting problems, for instance, precise mixing of chemicals and turbulent drag reduction. Employing actuators imposing in-plane wall oscillations are particularly popular. This paper investigates incompressible laminar rectangular channel and circular pipe flows driven by uniform and traveling wave in-plane wall oscillations. A comprehensive set of exact analytical solutions are presented describing parallel and concentric flows. Dimensionless groups are identified, and it is described how they characterize the one- and two-dimensional time-dependent velocity and pressure fields. The solutions enable to compute the oscillating boundary layer thickness. It is demonstrated that the dimensionless groups and the boundary layer thickness narrows the region of interest within the parameter space. In particular, the oscillating boundary layer thickness obtained from these laminar flows estimates a “radius of action” within which flow features can be altered to boost mixing or reduce turbulent friction drag. The results are suitable for software validation and verification, may open the way to promising complex wall oscillations, and ease the optimization task that delays the industrial application of flow controls

Analytical solutions of incompressible laminar channel and pipe flows driven by in-plane wall oscillations

Emerging flow control strategies have been proposed to tackle long-lasting problems, for instance, precise mixing of chemicals and turbulent drag reduction. Employing actuators imposing in-plane wall oscillations are particularly popular. This paper investigates incompressible laminar rectangular channel and circular pipe flows driven by uniform and traveling wave in-plane wall oscillations. A comprehensive set of exact analytical solutions are presented describing parallel and concentric flows. Dimensionless groups are identified, and it is described how they characterize the one- and two-dimensional time-dependent velocity and pressure fields. The solutions enable to compute the oscillating boundary layer thickness. It is demonstrated that the dimensionless groups and the boundary layer thickness narrows the region of interest within the parameter space. In particular, the oscillating boundary layer thickness obtained from these laminar flows estimates a “radius of action” within which flow features can be altered to boost mixing or reduce turbulent friction drag. The results are suitable for software validation and verification, may open the way to promising complex wall oscillations, and ease the optimization task that delays the industrial application of flow controls

Modelling the impact of clot fragmentation on the microcirculation after thrombectomy

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

On the sensitivity analysis of porous finite element models for cerebral perfusion estimation

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

Multiple new cryptic pathogenic Phytophthora species from Fagaceae forests in Austria, Italy and Portugal

During surveys of Phytophthora diversity in natural and semi-natural Fagaceae forests in Austria, Italy and Portugal, four new cryptic species were isolated from rhizosphere soil samples. Multigene phylogeny based on nuclear ITS, beta-tubulin and HSP90 and mitochondrial cox1 and NADH1 gene sequences demonstrated that two species, P. tyrrhenica and P. vulcanica spp. nov., belong to phylogenetic Clade 7a, while the other two species, P. castanetorum and P. tubulina spp. nov., clustered together with P. quercina forming a new clade, named here as Clade 12. All four new species are homothallic and have low optimum and maximum temperatures for growth and very slow growth rates at their respective optimum temperature. They differed from each other and from related species by a unique combination of morphological characters, cardinal temperatures, and growth rates. Pathogenicity of all Phytophthora species to the root system of their respective host species was demonstrated in soil infestation trials.Portuguese Science and Technology Foundation (FCT); Portuguese national funds the European BiodivERsA project RESIPATH: Responses of European Forests and Society to Invasive Pathogens [BIODIVERSA/0002/2012]; Czech Ministry for Education, Youth and Sports; European Regional Development Fund [CZ.02.1.01/0.0/0.0/15_003/0000453]; Hungarian Scientific Research Fund (OTKA) [K101914]; European Union's Horizon research and innovation programme [635646]; POnTE (Pest Organisms Threatening Europe); Sardinian Regional Governmentinfo:eu-repo/semantics/publishedVersio