Bong Jae Chung

Wall Mechanical Properties and Hemodynamics of Unruptured Intracranial Aneurysms

BACKGROUND AND PURPOSE: Aneurysm progression and rupture is thought to be governed by progressive degradation and weakening of the wall in response to abnormal hemodynamics. Our goal was to investigate the relationship between the intra-aneurysmal hemodynamic conditions and wall mechanical properties in human aneurysms. MATERIALS AND METHODS: A total of 8 unruptured aneurysms were analyzed. Computational fluid dynamics models were constructed from preoperative 3D rotational angiography images. The aneurysms were clipped, and the domes were resected and mechanically tested to failure with a uniaxial testing system under multiphoton microscopy. Linear regression analysis was performed to explore possible correlations between hemodynamic quantities and the failure characteristics and stiffness of the wall. RESULTS: The ultimate strain was correlated negatively to aneurysm inflow rate (P = .021), mean velocity (P = .025), and mean wall shear stress (P = .039). It was also correlated negatively to inflow concentration, oscillatory shear index, and measures of the complexity and instability of the flow; however, these trends did not reach statistical significance. The wall stiffness at high strains was correlated positively to inflow rate (P = .014), mean velocity (P = .008), inflow concentration (P = .04), flow instability (P = .006), flow complexity (P = .019), wall shear stress (P = .002), and oscillatory shear index (P = .004). CONCLUSIONS: In a study of 8 unruptured intracranial aneurysms, ultimate strain was correlated negatively with aneurysm inflow rate, mean velocity, and mean wall shear stress. Wall stiffness was correlated positively with aneurysm inflow rate, mean velocity, wall shear stress, flow complexity and stability, and oscillatory shear index. These trends and the impact of hemodynamics on wall structure and mechanical properties should be investigated further in larger studies.

Hemodynamic differences between unstable and stable unruptured aneurysms independent of size and location: a pilot study

Background While clinical and angiographic risk factors for intracranial aneurysm instability are well established, it is reasonable to postulate that intra-aneurysmal hemodynamics also have a role in aneurysm instability. Objective To identify hemodynamic characteristics that differ between radiologically unstable and stable unruptured intracranial aneurysms. Materials and methods 12 pairs of unruptured intracranial aneurysms with a 3D rotational angiographic set of images and followed up longitudinally without treatment were studied. Each pair consisted of one stable aneurysm (no change on serial imaging) and one unstable aneurysm (demonstrated growth of at least 1 mm diameter or ruptured during follow-up) of matching size (within 10%) and locations. Patient-specific computational fluid dynamics models were created and run under pulsatile flow conditions. Relevant hemodynamic and geometric variables were calculated and compared between groups using the paired Wilcoxon test. Results The area of the aneurysm under low wall shear stress (low shear stress area (LSA)) was 2.26 times larger in unstable aneurysms than in stable aneurysms (p=0.0499). The mean aneurysm vorticity was smaller by a factor of 0.57 in unstable aneurysms compared with stable aneurysms (p=0.0499). No statistically significant differences in geometric variables or shape indices were found. Conclusions This pilot study suggests there may be hemodynamic differences between unstable and stable unruptured cerebral aneurysms. In particular, the area under low wall shear stress was larger in unstable aneurysms. These findings should be considered tentative until confirmed by future larger studies.

