Modeling intracranial aneurysm stability and growth: An integrative mechanobiological framework for clinical cases

We present a novel patient-specific fluid-solid-growth framework to model the mechanobiological state of clinically detected intracranial aneurysms (IAs) and their evolution. The artery and IA sac are modeled as thick-walled, non-linear elastic fiber-reinforced composites. We represent the undulation distribution of collagen fibers: the adventitia of the healthy artery is modeled as a protective sheath whereas the aneurysm sac is modeled to bear load within physiological range of pressures. Initially, we assume the detected IA is stable and then consider two flow-related mechanisms to drive enlargement: (1) low wall shear stress; (2) dysfunctional endothelium which is associated with regions of high oscillatory flow. Localized collagen degradation and remodelling gives rise to formation of secondary blebs on the aneurysm dome. Restabilization of blebs is achieved by remodelling of the homeostatic collagen fiber stretch distribution. This integrative mechanobiological modelling workflow provides a step towards a personalized risk-assessment and treatment of clinically detected IAs

Vascular Instability and Neurological Morbidity in Sickle Cell Disease: An Integrative Framework

It is well-established that patients with sickle cell disease (SCD) are at substantial risk of neurological complications, including overt and silent stroke, microstructural injury, and cognitive difficulties. Yet the underlying mechanisms remain poorly understood, partly because findings have largely been considered in isolation. Here, we review mechanistic pathways for which there is accumulating evidence and propose an integrative systems-biology framework for understanding neurological risk. Drawing upon work from other vascular beds in SCD, as well as the wider stroke literature, we propose that macro-circulatory hyper-perfusion, regions of relative micro-circulatory hypo-perfusion, and an exhaustion of cerebral reserve mechanisms, together lead to a state of cerebral vascular instability. We suggest that in this state, tissue oxygen supply is fragile and easily perturbed by changes in clinical condition, with the potential for stroke and/or microstructural injury if metabolic demand exceeds tissue oxygenation. This framework brings together recent developments in the field, highlights outstanding questions, and offers a first step toward a linking pathophysiological explanation of neurological risk that may help inform future screening and treatment strategies

Computational investigations of a shape‐memory polymer foam embolization device for intracranial aneurysms

The objective of this research is to determine the efficacy of an intracranial aneurysm treatment option. An open‐source computational fluid dynamics software is used to simulate blood flow through 6 patient‐specific intracranial aneurysm geometries for 42 different cases. Virtual shape memory polymer foam embolization devices are created and implanted into the geometries. Different porous media parameters are considered for the embolic devices, and it is found that devices with a permeability of ∼5e-9 m2 can reduce aneurysmal inflow by 90% for various geometries of the treated aneurysm and its surrounding parent arterial vessel. For a wide‐necked aneurysm, devices with a permeability of 60%, indicating that they may be able to provide that level of performance for most aneurysm morphologies. As such, a permeability range of 5e-9–5e-8 m2 is recommended for the device. Furthermore, material removal from the center of the device is found to be feasible for larger aneurysm devices if compressibility is deemed a concern. For a high‐inflow case, the average aneurysmal velocity reduction is within 2% of the uncored device for all cored devices with a material thickness of at least 1.5 mm occluding the inlet area. Convective heat transfer is also modeled to determine the safety of the thermally stimulated shape memory polymer device. Steady‐state simulations identify the worst‐case geometry, a deep aneurysm with little opportunity for convection. Transient heat transfer during the device deployment process for 2 stimulus temperatures is modeled with this aneurysm, demonstrating that the vessel walls can reach the stimulus temperature of 40 °C and 45 °C within seconds and take over a minute to cool back to near body temperature. The threshold for brain tissue damage is not reached, but nonetheless, it is suggested that the temperature and heating time be kept as low as possible. Full model validation is not available, but general verification of the flow fields in untreated aneurysms is achieved by comparing simulation results to those obtained by other research groups in a modeling competition