Jianping Xiang

Hemodynamic–Morphologic Discriminants for Intracranial Aneurysm Rupture

Background and Purpose— The purpose of this study was to identify significant morphological and hemodynamic parameters that discriminate intracranial aneurysm rupture status using 3-dimensional angiography and computational fluid dynamics. Methods— One hundred nineteen intracranial aneurysms (38 ruptured, 81 unruptured) were analyzed from 3-dimensional angiographic images and computational fluid dynamics. Six morphological and 7 hemodynamic parameters were evaluated for significance with respect to rupture. Receiver operating characteristic analysis identified area under the curve (AUC) and optimal thresholds separating ruptured from unruptured aneurysms for each parameter. Significant parameters were examined by multivariate logistic regression analysis in 3 predictive models—morphology only, hemodynamics only, and combined—to identify independent discriminants, and the AUC receiver operating characteristic of the predicted probability of rupture status was compared among these models. Results— Morphological parameters (size ratio, undulation index, ellipticity index, and nonsphericity index) and hemodynamic parameters (average wall shear stress [WSS], maximum intra-aneurysmal WSS, low WSS area, average oscillatory shear index, number of vortices, and relative resident time) achieved statistical significance (P<0.01). Multivariate logistic regression analysis demonstrated size ratio to be the only independently significant factor in the morphology model (AUC, 0.83; 95% CI, 0.75 to 0.91), whereas WSS and oscillatory shear index were the only independently significant variables in the hemodynamics model (AUC, 0.85; 95% CI, 0.78 to 0.93). The combined model retained all 3 variables, size ratio, WSS, and oscillatory shear index (AUC, 0.89; 95% CI, 0.82 to 0.96). Conclusion— All 3 models—morphological (based on size ratio), hemodynamic (based on WSS and oscillatory shear index), and combined—discriminate intracranial aneurysm rupture status with high AUC values. Hemodynamics is as important as morphology in discriminating aneurysm rupture status.

High WSS or Low WSS? Complex Interactions of Hemodynamics with Intracranial Aneurysm Initiation, Growth, and Rupture: Toward a Unifying Hypothesis

Summary: Increasing detection of unruptured intracranial aneurysms, catastrophic outcomes from subarachnoid hemorrhage, and risks and cost of treatment necessitate defining objective predictive parameters of aneurysm rupture risk. Image-based computational fluid dynamics models have suggested associations between hemodynamics and intracranial aneurysm rupture, albeit with conflicting findings regarding wall shear stress. We propose that the “high-versus-low wall shear stress” controversy is a manifestation of the complexity of aneurysm pathophysiology, and both high and low wall shear stress can drive intracranial aneurysm growth and rupture. Low wall shear stress and high oscillatory shear index trigger an inflammatory-cell-mediated pathway, which could be associated with the growth and rupture of large, atherosclerotic aneurysm phenotypes, while high wall shear stress combined with a positive wall shear stress gradient trigger a mural-cell-mediated pathway, which could be associated with the growth and rupture of small or secondary bleb aneurysm phenotypes. This hypothesis correlates disparate intracranial aneurysm pathophysiology with the results of computational fluid dynamics in search of more reliable risk predictors.

Characterization of Critical Hemodynamics Contributing to Aneurysmal Remodeling at the Basilar Terminus in a Rabbit Model

