Size Of Intracranial Aneurysms Research Articles

Intra-aneurysmal high-resolution 4D MRI flow imaging for hemodynamic imaging markers in intracranial aneurysm instability.

Prediction of aneurysm instability is crucial to guide treatment decisions and to select appropriate patients with unruptured intracranial aneurysms (IAs) for preventive treatment. High resolution four-dimensional magnetic resonance (4D MRI) flow imaging and 3D quantification of aneurysm morphology could offer insights and new imaging markers for aneurysm instability. In this cross-sectional study, we aim to identify 4D MRI flow imaging markers for aneurysm instability by relating hemodynamics in the aneurysm sac to 3D morphological proxy parameters for aneurysm instability. In 35 patients with 37 unruptured IAs, a 3T MRA and a 7T 4D flow MRI scan was performed. Five hemodynamic parameters -peak-systolic (WSSMAX) and time-averaged wall shear stress (WSSMEAN), oscillatory shear index (OSI), mean velocity, and velocity pulsatility index (vPI)-were correlated to six 3D morphology proxy parameters of aneurysm instability -major axis length, volume, surface area (all three size parameters), flatness, shape index, and curvedness -by Pearson's correlation with 95% confidence intervals (CI). Scatterplots of hemodynamic parameters that correlated with IA size (major axis length) were created. WSSMAX and WSSMEAN correlated negatively with all three size parameters (strongest for WSSMEAN with volume (r = -0.70, 95% CI -0.83 to -0.49)) and OSI positively (strongest with major axis length (r = 0.87, 95% CI 0.76 to 0.93)). WSSMAX and WSSMEAN correlated positively with shape index (r = 0.61, 95% CI 0.36 to 0.78 and r = 0.49, 95% CI 0.20 to 0.70, respectively) and OSI negatively (r = 0.82, 95% CI -0.9 to -0.68). WSSMEAN and mean velocity correlated negatively with flatness (r = -0.35, 95% CI -0.61 to -0.029 and r = 0.33, 95% CI -0.59 to 0.007, respectively) and OSI positively (r = 0.54, 95% CI 0.26 to 0.74). vPI did not show any statistically significant correlation. Out of the five included hemodynamic parameters, WSSMAX, WSSMEAN, and OSI showed the strongest correlation with morphological 3D proxy parameters of aneurysm instability. Future studies should assess these promising new imaging marker parameters for predicting aneurysm instability in longitudinal cohorts of IA patients. IA = intracranial aneurysm; 3D = three dimensional; 4D MRI flow = four-dimensional Magnetic Resonance Imaging flow; TOF-MRA = Time-of-flight Magnetic Resonance Angiography; WSS = wall shear stress; WSSMAX = WSS calculated at peak systole; WSSMEAN = time averaged WSS; OSI = oscillatory shear index; vPI = velocity pulsatility index.

Natural history and growth rate of intracranial aneurysms in Loeys-Dietz syndrome: implications for treatment.

Loeys-Dietz syndrome (LDS) is a heritable aortopathy associated with craniofacial abnormalities and dilatation and dissection of the aorta and its branches, as well as increased risk for intracranial aneurysms (ICAs). Given the rarity of the disease, the authors aimed to better define the natural history and role for the treatment for ICAs in these patients. The medical records of 83 patients with LDS were retrospectively reviewed to obtain clinical and genetic history and vascular imaging of the aorta, aortic branches, and intracranial vessels. Serial radiology reports and cervical and intracranial vascular images were reviewed to determine presence, location, and size of ICAs. In total, 55 patients (66.3%) had at least two screening intracranial vascular examinations, and 19 (22.9%) had at least 1 ICA detected. Aneurysms were typically small (mean ± SD 3.2 ± 1.8 mm). ICAs were most often located in the cavernous carotid, followed by the ophthalmic and anterior cerebral artery vessels. The rate of ICA growth was 0.43 ± 0.53 mm/year, similar to that of the general population. Three patients underwent intervention for an ICA, with 1 procedure complicated by stroke and resulting in transient hemiparesis. Several illustrative cases detail the authors' experience with ICA growth, de novo aneurysm formation, and ICA intervention in this rare patient population. ICAs in patients with LDS are common, are frequently small, and have a growth rate similar to that of unruptured ICAs in the general population. More aggressive or earlier intervention for asymptomatic ICAs identified in LDS patients compared with the general population is likely unwarranted based on the authors' experience at their institution.

