Multiscale modelling of intracranial aneurysm evolution: A novel Patient-specific Fluid-Solid-Growth (p-FSG) framework incorporating endothelial mechanobiology

IAs (intracranial aneurysms) affect 2-5% of the adult population with a high fatality rate upon rupture. However, the rupture rate is around 0.1%-1% per year which indicates most aneurysms are stable. This leads to a strong demand for clinicians to have a better understanding of the aneurysm stability for treatment planning. Aneurysm stability is thought to be linked to its mechanical environment from both the blood flow and the pulsatile pressure giving the mechanistic signals to vascular cells. A cascade of subsequently biological reactions through the routine of cellular mechanotransduction within the aneurysm tissue determine the development of aneurysms. It is envisaged that mechanistic modelling of biological processes that govern aneurysm growth may help to distinguish between vulnerable and stable aneurysms.
We developed an integrated Patient-specific Fluid-Solid-Growth (p-FSG) framework for simulating the growth of existing intracranial aneurysms. An aneurysm and connected arteries are modelled as fibre-reinforced nonlinear elastic soft-tissue in the commercial software ANSYS. Computational Fluid Dynamics (CFD) simulation quantifies haemodynamic stimuli that act on endothelial cells. Here, we link the morphology of the cells (spindle, hexagonal) to a novel flow metric (Anisotropic Ratio, AR) that characterizes the oscillatory nature of the flow pattern. We then proposed a hypothesis that the endothelial permeability could be regarded as a function of the morphology of endothelial cells which is associated to the growth and remodelling of the aneurysmal tissue. Mass density of elastin and collagen decreases in the region of high endothelial permeability via the inflammatory pathway. Collagen growth (mass changes) is driven by stretch based stimuli of fibroblast cells. Collagen remodelling employs a stress-mediated method that restores the Cauchy stress on collagen fibres to homeostatic levels in the course of the aneurysm enlargement. Principal destructive and self-protective activities during the aneurysm evolution involving elastin, collagen fibres, endothelial cells and fibroblasts are mathematically represented by our p-FSG framework. Our research suggests that the collagen growth function is a vital mechanism for the stability of aneurysms.
This is the first framework models the aneurysm evolution on the basis of the patient-specific aneurysm geometry. Also, we incorporated the functionality of endothelial cells quantified by a novel flow metric to the aneurysm growth and remodelling (G&R) model. This automatic p-FSG framework fully integrated into ANSYS engineering software provides a foundational platform for modelling the aneurysm growth and might become a practical tool in the estimation of aneurysm stability.