Background and Purpose— Hemodynamic insult by bilateral common carotid artery ligation has been shown to induce aneurysmal remodeling at the basilar terminus in a rabbit model. To characterize critical hemodynamics that initiate this remodeling, we applied a novel hemodynamics–histology comapping technique. Methods— Eight rabbits received bilateral common carotid artery ligation to increase basilar artery flow. Three underwent sham operations. Hemodynamic insult at the basilar terminus was assessed by computational fluid dynamics. Bifurcation tissue was harvested on day 5; histology was comapped with initial postligation hemodynamic fields of wall shear stress (WSS) and WSS gradient. Results— All bifurcations showed internal elastic lamina loss in periapical regions exposed to accelerating flow with high WSS and positive WSS gradient. Internal elastic lamina damage happened 100% of the time at locations where WSS was >122 Pa and WSS gradient was >530 Pa/mm. The degree of destructive remodeling accounting for internal elastic lamina loss, medial thinning, and luminal bulging correlated with the magnitude of the hemodynamic insult. Conclusions— Aneurysmal remodeling initiates when local hemodynamic forces exceed specific limits at the rabbit basilar terminus. A combination of high WSS and positive WSS gradient represents dangerous hemodynamics likely to induce aneurysmal remodeling.

CFD: Computational Fluid Dynamics or Confounding Factor Dissemination? The Role of Hemodynamics in Intracranial Aneurysm Rupture Risk Assessment

SUMMARY: Image-based computational fluid dynamics holds a prominent position in the evaluation of intracranial aneurysms, especially as a promising tool to stratify rupture risk. Current computational fluid dynamics findings correlating both high and low wall shear stress with intracranial aneurysm growth and rupture puzzle researchers and clinicians alike. These conflicting findings may stem from inconsistent parameter definitions, small datasets, and intrinsic complexities in intracranial aneurysm growth and rupture. In Part 1 of this 2-part review, we proposed a unifying hypothesis: both high and low wall shear stress drive intracranial aneurysm growth and rupture through mural cell–mediated and inflammatory cell–mediated destructive remodeling pathways, respectively. In the present report, Part 2, we delineate different wall shear stress parameter definitions and survey recent computational fluid dynamics studies, in light of this mechanistic heterogeneity. In the future, we expect that larger datasets, better analyses, and increased understanding of hemodynamic-biologic mechanisms will lead to more accurate predictive models for intracranial aneurysm risk assessment from computational fluid dynamics.

Newtonian viscosity model could overestimate wall shear stress in intracranial aneurysm domes and underestimate rupture risk

Objective Computational fluid dynamics (CFD) simulations of intracranial aneurysm hemodynamics usually adopt the simplification of the Newtonian blood rheology model. A study was undertaken to examine whether such a model affects the predicted hemodynamics in realistic intracranial aneurysm geometries. Methods Pulsatile CFD simulations were carried out using the Newtonian viscosity model and two non-Newtonian models (Casson and Herschel-Bulkley) in three typical internal carotid artery saccular aneurysms (A, sidewall, oblong-shaped with a daughter sac; B, sidewall, quasi-spherical; C, near-spherical bifurcation). For each aneurysm model the surface distributions of shear rate, blood viscosity and wall shear stress (WSS) predicted by the three rheology models were compared. Results All three rheology models produced similar intra-aneurysmal flow patterns: aneurysm A had a slowly recirculating secondary vortex near the dome whereas aneurysms B and C contained only a large single vortex. All models predicted similar shear rate, blood viscosity and WSS in parent vessels of all aneurysms and in the sacs of B and C. However, large discrepancies in shear rate, viscosity and WSS among predictions by the various rheology models were found in the dome area of A where the flow was relatively stagnant. Here the Newtonian model predicted higher shear rate and WSS values and lower blood viscosity than the two non-Newtonian models. Conclusions The Newtonian fluid assumption can underestimate viscosity and overestimate shear rate and WSS in regions of stasis or slowly recirculating secondary vortices, typically found at the dome in elongated or complex-shaped saccular aneurysms as well as in aneurysms following endovascular treatment. Because low shear rates and low WSS in such flow conditions indicate a high propensity for thrombus formation and rupture, CFD based on the Newtonian assumption may underestimate the propensity of these events.

