基于血流动力学的大脑中动脉分叉处与侧壁动脉瘤破裂风险研究

目的旨在结合血流动力学研究大脑中动脉瘤(MCAA)分叉和侧壁部位对其破裂风险的影响。方法本研究回顾性分析术前行头颅CT血管成像(CTA)并经颅内血管造影或手术确诊的MCAA病人193例,未破裂组24例[(58.5±8.5)岁],破裂组169例[(54.9±10.3)岁],收集病人的临床资料及动脉瘤的形态学参数,同时对2组进行流体力学计算分析,获得壁剪应力、振荡剪切指数(OSICV)等血流动力学参数。采用独立样本t检验、Mann-Whitney U检验或χ2检验、Fisher精确检验比较破裂/未破裂组间各参数差异,采用Logistic回归分析破裂的独立风险因素,并分别比较分叉和侧壁处动脉瘤破裂相关的血流动力学差异。结果破裂和未破裂组间临床资料的差异无统计学意义(P>0.05)。与未破裂组相比,破裂组动脉瘤多分布于大脑中动脉分叉处,血流模式复杂、集中,血流冲击区域小且不稳定,OSICV低(均P<0.05)。Logistic回归分析显示复杂的血流模式、血流冲击面积小及小的OSICV是预测MCAA破裂状态的独立风险因素(均P<0.05)。侧壁动脉瘤破裂组的血流冲击小,而分叉处动脉瘤破裂组则血流更复杂、更集中,血流冲击区域更小,更不稳定(均P<0.05)。结论血流复杂程度、冲击面积和OSICV是MCAA破裂的独立危险因素,MCAA所处部位会影响破裂风险。     

Additional Value of Intra-Aneurysmal Hemodynamics in Discriminating Ruptured versus Unruptured Intracranial Aneurysms

BACKGROUND AND PURPOSE:Hemodynamics are thought to play an important role in the rupture of intracranial aneurysms. We tested whether hemodynamics, determined from computational fluid dynamics models, have additional value in discriminating ruptured and unruptured aneurysms. Such discriminative power could provide better prediction models for rupture.MATERIALS AND METHODS:A cross-sectional study was performed on patients eligible for endovascular treatment, including 55 ruptured and 62 unruptured aneurysms. Association with rupture status was tested for location, aneurysm type, and 4 geometric and 10 hemodynamic parameters. Patient-specific spatiotemporal velocities measured with phase-contrast MR imaging were used as inflow conditions for computational fluid dynamics. To assess the additional value of hemodynamic parameters, we performed 1 univariate and 2 multivariate analyses: 1 traditional model including only location and geometry and 1 advanced model that included patient-specific hemodynamic parameters.RESULTS:In the univariate analysis, high-risk locations (anterior cerebral arteries, posterior communicating artery, and posterior circulation), daughter sacs, unstable inflow jets, impingements at the aneurysm body, and unstable complex flow patterns were significantly present more often in ruptured aneurysms. In both multivariate analyses, only the high-risk location (OR, 3.92; 95% CI, 1.77–8.68) and the presence of daughter sacs (OR, 2.79; 95% CI, 1.25–6.25) remained as significant independent determinants.CONCLUSIONS:In this study population of patients eligible for endovascular treatment, we found no independent additional value of aneurysmal hemodynamics in discriminating rupture status, despite high univariate associations. Only traditional parameters (high-risk location and the presence of daughter sacs) were independently associated with ruptured aneurysms.

The prevalence of intracranial aneurysms in the general population is approximately 1%–5%.^1,2 Although most aneurysms remain asymptomatic, a minority rupture, and this scenario is associated with high morbidity and case fatality rates.² For unruptured aneurysms, the risk of treatment complications has to be carefully balanced against the future risk of rupture. At present, risk assessment of unruptured intracranial aneurysms and the decision to treat or observe are mainly based on patient age, family history, aneurysm size, and location.^3–5 However, the predictive value of these characteristics is limited. For example, most ruptured aneurysms are smaller than the recommended minimum of 7 mm for treatment.⁶Several researchers have attempted to better stratify rupture risk by assessments of the associations between local hemodynamic features and aneurysm formation, growth, and rupture by using computational fluid dynamics (CFD).^7–10 In general, due to the difficulty of obtaining patient-specific velocity measurements, assumptions are made for the inflow boundary conditions. However, several studies have shown a large interpatient variation of intracranial artery flow.^11,12The purpose of this study was to test whether estimation of local hemodynamics has additional value in discriminating ruptured and unruptured aneurysms. Thus, high-resolution 3D geometry and patient-specific measurements of local flow velocities in the afferent artery as boundary conditions for hemodynamic simulations were used.^13–15     

Wall shear stress on ruptured and unruptured intracranial aneurysms at the internal carotid artery

BACKGROUND AND PURPOSE: Hemodynamics is often recognized as one of the major factors in aneurysm rupture. Flow impingement, greater pressure, and abnormal wall shear stress are all indications for aneurysm rupture. Characterizing wall shear stress for intracranial aneurysms at similar anatomic locations may help in understanding its role.MATERIALS AND METHODS: Twenty-six intracranial aneurysms at the paraclinoid and superclinoid segments of the internal carotid artery from 25 patients between July 2006 and July 2007 were studied retrospectively. Among them, 8 aneurysms were ruptured and 18 were unruptured. Computational fluid dynamics was used to determine the wall shear distribution. Morphologic and hemodynamic variables was analyzed by using the Mann-Whitney rank sum test.RESULTS: Wall shear stress was qualitatively the same throughout the cardiac cycle; thus, only wall shear stress at the end of diastole was compared. Both ruptured and unruptured aneurysms have similar maximal wall shear stress (26 versus 23 N/m²), and mean wall shear stress is shown to be a function of the aneurysm area. Ruptured aneurysms also have a greater portion of aneurysm under low wall shear stress (27% versus 11% for unruptured aneurysms, P = .03).CONCLUSION: For intracranial aneurysms at the internal carotid artery, an area of low wall shear is associated with aneurysm rupture.