A modified Stokes-Einstein equation for Aβ aggregation

BackgroundIn all amyloid diseases, protein aggregates have been implicated fully or partly, in the etiology of the disease. Due to their significance in human pathologies, there have been unprecedented efforts towards physiochemical understanding of aggregation and amyloid formation over the last two decades. An important relation from which hydrodynamic radii of the aggregate is routinely measured is the classic Stokes-Einstein equation. Here, we report a modification in the classical Stokes-Einstein equation using a mixture theory approach, in order to accommodate the changes in viscosity of the solvent due to the changes in solute size and shape, to implement a more realistic model for Aβ aggregation involved in Alzheimer’s disease. Specifically, we have focused on validating this model in protofibrill lateral association reactions along the aggregation pathway, which has been experimentally well characterized.ResultsThe modified Stokes-Einstein equation incorporates an effective viscosity for the mixture consisting of the macromolecules and solvent where the lateral association reaction occurs. This effective viscosity is modeled as a function of the volume fractions of the different species of molecules. The novelty of our model is that in addition to the volume fractions, it incorporates previously published reports on the dimensions of the protofibrils and their aggregates to formulate a more appropriate shape rather than mere spheres. The net result is that the diffusion coefficient which is inversely proportional to the viscosity of the system is now dependent on the concentration of the different molecules as well as their proper shapes. Comparison with experiments for variations in diffusion coefficients over time reveals very similar trends.ConclusionsWe argue that the standard Stokes-Einstein’s equation is insufficient to understand the temporal variations in diffusion when trying to understand the aggregation behavior of Aβ 42 proteins. Our modifications also involve inclusion of improved shape factors of molecules and more appropriate viscosities. The modification we are reporting is not only useful in Aβ aggregation but also will be important for accurate measurements in all protein aggregation systems.

Vortex Induced Oscillations of Cylinders at Low and Intermediate Reynolds Numbers

We study the orientational behavior of a hinged cylinder suspended in a water tunnel in the presence of an incompressible flow with Reynolds number (Re), based on particle dimensions, ranging between 100 and 6000 and non-dimensional inertia of the body(I *) in the range 0.1–0.6. The cylinder displays four unique features, which include: steady orientation, random oscillations, periodic oscillations and autorotation.We illustrate these features displayed by the cylinder using a phase diagram which captures the observed phenomena as a function of Re and I *. We identify critical Re and I * to distinguish the different behaviors of the cylinders. We used the hydrogen bubble flow visualization technique to show vortex shedding structure in the cylinder’s wake which results in these oscillations.

Angioarchitectures and Hemodynamic Characteristics of Posterior Communicating Artery Aneurysms and Their Association with Rupture Status

The authors studied 313 posterior communicating artery aneurysms (145 ruptured, 168 unruptured) with image-based computational fluid dynamics. Aneurysms were classified into different angioarchitecture types depending on the location of the aneurysm with respect to parent artery bifurcation. Ruptured aneurysms had higher, more concentrated, and more oscillatory wall shear stress distributions; stronger and more concentrated inflow jets; and more complex and unstable flow patterns compared with unruptured aneurysms. They conclude that high-flow intrasaccular hemodynamic characteristics, commonly found in bifurcation-type angioarchitectures, are associated with the posterior communicating artery aneurysm rupture status. BACKGROUND AND PURPOSE: Intracranial aneurysms originating at the posterior communicating artery are known to have high rupture risk compared with other locations. We tested the hypothesis that different angioarchitectures (ie, branch point configuration) of posterior communicating artery aneurysms are associated with aneurysm hemodynamics, which in turn predisposes aneurysms to rupture. MATERIALS AND METHODS: A total of 313 posterior communicating artery aneurysms (145 ruptured, 168 unruptured) were studied with image-based computational fluid dynamics. Aneurysms were classified into different angioarchitecture types depending on the location of the aneurysm with respect to parent artery bifurcation. Hemodynamic characteristics were compared between ruptured and unruptured aneurysms, as well as among aneurysms with different angioarchitectures. RESULTS: Angioarchitecture was associated with rupture (P = .003). Ruptured aneurysms had higher, more concentrated, and more oscillatory wall shear stress distributions (maximum wall shear stress, P < .001; shear concentration index, P < .001; mean oscillatory shear index, P < .001), stronger and more concentrated inflow jets (represented as Q, P = .01; inflow concentration index, P < .001), and more complex and unstable flow patterns (vortex core length, P < .001; proper orthogonal decomposition entropy, P < .001) compared with unruptured aneurysms. These adverse conditions were more common in aneurysms with bifurcation-type angioarchitectures compared with those with lateral or sidewall angioarchitectures. Interestingly, ruptured aneurysms also had lower normalized mean wall shear stress (P = .02) and minimum wall shear stress (P = .002) than unruptured aneurysms. CONCLUSIONS: High-flow intrasaccular hemodynamic characteristics, commonly found in bifurcation-type angioarchitectures, are associated with the posterior communicating artery aneurysm rupture status. These characteristics include strong and concentrated inflow jets, concentrated regions of elevated wall shear stress, oscillatory wall shear stress, lower normalized wall shear stress, and complex and unstable flow patterns.

