Circumferential Aneurysm Wall Enhancement Research Articles

Teaching NeuroImages: High-resolution MRI before and during a sentinel headache demonstrates aneurysm wall hemorrhage

A 3T brain MRI, performed in a 48-year-old woman presenting with progressive headaches, demonstrated a 20-mm unruptured saccular basilar artery aneurysm. High-resolution vessel-wall MRI showed a chronic mural thrombus and a circumferential aneurysm wall enhancement (figure), an imaging marker of aneurysm instability.1 Two days later, she had a transient thunderclap headache, considered the worst headache she had ever reported. Repeated 3T MRI demonstrated acute mural hemorrhage without subarachnoid hemorrhage. Sentinel headaches, reported in every fourth patient preceding aneurysm rupture,2 have been interpreted as reflecting a warning for subarachnoid leak or, alternatively, structural wall changes, such as stretching or acute mural hemorrhage.

Comprehensive morphomechanical analysis of brain aneurysms.

Brain aneurysms comprise different compartments that undergo unique biological processes. A detailed multimodal analysis incorporating 3D aneurysm wall enhancement (AWE), computational fluid dynamics (CFD), and finite element analysis (FEA)data can provide insights into the aneurysm wall biology. Unruptured aneurysms were prospectively imaged with 7T high-resolution MRI (HR-MRI). 3D AWE color maps of the entire aneurysm wall were generated and co-registered with contour plots of morphomechanical parameters derived from CFD and FEA. A multimodal analysis of the entire aneurysm was performed using 3D circumferential AWE (3D-CAWE), wall tension (WT), time-averaged wall shear stress (TAWSS), wall shear stress gradient (WSSG), and oscillatory shear index (OSI). A detailed compartmental analysis of each aneurysm's dome, bleb, and neck was also performed. Twenty-six aneurysms were analyzed. 3D-CAWE + aneurysms had higher WT (p = 0.03) and higher TAWSS (p = 0.045) than 3D-CAWE- aneurysms. WT, TAWSS, and WSSG were lower in areas of focal AWE in the aneurysm dome compared to the neck (p = 0.009, p = 0.049, and p = 0.040, respectively), whereas OSI was higher in areas of focal AWE compared to the neck (p = 0.020). When compared to areas of no AWE of the aneurysm sac (AWE = 0.92 vs. 0.49, p = 0.001), blebs exhibited lower WT (1.6 vs. 2.45, p = 0.010), lower TAWSS (2.6 vs. 6.34), lower OSI (0.0007 vs. 0.0010), and lower WSSG (2900 vs. 5306). Fusiform aneurysms had a higher 3D-CAWE and WT than saccular aneurysms (p = 0.046 and p = 0.003, respectively). Areas of focal high AWE in the sac and blebs are associated with low wall tension, low wall shear stress, and low flow conditions (TAWSS and WSSG). Conversely, the neck had average AWE, high wall tension, high wall shear stress, and high flow conditions. The aneurysm dome and the aneurysm neck have different morphomechanical environments, with increased mechanical load at the neck.

Association of circumferential aneurysm wall enhancement with recurrence after coiling of unruptured intracranial aneurysms: a preliminary vessel wall imaging study.

