Growth Of Intracranial Aneurysms Research Articles

The clinical significance and reliability of self-reported smoking status in patients with intracranial aneurysms: A review

ObjectiveHere we present a review of the pathophysiology of tobacco smoking on intracranial aneurysms, self-reported smoking status in these patients, screening tools and assays available for assessing active nicotine use, means of impacting smoking cessation rates, and the potential impact of smoking cessation on risk of rupture and recurrence of treated intracranial aneurysms. MethodsA literature search using PubMed was done to identify all English language studies relating to tobacco use and intracranial aneurysms, smoking and subarachnoid hemorrhage, nicotine breakdown products, and smoking cessation in neurosurgery. Results from the studies were reviewed and summarized. ResultsTobacco use is an independent risk factor for formation, growth, and rupture of intracranial aneurysms. The pathogenesis of aneurysm formation is complex, and related to increased wall shear stress, endothelial dysfunction, atherosclerosis, and altered gene regulation. Furthermore 80% of all aneurysmal ruptures occur in patients who have used tobacco products. It is suboptimal to rely on self-reported smoking status in order to determine patient risk. Use of objective metrics for ongoing tobacco use may be indicated in selected patients, and may increase smoking cessation rates in these patients. A variety of laboratory and point-of-care tests are available for measurement of nicotine and nicotine breakdown products. Most assays in clinical practice measure the nicotine breakdown product cotinine, which constitutes 75% of nicotine metabolites excreted in the urine and has a substantial half-life of 16h, compared to nicotine's 2-h half-life. With proper identification, an astute physician may be able to assist in smoking cessation and foster improved patient care. By following recommended guidelines and prescribing pharmaceutical aid, a patient has a 2.5 times greater chance of smoking cessation compared with attempting to stop without physician assistance. ConclusionsSmoking increases risk for intracranial aneurysm formation, rupture, re-rupture and need for re-treatment. Measurement of nicotine breakdown products may have clinical utility in the management of patients with intracranial aneurysms. Smoking cessation interventions may be effective, and use of established smoking cessation tools use may lead to improved clinical outcomes in these patients. The effects of smoking cessation efforts on smoking cessation and intracranial aneurysm outcomes is a fertile field for future investigation.

An integrated, ontology-driven approach to constructing observational databases for research

The electronic health record (EHR) contains a diverse set of clinical observations that are captured as part of routine care, but the incomplete, inconsistent, and sometimes incorrect nature of clinical data poses significant impediments for its secondary use in retrospective studies or comparative effectiveness research. In this work, we describe an ontology-driven approach for extracting and analyzing data from the patient record in a longitudinal and continuous manner. We demonstrate how the ontology helps enforce consistent data representation, integrates phenotypes generated through analyses of available clinical data sources, and facilitates subsequent studies to identify clinical predictors for an outcome of interest. Development and evaluation of our approach are described in the context of studying factors that influence intracranial aneurysm (ICA) growth and rupture. We report our experiences in capturing information on 78 individuals with a total of 120 aneurysms. Two example applications related to assessing the relationship between aneurysm size, growth, gene expression modules, and rupture are described. Our work highlights the challenges with respect to data quality, workflow, and analysis of data and its implications toward a learning health system paradigm.

PHASES Score for Prediction of Intracranial Aneurysm Growth.

Growth of an intracranial aneurysm occurs in around 10% of patients at 2-year follow-up imaging and may be associated with aneurysm rupture. We investigated whether PHASES, a score providing absolute risks of aneurysm rupture based on 6 easily retrievable risk factors, also predicts aneurysm growth. In a multicenter cohort of patients with unruptured intracranial aneurysms and follow-up imaging with computed tomography angiography or magnetic resonance angiography, we performed univariable and multivariable Cox regression analyses for the predictors of the PHASES score at baseline, with aneurysm growth as outcome. We calculated hazard ratios and corresponding 95% confidence intervals (CI), with the PHASES score as continuous variable and after division into quartiles. We included 557 patients with 734 unruptured aneurysms. Eighty-nine (12%) aneurysms in 87 patients showed growth during a median follow-up of 2.7 patient-years (range 0.5-10.8). Per point increase in PHASES score, hazard ratio for aneurysm growth was 1.32 (95% CI, 1.22-1.43). With the lowest quartile of the PHASES score (0-1) as reference, hazard ratios were for the second (PHASES 2-3) 1.07 (95% CI, 0.49-2.32), the third (PHASES 4) 2.29 (95% CI, 1.05-4.95), and the fourth quartile (PHASES 5-14) 2.85 (95% CI, 1.43-5.67). Higher PHASES scores were associated with an increased risk of aneurysm growth. Because higher PHASES scores also predict aneurysm rupture, our findings suggest that aneurysm growth can be used as surrogate outcome measure of aneurysm rupture in follow-up studies on risk prediction or interventions aimed to reduce the risk of rupture.

