Multiscale Modelling of Intracranial Aneurysms: Cell Signalling, Hemodynamics and Remodelling

Abstract

The genesis, growth and rupture of intracranial aneurysms (IAs) involves physics at the molecular, cellular, blood vessel and organ levels that occurs over time scales ranging from seconds to years. Comprehensive mathematical modelling of IAs therefore requires the description and integration of events across length and time scales that span many orders of magnitude. In this letter we outline a strategy for mulstiscale modelling of IAs that involves the construction of individual models at each relevant scale and their subsequent combination into an integrative model that captures the overall complexity of IA development. An example of the approach is provided using three models operating at different length and time scales: (1) shear stress induced nitric oxide production; (2) smooth muscle cell apoptosis; and (3) fluid-structure-growth modelling. A computational framework for combining them is presented. We conclude with a discussion of the advantages and challenges of the approach.