Positive Correlation Between Thoracic Aortic Diameter and Intracranial Aneurysm Size–An Observational Cohort Study

ObjectiveTo investigate the association between intracranial aneurysms (IA) and thoracic aortic diameter. MethodsThis observational cohort study examined thoracic aortic diameters in IA patients. Patients were categorized by IA size (<7mm and ≥7mm) and IA status (ruptured / unruptured) based on radiological findings. We investigated the association between thoracic aortic diameter and IA size and status using binary and linear regression as univariate and multivariable analyses. ResultsA total of 409 patients were included. Mean age was 60 (± 11.7) years and 63 % were women. Thoracic aortic diameters were greater among patients who had an IA of ≥7 mm vs. IA <7mm (p<0.05). In the univariate analysis, the diameter of the ascending aorta (OR 1.07 [1.02–1.129] per 1 mm, p 0.002), aortic arch (OR 1.10 [1.04–1.15] per 1 mm, p < 0.001) and descending aorta (OR 1.10 [1.03 – 1.16] per 1 mm, p 0.003) were associated with IAs ≥ 7mm. In the multivariable regression model, larger ascending aorta (OR 1.09 [1.01–1.17] per 1 mm, p 0.018), aortic arch (OR 1.12 [1.02–1.22] per 1 mm, p 0.013) and descending aorta (OR 1.20 [1.08–1.33] per 1mm, p<0.001) were associated with ruptured IA. ConclusionGreater thoracic aortic diameters are associated with a higher risk of IA being larger than 7mm and IA rupture. Exploring the concomitant growth tendency in IA and thoracic aorta provides basis for future considerations regarding screening and risk management.

Evaluation of PHASES Score for Predicting Rupture of Intracranial Aneurysms: Significance of Aneurysm Size

IntroductionRecent data has identified that certain risk factors for rupture differ between small and larger intracranial aneurysms (IAs). Such differing risk factors make up 5 out of the 6 predictor variables used in the PHASES score which raises the question on whether IA size has a significant effect on the score’s performance. MethodsPatients which were diagnosed with an IA incidentally or due to a subarachnoid hemorrhage (SAH) between 2015-2023 were selected for potential inclusion. The median IA size of the cohort was chosen as the cutoff point to categorize small and large (6 mm). The PHASES score was calculated for all patients and a receiver operating characteristic curve analysis was performed to evaluate the classification accuracy of PHASES in predicting rupture for small and large IAs. ResultsA total of 677 IAs were included. Among the IAs, 400 (58.9%) presented as UIAs and 279 (41.0%) as SAH. The average PHASES score was 2.9 and 6.5 for small (n = 322) and large (n = 355) IAs, respectively. The PHASES score performed significantly lower for predicting rupture in smaller IAs (area under the curve [AUC]: 0.634) compared to the larger (AUC: 0.741) (p = 0.00083). ConclusionPHASES was shown to underperform on small IAs. The decision to treat small unruptured IAs remains highly controversial and the development of a new score to estimate the annual rupture rate while accounting for IA morphology is of great need. Our findings can help encourage future researchers to develop such a score.

The rupture risk factors of mirror intracranial aneurysms: A systematic review and meta-analysis based on morphological and hemodynamic parameters.