Abstract W MP48: Measurement of Intracranial Aneurysm Growth

Purpose: The aim of this study is to develop a method to accurately measure 3-D growth of intracranial aneurysms using geodesic active contours segmentation and gradient descent registration algorithms. The method is expected to generate fast and reliable indication of aneurysm growth in clinical settings. Method: The geodesic active contours algorithm was implemented to perform 3-D aneurysm segmentation. 3-D CT Angiography images of 10 subjects with follow up aneurysm images were included in this study. Each subject had images acquired at two distinct time points (average time interval: 126.8 ± 80.1 days). 5 subjects were known to have aneurysm growth between the two time points (growth group). The other 5 subjects were known to have stable aneurysm sizes between the two time points (non-growth group). Segmentation and registration algorithms were used on images from all 10 subjects in an attempt to reproduce the diagnosis results. This study also included 7 sets of computer-built 3-D models and dimensions, for the purpose of validation. Result: Based on segmentation results, the growth group showed an average 21.7 ± 10.2% increase in aneurysm volume, and non-growth group showed an average 0.2 ± 1.3% increase in aneurysm volume. The difference in sample means between the growth group and non-growth group was statistically significant (p ≤ 0.05). For subjects in the growth group, the registration algorithm was able to identify and to label the growing region. For validation, segmentation and registration algorithms were also used on 7 sets of computer built models; growth was correctly labeled. The average runtime for processing segmentation under 4th Generation Intel Core i7-4500U Processor (3.0GHz) was 31.7 ± 38.4 seconds, and 45.2 ± 40.3 for registration. Input images had Signal-to-Noise Ratio (SNR) within a range of 1.8 to 5.9. Conclusion: Geodesic active contours segmentation and gradient descent registration offer an efficient way of measuring and monitoring intracranial aneurysm growth. Further improvements in algorithms are expected to reduce runtime and numerical errors.

Abstract W MP45: RNA-seq Analysis of mRNA/miRNA in Rabbit Aneurysm Model Reveals Similar Expression Patterns to Human Intracranial Aneurysms

Background and Purpose: Rabbit aneurysm models are used in the testing of embolization devices as well as elucidating the mechanisms human intracranial aneurysm growth and healing. We employed ribonucleic acid sequencing (RNA-seq) technology to identify genes relevant to induced rabbit aneurysm biology and compare these with genes related to human intracranial aneurysms to identify genes of potential clinical interest. This included sequencing micro RNA, which are important regulatory non-coding RNA. Materials and Methods: Elastase-induced saccular aneurysms were created at the origin of the right common carotid artery (CCA) in 5 rabbits. Messenger ribonucleic acid (mRNA) and micro ribonucleic acid (miRNA) was isolated from the aneurysm and the control unoperated left CCA at 12 weeks and was processed using RNA-seq technology. The results from RNA-seq were analyzed using Ingenuity Pathway Analysis. Results: 9396 genes were analyzed using RNA-seq, of which 649 (6.9%) were found to be significantly differentially expressed between aneurysm and control tissues (p < 0.05, false discovery rate 2). Of these, 500 were up-regulated in the aneurysm and 149 were down-regulated as compared to controls. Using the same criteria, 3 miRNA were identified as down regulated and 5 were identified as up regulated. Pathway analysis associated these genes with inflammatory response, cellular migration, and coagulation, among other functions and pathologies. Conclusion: RNA-seq next-gen analysis of rabbit aneurysms shows similarities to human intracranial aneurysms with respect to regulation of some key pathways.

