Intracranial Aneurysm Wall Research Articles

Macrophage Infiltration in the Saccular Intracranial Aneurysm Wall as a Response to Locally Lysed Erythrocytes That Promote Degeneration.

Saccular intracranial aneurysm (sIA) rupture is often fatal. Rupture-prone sIA walls are infiltrated by macrophages expressing hemoglobin-receptor CD163, suggesting a role for erythrocyte lysis in the degenerative remodeling predisposing to rupture. We therefore studied erythrocyte remnants in 16 unruptured and 20 ruptured sIA walls using histology and immunohistochemistry. Glycophorin A (GPA), an erythrocyte membrane protein, was present in 34/36 (94%) sIA walls and correlated with loss of αSMA+ cells, reflecting loss of mural smooth muscle cells ([SMCs]; r = -0.592, p < 0.001), wall degeneration (p = 0.008), and rupture (p = 0.005). GPA correlated with high numbers of CD163+ and CD68+ phagocytes (r = 0.65 and r = 0.54, p ≤ 0.001 for both). CD163+ phagocytes were mostly HLA-DR-. Interestingly, single SMCs expressed HLA-DR and also CD163 was expressed in sporadic SMCs, which may reflect their response to hemoglobin accumulation. GPA associated with iron (p = 0.014) was detectable by MRI. An additional 11 sIAs were therefore imaged ex vivo with a 4.7 T MRI prior to histology. In the sIA walls, high GPA and iron accumulation associated with signal intensity in T1-weighted gradient echo MRI. We conclude that accumulation of lysed erythrocytes is a potential driver of inflammatory response in the sIA walls and is associated with the degenerative wall remodeling, thereby predisposing to rupture.

Intracranial Aneurysm Wall Enhancement Associated with Aneurysm Rupture: A Systematic Review and Meta-analysis

Aneurysm wall enhancement (AWE) on magnetic resonance vessel wall imaging has been proposed as an imaging marker of aneurysm wall inflammation and instability. We performed a systematic review and meta-analysis to summarize the association between AWE and aneurysm rupture. We performed a comprehensive literature search of studies evaluating the association between AWE and aneurysm rupture. We abstracted the following study data: study design, patient demographics, aneurysm characteristics, MRI protocols, and AWE assessment. We performed meta-analysis using a random-effects model. Study heterogeneity was assessed by using the Cochrane Q and I2 statistic, and publication bias was examined by using the Begg-Mazumdar test. Five studies with 492 subjects met eligibility for systematic review. We found a significant positive overall association between AWE and aneurysm rupture, with an odds ratio (OR) of 34.26 (95% confidence interval [CI] 10.20-115.07, p < 0.001). No significant heterogeneity (Q = 5.38, p = 0.25; I2 = 26%) or publication bias (p = 1.000) was present. In the separate analysis of circumferential AWE and aneurysm rupture, we identified marked heterogeneity across studies (Q = 21.23, p < 0.001; I2 = 86%). Further subgroup analysis considering the effect of aneurysm size showed that the strength of association between circumferential AWE and aneurysm rupture was significant in small aneurysms (<7 mm), with an OR of 26.12 (95% CI 6.11-111.75, p < 0.001), but limited in large aneurysms (OR = 0.56, 95% CI [0.21, 1.44], p = 0.23). AWE on magnetic resonance vessel wall imaging is significantly and independently associated with aneurysm rupture and may become a promising imaging marker to predict aneurysm behavior and identify high-risk aneurysms.