Intracranial aneurysms (IAs) are a prevalent form of vascular disease that can lead to fatal outcomes upon rupture. Mirror intracranial aneurysms (MIAs) are a specific type of multiple aneurysms situated symmetrically on both sides of the parent arteries. The factors contributing to the risk of MIA rupture, based on morphological and hemodynamic parameters, are currently controversial. Thus, we conducted a systematic review and meta-analysis to investigate the risk factors for MIA rupture. The study performed an electronic search of Chinese and English databases, including China national Knowledge Infrastructure (CNKI), WanFang, VIP, PubMed, Embase, Web of Science, Scopus, and the Cochrane Library databases, and adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The morphological parameters (IA size, aspect ratio [AR], size ratio [SR], bottleneck factor [BNF], height-width ratio [HWR], irregular shape) and hemodynamic parameters (wall shear stress [WSS], low WSS area [LSA], oscillatory shear index [OSI]) were analyzed for their significance in determining the risk of MIA rupture. The analysis comprised 18 retrospective studies involving 647 patients, with a total of 1294 IAs detected, including 605 ruptured and 689 unruptured. The meta-analysis revealed that IA size, AR, SR, and irregular shape exhibited significant differences between the ruptured and unruptured groups, but HWR did not. In terms of hemodynamic parameters, WSS, OSI, and LSA were found to have significant differences between the two groups. Our results demonstrate that larger IAs, higher AR, SR, and BNF are associated with a higher risk of rupture in patients with MIAs, regardless of their location. there is no significant difference in HWR between the ruptured and unruptured groups. These preliminary findings offer valuable insights for clinical decision-making and a more comprehensive comprehension of the current MIA status. Nevertheless, larger and multi-center studies are indispensable for corroborating these findings. Systematic review registration: https://www.crd.york.ac.uk/prospero/ identifier: CRD42022345587.

Risk of intracranial aneurysm recurrence after microsurgical clipping based on 3D digital subtraction angiography.

Current knowledge of recurrence rates after intracranial aneurysm (IA) surgery relies on 2D digital subtraction angiography (DSA), which fails to detect more than 75% of small aneurysm remnants. Accordingly, the discrimination between recurrence and growth of a remnant remains challenging, and actual assessment of recurrence risk of clipped IAs could be inaccurate. The authors report, for the first time, 3D-DSA-based long-term durability and risk factor data of IA recurrence and remnant growth after microsurgical clipping. Prospectively collected data for 305 patients, with a total of 329 clipped IAs that underwent baseline 3D-DSA, were evaluated. The incidence of recurrent IA was described by Kaplan-Meier curves. Risk factors for IA recurrence were analyzed by multivariable Cox proportional hazards and logistic regression models. The overall observed proportion of IA recurrence after clipping was 2.7% (9 of 329 IAs) at a mean follow-up of 46 months (0.7% per year). While completely obliterated IAs did not recur during follow-up, incompletely clipped aneurysms (76 of 329) demonstrated remnant growth in 11.8% (3.4% per year). Young age and large initial IA size significantly increased the risk of IA recurrence. The findings support those in previous studies that hypothesized that completely clipped IAs have an extremely low risk of recurrence. Conversely, the results highlight the significant risk posed by incompletely clipped IAs. Young patients with initial large IAs and incomplete obliteration have an especially high risk for IA recurrence and therefore should be monitored more closely.

No Sex Differences in the Prevalence of Intracranial Aneurysms in Patients with Ascending Thoracic Aortic Aneurysms: A Multi-Center Experience

Previous studies suggest a coprevalence of intracranial aneurysms (IA) in patients with infrarenal abdominal aortic aneurysms (AAA). We reviewed our multicenter experience in the detection/treatment of IAs in patients with ascending thoracic aortic aneurysms (ATAA) relative to patients without ATAA. Surgical cases of ATAA repaired at 3 sites from January 1998 to December 2018 were retrospectively reviewed. Out of these patients, those with intracranial vascular imaging were selected for our study, and these individuals were concurrently randomly matched with a control group of patients who underwent intracranial vascular imaging without an ATAA in a 1:1 ratio by age, sex, smoking history, and year of intracranial vascular imaging. Conditional logistic regression was used to calculate odds ratios (OR). We reviewed 2176 ATAA repairs. 74% (n=1,615) were men. Intracranial vascular imaging was available in 298 (13.7%) patients. Ninteen patients were found to have 22 IAs for a prevalence of 6.4%. Mean size of IA was 4.6±3.3mm; mean age at IA detection, 63.4±12.1years. IA was present on head imaging in 4.7% of male and 12.5% of female patients. Eleven (58%) patients were men. The OR of having IA in female versus male patients is 2.90, 95% confidence interval [CI] [1.08-7.50], P=0.029. Time from IA diagnosis to ATAA repair was 1.7±116.2months. Two patients underwent treatment for IA, one ruptured and one unruptured. All were diagnosed before ATAA repair. Treatment included 1 clipping and 1 coiling with subsequent reintervention of the coiling using a flow diversion device. In the matched group of patients who had intracranial vascular imaging without ATAA, the rate of IA is 5.0%. IA was detected in 3.8% of males and 9.4% of female patients for an OR of 2.59, 95% CI [0.84-7.47], P = 0.083. Association within our study and matched groups, the OR of developing an IA with and without ATAA was not statistically significant 1.29, 95% CI [0.642.59], P=0.48. There was also no evidence of sex differences in the association of ATAA with IA (interaction P=0.88). The OR for the association of ATAA with IA was 1.33, 95% CI [0.46-3.84], P=0.59 in females and 1.25, 95% CI [0.49-3.17], P=0.64 in males. Our study found that IA was present in 6.4% of patients with ATAA who had intracranial vascular imaging available. The odds of IA were 1.29 times higher than a matched cohort of patients who had intracranial vascular imaging without ATAA but this failed to achieve statistical significance. We found that the odds of IA were more than 2 times higher in females than males for both those with ATAA (OR=2.90) and those without ATAA (OR=2.59); however, it only reached statistical significance in those with ATAA.