Rapid growth of an infectious intracranial aneurysm with catastrophic intracranial hemorrhage

Infectious intracranial aneurysms are rare vascular lesions that classically occur in patients with infective endocarditis. We present a 49-year-old man with altered mental status and headache with rapid growth and rupture of an infectious intracranial aneurysm with catastrophic intracranial hemorrhage, and review issues related to open neurosurgical and endovascular interventions.

Clinical Implications

HomeHypertensionVol. 63, No. 6Clinical Implications Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBClinical Implications Originally published1 Jun 2014https://doi.org/10.1161/HYPERTENSIONAHA.114.03613Hypertension. 2014;63:1137Eligibility for Renal Denervation (page 1319)Based on the SYMPLICITY studies and Conformité Européenne certification, renal denervation is currently applied as a novel treatment of resistant hypertension in Europe. However, information on the proportion of patients with resistant hypertension qualifying for renal denervation after a thorough workup and treatment adjustment remains scarce. This issue of Hypertension includes a study that aimed to investigate the proportion of patients eligible for renal denervation and the reasons for noneligibility at 11 expert centers participating in the European Network COordinating Research on renal Denervation in treatment-resistant hypertension (ENCOReD). The analysis included 731 patients. After careful screening and treatment adjustment at hypertension expert centers, only ≈40% of patients referred for renal denervation, mostly by specialists, were eligible for the procedure. The main reasons of noneligibility were normalization of blood pressure after treatment adjustment (46.9%), unsuitable renal arterial anatomy (17.0%), and previously undetected secondary causes of hypertension (11.1%). Our findings highlight that hypertension centers with a record in clinical experience and research should remain the gatekeepers before renal denervation is considered. Moreover, assuming that renal denervation would be efficacious in a large number of patients with a variety of conditions may be overly optimistic. This groundless belief might well explain why SYMPLICITY HTN-3 failed to reach its primary end point for efficacy.Download figureDownload PowerPointEstrogen Receptor-β and Intracranial Aneurysm Rupture (page 1339)Clinical observations suggest that postmenopausal women have a higher incidence of aneurysmal subarachnoid hemorrhage than premenopausal women. In addition, hormone replacement regimens that contain estrogen seem to reduce the risk for subarachnoid hemorrhage in postmenopausal women. These clinical observations led to the hypothesis that estrogen may protect against the development of intracranial aneurysm rupture (subarachnoid hemorrhage) in postmenopausal women. In this issue of Hypertension, Tada et al sought to establish the causal relationship between estrogen treatment and the prevention of aneurysmal rupture in postmenopausal mice. They used a mouse model of intracranial aneurysm. This model recapitulates the key features of human intracranial aneurysms, including spontaneous rupture. In ovariectomized female mice, estrogen significantly reduced the rupture rates. The protective effect of estrogen seemed to occur through the activation of estrogen receptor-β, a predominant subtype of estrogen receptor in human intracranial aneurysms and cerebral arteries. Estrogen’s unwanted effects are often attributed to its agonistic activity without tissue specificity. Selective estrogen receptor modulators can exert agonistic or antagonistic actions on estrogen receptor subtypes in a tissue-specific fashion. Findings from this study may become the basis for testing selective estrogen receptor modulators with a favorable tissue and receptor subtype specificity profile for the prevention of the growth and rupture of intracranial aneurysms in humans, particularly in postmenopausal women.Download figureDownload PowerPointCardiometabolic Risk at 5 Years (page 1326)The time immediately before and after birth may be a sensitive period related to programming cardiometabolic risk. The present prospective study, performed in children born at term after a noncomplicated pregnancy, shows that birth weight and postnatal weight gain exert independent influences on cardiometabolic parameters at 5 years of age. Although birth weight influenced the metabolic parameters, insulin levels, homeostatic model assessment index, and postnatal weight gain influenced both metabolic parameters and blood pressure values. Throughout the study, systolic blood pressure was related to weight gain, and at 5 years the heaviest children had the highest systolic blood pressure. Moreover, the highest values of insulin, homeostatic model assessment index, and triglycerides were related to both weight gain and current weight. Interestingly, small for gestational age children had the highest values of fasting insulin and homeostatic model assessment index and the lowest high-density lipoprotein. Therefore, it stands to reason that subjects smaller at birth who gain more weight have more risk for metabolic alterations, a fingerprint of early subtle adaptations in the glucose-insulin metabolism. Furthermore, a clustering of higher blood pressure values, insulin levels, and uric acid levels has been observed early in life, indicating the potential for increased cardiometabolic risk later on. This information provides a window of opportunity for intervention to avoid an unbalanced weight gain and to reduce the potential increment of cardiometabolic risk later in life.Download figureDownload PowerPoint Previous Back to top Next FiguresReferencesRelatedDetails June 2014Vol 63, Issue 6 Advertisement Article InformationMetrics © 2014 American Heart Association, Inc.https://doi.org/10.1161/HYPERTENSIONAHA.114.03613 Originally publishedJune 1, 2014 PDF download Advertisement

