Computational modelling of cerebral oedema and osmotherapy following ischaemic stroke

Abstract

In ischaemic stroke, a large reduction in blood supply can lead to the breakdown of the blood brain barrier and to cerebral oedema after reperfusion therapy. Cerebral oedema is marked by elevated intracranial pressure (ICP), tissue herniation and reduced cerebral perfusion pressure. In clinical settings, osmotherapy has been a common practice to decrease ICP. However, there are no guidelines on the choice of administration protocol parameters such as injection doses, infusion time and retention time. Most importantly, the effects of osmotherapy have been proven controversial since the infusion of osmotic agents can lead to a range of side effects. Here, a new Finite Element model of brain oedema and osmotherapy is thus proposed to predict treatment outcome. The model consists of three components that simulate blood perfusion, oedema, and osmotherapy, respectively. In the perfusion model (comprising arteriolar, venous, and capillary blood compartments), an anatomically accurate brain geometry is used to identify regions with a perfusion reduction and potential oedema occurrence in stroke. The oedema model is then used to predict ICP using a porous circulation model with four fluid compartments (arteriolar blood, venular blood, capillary blood, and interstitial fluid). In the osmotherapy model, the osmotic pressure is varied and the changes in ICP during different osmotherapy episodes are quantified. The simulation results of the model show excellent agreement with available clinical data and the model is employed to study osmotherapy under various parameters. Consequently, it is demonstrated how therapeutic strategies can be proposed for patients with different pathological parameters based on simulations.