Intracranial aneurysms occur more frequently at bifurcation sites that typically experience higher hemodynamic stresses

BACKGROUND Intracranial aneurysms (IAs) occur more frequently at certain bifurcations than at others. Hemodynamic stress, which promotes aneurysm formation in animal models, also differs among bifurcations, depending on flow and vessel geometry. OBJECTIVE To determine whether locations that are more likely to develop IAs experience different hemodynamic stresses that might contribute to higher IA susceptibility. METHODS We characterized the hemodynamic microenvironment at 10 sites in or around the circle of Willis where IAs commonly occur and examined statistical relationships between hemodynamic factors and the tendency for a site to form IAs. The tendency for each site to develop IAs was quantified on the basis of the site distribution from systematic literature analysis of 19 reports including 26418 aneurysms. Hemodynamic parameters for these sites were derived from image-based computational fluid dynamics of 114 cerebral bifurcations from 31 individuals. Wall shear stress and its spatial gradient were calculated in the impact zone surrounding the bifurcation apex. Linear and exponential regression analyses evaluated correlations between the tendency for IA formation and the typical hemodynamics of a site. RESULTS IA susceptibility significantly correlated with the magnitudes of wall shear stress and positive wall shear stress gradient within the hemodynamic impact zone calculated for each site. CONCLUSION IAs occur more frequently at cerebral bifurcations that typically experience higher hemodynamic shear stress and stronger flow acceleration, conditions previously shown to promote aneurysm initiation in animals.

Challenges and limitations of patient-specific vascular phantom fabrication using 3D Polyjet printing

Additive manufacturing (3D printing) technology offers a great opportunity towards development of patient-specific vascular anatomic models, for medical device testing and physiological condition evaluation. However, the development process is not yet well established and there are various limitations depending on the printing materials, the technology and the printer resolution. Patient-specific neuro-vascular anatomy was acquired from computed tomography angiography and rotational digital subtraction angiography (DSA). The volumes were imported into a Vitrea 3D workstation (Vital Images Inc.) and the vascular lumen of various vessels and pathologies were segmented using a “marching cubes” algorithm. The results were exported as Stereo Lithographic (STL) files and were further processed by smoothing, trimming, and wall extrusion (to add a custom wall to the model). The models were printed using a Polyjet printer, Eden 260V (Objet-Stratasys). To verify the phantom geometry accuracy, the phantom was reimaged using rotational DSA, and the new data was compared with the initial patient data. The most challenging part of the phantom manufacturing was removal of support material. This aspect could be a serious hurdle in building very tortuous phantoms or small vessels. The accuracy of the printed models was very good: distance analysis showed average differences of 120 μm between the patient and the phantom reconstructed volume dimensions. Most errors were due to residual support material left in the lumen of the phantom. Despite the post-printing challenges experienced during the support cleaning, this technology could be a tremendous benefit to medical research such as in device development and testing.

Enhanced Aneurysmal Flow Diversion Using a Dynamic Push-Pull Technique: An Experimental and Modeling Study

BACKGROUND AND PURPOSE: Neurovascular flow diverters are flexible, braided stent-meshes for intracranial aneurysm treatment. We applied the dynamic push-pull technique to manipulate the flow-diverter mesh density at the aneurysm orifice to maximize flow diversion. This study investigated the hemodynamic impact of the dynamic push-pull technique on patient-specific aneurysms by using the developed high-fidelity virtual-stenting computational modeling technique combined with computational fluid dynamics. MATERIALS AND METHODS: We deployed 2 Pipeline Embolization Devices into 2 identical sidewall anterior cerebral artery aneurysm phantoms by using the dynamic push-pull technique with different delivery-wire advancements. We then numerically simulated these deployment processes and validated the simulated mesh geometry. Computational fluid dynamics analysis was performed to evaluate detailed hemodynamic changes by deployed flow diverters in the sidewall aneurysm and a fusiform basilar trunk aneurysm (deployments implemented previously). Images of manipulated flow diverter mesh from sample clinical cases were also evaluated. RESULTS: The flow diverters deployed in silico accurately replicated in vitro geometries. Increased delivery wire advancement (21 versus 11 mm) by using a dynamic push-pull technique produced a higher mesh compaction at the aneurysm orifice (50% metal coverage versus 36%), which led to more effective aneurysmal inflow reduction (62% versus 50% in the sidewall aneurysm; 57% versus 36% in the fusiform aneurysm). The dynamic push-pull technique also caused relatively lower metal coverage along the parent vessel due to elongation of the flow diverter. High and low mesh compactions were also achieved for 2 real patients by using the dynamic push-pull technique. CONCLUSIONS: The described dynamic push-pull technique increases metal coverage of pure braided flow diverters over the aneurysm orifice, thereby enhancing the intended flow diversion, while reducing metal coverage along the parent vessel to prevent flow reduction in nearby perforators.