Hemodynamics is recognized as one of the many factors responsible for aneurysm rupture.¹ Many hemodynamic variables, including flow pattern and wall shear stress, are hypothesized to be the causes.^2,3 Intra-aneurysmal flow results in complex flow structure and different flow impinging sites, some at the ostium and some at the dome.^3,4 This complex flow yields a variable wall shear stress distribution on the aneurysm wall. Because wall shear stress regulates endothelial functions,^5,6 understanding of wall shear distribution on the aneurysm wall becomes very important.Recent development of numerical tools has enabled us to study hemodynamics in realistic patient aneurysm geometries.^3,7 Studies based on patient-specific aneurysm models are benefited greatly by advanced 3D angiography because 3D images capture detailed anatomic features that are often neglected in idealized geometry.^7-9 Fine anatomic details render a different flow structure, and these studies have improved our knowledge of the influence of aneurysm morphology on intra-aneurysmal flow.¹⁰ Studying aneurysms at similar anatomic locations allows us to focus on intra-aneurysmal flow, wall shear stress, and aneurysm behaviors. Therefore, we studied the wall shear stress distribution on 26 intracranial aneurysms at the paraclinoid and superclinoid segments of the internal carotid artery and examined the role of hemodynamic variables.     

Rupture-Associated Changes of Cerebral Aneurysm Geometry: High-Resolution 3D Imaging before and after Rupture

BACKGROUND AND PURPOSE:Comparisons of geometric data of ruptured and unruptured aneurysms may yield risk factors for rupture. Data on changes of geometric measures associated with rupture are, however, sparse, because patients with ruptured aneurysms rarely have undergone previous imaging of the intracranial vasculature. We had the opportunity to assess 3D geometric differences of aneurysms before and after rupture. The purpose of this study was to evaluate possible differences between prerupture and postrupture imaging of a ruptured intracranial aneurysm.MATERIALS AND METHODS:Using high-quality 3D image data, we generated 3D geometric models before and after rupture and compared these for changes in aneurysm volume and displacement. A neuroradiologist qualitatively assessed aneurysm shape change, the presence of perianeurysmal hematoma, and subsequent mass effect exerted on aneurysm and parent vessels.RESULTS:Aneurysm volume was larger in the postrupture imaging in 7 of 9 aneurysms, with a median increase of 38% and an average increase of 137%. Three aneurysms had new lobulations on postrupture imaging; 2 other aneurysms were displaced up to 5 mm and had changed in geometry due to perianeurysmal hematoma.CONCLUSIONS:Geometric comparisons of aneurysms before and after rupture show a large volume increase, origination of lobulations, and displacement due to perianeurysmal hematoma. Geometric and hemodynamic comparison of series of unruptured and ruptured aneurysms in the search for rupture-risk-related factors should be interpreted with caution.

Unruptured intracranial aneurysms are found in approximately 3% of the population.¹ Once they are detected, the decision for preventive treatment has to be weighed against the risk of rupture, with inherent high case fatality and morbidity.² Prediction of rupture of intracranial aneurysms remains poor, with size as the most important risk factor. However, not all large aneurysms would rupture if left untreated; whereas small aneurysms, which are often left untreated, do sometimes rupture during follow-up. Better predictors are, therefore, needed. Intra-aneurysmal hemodynamic characteristics may have predictive value.^3,4Computational fluid dynamics have been applied to simulate hemodynamic flow patterns in the aneurysm and surrounding vessels to relate hemodynamic characteristics with aneurysmal rupture risk.^4,5 Several studies indeed found differences in flow patterns between ruptured and unruptured aneurysms.^3,4,6 However, if one compares ruptured with unruptured aneurysms, the potential changes of the aneurysm geometry before, during, or after rupture itself are neglected.The rupture of the aneurysm may result in shape changes of the aneurysm due to changes in the aneurysmal sac. These changes potentially alter the aneurysmal or perianeurysmal geometry and its related hemodynamic patterns. It is, therefore, pivotal to know whether changes before, during, or shortly after rupture of aneurysms in themselves affect aneurysm geometry and aneurysm hemodynamics; and if so, what these changes are. Such data are difficult to collect because high-quality images of intracranial aneurysms before and after rupture are rare. We had the opportunity to assess changes in aneurysm geometry associated with rupture in a series of 9 patients by using advanced image registration of high-quality 3D imaging data performed before and after rupture.     

MR angiography and surgery for unruptured familial intracranial aneurysms in persons with a family history of cerebral aneurysms.

OBJECTIVE: We used MR angiography to determine prevalence of unruptured familial intracranial aneurysms in a prepaid medical care program. We compared surgical outcomes and the cost of treating unruptured versus ruptured aneurysms. We compared the cost of MR angiography with the cost of screening mammography and with the cost of surgically treating a ruptured aneurysm. SUBJECTS AND METHODS: During a 30-month period, we performed MR angiography to show cerebral aneurysms in 63 surgical candidates who had one or more first-degree relatives with an aneurysm. Unruptured aneurysms seen on MR angiography were evaluated by digital subtraction angiography (DSA) and treated surgically. RESULTS: MR angiography showed nine unruptured aneurysms in six patients. Eight aneurysms were seen on MR angiography and nine were seen on DSA. Seven unruptured aneurysms were treated surgically. The mean treatment cost was 50% lower for an unruptured aneurysm than that for a ruptured aneurysm. No patient surgically treated for an unruptured aneurysm required rehabilitation, unlike 25% of patients with ruptured aneurysms. The annual total cost of MR angiography was equivalent to 2.9% of the annual cost of screening mammography. The annual cost of MR angiography equaled half the cost of treating one patient after aneurysm rupture. CONCLUSION: MR angiography showed a 9.5% prevalence of unruptured aneurysms among persons who had one or more first-degree relatives with a cerebral aneurysm. DSA confirmed 88% of aneurysms found on MR angiography. Persons with unruptured aneurysms had better treatment outcomes at lower cost than did patients treated for aneurysm rupture. The annual MR angiography cost was low compared with the cost of screening mammography and with the cost of treating one patient with aneurysm rupture.     