Recent histopathological studies of unruptured intracranial aneurysms (UIAs) have confirmed that aneurysm wall enhancement (AWE) on MR vessel wall imaging (VWI) is related to wall degeneration with in vivo inflammatory cell infiltration. Therefore, pretreatment aneurysm wall status on VWI may be associated with recurrence after endovascular treatment. VWI with gadolinium was performed on 67 consecutive saccular UIAs before endovascular treatment between April 2017 and June 2021. The mean (range) follow-up period after treatment was 24.4 (6-54) months. AWE patterns were classified as circumferential AWE (CAWE), focal AWE (FAWE), and negative AWE (NAWE). The authors retrospectively investigated the relationship between aneurysm recurrence and AWE patterns, as well as conventional risk factors. Sixty-seven patients with 67 saccular UIAs were eligible for the present study. AWE patterns were as follows: 10 CAWE (14.9%), 20 FAWE (29.9%), and 37 NAWE (55.2%). Follow-up MRA detected aneurysm recurrence in 18 of 69 cases (26.1%). Univariate analysis identified maximum diameter (mean ± SD 5.8 ± 2.2 mm in patients with stable aneurysms vs 7.7 ± 3.8 mm in those with unstable aneurysms, p = 0.02), aspect ratio (1.4 ± 0.5 vs 1.1 ± 0.4, p < 0.01), aneurysm location in posterior circulation (4.1% vs 27.8%, p < 0.01), volume embolization ratio (29.6% ± 7.8% vs 25.2% ± 6.1%, p = 0.02), and AWE pattern (p = 0.04) as significant predictive factors of recurrence. Among the 3 AWE patterns, CAWE was significantly more frequent in the unstable group, but no significant differences in stability of the treated aneurysms were observed with the FAWE and NAWE patterns. In multivariate logistic regression analysis, CAWE pattern (OR 14.2, 95% CI 1.8-110.8, p = 0.01) and volume embolization ratio ≥ 25% (OR 8.6, 95% CI 2.1-34.3, p < 0.01) remained as significant factors associated with aneurysm stability after coiling. VWI before coiling provides novel insights into the stability of treated aneurysms. Aneurysms with the CAWE pattern on VWI before coiling may be less stable after treatment.

Qualitative and quantitative wall enhancement associated with unstable intracranial aneurysms: a meta-analysis.

Unstable intracranial aneurysms (UIAs) are more likely to rupture and cause serious consequences. Evaluating the stability of unruptured aneurysms facilitates clinical management stratification. To compare and evaluate the predictive performance of qualitative and quantitative wall enhancement (aneurysmal wall enhancement [AWE], circumferential aneurysmal wall enhancement [CAWE], wall enhancement ratio [WER]) on high-resolution magnetic resonance imaging (MRI) of the vessel wall to predict the presence of UIA. Original articles describing the depiction of aneurysmal wall enhancement on 3.0-T or 1.5-T high-resolution vessel wall imaging were retrieved from the Web of Science, Medline/PubMed, the Cochrane Library, and EMBASE databases up to 15 February 2022. The combined sensitivity, specificity, and summary area under the receiver operating characteristic curve (AUC) were calculated, and meta-regression analysis was performed. In total, 12 original articles involving 1619 intracranial aneurysms (IAs) were included. The combined sensitivity and specificity of AWE, CAWE, and WER were 91% and 67%, 59% and 83%, and 86% and 75%, respectively, in the diagnosis of UIA. The summary AUC values of these items were, in order from high to low, 0.88 (WER), 0.84 (AWE), and 0.77 (CAWE), and the differences among them were significant (z = 2.976, P = 0.003 and z = 2.950, P = 0.003). The meta-regression analysis identified average size and 2D/3D magnetic imaging technology as possible sources of heterogeneity. Qualitative and quantitative wall enhancement showed moderate accuracy in predicting UIA, and WER had the highest accuracy among them in this meta-analysis. Two covariates were found to explain the heterogeneity.

Neutrophil-to-Lymphocyte Ratio Is Associated With Circumferential Wall Enhancement of Unruptured Intracranial Aneurysm

Background and PurposeNeutrophil-lymphocyte ratio (NLR) predicts clinical outcomes in patients with stroke. Aneurysm wall enhancement (AWE) on high-resolution vessel wall magnetic resonance imaging (HR-VWI) is an inflammation marker for intracranial aneurysm (IA). This study aims to evaluate the association of NLR as a peripheral blood inflammatory marker with circumferential AWE in patients with IA.MethodsWe analyzed data of consecutive patients harboring IAs between September 2017 and December 2021 at our institution. The peripheral blood inflammatory indicators were compared between patients with ruptured and unruptured IAs. The presence of circumferential AWE in unruptured IA was identified and quantitatively measured using the aneurysm-to-pituitary stalk contrast ratio (CRstalk) on HR-VWI. We used the optimal cutoff value of 0.5 for CRstalk to differentiate circumferential AWE in unruptured IAs. We assessed the relationship of clinical, laboratory, and radiological characteristics with circumferential AWE and CRstalk ≥0.5 in unruptured IAs.ResultsThe study group was composed of one hundred and twenty-five patients with 142 IAs. NLR level at admission was significantly higher in patients with ruptured IAs than those with unruptured IAs (7.55 vs. 1.81; P < 0.001). AWE on HR-VWI was present in 30 patients with unruptured IAs (38.5%), including 12 with focal AWE and 18 with circumferential AWE. NLR (odds ratio (OR), 2.168; 95% CI, 1.149–4.088) and size (odds ratio, 1.370; 95% CI, 1.126–1.667) were independently associated with circumferential AWE in unruptured IA. NLR was also independently associated with circumferential AWE in small unruptured IA (<7 mm). Furthermore, NLR level at admission was associated with CRstalk ≥.5 in patients with unruptured IA. The optimal cutoff value of NLR for circumferential AWE was 1.86.ConclusionNLR is a valuable peripheral blood inflammatory marker is more often in the rupture status of IA and was associated with circumferential AWE on HR-VWI in unruptured IA.