Non-equilibrium pattern selection in particle sedimentation

Abstract In this paper, we explain some well known experimental observations in fluid solid interaction from a thermodynamic perspective. In particular we use the extremum of the rate of entropy production to establish the stability of specific patterns observed in single and multiparticle sedimentation in an infinite fluid and the sedimentation of spheres in the presence of walls. While these phenomena have been explained numerically, there is no known rigorous theoretical argument to establish the stability of the observed configurations. We provide a very convincing theoretical basis using entropy based arguments that are considered by several scientists as the underlying theme of nature, life and evolution. In the absence of many rigorous examples for the entropy production principle, our paper advances this argument and lends it much credibility. In addition to looking at the rate of entropy production, we also put forth a very plausible heuristic argument based on the thermal gradients in the systems being studied, which could be the underlying causal principle for many known patterns in nature.

An In Vitro Device for Evaluation of Cellular Response to Flows Found at the Apex of Arterial Bifurcations

Intracranial aneurysms (ICA) are abnormal dilations of the cerebral arteries, most commonly located at the apices of bifurcations. The ability of the arterial wall, particularly the endothelial cells forming the inner lining of the wall, to respond appropriately to hemodynamic stresses is critical to arterial health. ICA initiation is believed to be caused by a breakdown in this homeostatic mechanism leading to wall degradation. Due to the complex nature of this process, there is a need for both controlled in vitro and in vivo studies. Chung et al. developed an in vitro chamber for analyzing the response of biological cells to the hemodynamic wall shear stress fields generated by the impinging flows found at arterial bifurcations [7, 6]. Here, we build on this work and design an in vitro flow chamber that can be used to reproduce specific magnitudes of wall shear stress (WSS) and gradients of wall shear stress. Particular attention is given to reproducing spatial distributions of these functions that have been shown to induce pre-aneurysmal changes in vivo [38]. We introduce a measure of the gradient of the wall shear stress vector (WSSVG) which is appropriate for complex 3D flows and reduces to expected measures in simple 2D flows. The WSSVG is a scalar invariant and is therefore appropriate for use in constitutive equations for vessel remodeling in response to hemodynamic loads [34, 35].

Hemodynamic Characteristics of Ruptured and Unruptured Multiple Aneurysms at Mirror and Ipsilateral Locations

BACKGROUND AND PURPOSE: Different hemodynamic patterns have been associated with aneurysm rupture. The objective was to test whether hemodynamic characteristics of the ruptured aneurysm in patients with multiple aneurysms were different from those in unruptured aneurysms in the same patient. MATERIALS AND METHODS: Twenty-four mirror and 58 ipsilateral multiple aneurysms with 1 ruptured and the others unruptured were studied. Computational fluid dynamics models were created from 3D angiographies. Case-control studies of mirror and ipsilateral aneurysms were performed with paired Wilcoxon tests. RESULTS: In mirror pairs, the ruptured aneurysm had more oscillatory wall shear stress (P = .007) than the unruptured one and tended to be more elongated (higher aspect ratio), though this trend achieved only marginal significance (P = .03, 1-sided test). In ipsilateral aneurysms, ruptured aneurysms had larger maximum wall shear (P = .05), more concentrated (P < .001) and oscillatory wall shear stress (P < .001), stronger (P < .001) and more concentrated inflow jets (P < .001), larger maximum velocity (P < .001), and more complex flow patterns (P < .001) compared with unruptured aneurysms. Additionally, ruptured aneurysms were larger (P < .001) and more elongated (P < .001) and had wider necks (P < .001) and lower minimum wall shear stress (P < .001) than unruptured aneurysms. CONCLUSIONS: High wall shear stress oscillations and larger aspect ratios are associated with rupture in mirror aneurysms. Adverse flow conditions characterized by high and concentrated inflow jets; high, concentrated, and oscillatory wall shear stress; and strong, complex and unstable flow patterns are associated with rupture in ipsilateral multiple aneurysms. In multiple ipsilateral aneurysms, these unfavorable flow conditions are more likely to develop in larger, more elongated, more wide-necked, and more distal aneurysms.