Computational fluid dynamics modeling of intracranial aneurysms: effects of parent artery segmentation on intra-aneurysmal hemodynamics

PURPOSE: The purpose of this study is to show the influence of the upstream parent artery geometry on intraaneurysmal hemodynamics of cerebral aneurysms. METHODS: Patient-specific models of 4 cerebral aneurysms (1 posterior communicating artery [PcomA], 2 middle cerebral artery [MCA], and 1 anterior communicating artery [AcomA]) were constructed from 3D rotational angiography images. Two geometric models were constructed for each aneurysm. One model had the native parent vessel geometry; the second model was truncated approximately 1 cm upstream from the aneurysm, and the parent artery replaced with a straight cylinder. Corresponding finite element grids were generated and computational fluid dynamics simulations were carried out under pulsatile flow conditions. The intra-aneurysmal flow patterns and wall shear stress (WSS) distributions were visualized and compared. RESULTS: Models using the truncated parent vessel underestimated the WSS in the aneurysms in all cases and shifted the impaction zone to the neck compared with the native geometry. These effects were more pronounced in the PcomA and AcomA aneurysms where upstream curvature was substantial. The MCA aneurysm with a long M1 segment was the least effected. The more laminar flow pattern within the parent vessel in truncated models resulted in a less complex intra-aneurysmal flow patterns with fewer vortices and less velocity at the dome. CONCLUSIONS: Failure to properly model the inflow stream contributed by the upstream parent artery can significantly influence the results of intra-aneurysmal hemodynamic models. The upstream portion of the parent vessel of cerebral aneurysms should be included to accurately represent the intra-aneurysmal hemodynamics.     

Computational fluid dynamics modeling of intracranial aneurysms: qualitative comparison with cerebral angiography

RATIONALE AND OBJECTIVE: The purpose of this study is to determine whether computational fluid dynamics modeling can correctly predict the location of the major intra-aneurysmal flow structures that can be identified by conventional angiography. MATERIALS AND METHODS: Patient-specific models of three cerebral aneurysms were constructed from three-dimensional rotational angiography images and computational fluid dynamic simulations performed. Using these velocity fields, contrast transport was simulated and visualizations constructed to provide a "virtual" angiogram. These models were then compared to images from high frame rate conventional angiography to compare flow structures. RESULTS: Computational fluid dynamics simulations showed three distinct flow types ranging from simple to complex. Virtual angiographic images showed good agreement with images from conventional angiography for all three aneurysms with analogous size and orientation of the inflow jet, regions of impaction, and flow type. Large intra-aneurysmal vortices and regions of outflow also corresponded between the images. CONCLUSIONS: Patient-specific image-based computational models of cerebral aneurysms can realistically reproduce the major intra-aneurysmal flow structures observed with conventional angiography. The agreement between computational models and angiographic structures is less for slower zones of recirculation later in the cardiac cycle.     

Quantitative comparison of the dynamic flow waveform changes in 12 ruptured and 29 unruptured ICA–ophthalmic artery aneurysms

Introduction

Studies have reported a correlation between blood flow dynamics in the cardiac cycle and vascular diseases, but research to analyze the dynamic changes of flow in cerebral aneurysms is limited. This quantitative study investigates the temporal changes in flow during a cardiac cycle (flow waveform) in different regions of aneurysms and their association with aneurysm rupture.

Methods

Twelve ruptured and 29 unruptured aneurysms from the internal carotid artery–ophthalmic artery segment were studied. Patient-specific aneurysm data were implemented to simulate blood flow. The temporal flow changes at different regions of the aneurysm were recorded to compare the flow waveforms.

Results

In more than 60 % of the cases, peak flow in the aneurysm sac occurred after peak flow in the artery. Flow rate varied among cases and no correlation with rupture, aneurysm flow rate, and aneurysm size was found. Higher pulsatility within aneurysm sacs was found when comparing with the parent artery (P?<?0.001). Pulsatility was high throughout ruptured aneurysms, but increased from neck to dome in unruptured ones (P?=?0.021). Significant changes between inflow and outflow flow profile were found in unruptured aneurysms (P?=?0.023), but not in ruptured aneurysms.

Conclusion

Quantitative analysis which considers temporal blood flow changes appears to provide additional information which is not apparent from aneurysmal flow at a single time point (i.e., peak of systole). By considering the flow waveform throughout the cardiac cycle, statistically significant differences were found between ruptured and unruptured cases — for flow profile, pulsatility and timing of peak flow.     