Circumferential wall enhancement with contrast ratio measurement in unruptured intracranial aneurysm for aneurysm instability.

BackgroundAneurysm wall enhancement on high‐resolution vessel wall imaging (HR‐VWI) may represent vessel wall inflammation for unruptured intracranial aneurysms (UIAs). Further evidence for the role of circumferential aneurysm wall enhancement (CAWE) in evaluating the instability of UIAs is required, especially in small aneurysms (<7 mm).MethodsWe analyzed patients with saccular UIAs who prospectively underwent HR‐VWI on a 3.0 T MRI scanner in our center from September 2017 to August 2021. The presence of AWE was identified and quantitatively measured using the aneurysm‐to‐pituitary stalk contrast ratio (CRstalk) with maximal signal intensity value. The PHASES and ELAPSS scores were used to assess the risk of aneurysm rupture and growth. We evaluated the association of CAWE and CRstalk value with intracranial aneurysm instability.ResultsOne hundred patients with 109 saccular UIAs were included in this study. Eighty‐three UIAs (76.1%) had a size smaller than 7 mm. PHASES and ELAPSS scores were significantly higher in UIAs with CAWE than in UIAs without CAWE (p < .01). The association of CAWE with PHASES and ELAPSS scores remained in small UIAs (<7 mm). The optimal cutoff value of CRstalk for CAWE was 0.5. PHASES and ELAPSS scores were significantly higher in UIAs with CRstalk ≥0.5 than in UIAs with CRstalk <0.5 (p < .01).ConclusionsCAWE on HR‐VWI is a valuable imaging marker for aneurysm instability in UIAs. CRstalk value ≥0.5 may be associated with a higher risk of intracranial aneurysm rupture and growth.

Segmentation of aneurysm wall enhancement in evolving unruptured intracranial aneurysms.

Morphological changes in unruptured intracranial aneurysms (UIAs) are an imaging marker of aneurysm instability. Recent studies have indicated the ability of MR vessel wall imaging (VWI) to stratify unstable UIAs based on a correlation with histopathological aneurysm wall inflammation. In the present study the authors investigated the relationships between aneurysm growth patterns and the segmentation of aneurysm wall enhancement (AWE) in VWI. A total of 120 aneurysms with serial angiography from a follow-up period of at least 2 years (mean 65 months, range 24-215 months) were assessed by VWI. Two readers independently evaluated the patterns of morphological changes (stable, whole sac expansion, and secondary aneurysm formation) and the segmentation of AWE (no, focal, and circumferential AWE). The contrast enhancement ratio of the aneurysm wall versus the pituitary stalk (CRstalk) was calculated for the quantitative assessment of AWE. Statistical analyses were performed to investigate the relationships between AWE patterns and patient baseline profiles, aneurysm characteristics, and morphological modifications. Forty-one of 120 UIAs (34%) exhibited aneurysm growth (whole sac expansion in 19 and secondary aneurysm formation in 22). AWE was detected in 35 of 120 UIAs (focal AWE in 25 and circumferential AWE in 10). The maximum diameter of, irregularities in, and morphological modifications in aneurysms were associated with the segmentation of AWE. Focal AWE correlated with secondary aneurysm formation, and circumferential AWE correlated with whole sac expansion. In focal AWE, CRstalk was significantly higher in secondary aneurysm formation than in stable UIAs. UIAs without AWE (categorized as no AWE) correlated with aneurysm stability. The segmentation of AWE was associated with aneurysm growth scenarios and may provide a novel insight into the evaluation of unstable UIAs.