Small intracranial aneurysms of the anterior circulation: A negligible risk?

According to the International Study of Unruptured Intracranial Aneurysms, small (<7 mm) unruptured intracranial aneurysms (IAs) of the anterior circulation (aC) carry a neglectable 5-year rupture risk. In contrast, some studies report frequencies of >20% of all ruptured IAs being small IAs of the aC. This contradiction was addressed in this study by analyzing the rates and risk factors for rupture of small IAs within the aC. Of the institutional observational cohort, 1676 small IAs of the aC were included. Different demographic, clinical, laboratory, and radiographic characteristics were collected. A rupture risk score was established using all independent prognostic factors. The score performance was checked using receiver operating characteristic curve analysis. Of all registered small IAs of the aC, 20.1% were ruptured. The developed small IAs of the aC (SIAAC) score (range = -4 to +13 points) contained five major risk factors: IA location and size, arterial hypertension, alcohol abuse, and chronic renal failure. In addition, three putative protective factors were also included in the score: hypothyroidism, dyslipidemia, and peripheral arterial disease. Increasing rates of ruptured IA with increasing SIAAC scores were observed, from 0% (≤-1 points) through >50% (≥8 points) and up to 100% in patients scoring ≥12 points. The SIAAC score achieved excellent discrimination (area under the curveSIAAC = 0.803) and performed better than the PHASES (Population,Hypertension, Age, Size of the aneurysm, Earlier SAH from another aneurysm, Site of aneurysm) score. Small IAs of the aC carry a considerable rupture risk. After external validation, the proposed rupture risk score might provide a basis for better decision-making regarding the treatment of small unruptured IAs of the aC.

Hemodynamic indicators of the formation of tandem intracranial aneurysm based on a vascular restoration algorithm.

Hemodynamic factors are believed to be closely related to IA growth. However, the underlying pathophysiological mechanism that induces the growth sequence in tandem intracranial aneurysms (IAs) remains unclear. This study involved five patients with tandem IAs. Aneurysm models were reconstructed based on image datasets. A novel vascular restoration algorithm was proposed to generate the hypothetical geometry of the healthy parent vessel before each IA formation in the concatenated structure. Detailed hemodynamic patterns and morphological features were revealed under various growth sequences of tandem IAs to investigate the flow-driven mechanism of IA growth. Potential hemodynamic indicators of IA formation were proposed. The patient cases were divided into two groups based on the size difference of tandem IAs. In the group with a similar size of tandem IAs, the position of the vortex core was associated with the site of the secondary aneurysm, while in the group with a significant size difference of the IAs, the position with the maximum curvature of the parent vessel plays a significant role in aneurysm formation. This study preliminarily revealed key hemodynamic and morphological indicators that determine the formation of tandem IAs. The proposed vascular restoration algorithm that provided the pre-aneurysm vasculature might be useful in investigating the flow-driven mechanism of IA growth, thus contributing to the risk evaluation of secondary aneurysm formation.

Intracranial Aneurysm Classifier Using Phenotypic Factors: An International Pooled Analysis.