Development and internal validation of an aneurysm rupture probability model based on patient characteristics and aneurysm location, morphology, and hemodynamics

PurposeUnruptured cerebral aneurysms pose a dilemma for physicians who need to weigh the risk of a devastating subarachnoid hemorrhage against the risk of surgery or endovascular treatment and their complications when deciding on a treatment strategy. A prediction model could potentially support such treatment decisions. The aim of this study was to develop and internally validate a model for aneurysm rupture based on hemodynamic and geometric parameters, aneurysm location, and patient gender and age.MethodsCross-sectional data from 1061 patients were used for image-based computational fluid dynamics and shape characterization of 1631 aneurysms for training an aneurysm rupture probability model using logistic group Lasso regression. The model’s discrimination and calibration were internally validated based on the area under the curve (AUC) of the receiver operating characteristic and calibration plots.ResultsThe final model retained 11 hemodynamic and 12 morphological variables, aneurysm location, as well as patient age and gender. An adverse hemodynamic environment characterized by a higher maximum oscillatory shear index, higher kinetic energy and smaller low shear area as well as a more complex aneurysm shape, male gender and younger age were associated with an increased rupture risk. The corresponding AUC of the model was 0.86 (95% CI [0.85, 0.86], after correction for optimism 0.84).ConclusionThe model combining variables from various domains was able to discriminate between ruptured and unruptured aneurysms with an AUC of 86%. Internal validation indicated potential for the application of this model in clinical practice after evaluation with longitudinal data.

Multiple Aneurysms AnaTomy CHallenge 2018 (MATCH): Phase I: Segmentation

PurposeAdvanced morphology analysis and image-based hemodynamic simulations are increasingly used to assess the rupture risk of intracranial aneurysms (IAs). However, the accuracy of those results strongly depends on the quality of the vessel wall segmentation.MethodsTo evaluate state-of-the-art segmentation approaches, the Multiple Aneurysms AnaTomy CHallenge (MATCH) was announced. Participants carried out segmentation in three anonymized 3D DSA datasets (left and right anterior, posterior circulation) of a patient harboring five IAs. Qualitative and quantitative inter-group comparisons were carried out with respect to aneurysm volumes and ostia. Further, over- and undersegmentation were evaluated based on highly resolved 2D images. Finally, clinically relevant morphological parameters were calculated.ResultsBased on the contributions of 26 participating groups, the findings reveal that no consensus regarding segmentation software or underlying algorithms exists. Qualitative similarity of the aneurysm representations was obtained. However, inter-group differences occurred regarding the luminal surface quality, number of vessel branches considered, aneurysm volumes (up to 20%) and ostium surface areas (up to 30%). Further, a systematic oversegmentation of the 3D surfaces was observed with a difference of approximately 10% to the highly resolved 2D reference image. Particularly, the neck of the ruptured aneurysm was overrepresented by all groups except for one. Finally, morphology parameters (e.g., undulation and non-sphericity) varied up to 25%.ConclusionsMATCH provides an overview of segmentation methodologies for IAs and highlights the variability of surface reconstruction. Further, the study emphasizes the need for careful processing of initial segmentation results for a realistic assessment of clinically relevant morphological parameters.