Myeloperoxidase Associates With Degenerative Remodeling and Rupture of the Saccular Intracranial Aneurysm Wall

Rupture of a saccular intracranial aneurysm (sIA) is often fatal. Thus, early detection of rupture-prone sIAs is vital. Myeloperoxidase (MPO), derived mainly from neutrophils, associates with sIA rupture, and therefore its role in sIA pathogenesis warrants further studies. We analyzed MPO and its association with other histological markers in 36 (16 unruptured and 20 ruptured) sIA samples by immunohistochemistry. MPO was present in all studied sIAs, and its expression associated with wall inflammatory cell infiltrations (r = 0.50, 0.63, and 0.75, all p ≤ 0.002), degenerative remodeling (p = 0.002) and rupture (p = 0.003). MPO associated strongly with the presence of organized luminal thrombi (p < 0.001), which also stained positive for MPO. Polymorphonuclear MPO+ cells were detected in the sIA walls, indicating neutrophils as MPO-source. MPO correlated strongly with accumulation of oxidized lipids (r = 0.67, p < 0.001) and loss of smooth muscle cells (r = -0.68, p < 0.001), suggesting that MPO is a relevant source of oxidative stress leading to cell death in the sIA wall. Furthermore, MPO associated with erythrocyte fragmentation (r = 0.74, p < 0.001) and iron deposition (p = 0.041), 2 outcomes known to amplify MPO-dependent oxidative stress. Taken together, these results suggest that MPO associates with degenerative remodeling predisposing to sIA wall rupture and may serve as a biomarker of a rupture-prone sIA wall.

Abstract 167: 4D Flow MRI in Patients With Intracranial Aneurysms: a Comparative Analysis Between Evolving vs. Stable Aneurysms

Purpose: Hemodynamic factors may play an important role in the initiation and growth of intracranial aneurysms (IA). In this study we sought to characterize the hemodynamic flow characteristics of evolving aneurysms and compare them against a cohort of patients with stable aneurysms using 4D-flow MRI. Methods: From our institution registry of untreated IA, 10 patients who had evolving aneurysm (defined as interval change in size or morphometry i.e. new lobulation, daughter sac, irregular wall) and 10 patients whose aneurysms remained completely stable during their sequential surveillance imaging were identified. These patients prospectively underwent a dedicated MR imaging protocol encompassing MRA, vessel wall imaging and 4D-flow using a 3T MR scanner (GE MR750). 4D-flow data was processed using Arterys software (San Francisco, CA) and hemodynamic parameters including flow velocity, peak wall-shear stress (WSS), flow eccentricity and flow-jet angle in each aneurysm were obtained. The associations of flow parameters and commonly used clinical variables and risk factors, size and morphometric features were assessed using univariate and multivariate analyses in evolving vs. stable IAs. Results: There was no significant difference between two groups in regards to age, sex, IA-size, aspect-ratio and size-ratio. The mean, IQR of aneurysm size were 5.4, 3.7-6.7mm in stable and 4.9, 3.5-6 mm in evolving IAs. The mean follow-up time was comparable (43 months in stable and 51 months in evolving IAs, p=0.58). The frequency of IA wall enhancement was higher in evolving IAs (70%) than stable IAs (30%), without statistical significance (p=0.09). The mean ± SD of flow parameters in evolving vs. stable IAs were: peak-WSS: 68.1 ± 18.3 cPa vs. 49.2 ± 17.2 cPa, p=0.04; flow eccentricity: 0.27 ± 0.13 vs. 0.15 ± 0.05, p=0.03; and flow-jet angle: 76.9 ±13.4° vs. 61 ±17.5°, p=0.05. After controlling for clinical and morphometric variables, multivariate logistic regression analysis identified Peak-WSS and flow eccentricity as independent predictors of evolving IAs. Conclusion: 4D-flow MRI-derived peak WSS and flow eccentricity may help distinguish evolving from stable IAs independent of commonly used size and morphometric features.

Imaging mass spectroscopy delineates the thinned and thickened walls of intracranial aneurysms