Intracranial aneurysms (IAs) are usually asymptomatic with a low risk of rupture, but consequences of aneurysmal subarachnoid hemorrhage (aSAH) are severe. Identifying IAs at risk of rupture has important clinical and socio-economic consequences. The goal of this study was to assess the effect of patient and IA characteristics on the likelihood of IA being diagnosed incidentally versus ruptured. Patients were recruited at 21 international centers. Seven phenotypic patient characteristics and three IA characteristics were recorded. The analyzed cohort included 7992 patients. Multivariate analysis demonstrated that: (1) IA location is the strongest factor associated with IA rupture status at diagnosis; (2) Risk factor awareness (hypertension, smoking) increases the likelihood of being diagnosed with unruptured IA; (3) Patients with ruptured IAs in high-risk locations tend to be older, and their IAs are smaller; (4) Smokers with ruptured IAs tend to be younger, and their IAs are larger; (5) Female patients with ruptured IAs tend to be older, and their IAs are smaller; (6) IA size and age at rupture correlate. The assessment of associations regarding patient and IA characteristics with IA rupture allows us to refine IA disease models and provide data to develop risk instruments for clinicians to support personalized decision-making.

Bayesian network analysis reveals the interplay of intracranial aneurysm rupture risk factors

Clinical decision making regarding the treatment of unruptured intracranial aneurysms (IA) benefits from a better understanding of the interplay of IA rupture risk factors. Probabilistic graphical models can capture and graphically display potentially causal relationships in a mechanistic model. In this study, Bayesian networks (BN) were used to estimate IA rupture risk factors influences.From 1248 IA patient records, a retrospective, single-cohort, patient-level data set with 9 phenotypic rupture risk factors (n=790 complete entries) was extracted. Prior knowledge together with score-based structure learning algorithms estimated rupture risk factor interactions. Two approaches, discrete and mixed-data additive BN, were implemented and compared. The corresponding graphs were learned using non-parametric bootstrapping and Markov chain Monte Carlo, respectively. The BN models were compared to standard descriptive and regression analysis methods.Correlation and regression analyses showed significant associations between IA rupture status and patient’s sex, familial history of IA, age at IA diagnosis, IA location, IA size and IA multiplicity. BN models confirmed the findings from standard analysis methods. More precisely, they directly associated IA rupture with familial history of IA, IA size and IA location in a discrete framework. Additive model formulation, enabling mixed-data, found that IA rupture was directly influenced by patient age at diagnosis besides additional mutual influences of the risk factors.This study establishes a data-driven methodology for mechanistic disease modelling of IA rupture and shows the potential to direct clinical decision-making in IA treatment, allowing personalised prediction.

Geometric and Morphologic Features of Ruptured Intracranial Aneurysms Associated with Methamphetamine Use

Methamphetamine (MA) use is associated with poor outcomes after aneurysmal subarachnoid hemorrhage (aSAH). MA exerts both hemodynamic and inflammatory effects, but whether these manifest with altered intracranial aneurysm (IA) remodeling is unknown. The objective of this study was to compare IA geometric and morphologic features in patients with and without MA detected on urine toxicology (Utox) at presentation. We retrospectively reviewed 160 consecutive patients with SAH and Utox at time of admission. Geometric-morphologic IA characteristics were assessed by blinded neuroradiologists. Studied features were maximum sac diameter, location, size, ellipsoid volume, aspect ratio, size ratio, volume: neck ratio, dome: neck ratio, bottleneck factor, morphology (saccular, fusiform/dissecting, blister, mycotic), and presence of bleb, vasculopathy, or additional unruptured IA. Of 139/160 patients with aSAH, 23/139 (16.5%) were Utox MA+. There was no difference in aneurysm subtype frequency, presence of bleb, vasculopathy, or presence of an additional (unruptured) aneurysm with a trend toward posterior circulation location and higher Hunt and Hess grade (P= 0.09 for both) in the MA+ group. Maximum IA sac diameter, ellipsoid volume, dome-neck ratio, and size ratio were similar between groups. Only the aspect ratio (AR) differed between groups (MA+= 2.20 vs. MA-= 1.74, P= 0.02). The AR remained a significant predictor of Utox MA+ in a multiple logistic regression analysis (odds ratio 1.87, 95% confidence interval 1.06-3.39). Active use of methamphetamine is independently associated with larger AR in patients with ruptured IA. This may indicate hazardous remodeling due to hemodynamic and/or inflammatory changes.