Periprocedural morbidity and mortality associated with endovascular treatment of intracranial aneurysms

BACKGROUND AND PURPOSE: Despite experience and technological improvements, endovascular treatment of intracranial aneurysms still has inherent risks. We evaluated cerebral complications associated with this treatment. METHODS: From October 1998 to October 2002, 180 consecutive patients underwent 131 procedures for 118 ruptured aneurysms and 79 procedures for 72 unruptured aneurysms. We retrospectively reviewed their records and images to evaluate their morbidity and mortality. RESULTS: Thirty-seven (17.6%) procedure-related complications occurred: 27 and six with initial embolization of ruptured and unruptured aneurysms, respectively, and four with re-treatment. Complications included 22 cerebral thromboembolisms, nine intraprocedural aneurysm perforations, two coil migrations, two parent vessel injuries, one postprocedural aneurysm rupture, and one cranial nerve palsy. Fourteen complications had no neurologic consequence. Three caused transient neurologic morbidity; 10, persistent neurologic morbidity; and 10, death. Procedure-related neurologic morbidity and mortality rates, respectively, were as follows: overall, 4.8% and 4.8%; ruptured aneurysms, 5.9% and 7.6%; unruptured aneurysms, 1.4% and 1.4%; and re-treated aneurysms, 10% and 0%. Combined procedure-related morbidity and mortality rates for ruptured, unruptured, and re-treated aneurysms were 13.5%, 2.8%, and 10%, respectively. Nonprocedural complications attributable to subarachnoid hemorrhage in 118 patients with ruptured aneurysm were early rebleeding before coil placement (0.9%), symptomatic vasospasm (5.9%), and shunt-dependent hydrocephalus (5.9%); mortality from complications of subarachnoid hemorrhage itself was 11.9%. CONCLUSION: Procedural morbidity and mortality rates were highest in ruptured aneurysms and lowest in unruptured aneurysms. Morbidity rates were highest in re-treated aneurysms and lowest in unruptured aneurysms. No procedural mortality occurred with re-treated aneurysms. The main cause of morbidity and mortality was thromboembolism.     

Transluminal color-coded three-dimensional magnetic resonance angiography for visualization of signal Intensity distribution pattern within an unruptured cerebral aneurysm: preliminarily assessment with anterior communicating artery aneurysms

The natural history of unruptured cerebral aneurysm is not known; also unknown is the potential growth and rupture in any individual aneurysm. The authors have developed transluminal color-coded three-dimensional magnetic resonance angiography (MRA) obtained by a time-of-flight sequence to investigate the interaction between the intra-aneurysmal signal intensity distribution patterns and configuration of unruptured cerebral aneurysms. Transluminal color-coded images were reconstructed from volume data of source magnetic resonance angiography by using a parallel volume-rendering algorithm with transluminal imaging technique. By selecting a numerical threshold range from a signal intensity opacity chart of the three-dimensional volume-rendering dataset several areas of signal intensity were depicted, assigned different colors, and visualized transparently through the walls of parent arteries and an aneurysm. Patterns of signal intensity distribution were analyzed with three operated cases of an unruptured anterior communicating artery aneurysm and compared with the actual configurations observed at microneurosurgery. A little difference in marginal features of an aneurysm was observed; however, transluminal color-coded images visualized the complex signal intensity distribution within an aneurysm in conjunction with aneurysmal geometry. Transluminal color-coded three-dimensional magnetic resonance angiography can thus provide numerical analysis of the interaction between spatial signal intensity distribution patterns and aneurysmal configurations and may offer an alternative and practical method to investigate the patient-specific natural history of individual unruptured cerebral aneurysms.     

Noninvasive measurement of intra-aneurysmal pressure and flow pattern using phase contrast with vastly undersampled isotropic projection imaging

BACKGROUND AND PURPOSE: Currently, more reliable parameters to predict the risk of aneurysmal rupture are needed. Intra-aneurysmal pressure gradients and flow maps could provide additional information regarding the risk of rupture. Our hypothesis was that phase contrast with vastly undersampled isotropic projection reconstruction (PC-VIPR), a novel 3D MR imaging sequence, could accurately assess intra-aneurysmal pressure gradients in a canine aneurysmal model when compared with invasive measurements. MATERIALS AND METHODS: A total of 13 surgically created aneurysms in 8 canines were included in this study. Pressure measurements were performed in the parent vessel, aneurysm neck, and 5 regions within the aneurysmal sac with a microcatheter. PC-VIPR sequence was used to obtain cardiac-gated velocity measurements in a region covering the entire aneurysm. The velocity and pressure gradient maps derived from the PC-VIPR data were then coregistered with the anatomic DSA images and compared with catheter measurements. RESULTS: In 7 of the bifurcation aneurysms, the velocity flow maps demonstrated a recirculation flow pattern with a small neck-to-dome pressure gradient (mean, +0.5 mm Hg). In 1 bifurcation aneurysm, a flow jet extending from the neck to the dome with significantly greater pressure gradient (+50.2 mm Hg) was observed. All sidewall aneurysms had low flow in the sac with intermediate pressure gradients (mean, +8.3 mm Hg). High statistical correlation existed between PC-VIPR aneurysmal pressures and microcatheter pressure measurements (R = 0.82, P < .01). CONCLUSION: PC-VIPR can provide anatomic as well as noninvasive quantitative and qualitative hemodynamic information in the canine aneurysm model. The PC-VIPR intra-aneurysmal pressure measurements correlated well with catheter measurements.     

Inflow hemodynamics evaluated by using four-dimensional flow magnetic resonance imaging and the size ratio of unruptured cerebral aneurysms

Purpose

Prediction of the rupture risk is critical for the identification of unruptured cerebral aneurysms (UCAs) eligible for invasive treatments. The size ratio (SR) is a strong morphological predictor for rupture. We investigated the relationship between the inflow hemodynamics evaluated on four-dimensional (4D) flow magnetic resonance (MR) imaging and the SR to identify specific characteristics related to UCA rupture.

