| Background and Objective:An intracranial aneurysm is a weakness in the wall of an artery which is thought to be caused by congenital defects in the vascular wall combined with degenerative changes that cause bulging or outpouching of an intracranial blood vessel wall and may eventually lead to rupture. It is the3rd etiological factor in cerebral vascular diseases (CVD) and is the leading cause of subarachnoid hemorrhage (SAH). The incidence of intracranial aneurysm is reported to be present in3.6%to6%of the general population, and1%-3%of them suffered from bleeding ascribed to aneurysm rupture. Both estimated initial mortality and disable rate approximately varies from22%-25%and show a rising a tendency. It is demonstrated that15%-50%of ruptured patients died at the first bleeding. The mortality would rises up to75%-85%in case of inappropriate treating or delaying. Half of the patients are severely disabled with a poor overall outcome, eating great physical and mental suffering and bearing heavy economic burden. How to accurately estimate the risk factors of aneurysm formation and rupture to guide the clinical prevention and treatment decision making is being the focus of the medical field.Regardless of large number of animal experiments and clinical studies, the pathogenesis of aneurysm formation is still unclear. The origin, growth, and configuration of intracranial aneurysms are usually influenced by multiple factors which can be summarized in congenital and acquired vascular degeneration. The degeneration of vessel structure, atherosclerosis, configuration changes of direction of flow and the variation of Circle of Willis due to the hemodynamic forces alteration and others, including trauma, infection, tumor, drug abuse, etc., are supposed to be the critical factors for intracranial aneurysm formation. Published risk factors for aneurysm rupture have been proved to be closely related to age, hypertension, aneurysm size, location and any alteration of hemodynamic forces, and so on.In recent years, many researches regarding aneurysm formation and rupture more emphasis on the cerebral vessel morphology and hemodynamic forces, using numeral simulation of computational fluid dynamics (CFD). However, digital subtraction angiograph (DSA) is incapable of detecting the hemodynamic parameters. In spite of of wide application of CFD simulation, the results are skeptical due to the ignorance of some parameters, such as flow gravity affected by aneurysm location, aneurysmal wall thickness, etc., and may result in wrong conclusion.In this term, we mainly assess the multivariate predictors of intracranial aneurysm formation and rupture by regression analysis with emphasis on the natural history of intracranial aneurysm, Al dominance, variation of Circle of Willis, aneurysm size, size ratio (SR), aneurysmal neck area/diameter of parent artery (AD), angle between A2segments of bilateral AC A, angle between aneurysmal longitudinal axis and parent artery as well as the hemodynamic forces parameters, such as wall shear stress (WSS) and mechanical stretch, using3D-DSA and TCD from the aspect of variation of Circle of Willis evaluation and hemodynamic forces alteration in order to guide the clinical prevention and treatment decision making.Section I Multivariate predictors of intracranial aneurysm formation.Objective:This section mainly involved the natural history of intracranial aneurysm using3D-DSA and TCD with emphasis on the variation of Circle of Willis evaluation and hemodynamic forces alteration, and the assessment of multivariate predictors of intracranial aneurysm formation by regression analysis for the purpose of high-risk population screening for intracranial aneurysm in the future.Methods and materials:223cases of patients with intracranial aneurysm, admitted to the Southern Medical University Zhujiang Hospital from November2010to November2011, confirmed by DSA, were selected as aneurysm group. And118patients who have a negative result checked by DSA were chosen as controls at the same period. The distribution and composition of age and gender were compared as baseline.3D-DSA images were carefully evaluated to confirm the presence of Al dominance and variation of Circle of Willis. Multivariate predictors of intracranial aneurysm formation were analyzed by using multivariate logistic regression. Variables were chosen for the model based on previously established importance in regards to the risk factors of aneurysm formation (e.g. hypertension), posing hemodynamic factors (e.g. A1dominance and variation of Circle of Willis), and epidemiological factors known to influence vascular biology that may influence aneurysm formation. Additionally, TCD was performed to patients with AcoA aneurysm which has a high morbidity and is susceptible to hemodynamic factors, and the hemodynamic parameters were record to calculate WSS and mechanical stretch. Moreover, angle between A2segments of bilateral anterior communicating artery (ACA) were measured with the assistance of3D-DSA images. The risk factors of anterior communicating artery (AcoA) aneurysm formation were analyzed by using ROC Curve and multivariate logistic regression with emphasis on the variation of Circle of Willis evaluation and hemodynamic forces