Associations between haemodynamics and wall enhancement of intracranial aneurysm

Background and purposePrevious studies have reported about inflammation processes (IPs) that play important roles in aneurysm formation and rupture, which could be driven by blood flow. IPs can be identified...

Aneurysm Wall Enhancement in Unruptured Intracranial Aneurysms: A Histopathological Evaluation.

BackgroundUnruptured intracerebral aneurysm wall enhancement (AWE) on vessel wall magnetic resonance imaging scans may be a promising predictor for rupture‐prone intracerebral aneurysms. However, the pathophysiology of AWE remains unclear. To this end, the association between AWE and histopathological changes was assessed in this study.Methods and ResultsA total of 35 patients with 41 unruptured intracerebral aneurysms who underwent surgical clipping were prospectively enrolled. A total of 27 aneurysms were available for histological evaluation. The macroscopic and microscopic features of unruptured intracerebral aneurysms with and without enhancement were assessed. The microscopic features studied included inflammatory cell invasion and vasa vasorum, which were assessed using immunohistochemical staining with CD68, CD3, CD20, and myeloperoxidase for the former and CD34 for the latter. A total of 21 (51.2%) aneurysms showed AWE (partial AWE, n=7; circumferential AWE, n=14). Atherosclerotic and translucent aneurysms were identified in 17 and 14 aneurysms, respectively. Aneurysm size, irregularity, and atherosclerotic and translucent aneurysms were associated with AWE on univariate analysis (P<0.05). Multivariate logistic regression analysis showed that atherosclerosis was the only factor significantly and independently associated with AWE (P=0.027). Histological assessment revealed that inflammatory cell infiltration, intraluminal thrombus, and vasa vasorum were significantly associated with AWE (P<0.05).ConclusionsThough AWE on vessel wall magnetic resonance imaging scans may be associated with the presence of atherosclerotic lesions in unruptured intracerebral aneurysms, inflammatory cell infiltration within atherosclerosis, intraluminal thrombus, and vasa vasorum may be the main pathological features associated with AWE. However, the underlying pathological mechanism for AWE still needs to be further studied.

Qualitative and Quantitative Wall Enhancement on Magnetic Resonance Imaging Is Associated With Symptoms of Unruptured Intracranial Aneurysms.

Aneurysmal wall enhancement (AWE) on vessel wall magnetic resonance imaging (VW-MRI) has been described as a new imaging biomarker of unstable unruptured intracranial aneurysms (UIAs). Previous studies of symptomatic UIAs are limited due to small sample sizes and lack of AWE quantification. Our study aims to investigate whether qualitative and quantitative assessment of AWE can differentiate symptomatic and asymptomatic UIAs. Consecutive patients with UIAs were prospectively recruited for vessel wall magnetic resonance imaging at 3T from October 2014 to October 2019. UIAs were categorized as symptomatic if presenting with sentinel headache or oculomotor nerve palsy directly related to the aneurysm. Evaluation of wall enhancement included enhancement pattern (0=none, 1=focal, and 2=circumferential) and quantitative wall enhancement index (WEI). Univariate and multivariate analyses were used to identify the parameters associated with symptoms. Two hundred sixty-seven patients with 341 UIAs (93 symptomatic and 248 asymptomatic) were included in this study. Symptomatic UIAs more frequently showed circumferential AWE than asymptomatic UIAs (66.7% versus 17.3%, P<0.001), as well as higher WEI (median [interquartile range], 1.3 [1.0-1.9] versus 0.3 [0.1-0.9], P<0.001). In multivariate analysis, both AWE pattern and WEI were independent factors associated with symptoms (odds ratio=2.03 across AWE patterns [95% CI, 1.21-3.39], P=0.01; odds ratio=3.32 for WEI [95% CI, 1.51-7.26], P=0.003). The combination of AWE pattern and WEI had an area under the curve of 0.91 to identify symptomatic UIAs, with a sensitivity of 95.7% and a specificity of 73.4%. In a large cohort of UIAs with vessel wall magnetic resonance imaging, both AWE pattern and WEI were independently associated with aneurysm-related symptoms. The qualitative and quantitative features of AWE can potentially be used to identify unstable intracranial aneurysms.