ObjectThe wall thickness of intracranial aneurysms (IAs) is heterogeneous. Although thinning of the IA wall is thought to contribute to IA rupture, the underlying mechanism remains poorly understood. Recently, imaging mass spectroscopy (IMS) has been used to reveal the distribution of phospholipids in vascular diseases. To investigate the feature of phospholipid composition of IA walls, we conducted IMS in a rat model of experimentally induced IA. Material and methodsIAs were surgically induced in 7-week-old male rats and analyzed by IMS in negative-ion mode. ResultsA molecule at m/z 885.5 was more abundant in the thickened wall than in the thinned wall (P = 0.03). Multiple-stage mass spectroscopy revealed the molecule to be phosphatidylinositol containing stearic acid and arachidonic acid (PI 18:0/20:4). Immunohistochemistry indicated that vascular smooth muscle cells (SMCs) in the thickened wall had dedifferentiated phenotypes. To investigate the relationship between accumulation of PI (18:0/20:4) and phenotypic changes in SMCs, we subjected primary mouse aortic SMCs to liquid chromatography–tandem mass spectrometry. Notably, dedifferentiated SMCs had 1.3-fold more PI (18:0/20:4) than partly differentiated SMCs. ConclusionsOur study demonstrated the heterogeneity in phospholipid composition of the aneurysmal walls using experimentally induced IAs. PI (18:0/20:4) accumulated at high levels in the thickened aneurysmal wall where synthetic dedifferentiated SMCs exist, suggesting that this phospholipid may be involved in the phenotypic switching of medial SMCs in the IA wall.

Recurrence of endovascularly and microsurgically treated intracranial aneurysms-review of the putative role of aneurysm wall biology.

Although endovascular therapy has been proven safe and has become in many centers the primary method of treatment for intracranial aneurysms, the long-term durability of endovascular embolization remains a concern; at least for some aneurysms despite initial good result. While healing after clipping relies on mechanical occlusion, restoration after endovascular occlusion mainly requires the induction of a biological response. Healing after embolization depends on the growth of new tissue over the thrombus formed by the embolization material, or alternatively, on the organization of thrombus into fibrous tissue. This review highlights the fundamental importance of aneurysm wall biology on the healing process and long-term occlusion after intracranial aneurysm (IA) treatment. It seems likely that the effect of luminal thrombus on the IA wall, as well as the IA wall condition at the time of thrombosis, determine if thrombus organizes into scar tissue (neointima formation by infiltration of cells originating from the IA wall) or if the wall undergoes continuous remodeling, which is primarily destructive (loss of mural cells). In the latter, intraluminal thrombus organization fails and the impaired healing increases the chance of recurrence. Mechanisms underlying IA reopening, the influence of intraluminal thrombosis on the IA wall, and clinical implications of the IA wall condition are discussed in detail, along with how knowledge of IA wall biology can offer new solutions for IA treatment and affect the patient selection for and follow-up after endovascular treatment.

T cell function is dispensable for intracranial aneurysm formation and progression.

Given the social importance of intracranial aneurysm as a major cause of a lethal subarachnoid hemorrhage, clarification of mechanisms underlying the pathogenesis of this disease is essential for improving poor prognosis once after rupture. Previous histopathological analyses of human aneurysm walls have revealed the presence of T cells in lesions suggesting involvement of this type of cell in the pathogenesis. However, it remains unclear whether T cell actively participates in intracranial aneurysm progression. To examine whether T cell is involved in aneurysm progression, intracranial aneurysm model of rat was used. In this model, aneurysm is induced by increase in hemodynamic force loaded on bifurcation site of intracranial arteries where aneurysms are developed. Deficiency in T cells and pharmacological inhibition of T cell function were applied to this model. CD3-positive T cells were present in human aneurysm walls, whose number was significantly larger compared with that in control arterial walls. Deficiency in T cells in rats and pharmacological inhibition of T cell function by oral administration of Cyclosporine A both failed to affect intracranial aneurysm progression, degenerative changes of arterial walls and macrophage infiltration in lesions. Although T cells are detectable in intracranial aneurysm walls, their function is dispensable for macrophage-mediated inflammation and degenerative changes in arterial walls, which presumably leads to intracranial aneurysm progression.