Should we screen for intracranial aneurysms in children with autosomal dominant polycystic kidney disease?

This is an overview of the challenges associated with screening for asymptomatic intracranial aneurysms (ICA) in children with autosomal dominant polycystic kidney disease (ADPKD). ADPKD is the most common inherited kidney disease affecting 1 in 1,000 people. ICAs are an extra-kidney manifestation of ADPKD, and while the exact pathophysiology of how they develop is unknown, we know that they more commonly occur in the adult rather than paediatric population. ICAs can be found in up to 9–11.5% of adults with ADPKD, but ICA rupture remains a rare event in adults with an incidence of 0.04 per 100 patient years. ICA size is an important factor in determining the risk of aneurysm rupture and therefore affects the decision on intervention in asymptomatic adults. For some, unruptured aneurysms cause no clinical significance, but those that rupture can be associated with devastating morbidity and mortality. Therefore, if detected, the treatment for unruptured ICAs is usually endovascular coiling, alongside recognising the importance of preventative interventions such as hypertension management. There are, however, no current guidelines for either adult or paediatric patients with ADPKD supporting regular screening for asymptomatic ICAs, although there is a suggestion for individualised practice, for example, with those with a positive family history. The UK clinical guidelines for ADPKD in children make research recommendations due to a lack of published literature, which in itself indicates that ICA rupture is an extremely rare phenomenon in children.

Abstract WP10: Automated Methods Of Aneurysm Growth Detection Compared With Clinical Assessment And Follow-up

Introduction: In cases where the risk of intracranial aneurysms (IA) rupture is low or secondary to other patient health concerns, unruptured IA may be monitored through imaging. In this work, we applied different computational methods to detect IA growth and compared the results to clinical findings. Hypothesis: We hypothesize that automated methods of IA growth detection are comparable to clinical assessment. Methods: The study cohort consisted of 20 female patients with saccular IA diagnosed between 2005-2011 in UCLA Medical Center. 6 were located at the PcoA, 10 at the superior hypophyseal artery, and 4 at the ophthalmic artery. 8 IA were determined to be growing. Baseline IA size was 3.85±4.30 mm. For each case, initial and first follow-up CTA image studies (interval 2.50±2.75 yrs) were analyzed. Cohort follow-up continued for an average of 8.5±5.75 yrs. Automated methods to detect IA growth included maximum diameter (HMAX), surface area (SA), volume (V), and a novel 2-stage morphing approach which deforms the baseline IA surface mesh to that of the subsequent scan and yields a set of characteristics that describe the changes: dMPL, dSA, dV, and dICDD. Statistical methods used included the Mann-Whitney U test and Chi-Square Test with significance set at p &lt;0.01, and ROC AUC analysis. Results: The stable and growth groups did not significantly differ with respect to case details and medical history, including IA size, location, imaging interval, age, family history, stroke, hypertension, thyroid disease, cancer, and atherosclerosis. Clinically determined change in IA diameter (p=0.007, AUC=0.927), computed HMAX (p=0.0002, AUC=0.958), SA (p=0.001, AUC=0.917), V (p=0.001, AUC=0.927), and dSA (p=0.005, AUC=0.865) were significantly different between the groups. The duration of follow-up significantly differed between the groups (p&lt;0.01), largely due to treatment of growing IA. During follow-up only one IA changing from stable to growing, and 5 of 6 subsequently treated IA were from within the initial growth group. Conclusion: Several automated measures provided comparable performance to clinical size when assessing IA growth. HMAX in particular may be useful to assist clinical evaluation, as it was slightly more effective than recorded clinical size alone.