Morphologic and hemodynamic analysis of paraclinoid aneurysms: ruptured versus unruptured

Background In order to determine the risk factors related to aneurysm rupture, we studied the aneurysms at the paraclinoid segment of the internal carotid artery by applying morphologic and hemodynamic numerical analyzes. Methods 107 patients with 110 paraclinoid aneurysms (26 ruptured, 84 unruptured) were analyzed using computational fluid dynamics based on patient-specific three-dimensional geometrical models. A series of morphologic and hemodynamic parameters were evaluated to find the potential indicators of aneurysm rupture. Results Aneurysms with an irregular shape accounted for 23.1% of the ruptured group and only 8.3% of the unruptured group. The difference was statistically significant (p=0.042, χ2 test). Ruptured paraclinoid aneurysms were found to be significantly smaller than unruptured aneurysms (p=0.041), which is different from the results of most previous studies. Energy loss (EL) and inflow concentration showed a level of statistical significance to assess the risk of rupture in paraclinoid aneurysms. By multivariate logistic regression analysis, aneurysm shape (regular or irregular), EL and inflow concentration were retained as independently significant parameters. The odds of rupture were increased by 1.65 times for a 10% increase in EL, by 4.88 times for an aneurysm with an irregular shape and by 2.91 times for an aneurysm with concentrated inflow jet. Conclusions Irregular shape, larger EL and concentrated inflow jet were independently associated with the rupture status of paraclinoid aneurysms. These findings need to be further confirmed based on large multicenter and multipopulation data.

The effect of inlet waveforms on computational hemodynamics of patient-specific intracranial aneurysms.

Due to the lack of patient-specific inlet flow waveform measurements, most computational fluid dynamics (CFD) simulations of intracranial aneurysms usually employ waveforms that are not patient-specific as inlet boundary conditions for the computational model. The current study examined how this assumption affects the predicted hemodynamics in patient-specific aneurysm geometries. We examined wall shear stress (WSS) and oscillatory shear index (OSI), the two most widely studied hemodynamic quantities that have been shown to predict aneurysm rupture, as well as maximal WSS (MWSS), energy loss (EL) and pressure loss coefficient (PLc). Sixteen pulsatile CFD simulations were carried out on four typical saccular aneurysms using 4 different waveforms and an identical inflow rate as inlet boundary conditions. Our results demonstrated that under the same mean inflow rate, different waveforms produced almost identical WSS distributions and WSS magnitudes, similar OSI distributions but drastically different OSI magnitudes. The OSI magnitude is correlated with the pulsatility index of the waveform. Furthermore, there is a linear relationship between aneurysm-averaged OSI values calculated from one waveform and those calculated from another waveform. In addition, different waveforms produced similar MWSS, EL and PLc in each aneurysm. In conclusion, inlet waveform has minimal effects on WSS, OSI distribution, MWSS, EL and PLc and a strong effect on OSI magnitude, but aneurysm-averaged OSI from different waveforms has a strong linear correlation with each other across different aneurysms, indicating that for the same aneurysm cohort, different waveforms can consistently stratify (rank) OSI of aneurysms.