Association between hemodynamics, morphology, and rupture risk of intracranial aneurysms: a computational fluid modeling study

The objective of the study was to examine the correlations between intracranial aneurysm morphology and wall shear stress (WSS) to identify reliable predictors of rupture risk. Seventy-two intracranial aneurysms (41 ruptured and 31 unruptured) from 63 patients were studied retrospectively. All aneurysms were divided into two categories: narrow (aspect ratio ≥1.4) and wide-necked (aspect ratio <1.4 or neck width ≥4 mm). Computational fluid dynamics was used to determine the distribution of WSS, which was analyzed between different morphological groups and between ruptured and unruptured aneurysms. Sections of the walls of clipped aneurysms were stained with hematoxylin–eosin, observed under a microscope, and photographed. Ruptured aneurysms were statistically more likely to have a greater low WSS area ratio (LSAR) (P = 0.001) and higher aneurysms parent WSS ratio (P = 0.026) than unruptured aneurysms. Narrow-necked aneurysms were statistically more likely to have a larger LSAR (P < 0.001) and lower values of MWSS (P < 0.001), mean aneurysm-parent WSS ratio (P < 0.001), HWSS (P = 0.012), and the highest aneurysm-parent WSS ratio (P < 0.001) than wide-necked aneurysms. The aneurysm wall showed two different pathological changes associated with high or low WSS in wide-necked aneurysms. Aneurysm morphology could affect the distribution and magnitude of WSS on the basis of differences in blood flow. Both high and low WSS could contribute to focal wall damage and rupture through different mechanisms associated with each morphological type.

Growth of giant intracranial aneurysms: An aneurysmal wall disorder?

The enlargement of giant intracranial aneurysms (IA) can be observed in 30 % of cases resulting in a neurological deficit and epilepsy due to its mass effect. This growth process could be due to a morphological disorder of the IA wall. The authors report on 2 cases of giant IA growth responsible for intracranial hypertension. The treatment of these giant IA required a microsurgical excision combined with a series of cerebral revascularization procedures. The role of vasa vasorum on the inflammatory granuloma outside the vessel, which induced the enlargement, is discussed. These cases illustrate the abluminal vasculopathy as the main involvement of this unfavourable natural history.

Research of vascular smooth muscle cell proliferation activity of intracranial aneurysms in spontaneously hypertensive rats

Objective To investigate the proliferative activity of vascular smooth muscle cell (VSMC) in the formation of intracranial aneurysm (IA) in spontaneously hypertensive rats (SHR). Methods A total of 180 adult male rats were randomly divided into 6 groups including the control, 1-, 2-, 3-, 4- and 5-month experiment groups (n = 30 in each group). In the 5 experiment groups, the left common carotid artery and posterior branches of both renal arteries of rats were ligated to establish the rat model of spontaneous hypertensive intracranial aneurysms. The arterial blood pressure of the rats in each group was measured, and intracranial arteries were examined with MRA to observe the formation of IAs in rats. The specimens of aneurysms were obtained and morphological changes of IA were observed by HE staining. The expression of proliferating cell nuclear antigen (PCNA) of IA wall in each group was explored with immunohistochemistry. Apoptosis of IA wall VSMC was detected with the method of TUNEL.The protein levels of α-smooth muscle actin (α-SMA), β-tubulin and osteopontin (OPN) in IA wall were detected by Western blot. The mRNA relative levels of SM22α and hypertension-related gene (HRG-1) were tested with quantitative real-time PCR. Results Compared with controls, in experimental groups, the blood pressure of SHR was significantly increased after operation (all P<0.05). Intracranial aneurysms could be observed in 4-month and 5-month experiment groups.The expressions of PCNA were significantly increased, reached the highest levels in the 4-month group, and began to decrease in the 5-month group. The percentage of apoptosis of VSMC of aneurysm wall in the experimental groups was increased significantly.In experimental groups, levels of α-SMA and β-tubulin expression were significantly decreased(all P<0.05). The expression levels of OPN were increased gradually, reached the highest levels in the 4-month group, and began to decrease in the 5-month group. SM22α and HRG-1 mRNA expressions were gradually decreased(all P<0.05). Conclusions In the process of IA formation, the aneurysm wall VSMCs demonstrate proliferation activity; and the formation of IA seems to be closely related to the weakening of proliferation activity and number decrease of aneurysmal wall VSMCs. Key words: Intracranial aneurysm; Cell proliferation; Apoptosis; Rats, spontaneously hypertensive; Vascular smooth muscle cell

Flow Conditions in the Intracranial Aneurysm Lumen Are Associated with Inflammation and Degenerative Changes of the Aneurysm Wall.

