Towards Multiscale, Multiphysics In Silico Simulations of Cerebral Ischemia

Motivation: While clinical trials of stroke have advanced understanding and treatment, mechanistic spatio-temporal information connecting vascular occlusion to cellular viability is limited. Goal(s): Develop new information-rich avenue for studying stroke. Approach: We are developing a 4D multi-scale, multi-physics computational model of stroke. Results: Results are shown for 1) fine-resolution simulation of cellular metabolism during ischemia between capillaries with spatially-dependent diffusion of nutrients through extravascular space and 2) whole-brain simulation of stroke with and without cellular metabolism having temperature dependence. Results show 1) neurons further from capillaries are more susceptible to damage and 2) increased temperature in region of reduced ischemia will exacerbate cell damage. Impact: Multiphysics, multi-scale 4D numerical models can provide a platform for improved mechanistic understanding of disease process and evaluation of potential treatments of ischemic stroke. This will complement and augment information available from imaging in clinical and preclinical studies.