Biological Mechanisms Underlying Growth and Rupture of Saccular Intracranial Aneurysm

Biological Mechanisms Underlying Growth and Rupture of Saccular Intracranial Aneurysm

Abstract W P73: Feasibility and Preliminary Results of Whole Blood RNA-Sequencing Analysis in Patients With Intracranial Aneurysms

Introduction: Intracranial aneurysms (IA) growth and rupture have been associated with chronic remodeling of the arterial wall. However, the pathobiology of this process remains poorly understood. The objective of the present study was to evaluate the feasibility of analyzing gene expression patterns in peripheral blood of patients with ruptured and unruptured saccular IAs. Materials and Methods: We analyzed human whole blood transcriptomes by performing paired-end, 100 bp RNA-sequencing (RNAseq) using the Illumina platform. We used STAR to align reads to the genome, HTSeq to count reads, and DESeq to normalize counts across samples. Self-reported patient information was used to correct expression values for ancestry, age, and sex. We utilized weighted gene co-expression network analysis (WGCNA) to identify gene expression network modules associated with IA size and rupture. The DAVID tool was employed to search for Gene Ontology enrichment in relevant modules. Results: Samples from 12 patients (9 females, age 57.6 +/-12) with IAs were analyzed. Four had ruptured aneurysms. RNA isolation and application of the methodology described above was successful in all samples. Although the small sample size prevents us from drawing definite conclusions, we observed promising novel co-expression networks for IAs: WCGNA analysis showed down-regulation of two transcript modules associated with ruptured IA status (r=-0.78, p=0.008 and r=-0.77, p=0.009), and up-regulation of two modules associated with aneurysm size (r=0.86, p=0.002 and r=0.9, p=4e-04), respectively. DAVID analyses showed that genes upregulated in an IA size-associated module were enriched with genes involved in cellular respiration and translation, while genes involved in transcription were down-regulated in a module associated with ruptured IAs. Conclusions: Whole blood RNAseq analysis is a feasible tool to capture transcriptome dynamics and achieve a better understanding of the pathophysiology of IAs. Further longitudinal studies of patients with IAs using network analysis are justified.

The use of k-t PCA accelerated dual-venc 3D flow MRI to assess hemodynamics before and after flow diverting stent implantation in cerebral aneurysm models

Background Hemodynamic parameters are known to play a crucial role in the growth and rupture of intracranial aneurysms [Appanaboyina IntJNumerMethodsFluids2008]. Flow diverting stents have emerged as an alternative to coiling by using fine meshes to divert flow away from the aneurysm sac to promote thrombus formation and remodeling of the aneurysm while keeping side branches and perforating arteries patent. However, the post procedural course of these aneurysms is not fully predictable. Time-resolved 3D phase-contrast MRI allows for the assessment of three-directional velocity fields. Due to intrinsic long acquisition times, a single velocity encoding step (venc) is typically used [Acevedo-Bolton JCMR2013]. In this work, we use k-t Principal Component Analysis (PCA) [Pedersen MRM2009] in combination with a dual-venc acquisition to acquire highly undersampled 3D flow data for improved accuracy of lower velocities. Flow patterns within the aneurysms are analysed for different stent sizes, including optimal and oversized stents, and compared to the native models.