Saccular intracranial aneurysm is a common disease that may cause devastating intracranial hemorrhage. Hemodynamics, wall remodeling, and wall inflammation have been associated with saccular intracranial aneurysm rupture. We investigated how saccular intracranial aneurysm hemodynamics is associated with wall remodeling and inflammation of the saccular intracranial aneurysm wall. Tissue samples resected during a saccular intracranial aneurysm operation (11 unruptured, 9 ruptured) were studied with histology and immunohistochemistry. Patient-specific computational models of hemodynamics were created from preoperative CT angiographies. More stable and less complex flows were associated with thick, hyperplastic saccular intracranial aneurysm walls, while slower flows with more diffuse inflow were associated with degenerated and decellularized saccular intracranial aneurysm walls. Wall degeneration (P = .041) and rupture were associated with increased inflammation (CD45+, P = .031). High wall shear stress (P = .018), higher vorticity (P = .046), higher viscous dissipation (P = .046), and high shear rate (P = .046) were associated with increased inflammation. Inflammation was also associated with lack of an intact endothelium (P = .034) and the presence of organized luminal thrombosis (P = .018), though overall organized thrombosis was associated with low minimum wall shear stress (P = .034) and not with the flow conditions associated with inflammation. Flow conditions in the saccular intracranial aneurysm are associated with wall remodeling. Inflammation, which is associated with degenerative wall remodeling and rupture, is related to high flow activity, including elevated wall shear stress. Endothelial injury may be a mechanism by which flow induces inflammation in the saccular intracranial aneurysm wall. Hemodynamic simulations might prove useful in identifying saccular intracranial aneurysms at risk of developing inflammation, a potential biomarker for rupture.

RNA Sequencing Analysis of Intracranial Aneurysm Walls Reveals Involvement of Lysosomes and Immunoglobulins in Rupture.

Analyzing genes involved in development and rupture of intracranial aneurysms can enhance knowledge about the pathogenesis of aneurysms, and identify new treatment strategies. We compared gene expression between ruptured and unruptured aneurysms and control intracranial arteries. We determined expression levels with RNA sequencing. Applying a multivariate negative binomial model, we identified genes that were differentially expressed between 44 aneurysms and 16 control arteries, and between 22 ruptured and 21 unruptured aneurysms. The differential expression of 8 relevant and highly significant genes was validated using digital polymerase chain reaction. Pathway analysis was used to identify enriched pathways. We also analyzed genes with an extreme pattern of differential expression: only expressed in 1 condition without any expression in the other. We found 229 differentially expressed genes in aneurysms versus controls and 1489 in ruptured versus unruptured aneurysms. The differential expression of all 8 genes selected for digital polymerase chain reaction validation was confirmed. Extracellular matrix pathways were enriched in aneurysms versus controls, whereas pathways involved in immune response and the lysosome pathway were enriched in ruptured versus unruptured aneurysms. Immunoglobulin genes were expressed in aneurysms, but showed no expression in controls. For rupture of intracranial aneurysms, we identified the lysosome pathway as a new pathway and found further evidence for the role of the immune response. Our results also point toward a role for immunoglobulins in the pathogenesis of aneurysms. Immune-modifying drugs are, therefore, interesting candidate treatment strategies in the prevention of aneurysm development and rupture.

Thinner Regions of Intracranial Aneurysm Wall Correlate with Regions of Higher Wall Shear Stress: A 7T MRI Study.