Methods

We evaluated the inflow jet patterns and inflow hemodynamic parameters of 70 UCAs on 4D flow MR imaging and compared them among 23 aneurysms with an SR ≧2.1 and 47 aneurysms with an SR ≦2.0. Based on the shape of inflow streamline bundles with a velocity ≧75% of the maximum flow velocity in the parent artery, the inflow jet patterns were classified as concentrated (C), diffuse (D), neck-limited (N), and unvisualized (U).

Results

The incidence of patterns C and N was significantly higher in aneurysms with an SR ≧2.1. The rate of pattern U was significantly higher in aneurysms with an SR ≦2.0. The maximum inflow rate and the inflow rate ratio were significantly higher in aneurysms with an SR ≧2.1.

Conclusions

The SR affected the inflow jet pattern, the maximum inflow rate, and the inflow rate ratio of UCAs. In conjunction with the SR, inflow hemodynamic analysis using 4D flow MR imaging may contribute to the risk stratification for aneurysmal rupture.

     

Hemodynamic Differences in Intracranial Aneurysms before and after Rupture

BACKGROUND AND PURPOSE:Rupture risk of intracranial aneurysms may depend on hemodynamic characteristics. This has been assessed by comparing hemodynamic data of ruptured and unruptured aneurysms. However, aneurysm geometry may change before, during, or just after rupture; this difference causes potential changes in hemodynamics. We assessed changes in hemodynamics in a series of intracranial aneurysms, by using 3D imaging before and after rupture.MATERIALS AND METHODS:For 9 aneurysms in 9 patients, we used MRA, CTA, and 3D rotational angiography before and after rupture to generate geometric models of the aneurysm and perianeurysmal vasculature. Intra-aneurysmal hemodynamics were simulated by using computational fluid dynamics. Two neuroradiologists qualitatively assessed flow complexity, flow stability, inflow concentration, and flow impingement in consensus, by using flow-velocity streamlines and wall shear stress distributions.RESULTS:Hemodynamics changed in 6 of the 9 aneurysms. The median time between imaging before and after rupture was 678 days (range, 14–1461 days) in these 6 cases, compared with 151 days (range, 34–183 days) in the 3 cases with unaltered hemodynamics. Changes were observed for flow complexity (n = 3), flow stability (n = 3), inflow concentration (n = 2), and region of flow impingement (n = 3). These changes were in all instances associated with aneurysm displacement due to rupture-related hematomas, growth, or newly formed lobulations.CONCLUSIONS:Hemodynamic characteristics of intracranial aneurysms can be altered by geometric changes before, during, or just after rupture. Associations of hemodynamic characteristics with aneurysm rupture obtained from case-control studies comparing ruptured with unruptured aneurysms should therefore be interpreted with caution.

Intracranial aneurysms are found in 1%–5% of the adult population.^1,2 For ruptured intracranial aneurysms, case morbidity and fatality rates are high.^1,3 However, 50%–80% of all intracranial aneurysms do not rupture during an individual''s lifetime.¹ More commonly, unruptured aneurysms are incidentally found due to increasing use of imaging.^4,5 The risk of rupture should be balanced against the risk of treatment when deciding whether an aneurysm should be treated. In clinical practice, the location and size of the aneurysm are the most important parameters for determining the risk of rupture.^1,6 However, these geometric predictors are insufficient for optimal treatment selection. Therefore, the search for better predictors for rupture continues.^7–9 Previous studies have associated intra-aneurysmal flow patterns and wall shear stress (WSS) distributions with aneurysm rupture status.^7,8,10 However, these results are still controversial. For example, both high and low aneurysmal WSS were separately associated with aneurysm growth and rupture.^11,12 In these risk-assessment studies, potential changes in hemodynamics due to the rupture itself were systematically neglected. Recently, 2 studies have shown changes in aneurysm geometry after rupture.^13,14 These rupture-associated geometric changes may result in differences in hemodynamic characteristics as well.In this study, we had the opportunity to use high-quality 3D imaging data of 9 patients with intracranial aneurysms, obtained before and after rupture, to assess potential differences in hemodynamic characteristics associated with rupture.     

Inflow Jet Patterns of Unruptured Cerebral Aneurysms Based on the Flow Velocity in the Parent Artery: Evaluation Using 4D Flow MRI

BACKGROUND AND PURPOSE:Inflow jet characteristics may be related to aneurysmal bleb formation and rupture. We investigated the visualization threshold on the basis of the flow velocity in the parent artery to classify the inflow jet patterns observed on 4D flow MR imaging.MATERIALS AND METHODS:Fifty-seven unruptured aneurysms (24 bifurcation and 33 sidewall aneurysms) were subjected to 4D flow MR imaging to visualize inflow streamline bundles whose velocity exceeded visualization thresholds corresponding to 60%, 75%, and 90% of the maximum flow velocity in the parent artery. The shape of the streamline bundle was determined visually, and the inflow jet patterns were classified as concentrated, diffuse, neck-limited, and unvisualized.RESULTS:At the 75% threshold, bifurcation aneurysms exhibited a concentrated inflow jet pattern at the highest rate. At this threshold, the inflow jets were concentrated in 13 aneurysms (group C, 22.8%), diffuse in 18 (group D, 31.6%), neck-limited in 11 (group N, 19.3%), and unvisualized in 15 (group U, 26.3%). In 16 (28.1%) of the 57 aneurysms, the inflow jet pattern was different at various thresholds. Most inflow parameters, including the maximum inflow velocity and rate, the inflow velocity ratio, and the inflow rate ratio, were significantly higher in groups C and D than in groups N and U.CONCLUSIONS:The inflow jet pattern may depend on the threshold applied to visualize the inflow streamlines on 4D flow MR imaging. For the classification of the inflow jet patterns on 4D flow MR imaging, the 75% threshold may be optimal among the 3 thresholds corresponding to 60%, 75%, and 90% of the maximum flow velocity in the parent artery.