alteration.Results:There is no statistically significant difference regarding to the composition of age and gender between two groups (P>0.05). However, in terms of distribution of gender and age, it is characteristic with a female predominance, accounting for58.74%(131/223). The peak incidence of aneurysms in the aneurysm group was found in patients with age over60years old, accounting for61.44%(43/118).40-60years was the second peak period, accounting for30.94%(67/118). By contrast, the incidence of aneurysms was only7.52%(8/118) in aneurysm patients with age under40years old. Whether it is in aneurysm group or in control group, the incidence rate of variation of anterior Circle of Willis was higher than those of variation of posterior Circle of Willis. A1dominance on the left side was the most common asymmetry, which also can be found in AcoA aneurysms. Gender (OR2.360,95%CI1.138～4.892, P=0.021), hypertension (grade Ⅱ)(OR3.294,95%CI1.246～8.711, P=0.016), fasting blood glucose (FBG)(6.1<FBG<11.1mmol/L)(OR63.759,95%CI2.219～20.591, P=0.001) and variation of Circle of Willis (OR27.326,95%CI9.019～82.789, P=0.000) are risk factors of intracranial aneurysm formation.Age (<40years old)(OR0.028,95%CI0.59～0.739, P=0.002) is identified as protective factors. For AcoA aneurysms, gender (OR5.067,95%CI1.011～25.403, P=0.048), hypertension (grade Ⅱ)(OR6.6734,95%CI1.023～43.501, P=0.047), variation of Circle of Willis (OR14.152,95%CI1.006～199.012, P=0.049), Al dominance (OR25.048,95%CI1.438～436.337, P=0.027) are risk factors of AcoA aneurysm formation. Diabetes (FBG at the normal level)(OR0.061,95%CI0.005～0.689, P=0.024), WSS (OR0.053,95%CI0.011～0.249, P=0.000), angle between A2segments of bilateral ACA (OR0.037,95%CI0.007～0.211, P=0.000) are identified as protective factors. Age, angle between A2segments of bilateral ACA and WSS have a great value for evaluating probability of AcoA aneurysm formation. The closer to62.50years old of age, the angle between A2segments of bilateral ACA close to104.9250degrees and the WSS close to9.3050dyn/cm2, the greater the probability of harboring AcoA aneurysm.Conclusion:Whether it is in aneurysm group or in control group, the incidence rate of variation of anterior Circle of Willis was higher than those of variation of posterior Circle of Willis. A１dominance on the left side was the most common asymmetry, indicating the left A1dominance tendency. Gender, hypertension (grade Ⅱ), FBG (6.1<FBG<11.1mmol/L) and the variation of Circle of Willis are risk factors of intracranial aneurysm formation. Person who is under40years old has the very low probability of harboring intracranial aneurysm.For AcoA aneurysms, gender, hypertension (grade Ⅱ), the variation of Circle of Willis, Al dominance are risk factors of AcoA aneurysm formation. Diabetes (FBG at the normal level), WSS, angle between A2segments of bilateral ACA are identified as protective factors. Age. angle between A2segments of bilateral ACA and WSS have the positive correlation with probability of harboring AcoA aneurysm. Section ⅡEffect of variation of Circle of Willis and hemodynamic forces alteration on the intracranial aneurysm rupture.Objective:This section mainly focus on the effect of variation of Circle of Willis and hemodynamic forces alteration on the intracranial aneurysm rupture, using3D-DSA and TCD detection, and the assessment of multivariate predictors of intracranial aneurysm rupture by regression analysis for the purpose of guiding the clinical prevention and treatment decision making in the future.Methods and materials:223cases of patients with intracranial aneurysm, admitted to the Southern Medical University Zhujiang Hospital from November2010to November2011, confirmed by DSA, were divided into ruptured aneurysm group (182cases) and unruptured aneurysm group (41cases).3D-DSA was applied to all patients to carefully evaluate aneurysm size, location, morphous feature, and to confirm the presence of Al dominance and variation of Circle of Willis. Moreover, aneurysmal neck area, diameter of parent artery, angle between A2segments of bilateral ACA, angle between aneurysmal longitudinal axis and parent artery, SR and AD were measured with the assistance of3D-DSA images. Besides, TCD was applied to all patients, and the hemodynamic parameters were record to calculate WSS and mechanical stretch. The risk factors of intracranial aneurysm rupture were analyzed by using ROC Curve and multivariate logistic regression with emphasis on the variation of Circle of Willis evaluation and hemodynamic forces alteration.Results:There is no statistically significant difference regarding to the gender composition between two groups (P>0.05). However, in terms of frequency of gender, it is characteristic with a female predominance, accounting for60.99%(111/182). There is a statistically significant difference regarding to the age composition between two groups (P<0.01). In terms of frequency of age, the peak incidence of ruptured aneurysms in ruptured aneurysm group was found in patients with age over60years old, accounting for67.03%(122/182).40-60years was the second peak period, accounting for26.92%(49/182). By contrast, the incidence of ruptured aneurysms was only6.04%(11/182) in ruptured aneurysm group with age under40years