Both hemodynamics and aneurysm wall thickness are important parameters in aneurysm pathophysiology. Our aim was to develop a method for semi-quantitative wall thickness assessment on in vivo 7T MR images of intracranial aneurysms for studying the relation between apparent aneurysm wall thickness and wall shear stress. Wall thickness was analyzed in 11 unruptured aneurysms in 9 patients who underwent 7T MR imaging with a TSE-based vessel wall sequence (0.8-mm isotropic resolution). A custom analysis program determined the in vivo aneurysm wall intensities, which were normalized to the signal of nearby brain tissue and were used as measures of apparent wall thickness. Spatial wall thickness variation was determined as the interquartile range in apparent wall thickness (the middle 50% of the apparent wall thickness range). Wall shear stress was determined by using phase-contrast MR imaging (0.5-mm isotropic resolution). We performed visual and statistical comparisons (Pearson correlation) to study the relation between wall thickness and wall shear stress. 3D colored apparent wall thickness maps of the aneurysms showed spatial apparent wall thickness variation, which ranged from 0.07 to 0.53, with a mean variation of 0.22 (a variation of 1.0 roughly means a wall thickness variation of 1 voxel [0.8 mm]). In all aneurysms, apparent wall thickness was inversely related to wall shear stress (mean correlation coefficient, -0.35; P < .05). A method was developed to measure the wall thickness semi-quantitatively, by using 7T MR imaging. An inverse correlation between wall shear stress and apparent wall thickness was determined. In future studies, this noninvasive method can be used to assess spatial wall thickness variation in relation to pathophysiologic processes such as aneurysm growth and rupture.

Detection of wall and neck calcification of unruptured intracranial aneurysms with flat-detector computed tomography.

Microsurgical clipping is a widely used surgical technique in intracranial aneurysm treatment. It can be difficult in large sized aneurysms, and those with wide necks, thick walls and calcification located in the vicinity of the neck. This study reviewed calcification of the intracranial aneurysm wall and its relation to patient age, gender, location and size of the aneurysm. A possible cut-off value after which the aneurysm calcification rate increases was also investigated to classify patients' risk factors for microclipping. A retrospective review of all unruptured intracranial aneurysms that underwent digital subtraction angiography at a single centre was performed. Flat-detector computed tomography images of the aneurysm were reviewed for aneurysm location, size and calcification. The independent samples t test and χ(2) test were used to show the relation between aneurysm wall calcification and patient age, gender, aneurysm localisation and size. None of the reviewed factors were statistically significantly related to aneurysm calcification except aneurysm size (P < 0.01). Receiver operating characteristic curves showed aneurysms greater than 10.5 mm could be predicted to be calcified with a sensitivity of 80% and specificity of 63%. In this study, the presence of calcification was related to aneurysm size. Larger aneurysms were more likely to be calcified. Aneurysms greater than 10.5 mm should be further investigated with a modality such as flat-detector computed tomography to show the calcification in detail, especially if microclipping is considered.

Abstract 13: Wall Shear Stress Associated to Intracranial Aneurysm Wall Inflammation

Introduction: Inflammation has been proposed as a possible mechanism involved in the degradation and weakening of the walls of intracranial aneurysms. Hypothesis: Abnormal wall shear stress (WSS) levels induce wall inflammation which then affects the wall structure and mechanics Methods: A total of 20 aneurysms which underwent surgical clipping were studied. Patient-specific computational fluid dynamics models were constructed from pre-surgical CTA images. Numerical simulations were carried out using pulsatile flows. After clipping the aneurysm, a tissue sample was resected from the dome and analyzed histologically with CD45 to search for evidence of wall inflammation. For analysis, the aneurysm series was divided in two different manners. First, aneurysms were classified into an “inflammation” group if the number of CD45+ cells was larger than the median of CD45+ cells in the entire sample of 20 aneurysms; otherwise they were classified as “no-inflammation”. Hemodynamic variables were then statistically compared between these two groups. Secondly, aneurysms were subdivided into three groups according to their mean WSS: 1) “low WSS” if WSS&lt;0.5*median(WSS), 2) “high WSS” if WSS&gt;2*median(WSS), and 3) “mid WSS” otherwise. The numbers of CD45+ cells in each group were then statistically compared. Results: Aneurysms in the “inflammation” group had significantly larger mean WSS (p=0.018), shear rate (p=0.015), vorticity (p=0.018), and viscous dissipation (p=0.015) than aneurysms in the “no-inflammation” group. Conversely, aneurysms in the “high WSS” group had significantly larger numbers of CD45+ cells (p=0.0046) than the “mid WSS” and “low WSS” groups. Interestingly, aneurysms with stable flow patterns also tended to have larger numbers of inflammatory cells (p=0.040) than aneurysms with unstable flows. Conclusion: These preliminary results suggest that there is a connection between intra-aneurysmal flow characteristics and wall inflammation in cerebral aneurysms. In particular, inflamed walls seem to be associated with higher levels of wall shear stress.

