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

Direct estimation of wall shear stress from aneurysmal morphology: A statistical approach

Computational fluid dynamics (CFD) is a valuable tool for studying vascular diseases, but requires long computational time. To alleviate this issue, we propose a statistical framework to predict the aneurysmal wall shear stress patterns directly from the aneurysm shape. A database of 38 complex intracranial aneurysm shapes is used to generate aneurysm morphologies and CFD simulations. The shapes and wall shear stresses are then converted to clouds of hybrid points containing both types of information. These are subsequently used to train a joint statistical model implementing a mixture of principal component analyzers. Given a new aneurysmal shape, the trained joint model is firstly collapsed to a shape only model and used to initialize the missing shear stress values. The estimated hybrid point set is further refined by projection to the joint model space. We demonstrate that our predicted patterns can achieve significant similarities to the CFD-based results

The effect of aneurysm geometry on the intra-aneurysmal flow condition

Various anatomical parameters affect on intra-aneurysmal hemodynamics. Nevertheless, how the shapes of real patient aneurysms affect on their intra-aneurysmal hemodynamics remains unanswered. Quantitative computational fluid dynamics simulation was conducted using eight patients’ angiograms of internal carotid artery–ophthalmic artery aneurysms. The mean size of the intracranial aneurysms was 11.5 mm (range 5.8 to 19.9 mm). Intra-aneurysmal blood flow velocity and wall shear stress (WSS) were collected from three measurement planes in each aneurysm dome. The correlation coefficients (r) were obtained between hemodynamic values (flow velocity and WSS) and the following anatomical parameters: averaged dimension of aneurysm dome, the largest aneurysm dome dimension, aspect ratio, and dome–neck ratio. Negative linear correlations were observed between the averaged dimension of aneurysm dome and intra-aneurysmal flow velocity (r = −0.735) and also WSS (r = −0.736). The largest dome diameter showed a negative correlation with intra-aneurysmal flow velocity (r = −0.731) and WSS (r = −0.496). The aspect ratio demonstrated a weak negative correlation with the intra-aneurysmal flow velocity (r = −0.381) and WSS (r = −0.501). A clear negative correlation was seen between the intra-aneurysmal flow velocity and the dome–neck ratio (r = −0.708). A weak negative correlation is observed between the intra-aneurysmal WSS and the dome–neck ratio (r = −0.392). The aneurysm dome size showed a negative linear correlation with intra-aneurysmal flow velocity and WSS. Wide-necked aneurysm geometry was associated with faster intra-aneurysmal flow velocity

Robustness of common hemodynamic indicators with respect to numerical resolution in 38 middle cerebral artery aneurysms

Background: Using computational fluid dynamics (CFD) to compute the hemodynamics in cerebral aneurysms has received much attention in the last decade. The usability of these methods depends on the quality of the computations, highlighted in recent discussions. The purpose of this study is to investigate the convergence of common hemodynamic indicators with respect to numerical resolution. Methods: 38 middle cerebral artery bifurcation aneurysms were studied at two different resolutions (one comparable to most studies, and one finer). Relevant hemodynamic indicators were collected from two of the most cited studies, and were compared at the two refinements. In addition, correlation to rupture was investigated. Results: Most of the hemodynamic indicators were very well resolved at the coarser resolutions, correlating with the finest resolution with a correlation coefficient >0.95. The oscillatory shear index (OSI) had the lowest correlation coefficient of 0.83. A logarithmic Bland-Altman plot revealed noticeable variations in the proportion of the aneurysm under low shear, as well as in spatial and temporal gradients not captured by the correlation alone. Conclusion: Statistically, hemodynamic indicators agree well across the different resolutions studied here. However, there are clear outliers visible in several of the hemodynamic indicators, which suggests that special care should be taken when considering individual assessment

Disturbed flow induces a sustained, stochastic NF-κB activation which may support intracranial aneurysm growth in vivo