Qualitative and Quantitative Wall Enhancement Analyses in Unruptured Aneurysms Are Associated With an Increased Risk of Aneurysm Instability.

ObjectiveIntracranial aneurysm wall enhancement (AWE) is independently associated with unstable aneurysms. However, a quantitative analysis of wall enhancement is lacking. This study aims to investigate the relationship between qualitative and quantitative wall enhancement indices (WEIs), traditional risk factors for aneurysms, and clinical ELAPSS/PHASES scores in a large cohort of intracranial saccular aneurysms.Materials and MethodsIn this cross-sectional study, a total of 174 patients (mean age 60.4 ± 9.5 years; 53% women) with 248 asymptomatic unruptured intracranial aneurysms underwent pre- and post-contrast black-blood magnetic resonance imaging (MRI). The extent of AWE was defined as non-AWE (pattern 0), focal AWE (pattern 1), or circumferential AWE (pattern 2). WEI was calculated using wall signal intensities on pre- and post-contrast images. Predicted 3- and 5-year growth risk and 5-year rupture risk were obtained from ELAPSS and PHASES scores, respectively. Uni- and multivariate analyses were conducted to explore the relationship between AWE characteristics, risk-related factors, and aneurysm instability.ResultsAneurysm size [odds ratio (OR), 1.3; 95% confidence interval (CI), 1.2–1.4; P < 0.001], non-internal carotid artery/middle cerebral artery location (OR, 1.9; 95% CI, 1.0–3.6; P = 0.045), and irregular shape (OR, 2.4; 95% CI, 1.2–4.5; P = 0.009) were independently associated with AWE. For aneurysms with AWE, the estimated 3- and 5-year growth risk (25.3 ± 13.0% and 38.0 ± 17.4%) and the 5-year rupture risk (3.9 ± 5.2%) were 1.9–3.3 times higher than those for aneurysms without AWE (12.8 ± 9.1%, 20.3 ± 13.0%, and 1.2 ± 1.6%, respectively; all P < 0.001). Larger areas and higher WEIs of enhancement positively correlated with aneurysm size (r = 0.43 and 0.38, respectively), 3- and 5-year growth risk, and 5-year rupture risk (r = 0.49 and 0.40, r = 0.49 and 0.40, r = 0.36 and 0.24, respectively; all P < 0.001). In sum, a larger aneurysm size, non-internal carotid artery/middle cerebral artery location, and irregular shape were independently associated with AWE. Larger areas and higher WEIs were associated with an increased risk of aneurysm growth and rupture. These findings suggest that quantitative AWE metrics should be considered in future large-scale longitudinal studies to evaluate their value in aneurysm risk management.

Increased contrast enhancement of the parent vessel of unruptured intracranial aneurysms in 7T MR imaging

BackgroundInflammation of the arterial wall may lead to aneurysm formation. The presence of aneurysm enhancement on high-resolution vessel wall imaging (HR-VWI) is a marker of wall inflammation and instability. We...

Abstract WMP29: Contrast Enhancement Measurement of Unruptured Intracranial Aneurysms: A 3T High-Resolution Vessel Wall Imaging Validation Study