Visit-To-Visit Variability in Systolic Blood Pressure Is a Novel Risk Factor for the Growth of Intracranial Aneurysms

Background: Although rupture of unruptured intracranial aneurysms (UIAs) is closely associated with UIA growth during follow-up, few studies have investigated how UIAs grow during observation. Hypertension appears to affect the formation of intracranial aneurysms. However, few studies have investigated the association of blood pressure variability with UIA growth. Visit-to-visit variability (VVV) in systolic blood pressure (SBP) is a newly defined concept which appears to be a good predictor of stroke. With this factor in mind, here we conducted a prospective analysis of the results of 2 years of observation of UIAs by magnetic resonance angiography (MRA) and sought to identify risk factors for UIA growth and rupture. Methods: From December 2006 through June 2010, two hundred patients with 212 UIAs were followed for 2 years. Patient ages ranged from 31 to 91 years. Putative risk factors for the growth of UIAs were evaluated. Subjects were divided into two groups: a UIA growth group consisting of patients whose UIAs increased by 1 mm or more in size or who developed subarachnoid hemorrhage (SAH), and an unchanged group. Brachial blood pressure values were recorded at the time of diagnosis and during follow-up in the outpatient clinic. All blood pressure values were then averaged, and the VVV of SBP was defined as the standard deviation (SD) of a minimum of 5 blood pressure measurements at outpatient visits. Results: UIA growth occurred in 20 patients and SAH occurred in 1 patient. Current smoking tended to be more prevalent in the UIA growth group (p < 0.01). Five of the 12 patients with multiple UIAs showed UIA growth within 2 years and multiplicity was a significant risk factor for UIA growth (p < 0.01). The mean baseline size in the UIA growth group was larger than that in the unchanged group (p = 0.01) and 7 of the 18 patients with large UIAs, categorized as having an initial diameter of 7 mm or more, had an increase in UIA size over the 2 years (p < 0.01). On multivariable logistic regression analysis, current smoking, multiplicity, and UIA size ≥7 mm were significant risk factors for UIA growth. Although no significant difference was seen between the UIA growth and unchanged groups in office SBP during the observation period, VVV in SBP was significantly higher in the UIA growth group than in the unchanged group, and it was significantly and independently associated with UIA growth. Conclusions: VVV in SBP is a novel risk factor for the growth of UIAs and may be a key factor for the prevention of UIA rupture. Future research is needed to confirm that SBP stability prevents UIA rupture.

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

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.

Quantifying the Large-Scale Hemodynamics of Intracranial Aneurysms

Hemodynamics play an important role in the mechanisms that govern the initiation, growth, and possible rupture of intracranial aneurysms. The purpose of this study was to objectively characterize these dynamics, classify them, and connect them to aneurysm rupture. Image-based computational fluid dynamic simulations were used to re-create the hemodynamics of 210 patient-specific intracranial aneurysm geometries. The hemodynamics were then classified according to their spatial complexity and temporal stability by using quantities derived from vortex core lines and proper orthogonal decomposition. The quantitative classification was compared with a previous qualitative classification performed by visual inspection. Receiver operating characteristic curves provided area-under-the-curve estimates for spatial complexity (0.905) and temporal stability (0.85) to show that the 2 classifications were in agreement. Statistically significant differences were observed in the quantities describing the hemodynamics of ruptured and unruptured intracranial aneurysms. Specifically, ruptured aneurysms had more complex and more unstable flow patterns than unruptured aneurysms. Spatial complexity was more strongly associated with rupture than temporal stability. Complex-unstable blood flow dynamics characterized by longer core line length and higher entropy could induce biologic processes that predispose an aneurysm for rupture.