Abstract TMP10: Patient-specific Analyses Reveal Differences In Hemodynamic And Morphological Parameters Between Growing And Stable Unruptured Intracranial Aneurysms

Introduction: Although image-derived parameters such as wall shear stress (WSS), flow rate (FR), aspect ratio (AR), size ratio (SR), and non-sphericity index (NSI) were previously linked to risks of intracranial aneurysm (IA) growth, findings across studies have been inconsistent. Here, we revisit existing hemodynamic and morphological metrics and compare them between stable and growing IAs. We hypothesize that some may differentiate growing and stable trajectories of IAs. Methods: Unruptured IA cases between 2018-2020 were identified from UCLA Medical Center electronic medical records, with follow-up data used to determine growth status. From CTA/MRA images, models of 16 stable and 20 growing unruptured IA cases were reconstructed. Aneurysm diameter, height, neck width, surface area, volume, parent artery diameter, AR, SR, NSI, volume ratio, and surface area ratio were calculated. With data from hemodynamic simulations, we also measured FR and WSS. To capture spatial variations in hemodynamics, we calculated location-dependent mean deviation of WSS and FR at 3 locations within an aneurysm: neck, body, and dome. Pearson chi-square tests were used to compare background variables between groups. MANOVA was employed to compare the index values between stable and growing IAs. Results: Variables including location, diameter, race, history of smoking, and SAH were not significantly different between groups (p&gt;&gt;.05). Gender (p=0.06) and multiplicity (p=0.06) approached significance. Among the size-related and morphological parameters described above, only IA height (3.07±1.94mm vs. 5.49±3.61mm, p=0.03), neck width (4.93±1.42mm vs. 7.14±3.78mm, p=0.04), and size ratio (1.40±0.62 vs. 2.27±1.27, p =0.02) were significantly different (stable vs. growing, respectively). Growing IA had significantly higher FR spatial variation (0.43±0.35 vs. 0.75±0.44; p=0.03) and WSS spatial variations (0.24±0.20 vs. 0.49±0.28; p=0.008). Conclusions: Our findings support that location-dependent hemodynamic variations and SR may be potential risk factors of IA growth. Upon validation in larger studies, these parameters may aid in early identification of incidentally found IAs’ trajectories.

Abstract 14307: Circulating Whole Blood Gene Expression Profiles Correlate With Intracranial Aneurysm Risk Across Multiple Metrics

Introduction: Intracranial aneurysm (IA) rupture is the primary cause of non-traumatic hemorrhagic stroke. Deciding which unruptured IA should be treated is difficult, as rupture rates are low but complication risks of treatment can be high. Thus, there is a critical need for biomarkers of high-risk IAs. Hypothesis: Patients harboring high-risk IAs have distinct gene expression profiles in their circulating blood. Methods: We collected whole blood RNA, imaging, and data from patients with IA undergoing angiographic imaging. Next-generation RNA sequencing was used to obtain transcriptomes. Based on images and medical data, high-risk IAs were defined by two metrics: 1) IA size (≥5 mm) from UCAS study and 2) morphologic Rupture Resemblance Score, based on IA Size Ratio (RRS≥0.30). We implemented the widely-used bioinformatics pipeline edgeR to identify significantly differentially expressed genes (q-value&lt;0.05) between high-and low risk groups. Pearson correlation analysis was used to identify which significant genes were correlated with each risk metric (r &gt;0.3). These genes were then used to train a multivariate regression model of IA risk, using 500 Monte-Carlo cross-validation iterations with a 70%:30% training:testing split. Results: This study included 91 IAs from 70 patients. Differential whole blood RNA expression was able to delineate high- and low-risk IAs on principal component analysis. 16 differentially expressed genes associated with IA size produced a 4-gene classifier with average AUC=0.82, accuracy=71%, sensitivity=67%, and specificity=76%. Conversely, the 14 differentially expressed genes associated with RRS yielded a 7-gene classifier with better performance, with average AUC=0.84, accuracy=79%, sensitivity=39%, and specificity=93%. Conclusions: Whole blood transcriptomes have the potential to reflect IA risk. This work lays the foundation to develop minimally invasive, low cost blood diagnostics for IA risk assessment.