Background: High-resolution vessel wall imaging (HR-VWI) has emerged as a valuable tool in assessing unruptured intracranial aneurysms (UIAs). There is no standardized method to quantify contrast enhancement of the aneurysmal wall. Contrast enhancement is reflected as signal intensity (SI) at the time of objective quantification. This study compares all the existing methods to objectively quantify contrast enhancement of UIAs. Methods: 3T HR-VWI was used to prospectively image patients with UIAs. Three different methods were analyzed in T1 pre- and post-contrast sequences: (1) circumferential aneurysm wall enhancement (CAWE) = mean post-contrast SI; (2) aneurysm-to-pituitary enhancement ratio (CR stalk ) = ratio of CAWE over pituitary stalk enhancement; and (3) enhancement ratio (ER) = max post-contrast SI - max pre-contrast SI/max pre-contrast SI x 100%. Known risks factors of aneurysm instability such as size ≥7mm and location in the anterior communicating (ACOM) and basilar arteries (BA) were used for analysis. Results: Forty-seven patients with 53 UIAs were included in the study. Mean age was 63.5 years, and 35 (74.5%) were women. UIAs ≥ 7mm showed significantly higher SI measurements for CAWE (273.1 vs 206.9, P =.05), CR stalk (0.49 vs 0.38, P =.006), and ER (85.7% vs 52.5%, P =.002) compared to smaller UIAs. SI was higher in UIAs located in the ACOM and BA (279.6 vs 235.7; 0.45 vs 0.44; 75.1% vs 61.3%) for CAWE, CR stalk and ER, respectively. ROC curves demonstrated sensitivity/specificity values of 0.74/0.64 for CAWE ≥ 205, 0.74/0.60 for CR stalk ≥ 0.398, and 0.71/0.73 for ER ≥ 62.1%. We found a moderately strong correlation between CAWE and CR stalk (Spearman = 0.69), CAWE and ER (Spearman = 0.52) and CR stalk and ER (Spearman = 0.47), with P &lt;.001 in all cases. Conclusion: Three different methods: CAWE, CR stalk and ER may be used reliably to quantify SI in the wall of UIAs. Figure: ROC curves for (A) CAWE, (B) CR stalk and (C) ER.

Abstract 143: Increased Contrast Enhancement of the Parent Vessel of Unruptured Intracranial Aneurysms in 7T Magnetic Resonance Imaging

Background: Aneurysm formation and growth might be explained by a local inflammatory/vasculopathic process that debilitates the wall of the parent artery. Recently, the presence of aneurysm enhancement on high-resolution vessel wall imaging (HR-VWI) has been proposed as a surrogate for vessel wall inflammation. However, no studies have correlated circumferential aneurysm wall enhancement (CAWE) and aneurysm-to-pituitary enhancement ratio (CR stalk ) on HR-VWI with parent vessel enhancement (PVE) and reference vessel enhancement (RVE). Methods: Patients with unruptured intracranial aneurysms prospectively underwent HR-VWI using 7T MRI. CAWE, CR stalk , PVE and RVE were objectively analyzed by measuring signal intensity in T1 post-contrast sequences using manual 3D co-registration and segmentation of the vessel wall. CR stalk was calculated as the ratio of post-contrast CAWE over pituitary stalk enhancement. RVE was assessed in the mid-BA for aneurysms in the anterior circulation, and the MCA (M1 segment) for posterior circulation aneurysms. Correlation statistics were performed to find any significant association between CAWE, CR stalk , PVE and RVE. Results: Nineteen patients with 20 aneurysms were included. Mean age was 68.9 ± 9.9 years old, and 16 (84.2%) were women. Pearson and Spearman coefficients’ analyses demonstrated a strong positive correlation between post-contrast CAWE and PVE (0.72 and 0.73, both P &lt;.001), whereas the correlation between post-contrast CAWE and RVE was low (both 0.47, P =.04). A stronger correlation was found between CR stalk and post-contrast PVE (Pearson = 0.82, Spearman = 0.71, both P &lt;.001), while the correlation between CR stalk and post-contrast RVE was negligible (Pearson = 0.33, P =.15; Spearman = 0.38, P =.09). Conclusion: This HR-VWI study shows that the parent vessel of unruptured intracranial aneurysms enhances more with contrast than vessels located in other vascular territories. This finding suggests that a local inflammatory/vasculopathic process in the wall of the parent artery may lead to aneurysm formation.