Correlation between MMP-2 and NF-κ B expression of intracranial aneurysm

ObjectiveTo investigate the correlation between expressions of MMP-2 and NF-κ B in the intracranial aneurysm wall, and explore their role in the mechanism of the occurrence, growth and rupture of intracranial aneurysms. MethodsRT-PCR was used to detect the expression of MMP-2 and NF-κ B mRNA of 30 cases of intracranial aneurysm tissue and 10 cases of normal intracranial arterial tissue; Immunohistochemical method was used to detect the expression of MMP-2 and NF-κ B protein. ResultsThe semi-quantitative analysis of MMP-2 and NF-κ B in aneurysms tissues and normal tissues were statistically significant different from each other (P<0 05). Immunohistochemical staining results showed NF-κ B was expressed in different layers. The expression of them were positive in intimal and medial, and the expression sites were located in the nucleus. MMP-2 were expressed in different layers of the aneurysm wall, and the expressions were positive in media and extima. The MMP-2 and NF- κ B-positive expression of aneurysm wall were significantly higher than in normal cerebral arteries (P <0.05). MMP-2 and NF-κ B mRNA expression showed positive correlation in the aneurysm wall tissue (r = 0.689, P = 0.005). ConclusionsThe expressions of MMP-2 and NF-κ B in the intracranial aneurysm wall tissue were significantly higher than in the normal intracranial arterial tissues. They have a synergistic effect on the formation of intracranial aneurysms.

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

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.

Wall shear stress in intracranial aneurysms and adjacent arteries.

Hemodynamic parameters play an important role in aneurysm formation and growth. However, it is difficult to directly observe a rapidly growing de novo aneurysm in a patient. To investigate possible associations between hemodynamic parameters and the formation and growth of intracranial aneurysms, the present study constructed a computational model of a case with an internal carotid artery aneurysm and an anterior communicating artery aneurysm, based on the CT angiography findings of a patient. To simulate the formation of the anterior communicating artery aneurysm and the growth of the internal carotid artery aneurysm, we then constructed a model that virtually removed the anterior communicating artery aneurysm, and a further two models that also progressively decreased the size of the internal carotid artery aneurysm. Computational simulations of the fluid dynamics of the four models were performed under pulsatile flow conditions, and wall shear stress was compared among the different models. In the three aneurysm growth models, increasing size of the aneurysm was associated with an increased area of low wall shear stress, a significant decrease in wall shear stress at the dome of the aneurysm, and a significant change in the wall shear stress of the parent artery. The wall shear stress of the anterior communicating artery remained low, and was significantly lower than the wall shear stress at the bifurcation of the internal carotid artery or the bifurcation of the middle cerebral artery. After formation of the anterior communicating artery aneurysm, the wall shear stress at the dome of the internal carotid artery aneurysm increased significantly, and the wall shear stress in the upstream arteries also changed significantly. These findings indicate that low wall shear stress may be associated with the initiation and growth of aneurysms, and that aneurysm formation and growth may influence hemodynamic parameters in the local and adjacent arteries.

Physical Factors Effecting Cerebral Aneurysm Pathophysiology

Many factors that are either blood-, wall-, or hemodynamics-borne have been associated with the initiation, growth, and rupture of intracranial aneurysms. The distribution of cerebral aneurysms around the bifurcations of the circle of Willis has provided the impetus for numerous studies trying to link hemodynamic factors (flow impingement, pressure, and/or wall shear stress) to aneurysm pathophysiology. The focus of this review is to provide a broad overview of such hemodynamic associations as well as the subsumed aspects of vascular anatomy and wall structure. Hemodynamic factors seem to be correlated to the distribution of aneurysms on the intracranial arterial tree and complex, slow flow patterns seem to be associated with aneurysm growth and rupture. However, both the prevalence of aneurysms in the general population and the incidence of ruptures in the aneurysm population are extremely low. This suggests that hemodynamic factors and purely mechanical explanations by themselves may serve as necessary, but never as necessary and sufficient conditions of this disease's causation. The ultimate cause is not yet known, but it is likely an additive or multiplicative effect of a handful of biochemical and biomechanical factors.

