Abstract
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.
Highlights
Cerebrovascular diseases including stroke impose a heavy burden on society.[59]
The present study focuses on a porous perfusion Finite Element (FE) model developed to capture blood flow changes in ischaemic stroke[39] as part of the in silico trial pipeline of INSIST.[40]
Following the framework of the American Society of Mechanical Engineers (ASME) V&V40 standard shown in Fig. 3, the question of interest can be phrased as ‘‘what is the best available treatment option in terms of functional outcome using stent retrievers and tissue plasminogen activator?’’ The context of use of the porous finite element model is quantifying how cerebral blood flow is altered in the microcirculation during ischaemic stroke and post-treatment compared to the healthy baseline case
Summary
Cerebrovascular diseases including stroke impose a heavy burden on society.[59]. The majority of stroke cases are caused by a thrombus blocking a major cerebral artery leading to severe blood shortage in the brain (ischaemic stroke). Once reliable models are available, in silico clinical trials could sharpen the focus of clinical trials and save time and money.[32,55,76]
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