The inflow jets of cerebral aneurysms have been characterized as flow structures composed of strongly directed inflow with higher speeds than in other parts of the aneurysm.^1,2 Computational fluid dynamics analyses by using human cerebral aneurysm models suggested that inflow jets may be related to bleb formation and aneurysmal rupture.^3–5 Cebral et al³ reported that most blebs formed at sites where the inflow jet impacted the aneurysmal wall, and they qualitatively classified the inflow jets of ruptured and unruptured cerebral aneurysms into concentrated and diffuse inflow jets.^3–5 They found that most ruptured aneurysms featured concentrated inflow jets, while diffuse inflow jets tended to be seen in unruptured aneurysms.^4,5 This finding suggests that bleb formation and aneurysm rupture may be attributable to a degenerative change in the aneurysm wall exposed to the increased hemodynamic stress exerted by the inflow jet. Therefore, the assessment of inflow jet patterns and quantitative estimation of the inflow hemodynamics may contribute to a more precise prediction of the risk for bleb formation and aneurysm rupture.Computational fluid dynamics analysis uses human aneurysm models based on a number of assumptions and approximations regarding blood properties, vessel wall compliance, and flow conditions.^3–8 For the quantitative evaluation of the hemodynamics in real human cerebral aneurysms, 4D flow MR imaging, which is based on time-resolved 3D cine phase-contrast MR imaging techniques, has been used.^9–20 In this study, we investigated the visualization threshold on the basis of the flow velocity in the parent artery to classify the inflow jet patterns of unruptured cerebral aneurysms on 4D flow MR imaging. We applied different thresholds to visualize the inflow streamlines, evaluated the inflow jet patterns, and examined the relationship between the inflow jet pattern and the inflow hemodynamics.     

Complications of endovascular treatment of cerebral aneurysms

The number of neuroendovascular treatments of both ruptured and unruptured aneurysms has increased substantially in the last two decades. Complications of endovascular treatments of cerebral aneurysms are rare but can potentially lead to acute worsening of the neurological status, to new neurological deficits or death. Some of the possible complications, such as vascular access site complications or systemic side effects associated with contrast medium (e.g. contrast medium allergy, contrast induced nephropathy) can also be encountered in diagnostic angiography. The most common complications of endovascular treatment of cerebral aneurysms are related to acute thromboembolic events and perforation of the aneurysm. Overall, the reported rate of thromboembolic complications ranges between 4.7% and 12.5% while the rate of intraprocedural rupture of cerebral aneurysms is about 0.7% in patients with unruptured aneurysms and about 4.1% in patients with previously ruptured aneurysms.     

Morphologic and Hemodynamic Risk Factors in Ruptured Aneurysms Imaged before and after Rupture

BACKGROUND AND PURPOSE:Due to limited information about aneurysm natural history, choosing the appropriate management strategy for an unruptured aneurysm is challenging. By comparing unruptured and ruptured cases, studies have identified a variety of aneurysm morphologic and hemodynamic properties as risk factors for rupture. In this study, we investigated changes in 4 ruptured aneurysms before and after rupture and tested whether previously published risk factors identified a risk before rupture.MATERIALS AND METHODS:A retrospective review of ruptured aneurysms based on the inclusion criteria of documenting angiographic images before and after rupture was performed. Such cases are extremely rare. To minimize hemodynamic influence due to location, we selected 4 cases at the posterior communicating artery. 3D morphologic and hemodynamic analyses were applied to examine qualitative and quantitative risk factors in aneurysms before and after rupture.RESULTS:When we compared aneurysms before and after rupture, all increased in size. Volume, surface area, and morphology changed in both high and low wall shear stress areas. Aneurysm surface ratio, nonsphericity index, and pulsatility index were the only risk factors to consistently identify risk before and after aneurysm rupture for all aneurysms.CONCLUSIONS:Although changes in shape and flow properties were found before and after aneurysm rupture, in this small study, we found that some risk factors were evident as early as 2 years before rupture.

Due to limited information about aneurysm natural history, one of the biggest challenges in clinical aneurysm management is determining the risk of rupture for incidentally found aneurysms. Currently, size guidelines identified by the International Study of Unruptured Intracranial Aneurysms are the dominant criteria guiding treatment decisions.¹ Studies have suggested that the mechanisms underlying aneurysm rupture are multifactorial, and they have likewise identified different types of risk factors. For example, researchers have found that certain aneurysm shapes are risk factors that may associate aneurysm morphology with rupture.^2–4 By analyzing blood flow properties in groups of ruptured and unruptured aneurysms, reports have also shown that certain hemodynamic factors may play an important role in aneurysm rupture.^5–9 However, the morphologic and hemodynamic risk factors analyzed in these studies have generally been identified by analyzing ruptured aneurysms after rupture. Because clinical reports also suggest that aneurysms change due to rupture, how well these risk factors can actually help predict rupture has been controversial.^10–12In general, it is expected that the predictive ability of any aneurysm rupture risk factor will be higher as an aneurysm is closer to rupture. The fundamental rationale in aneurysm risk analysis based on comparing ruptured and unruptured aneurysm groups is that aneurysms that rupture have the same risk characteristics in the unruptured and ruptured states.^5–9,13 In that case, the results obtained by comparing ruptured with unruptured aneurysms can help assess the risk of rupture in as-yet-unruptured aneurysms. However, there are limited studies testing this hypothesis.In this study, we re-examined morphologic and hemodynamic risk factors that have been reported in the literature by using a unique dataset of aneurysms imaged in both their unruptured and ruptured states.^{4,6–8,14–17} Our objective was to investigate morphology and flow properties of aneurysms before and after rupture and find whether previously identified risk factors were present in aneurysms before rupture. We sought to identify risk factors that consistently existed in ruptured aneurysms in both unruptured and ruptured states to guide early determination of aneurysm rupture risk.     