Bacterial DNA findings in ruptured and unruptured intracranial aneurysms

Objective Chronic inflammation has earlier been detected in ruptured intracranial aneurysms. A previous study detected both dental bacterial DNA and bacterial-driven inflammation in ruptured intracranial aneurysm walls. The aim of this study was to compare the presence of oral and pharyngeal bacterial DNA in ruptured and unruptured intracranial aneurysms. The hypothesis was that oral bacterial DNA findings would be more common and the amount of bacterial DNA would be higher in ruptured aneurysm walls than in unruptured aneurysm walls. Materials and methods A total of 70 ruptured (n = 42) and unruptured (n = 28) intracranial aneurysm specimens were obtained perioperatively in aneurysm clipping operations. Aneurysmal sac tissue was analysed using a real-time quantitative polymerase chain reaction to detect bacterial DNA from several oral species. Both histologically non-atherosclerotic healthy vessel wall obtained from cardiac by-pass operations (LITA) and arterial blood samples obtained from each aneurysm patient were used as control samples. Results Bacterial DNA was detected in 49/70 (70%) of the specimens. A total of 29/42 (69%) of the ruptured and 20/28 (71%) of the unruptured aneurysm samples contained bacterial DNA of oral origin. Both ruptured and unruptured aneurysm tissue samples contained significantly more bacterial DNA than the LITA control samples (p-values 0.003 and 0.001, respectively). There was no significant difference in the amount of bacterial DNA between the ruptured and unruptured samples. Conclusion Dental bacterial DNA can be found using a quantitative polymerase chain reaction in both ruptured and unruptured aneurysm walls, suggesting that bacterial DNA plays a role in the pathogenesis of cerebral aneurysms in general, rather than only in ruptured aneurysms.

Paradoxical Increase in Mortality and Rupture of Intracranial Aneurysms in Microsomal Prostaglandin E2 Synthase Type 1-Deficient Mice: Attenuation by Aspirin.

Inflammation plays an important role in formation and rupture of intracranial aneurysms. Expression of microsomal prostaglandin E2 (PGE2) synthase type 1 (mPGES-1) is increased in the wall of intracranial aneurysms in humans. PGE2, a by-product of mPGES-1, is associated with inflammation and cerebrovascular dysfunction. To test the hypothesis that deletion of mPGES-1 decreases the formation and rupture of intracranial aneurysms in a murine model. Intracranial aneurysms were induced in wild-type and mPGES-1 knockout (mPGES-1 KO) mice by using a combination of deoxycorticosterone acetate-salt-induced hypertension and intracranial injection of elastase in the basal cistern. Prevalence of aneurysms, subarachnoid hemorrhage, and mortality were assessed. We also tested the effects of administration of aspirin (6 mg/kg/d) by gavage and PGE2 (1 mg/kg/d) by subcutaneous infusion. Systolic blood pressure and prevalence of aneurysm were similar in wild-type and mPGES-1 KO mice. However, mortality and the prevalence of subarachnoid hemorrhage were markedly increased in mPGES-1 KO mice (P < .05). Bone marrow reconstitution studies suggest that mPGES-1 derived from leukocytes does not appear to increase rupture of intracranial aneurysms. Aspirin, but not PGE2, attenuated the increased mortality in mPGES-1 KO mice (P < .05). Vascular mPGES-1 plays a protective role in blood vessels and attenuates rupture of cerebral aneurysms. In contrast to effects on abdominal aneurysms, mPGES-1 deficiency is associated with an increase in rupture of cerebral aneurysms and mortality, which are attenuated by low-dose aspirin.

