![]() On the cellular scale, models including ion channels, cell metabolism and apoptosis have been used to study penumbra and lesion evolution following stroke 13, 14, 15. On the large vessel scale, the motion of emboli through various circle of Willis (CoW) variations has been studied using computational fluid dynamics (CFD), neglecting small vessels or embolus-flow interactions 11, 12. Various numerical methods have previously been used to understand the motion of emboli through the cerebral vasculature. In this paper we demonstrate how 3D stroke simulations can be used to determine lesion volumes and locations from embolus properties, and perform an in-silico study leading to a conjectured relationship between lesion volume and embolus diameter. ![]() By testing medical scenarios, computational (in-silico) models can be used to provide and assess initial hypotheses for clinical studies, potentially saving time and resources allocated to clinical trials that have no prospect of success. This is important because results from animal studies of stroke may be difficult to apply to human trials 10, recruitment to clinical trials may be challenging, and imaging techniques have limited resolution. embolus fragmentation, decompression sickness and embolisation during surgical procedures), provide complementary information about the role of embolisation in parts of the cerebral vasculature that are inaccessible to imaging, and eventually to complement or replace aspects of animal models. Numerical models of stroke have various potential benefits, including the potential to run in-silico “clinical” trials, explore medical scenarios (e.g. There is a need for numerical models of embolic stroke to run in-silico trials, explore clinical scenarios to develop hypotheses for clinical studies, and provide interpretation for intraoperative monitoring. Overall, embolism accounts for approximately 40% of strokes, perhaps the largest single cause 9. There are several situations where large numbers of emboli can be formed, such as during cardiac surgery 3, 4, 5 carotid surgery 6 diving decompression 7 and from mechanical heart valves 8 which can lead to varying risks of neurocognitive decline and stroke. extracranial atherosclerosis) and also cause severe ischemia 2. Large emboli can also form from other sources (e.g. Cardioembolic stroke (typically caused by a small number of large solid emboli) results in severe stroke presentations, and the incidence is projected to triple by 2050 1. The consequences of emboli entering the cerebral vasculature can be devastating, and given the wide range of origins for embolic stroke, a numerical model that links disparate patterns of embolisation to stroke outcomes could be transformative for stroke research. We anticipate this work will form the basis of clinical applications including intraoperative monitoring, determining stroke origins, and in silico trials for complex situations such as multiple embolisation. In conclusion, this article showed proof-of-concept for large in silico trials of embolic stroke including 3D information, identifying that embolus diameter could be determined from infarct volume and that embolus size is critically important to the resting place of emboli. A power law relationship between lesion volume and embolus diameter was found. For large emboli, MCA, PCA and anterior cerebral artery (ACA) lesions were comparable to clinical observations, with MCA, PCA then ACA territories identified as the most to least probable regions for lesions to occur. Mid-sized emboli were preferentially found in posterior cerebral artery (PCA) and posterior region of the middle cerebral artery (MCA) territories. Probabilistic lesion overlap maps showed that the lesions from small emboli are homogeneously distributed throughout the cerebral vasculature. The key result of this study is development of a three-dimensional simulation for embolic stroke and its application to an in silico clinical trial. Computer-generated lesions were assessed by clinicians and compared with radiological images. Infarct volume distributions and probabilistic lesion overlap maps were determined. Simulated emboli were released into an in silico vasculature to simulate 1000 s of strokes. We describe proof-of-concept three-dimensional stroke simulations, carrying out in silico trials to relate lesion volume to embolus diameter and calculate probabilistic lesion overlap maps, building on our previous Monte Carlo method. Stroke simulations are needed to run in-silico trials, develop hypotheses for clinical studies and to interpret ultrasound monitoring and radiological imaging.
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