Incidence of growth and rupture of unruptured intracranial aneurysms followed by serial MRA

The natural history, including growth and rupture, of unruptured intracranial aneurysms (UIAs) remains unknown. Here, we present the results of serial magnetic resonance angiography (MRA) follow-up study in 111 patients with 136 UIAs. A total of 111 patients with 136 UIAs were followed annually over the past 12years, using 1.5-Tesla MRA. Follow-up was ended when UIAs were treated surgically, or the patients died of subarachnoid hemorrhage or other causes. Various factors influencing aneurysm rupture or growth were examined statistically. Aneurysm rupture and growth occurred in six and 13 of the 111 patients, respectively. Annual rupture rate was 1.8% per year and annual growth rate was 3.9% per year. Aneurysm size was the sole factor influencing rupture(H.R. 1.214, 95% CI, 1.078-1.368) and multiplicity was the sole factor influencing aneurysm growth (H.R. 5.174, 95% CI 1.81-14.80). Serial MRA study showed that the incidence of UIA growth was twice as high as that of UIA rupture. As four patients showed aneurysm rupture or growth within 1year, further investigations are necessary to determine the optimum interval of radiological investigation and to identify which UIAs grow or rupture within a short time.

Editorial: Aneurysm geometry

Treatment of small, unruptured intracranial aneurysms is controversial, and the decision of whether to intervene is a difficult one. While a very small subset of unruptured aneurysms go on to rupture, the vast majority remain quiescent for years. Different factors (related to patient, aneurysm, and surgeon/technique) are taken into consideration to guide the decision-making process. The development of 3D imaging techniques has triggered an expanding number of reports on the predictive role of various geometric and hemodynamic measurements on the formation, growth, and rupture of intracranial aneurysms. While estimation of the putative role of these measurements is appealing and sophisticated, most of the studies suffer from a major methodological flaw: unruptured aneurysms are compared with ruptured aneurysms. As most surgeons who have operated on patients with ruptured and unruptured aneurysms are well aware, the 2 entities are often completely different. In their article, Lin and coworkers1 analyze a relatively large cohort of middle cerebral artery (MCA) aneurysms and compare unruptured and ruptured aneurysms with respect to various geometric measurements calculated on 3D CT angiography reconstructions. The authors conclude that aspect ratio, flow angle, and parentdaughter angle were more common in the ruptured rather than in the unruptured cohort. The authors of this study make an attempt to consider a homogeneous group of aneurysms by selecting only patients with MCA aneurysms. However, the 2 groups under consideration are still quite different, and the study is not devoid of the significant methodological flaws of similar studies. I suspect that composition and strength of the aneurysm wall and time elapsed from aneurysm formation to its detection are much more important differences between ruptured and unruptured aneurysms than are geometric differences. Most aneurysms that go on to rupture most likely do so shortly after their formation at a time when the aneurysm wall is more vulnerable to hemodynamic stress.2,3 It is possible that aneurysm geometry plays a role in this early stage of vulnerability, hence the differences between ruptured and unruptured aneurysms. While the growing body of literature on fluid dynamics and aneurysm geometry has had important repercussions in designing newer treatments for intracranial aneurysms (such as flow diverters), the ever-increasing list of complex geometric factors associated with “rupture” has done little to change our decision making in patients with unruptured aneurysms or our understanding of the formation, growth, and rupture of intracranial aneurysms. A prospective study of conservatively treated unruptured aneurysms with analysis of geometric factors associated with rupture risk may provide useful information, but even such a study could be inconclusive because of the small number of end points (that is, ruptures) and the interaction with other important variables (aneurysm size, patient age, aneurysm location, and correctable risk factors for aneurysm rupture). Despite the growing body of literature on aneurysm/parent artery geometry and computational fluid analysis, the decision making in treating unruptured intracranial aneurysms continues to be based on art rather than science. (http://thejns.org/doi/abs/10.3171/2012.3.JNS112260)

Unsteady velocity measurements in a realistic intracranial aneurysm model

The initiation, growth and rupture of intracranial aneurysms are intensively studied by computational fluid dynamics. To gain confidence in the results of numerical simulations, validation of the results is necessary. To this end the unsteady flow was measured in a silicone phantom of a realistic intracranial aneurysm. A flow circuit was built with a novel unsteady flow rate generating method, used to model the idealised shape of the heartbeat. This allowed the measurement of the complex three-dimensional velocity distribution by means of laser-optical methods such as laser doppler anemometry (LDA) and particle image velocimetry (PIV). The PIV measurements, available with high temporal and spatial distribution, were found to have good agreement with the control LDA measurements. Furthermore, excellent agreement was found with the numerical results.