old. Besides, there is no statistically significant difference regarding to the aneurysm size, location and morphous feature between two groups (P>0.05, P>0.05, P>0.05). However, in terms of frequency of aneurysm size, location and morphous in all ruptured aneurysms, middle-sized aneurysms (6-15mm) were the most common size, accounting for52.20%(95/182), small aneurysms (2-5mm) were the second common size, accounting for20.88%(38/182). By contrast, giant aneurysms were only8.79%(16/182). AcoA aneurysms were the most common type, accounting for35.71%(65/182), posterior communicating artery (PcoA) aneurysms were the second common type, accounting for28.02%(51/182), and ACA aneurysms was only2.75%(5/182). AcoA aneurysms were the most common type, accounting for35.71%(65/182), posterior communicating artery (PcoA) aneurysms were the second common type, accounting for28.02%(51/182), and ACA aneurysms was only2.75%(5/182). The morphous feature is characteristic with regular shape predominance, accounting for78.02%(142/182). The remaining has an irregular shape, accounting for21.98%(40/182). Whether it is in ruptured aneurysm group or in unruptured aneurysm group, the incidence rate of variation of anterior Circle of Willis was higher than those of variation of posterior Circle of Willis. A1dominance on the left side was the most common asymmetry, which also can be found in AcoA aneurysms. Age (OR8.618,95%CI2.866～25.917, P=0.000), hypertension (grade Ⅲ)(OR16.320,95%CI1.628～163.556, P=0.018), angle between aneurysmal longitudinal axis and parent artery (OR3.053,95%CI1.131-8.242, P=0.028), AD (OR5.638,95%CI1.507～20.251, P=0.008) and mechanical stretch (OR4.230,95%CI1.554～11.516, P=0.000) are risk factors of intracranial aneurysm rupture. A1dominance (OR0.242,95%CI0.074～0.785, P=0.018), small aneurysms (2-5mm)(OR0.207,95%CI0.054～0.788, P=0.002) and WSS (OR0.021,95%CI0.060～0.672, P=0.009) are identified as protective factors. Age, AD, angle between aneurysmal longitudinal axis and parent artery, mechanical stretch and WSS have, a great value for evaluating the high risk of intracranial aneurysm rupture. The closer to62.50years old of age, the angle between aneurysmal longitudinal axis and parent artery close to114.9350degrees, mechanical stretch close to3.5750dyn/cm2, the greater the probability of intracranial aneurysm rupture. However, the WSS close to9.3050dyn/cm2, the lower the probability of intracranial aneurysm rupture.For AcoA aneurysms, female patient is apt to rupture. WSS (P=0.023), angle between A2segments of bilateral ACA (P=0.008), age (P=0.020), angle between aneurysmal longitudinal axis and parent artery (P=0.015) and mechanical stretch (P=0.017) have a great value for evaluating the high risk of AcoA aneurysm rupture. The WSS close to11.2350dyn/cm2, the angle between A2segments of bilateral ACA close to106.3350degree, the lower the probability of AcoA aneurysm rupture. However, the closer to62.50years old of age, angle between aneurysmal longitudinal axis and parent artery close to108.9250degree and the mechanical stretch close to3.5750dyn/cm2, the greater the probability of AcoA aneurysm rupture.Conclusion:Whether it is in ruptured aneurysm group or in unruptured aneurysm group, the incidence rate of variation of anterior Circle of Willis was higher than those of variation of posterior Circle of Willis. A1dominance on the left side was the most common asymmetry, indicating the left A1dominance tendency. Intracranial aneurysm rupture is usually influenced by multiple factors. Age, hypertension (grade Ⅲ), angle between aneurysmal longitudinal axis and parent artery, AD and mechanical stretch are risk factors of intracranial aneurysm rupture. Al dominance, small aneurysms (2-5mm) and WSS are identified as protective factors. Age, AD, angle between aneurysmal longitudinal axis and parent artery and mechanical stretch have the positive correlation with high risk of intracranial aneurysm rupture. Oppositely, WSS has the negative correlation with high risk of intracranial aneurysm rupture. For AcoA aneurysm, female patient is apt to rupture. WSS and angle between A2segments of bilateral ACA have the negative correlation with high risk of AcoA aneurysm rupture. However, age, angle between aneurysmal longitudinal axis and parent artery and mechanical stretch have the positive correlation with high risk of AcoA aneurysm rupture.Angle between A2segments of bilateral ACA has a great value for both evaluating the probability of harboring AcoA aneurysm and high risk of AcoA aneurysm rupture. Angle between A2segments of bilateral ACA ranged from104.9250～106.3350degree is the overlapping region. Both of the high probability of harboring aneurysm and high risk of aneurysm rupture are presumed in this overlapping region which we called it as the relative dangerous area. Similarly, WSS also has a great value for both evaluating the probability of harboring AcoA aneurysm and high risk of AcoA aneurysm rupture. WSS ranged from9.3050～11.2350dyn/cm2degree is the overlapping region. In this overlapping region, both of the high probability of harboring aneurysm and high risk of aneurysm rupture are presumed which we called it as the relative dangerous area. |
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