Patient-specific computational modeling of cerebral aneurysms with multiple avenues of flow from 3D rotational angiography images

RATIONALE AND OBJECTIVES: Previous studies of aneurysm flow dynamics based on three-dimensional (3D) rotational angiography (RA) images were limited to aneurysms with a single route of blood inflow. However, aneurysms of the circle of Willis frequently involve locations with more than one source of inflow, such as aneurysms of the anterior communicating artery. The highest resolution images of cerebral vessels are from RA images, but this technique is limited to visualizing only one route of inflow at a time, leaving a significant limitation in the application of 3DRA image sets for clinical studies of patient-specific computational fluid dynamics (CFD) simulations. In this report, subject-specific models of cerebral aneurysms with multiple avenues of flow are constructed from RA images by using a novel combination of image co-registration and surface merging techniques. MATERIALS AND METHODS: RA images are obtained by means of contrast injection in each vessel that provides inflow to the aneurysm. Anatomic models are constructed independently of each of these vascular trees and fused together into a single model. The model is used to construct a finite element grid for CFD simulations of hemodynamics. RESULTS: Three examples of patient-specific models are presented: an anterior communicating artery aneurysm, a basilar tip aneurysm, and a model of an entire circle of Willis with five coincident aneurysms. The method is evaluated with a numeric phantom of an aneurysm in the anterior communicating artery. CONCLUSION: These examples show that this new technique can be used to create merged network numeric models for CFD modeling. Furthermore, intra-aneurysmal flow patterns are influenced strongly by merging of the two inflow streams. This effect decreases as distance from the merging streams increases.     

Patient-specific computational fluid dynamics modeling of anterior communicating artery aneurysms: a study of the sensitivity of intra-aneurysmal flow patterns to flow conditions in the carotid arteries

BACKGROUND AND PURPOSE: The purpose of this study was to investigate the effects of unequal physiologic flow conditions in the internal carotid arteries (ICAs) on the hemodynamics of anterior communicating artery aneurysms. METHODS: Patient-specific computational fluid dynamics models of 2 cerebral aneurysms were constructed from bilateral 3D rotational angiograms. The flow dynamics of the aneurysm sac were analyzed under the effect of unequal mean flows, phase shifts, and waveforms between the ICAs. A total of 9 simulations were performed for each patient; cine flow velocity simulations and unsteady wall shear stress (WSS) maps were created for each flow condition. Time-dependent curves of average WSS magnitude over selected regions on the aneurysms were constructed. RESULTS: Mean flow unbalances in the feeding vessels tended to shift the regions of elevated WSS towards the dominating inflow jet and to change the magnitude of the WSS peaks. The overall qualitative appearance of the WSS distribution and velocity simulations was not substantially affected. Phase and waveform asymmetry increased the temporal complexity of the hemodynamic patterns and tended to destabilize the flow pattern. CONCLUSIONS: Differences in the relative phase and waveform shape in ICAs can significantly affect the complexity and stability of the hemodynamic force distributions. The magnitude of these effects is related to the geometry of the aneurysm and the feeding vessels. Conditions affecting the flow characteristics in the parent arteries of cerebral aneurysms with more than 1 avenue of inflow should be incorporated into flow models.     

Intra-Aneurysmal Flow Patterns: Illustrative Comparison among Digital Subtraction Angiography,Optical Flow,and Computational Fluid Dynamics

BACKGROUND AND PURPOSE:Digital subtraction angiography is the gold standard vascular imaging and it is used for all endovascular treatment of intracranial anerysms. Optical flow imaging has been described as a potential method to evaluate cerebral hemodynamics through DSA. In this study, we aimed to compare the flow patterns measured during angiography, by using an optical flow method, with those measured by using computational fluid dynamics in intracranial aneurysms.MATERIALS AND METHODS:A consecutive series of 21 patients harboring unruptured saccular intracranial aneurysms who underwent diagnostic angiography before treatment was considered. High-frame-rate digital subtraction angiography was performed to obtain an intra-aneurysmal velocity field by following the cardiac-modulated contrast wave through the vascular structures by using optical flow principles. Additionally, computational fluid dynamics modeling was performed for every case by using patient-specific inlet-boundary conditions measured with the optical flow method from both DSA and 3D rotational angiography datasets. Three independent observers compared qualitatively both the inflow direction and the apparent recirculation in regular DSA, optical flow images, and computational fluid dynamics flow patterns for each patient; κ statistics were estimated.RESULTS:We included 21 patients. In 14 of these 21, the flow patterns were conclusive and matching between the optical flow images and computational fluid dynamics within the same projection view (κ = .91). However, in only 8 of these 14 patients the optical flow images were conclusive and matching regular DSA images (observer κ = 0.87). In 7 of the 21 patients, the flow patterns in the optical flow images were inconclusive, possibly due to improper projection angles.CONCLUSIONS:The DSA-based optical flow technique was considered qualitatively consistent with computational fluid dynamics outcomes in evaluating intra-aneurysmal inflow direction and apparent recirculation. Moreover, the optical flow technique may provide the premises for new solutions for improving the visibility of flow patterns when contrast motion in DSA is not apparent. This technique is a diagnostic method to evaluate intra-aneurysmal flow patterns and could be used in the future for validation and patient evaluation.