Intracranial aneurysms are associated with disturbed velocity patterns, and chronic inflammation, but the relevance for these findings are currently unknown. Here, we show that (disturbed) shear stress induced by vortices is a sufficient condition to activate the endothelial NF-kB pathway, possibly through a mechanism of mechanosensor de-activation. We provide evidence for this statement through in-vitro live cell imaging of NF-kB in HUVECs exposed to different flow conditions, stochastic modelling of flow induced NF-kB activation and induction of disturbed flow in mouse carotid arteries. Finally, CFD and immunofluorescence on human intracranial aneurysms showed a correlation similar to the mouse vessels, suggesting that disturbed shear stress may lead to sustained NF-kB activation thereby offering an explanation for the close association between disturbed flow and intracranial aneurysms

Flow Residence Time and Regions of Intraluminal Thrombus Deposition in Intracranial Aneurysms

Thrombus formation in intracranial aneurysms, while sometimes stabilizing lesion growth, can present additional risk of thrombo-embolism. The role of hemodynamics in the progression of aneurysmal disease can be elucidated by patient-specific computational modeling. In our previous work, patient-specific computational fluid dynamics (CFD) models were constructed from MRI data for three patients who had fusiform basilar aneurysms that were thrombus-free and then proceeded to develop intraluminal thrombus. In this study, we investigated the effect of increased flow residence time (RT) by modeling passive scalar advection in the same aneurysmal geometries. Non-Newtonian pulsatile flow simulations were carried out in base-line geometries and a new postprocessing technique, referred to as “virtual ink” and based on the passive scalar distribution maps, was used to visualize the flow and estimate the flow RT. The virtual ink technique clearly depicted regions of flow separation. The flow RT at different locations adjacent to aneurysmal walls was calculated as the time the virtual ink scalar remained above a threshold value. The RT values obtained in different areas were then correlated with the location of intra-aneurysmal thrombus observed at a follow-up MR study. For each patient, the wall shear stress (WSS) distribution was also obtained from CFD simulations and correlated with thrombus location. The correlation analysis determined a significant relationship between regions where CFD predicted either an increased RT or low WSS and the regions where thrombus deposition was observed to occur in vivo. A model including both low WSS and increased RT predicted thrombus-prone regions significantly better than the models with RT or WSS alone

Patient-Specific Computational Modeling of Upper Extremity Arteriovenous Fistula Creation: Its Feasibility to Support Clinical Decision-Making

<div><h3>Introduction</h3><p>Inadequate flow enhancement on the one hand, and excessive flow enhancement on the other hand, remain frequent complications of arteriovenous fistula (AVF) creation, and hamper hemodialysis therapy in patients with end-stage renal disease. In an effort to reduce these, a patient-specific computational model, capable of predicting postoperative flow, has been developed. The purpose of this study was to determine the accuracy of the patient-specific model and to investigate its feasibility to support decision-making in AVF surgery.</p> <h3>Methods</h3><p>Patient-specific pulse wave propagation models were created for 25 patients awaiting AVF creation. Model input parameters were obtained from clinical measurements and literature. For every patient, a radiocephalic AVF, a brachiocephalic AVF, and a brachiobasilic AVF configuration were simulated and analyzed for their postoperative flow. The most distal configuration with a predicted flow between 400 and 1500 ml/min was considered the preferred location for AVF surgery. The suggestion of the model was compared to the choice of an experienced vascular surgeon. Furthermore, predicted flows were compared to measured postoperative flows.</p> <h3>Results</h3><p>Taken into account the confidence interval (25^th and 75^th percentile interval), overlap between predicted and measured postoperative flows was observed in 70% of the patients. Differentiation between upper and lower arm configuration was similar in 76% of the patients, whereas discrimination between two upper arm AVF configurations was more difficult. In 3 patients the surgeon created an upper arm AVF, while model based predictions allowed for lower arm AVF creation, thereby preserving proximal vessels. In one patient early thrombosis in a radiocephalic AVF was observed which might have been indicated by the low predicted postoperative flow.</p> <h3>Conclusions</h3><p>Postoperative flow can be predicted relatively accurately for multiple AVF configurations by using computational modeling. This model may therefore be considered a valuable additional tool in the preoperative work-up of patients awaiting AVF creation.</p> </div