Apolipoproteins and lipids accumulate, become oxidatively modified, and associate with inflammation and degenerative changes of intracranial artery aneurysm walls

Aim: Saccular intracranial artery aneurysm (sIA) rupture causes subarachnoidal hemorrhage with 50% mortality. Chronic inflammation and vascular wall remodeling associate with sIA degeneration and rupture. The histopathological changes observed in sIA walls are also hallmarks of atherosclerotic plaques. We studied the role of lipoproteins, lipid accumulation, and lipid modification in sIA pathobiology.

Vascular Wall Imaging of Unruptured Cerebral Aneurysms with a Hybrid of Opposite-Contrast MR Angiography.

Inflammation and degeneration of the intracranial saccular aneurysm wall play a major role in aneurysm formation, development and subsequent rupture. The aim of this study was to characterize the walls of unruptured intracranial aneurysms by using a hybrid of opposite-contrast MRA at 3T. Fourteen consecutive patients with 17 unruptured intracranial aneurysms who initially underwent clipping surgery were prospectively evaluated. All aneurysms were scanned preoperatively by using a hybrid of opposite-contrast MRA in 3T high-resolution MR imaging. We classified intraoperative findings of atherosclerotic plaques in the aneurysms into 3 grades: grade A (major plaques), grade B (minor plaques), and grade C (no plaques). The contrast ratio of the high-intensity area was also measured relative to the background low-intensity area inside the carotid artery. Findings from preoperative plaque imaging of the aneurysm corresponded to the intraoperative findings in 15 of 16 aneurysms (excluding 1 that was impossible to visualize in its entirety due to anatomic reasons). Overall sensitivity and specificity of the hybrid of opposite-contrast MRA were 88.9% and 100%, respectively. During the operation, 4 aneurysms were classified as grade A; 5, as grade B; and 7, as grade C. The means of the contrast ratio for grades A, B, and C were 0.72 ± 0.03, 0.34 ± 0.30, and -0.02 ± 0.09, respectively. The hybrid of opposite-contrast MRA can detect visible atherosclerotic plaques in the unruptured aneurysm wall, and the contrast ratio in intracranial aneurysms correlated with their presence and extent. A study including a larger series is needed to validate the diagnostic potential of this imaging technique.

Quantifying Intracranial Aneurysm Wall Permeability for Risk Assessment Using Dynamic Contrast-Enhanced MRI: A Pilot Study.

Pathological changes in the intracranial aneurysm wall may lead to increases in its permeability; however the clinical significance of such changes has not been explored. The purpose of this pilot study was to quantify intracranial aneurysm wall permeability (K(trans), VL) to contrast agent as a measure of aneurysm rupture risk and compare these parameters against other established measures of rupture risk. We hypothesized K(trans) would be associated with intracranial aneurysm rupture risk as defined by various anatomic, imaging, and clinical risk factors. Twenty-seven unruptured intracranial aneurysms in 23 patients were imaged with dynamic contrast-enhanced MR imaging, and wall permeability parameters (K(trans), VL) were measured in regions adjacent to the aneurysm wall and along the paired control MCA by 2 blinded observers. K(trans) and VL were evaluated as markers of rupture risk by comparing them against established clinical (symptomatic lesions) and anatomic (size, location, morphology, multiplicity) risk metrics. Interobserver agreement was strong as shown in regression analysis (R(2) > 0.84) and intraclass correlation (intraclass correlation coefficient >0.92), indicating that the K(trans) can be reliably assessed clinically. All intracranial aneurysms had a pronounced increase in wall permeability compared with the paired healthy MCA (P < .001). Regression analysis demonstrated a significant trend toward an increased K(trans) with increasing aneurysm size (P < .001). Logistic regression showed that K(trans) also predicted risk in anatomic (P = .02) and combined anatomic/clinical (P = .03) groups independent of size. We report the first evidence of dynamic contrast-enhanced MR imaging-modeled contrast permeability in intracranial aneurysms. We found that contrast agent permeability across the aneurysm wall correlated significantly with both aneurysm size and size-independent anatomic risk factors. In addition, K(trans) was a significant and size-independent predictor of morphologically and clinically defined high-risk aneurysms.