While unruptured intracranial aneurysms have become increasingly diagnosed,¹ more questions have been raised about the improvement of patient care management, requiring the knowledge of risks for both treatment and conservative follow-up, which still remain unknown. In particular, the role of hemodynamics in predicting both aneurysm rupture and treatment efficacy for flow-diverter stents still remains ambiguous, despite the sustained research effort.^2,3 Recently, a novel method has been developed based on digital subtraction angiography and 3D rotational angiography images by using optical flow (OF) principles, permitting the observation and measurement of intracranial hemodynamic characteristics in patients with intracranial aneurysms. Bonnefous et al⁴ have successfully validated this OF method for measuring the volumetric flow rate by using in vitro experiments, and Pereira et al⁵ have validated blood flow rate measurements in patients by using Doppler sonography. This technique has also been applied to quantify flow reduction after flow-diverter stent implantation and seems to be a good predictor of aneurysm thrombosis.⁶ The key success factors for this approach include low contrast-injection rates and an adaptive application of OF principles to high-frame-rate angiograms. These prerequisites allowed capturing the physiologic modulation of the contrast attenuation in blood flow, hence providing measurements of conebeam flat panel detector velocity fields (DVF). As a preliminary step ahead of OF in vivo validation in intracranial aneurysms, we propose to qualitatively compare the intra-aneurysmal flow patterns among DSA sequences (showing the qualitative gross flow structures), OF vectors in a 2D plane, and 3D streamlines based on computational fluid dynamics (CFD).     

Machine Learning–Based Prediction of Small Intracranial Aneurysm Rupture Status Using CTA-Derived Hemodynamics: A Multicenter Study

BACKGROUND AND PURPOSE:Small intracranial aneurysms are being increasingly detected while the rupture risk is not well-understood. We aimed to develop rupture-risk models of small aneurysms by combining clinical, morphologic, and hemodynamic information based on machine learning techniques and to test the models in external validation datasets.MATERIALS AND METHODS:From January 2010 to December 2016, five hundred four consecutive patients with only small aneurysms (<5 mm) detected by CTA and invasive cerebral angiography (or surgery) were retrospectively enrolled and randomly split into training (81%) and internal validation (19%) sets to derive and validate the proposed machine learning models (support vector machine, random forest, logistic regression, and multilayer perceptron). Hemodynamic parameters were obtained using computational fluid dynamics simulation. External validation was performed in other hospitals to test the models.RESULTS:The support vector machine performed the best with areas under the curve of 0.88 (95% CI, 0.85–0.92) and 0.91 (95% CI, 0.74–0.98) in the training and internal validation datasets, respectively. Feature ranks suggested hemodynamic parameters, including stable flow pattern, concentrated inflow streams, and a small (<50%) flow-impingement zone, and the oscillatory shear index coefficient of variation, were the best predictors of aneurysm rupture. The support vector machine showed an area under the curve of 0.82 (95% CI, 0.69–0.94) in the external validation dataset, and no significant difference was found for the areas under the curve between internal and external validation datasets (P = .21).CONCLUSIONS:This study revealed that machine learning had a good performance in predicting the rupture status of small aneurysms in both internal and external datasets. Aneurysm hemodynamic parameters were regarded as the most important predictors.

Unruptured intracranial aneurysms are common, with an overall prevalence of 3.2% in adults worldwide.¹ In the past decades, increasing unruptured aneurysms have been detected because of wide application of CTA and MRA. Notably, large numbers of incidentally detected aneurysms (≤87.6%) have small sizes (<3–4 mm) and are usually asymptomatic.² To date, small aneurysms account for 35%–47% of ruptured aneurysms and may impose a great burden on intracranial vessel diseases.^3,4Treatment of patients with unruptured small aneurysms remains controversial. Some researchers recommend no preventive treatment or imaging follow-up for patients with aneurysms of <3 mm based on the evidence of low annual growth and rupture rates of small aneurysms.^5,6 Current guidelines from the American Heart Association and American Stroke Association have no consensus opinion regarding the management of unruptured aneurysms with small (3–5 mm) and extra-small (≤3 mm) sizes.⁷ Thus, it is imperative to evaluate the rupture risk of small aneurysms to derive optimal clinical decision-making for further treatment and follow-up.Various rupture risk factors and constructed scoring systems have been advocated by researchers.^8,9 The correlation of risk factors (such as clinical, morphologic, and hemodynamic parameters) makes the prediction of aneurysm rupture complicated, leading to the unreliability of conventional methods such as logistic regression. Current scoring systems are not robust, especially for small aneurysms, which have to be modelled specifically due to their unique histologic characteristics.^10-12 Therefore, novel methodologies are required to construct rupture-risk models for small aneurysms to facilitate clinical decisions.^13,14 Aneurysms were often treated only if any change in size or morphology of the aneurysm was detected during follow-up, which would result in a serious bias in the longitudinal study.¹³ It is feasible to perform a cross-sectional study to discriminate the ruptured aneurysms and, further, to apply the model in predicting rupture risk of unruptured aneurysms.Machine learning (ML) techniques have attracted attention for their ability to identify patterns from a large sample dataset with multiple variables, using a highly effective method that facilitates the model construction for data-driven prediction or classification.^15-17 Evidence has suggested that ML algorithms are superior to traditional counterparts in contexts in which data input is abundant and have potential for complex interactions.^17,18 ML has also been used in the classification of aneurysm rupture status with relatively high accuracy.^19,20 However, to the best of our knowledge, no report to date has developed ML methods for small aneurysm rupture prediction with routine clinical and morphologic features combined with hemodynamic variables.The aim of this study was to characterize patients who have a higher risk of aneurysm rupture through developing and validating ML models using routinely collected clinical, morphologic, and hemodynamic variables in an internal cohort and to further test the indicated models in external datasets from other hospitals.