Focal Aneurysm Wall Enhancement on Magnetic Resonance Imaging Indicates Intraluminal Thrombus and the Rupture Point

The precise mechanism of aneurysm wall enhancement (AWE) in ruptured intracranial aneurysms on magnetic resonance vessel wall imaging (VWI) remains unclear. We explored patterns of VWI findings and correlations with intraoperative or histopathologic aneurysm wall architecture. Twenty-four patients were evaluated by VWI before microsurgical clipping or endovascular coiling. The patterns of AWE were categorized, and the contrast ratio of AWE area was measured relative to the pituitary stalk. A total of 13 aneurysms were microsurgically inspected of the aneurysm wall and 4 were available for histopathologic evaluation. AWE was identified in 20 of 24 ruptured aneurysms. Among these 20 aneurysms, AWE was focal in 15 and circumferential in 5. Focal AWE showed significantly higher contrast ratio than circumferential AWE (P= 0.002). Histopathologic studies suggested that focal AWE indicating contrast ratio over 0.1 could be associated with fresh intraluminal thrombus at the rupture site. On the contrary, circumferential AWE suggested potential wall thickening with abundant neovascularization and inflammatory cells. Two AWE patterns were seen in ruptured intracranial aneurysms. Focal AWE on magnetic resonance imaging might indicate the presence of intraluminal thrombus, and detection of this sign could be useful for identification of the rupture point before treatment.

Abstract 44: Histopathological Interpretation of Vessel Wall Imaging of Intracranial Aneurysms

Background and purpose: It remains a challenge to predict unruptured intracranial aneurysms (UIAs) that are prone to rupture. MR- Vessel wall imaging (VWI) is a current topic whether it could predict unstable aneurysms. We investigated the correlations between aneurysm wall imaging findings and aneurysmal risk factors with a focus on the histopathological vessel wall architecture to clarify the interpretation of VWI of intracranial aneurysms. Methods: A total of 117 intracranial aneurysms, including 21 ruptured and 96 UIAs were investigated by VWI and visualization of the aneurysm wall enhancement (AWE) was evaluated. Univariate analysis was performed to assess the correlation between VWI findings and the PHASES score (calculating patient demographic and aneurysm morphologic risk factors). Fifteen intracranial aneurysms, including 6 ruptured and 9 UIAs were available for histopathological examination. Results: In UIAs, AWE was identified in 30 of 96 UIAs (31%). The PHASES score was associated with AWE (9.1 ± 0.7 versus 6.0 ± 0.3, p= 0.001). Histopathological studies revealed that wall thickening accompanied by atherosclerosis, neovascularization, and macrophage infiltration corresponded to AWE. The thicken wall was characterized by loss of mural cells and mucinous degeneration as well. On contrary, AWE was identified in 17 of 21 ruptured aneurysms (81%). Three AWE patterns (focal, circumferential, and both) were identified in ruptured ones. Histopathological studies revealed that focal AWE was associated with very thin aneurysm wall and fresh intraluminal thrombus at the rupture site, whereas circumferential AWE suggested wall thickening with abundant neovascularization and inflammatory cells. Conclusions: In the present study, one-third of UIAs showed AWE and might not provide informative rupture risk estimation beyond PHASES score at this moment. However, VWI of intracranial aneurysms can detect what is going on in the aneurysm wall. Histopathological interpretation of VWI in ruptured aneurysms differed from that of UIAs, especially in focal AWE. Focal AWE could identify the intraluminal thrombus suggesting rupture site of the wall before treatments.

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.

Clinical Significance of Circumferential Aneurysmal Wall Enhancement in Symptomatic Patients with Unruptured Intracranial Aneurysms: aHigh-resolution MRI Study.

The estimates on the risk of rupture of intracranial aneurysms remain acontroversial topic. Circumferential aneurysmal wall enhancement (CAWE) on vessel wall magnetic resonance imaging (MRI) has been described in unstable aneurysms. Sentinel headaches and third nerve palsy are possible symptoms prior to the rupture of intracranial aneurysms. In this study, we aimed to demonstrate that CAWE could be associated with these symptoms. We performed aretrospective analysis of consecutive symptomatic or asymptomatic patients with unruptured intracranial aneurysms who were examined by high-resolution MRI from October 2014 to November 2016. Two experienced neurovascular radiologists read the images independently and determined whether there was CAWE of the unruptured intracranial aneurysms. Then, we compared variable factors between patients with and without symptoms through univariate comparison and multivariable logistic regression analyses. A total of 45 unruptured intracranial aneurysms were detected in 37patients. The agreement between 2 experienced readers for CAWE was good (kappa = 0.82; 95% confidence interval 0.66-0.99). CAWE of unruptured intracranial aneurysm was more frequently observed in symptomatic than in asymptomatic patients (16/23, 69.6% versus 6/22, 27.3%, respectively, P< 0.05). The CAWE was the only independent factor associated with symptoms in the multivariable logistic regression analysis (odds ratio 5.17; 95% confidence interval 1.30-20.52; P= 0.02). Our study demonstrates that CAWE correlated with sentinel headaches and third nerve palsy caused by unruptured aneurysms, and this may be an additional clue to distinguish the cause of these symptoms.

Vessel Wall Magnetic Resonance Imaging, Inflammatory Cascade, Aspirin, and Aneurysm Rupture: Future Paradigms?

Figure 1. A new perspective has come to cerebral aneurysm management. It is possible that the risk of aneurysm rupture, such as this internal carotid artery aneurysm, may be evaluated through modern imaging techniques. Intracranial aneurysms are common cerebrovascular lesions (Figure 1). Approximately 12% of patients die before receiving medical attention, 40% within 1 month after the event, and among those who survive, almost 30% will develop major neurologic deficits. Morbidity and mortality remain high despite advances in endovascular coiling and microsurgical clipping (4, 5). The need for noninvasive treatment is urgent, and in this context recent studies have shown the key role of inflammation in aneurysms progression to rupture. Leukocyte invasion, especially macrophage accumulation, is commonly observed in intracranial ruptured aneurysms. Innumerous mediators are involved, such as MMP-2, MMP-9, MCP-1, IL-1b, and TNF-a (6). The development of molecular and cellular imaging to monitor inflammation will lead to better prediction of the probability of intracranial aneurysm rupture (1). Hasan et al. visualized macrophages in the wall of cerebral aneurysm using a special T2*emagnetic resonance imaging sequence. Human patients with cerebral aneurysms were infused with ferumoxytol, and aneurysms with early ferumoxytol uptake showed increased expression of inflammatory molecules and cells when compared with those presenting later uptake. These results suggest that this “early uptake” points to vessel wall instability. Could such a radiological imaging technique play an essential role in clinical assessment and management of intracranial aneurysms? Edijali et al. described a technique in which circumferential aneurysmal wall enhancement could be an indirect marker of wall inflammation and therefore would be more frequent in unstable intracranial aneurysms. These authors studied 87 patients harboring 108 intracranial aneurysms and demonstrated that circumferential aneurysmal wall enhancement was the only independent factor associated with unstable status after a multivariate analysis (2). Recently Hasan et al. performed a secondary analysis of the International Study of Unruptured Intracranial Aneurysms (ISUIA) study and showed that frequent aspirin use leads to decreased risk of aneurysm rupture by 60%. Using radiological and histological techniques, the same group shows that a low-dose (81 mg) of acetylsalicylic acid for 3 months may attenuate inflammation. They

Does aneurysmal wall enhancement on vessel wall MRI help to distinguish stable from unstable intracranial aneurysms?

Arterial wall enhancement on vessel wall MRI was described in intracranial inflammatory arterial disease. We hypothesized that circumferential aneurysmal wall enhancement (CAWE) could be an indirect marker of aneurysmal wall inflammation and, therefore, would be more frequent in unstable (ruptured, symptomatic, or undergoing morphological modification) than in stable (incidental and nonevolving) intracranial aneurysms. We prospectively performed vessel wall MRI in patients with stable or unstable intracranial aneurysms. Two readers independently had to determine whether a CAWE was present. We included 87 patients harboring 108 aneurysms. Interreader and intrareader agreement for CAWE was excellent (κ=0.85; 95% confidence interval, 0.75-0.95 and κ=0.90; 95% confidence interval, 0.83-0.98, respectively). A CAWE was significantly more frequently seen in unstable than in stable aneurysms (27/31, 87% versus 22/77, 28.5%, respectively; P<0.0001). Multivariate logistic regression, including CAWE, size, location, multiplicity of aneurysms, and daily aspirin intake, revealed that CAWE was the only independent factor associated with unstable status (odds ratio, 9.20; 95% confidence interval, 2.92-29.0; P=0.0002). CAWE was more frequently observed in unstable intracranial aneurysms and may be used as a surrogate of inflammatory activity in the aneurysmal wall.