Prevalence of bicuspid aortic valve in patients with aneurysmal sub-arachnoid hemorrhage: neurologic features and outcomes

Abstract Background Intracranial aneurysm (IA) has been associated with bicuspid aortic valve (BAV) with prevalence of 6–10% which has led some to recommend routine surveillance for IA in BAV patients. Higher incidence of IA in BAV could signal towards systemic arteriopathy beyond the thoracic aorta. With CoA as an independent risk factor for IA formation, it is currently uncertain if the association between IA and BAV reflects the association of BAV and CoA, or the result of BAV-related systemic arterial changes. Purpose Despite this association, 2 small studies suggest no increased risk of the most important patient outcome: aneurysmal sub-arachnoid hemorrhage (aSAH). Our primary aim was identifying the prevalence of BAV in aSAH patients and compare it with that of a control group without aSAH. Secondary aims included neurologic outcomes of aSAH and anatomical characteristics of IA in BAV, and final disposition and outcome. Methods Patients (&amp;gt;18 years age) with an accurate diagnosis of aSAH and at least one echocardiogram in the system between January 2000-December 2019 were identified from a prospectively maintained registry of aSAH admissions. Controls, without a diagnosis of SAH ever, were age- and gender-matched (1:2 cases:controls). BAV prevalence was echocardiographically-confirmed in all patients. Severity of aSAH was categorized using the modified Fisher (mFisher) and the World Federation of Neurological Scale (WFNS). Results A total of 488 aSAH cases and 990 controls were included in the final analysis with confirmed aortic valve status. The prevalence of BAV in aSAH patients was 1.2% (6/488) vs 3.5% (35/990) in controls, p=0.01. None of the aSAH cases were noted to have CoA, whereas 3 (0.3%; p=0.12) control patients had presence of both BAV and CoA. Within aSAH patients, BAV+aSAH were noted to be younger than tricuspid aortic valve (TAV)+aSAH (56±11 vs 68±14; p=0.03). Aneurysm size was smaller in the BAV+aSAH group (5±2 vs 7±4 in TAV+aSAH; p=0.31). The severity of the bleed was lesser in BAV+aSAH than TAV+aSAH (mFisher grade &amp;gt;2 50% vs 74%; p=0.19, WFNS grade &amp;gt;3 17% vs 36%; p=0.43) which is clinically significant. The BAV+aSAH group had higher disposition rate to home (67% vs 39%; p=0.21) with no difference in in-hospital mortality rates (17% vs 18%; p=0.93). BAV had lower odds on univariate and multivariate analyses adjusted for age/sex/body mass index (OR 0.33 [CI 0.14–0.81]; p=0.01, OR 0.23 [CI 0.08–0.65]; p=0.01) of presenting with aSAH. Conclusion Within a large prospective registry with accurate aSAH diagnoses, we found 3-times lower prevalence of echocardiographically-confirmed BAV as compared to non-aSAH controls. We observed 3-times higher prevalence of BAV in controls than among aSAH cases. In addition, size of intracranial aneurysms was clinically smaller in BAV patients, and the severity of SAH was significantly lesser in BAV from a clinical standpoint. Our findings argue against routine surveillance for IA in BAV patients without CoA. Funding Acknowledgement Type of funding sources: None.

Definitions of intracranial aneurysm size and morphology: A call for standardization.

Background: Intracranial aneurysms (IAs) are classified based on size (maximal dome diameter) as well as additional parameters such as neck diameter and dome-to-neck ratio (DNR). The neurosurgical literature includes a wide variety of definitions for both IA size and neck classifications. Standardizing the definitions of IA size and wide-neck classifications would help eliminate inconsistencies and potential misunderstandings of aneurysm morphology and rupture risk.Methods: We queried the MEDLINE (EBSCO) database using the terms “unruptured IA” and (“small” or “medium” or “large”) and filtered based on publication date, language, and scholarly journals. The resulting articles and their references were further screened for eligibility. This identified 286 records, of which 104 were excluded, leaving 182 articles for analysis. The review found several different IA size classifications and neck classifications.Results: A review of the existing literature describing size and neck classifications revealed 13 size classifications for small aneurysms, four classifications for medium aneurysms, 15 classifications for large aneurysms, and one classification for giant aneurysms. There were also seven different wide-neck classifications found.Conclusion: It is imperative that a standardization in classification be implemented to help interventionalists make the most informed decisions regarding emerging treatment options as new endovascular technologies and devices are emerging with indications based around these classifications. Based on the database findings, this article recommends standardized quantitative measurement ranges for IA size and neck classifications.

Aberrant Whole Blood Gene Expression in the Lumen of Human Intracranial Aneurysms.

The rupture of an intracranial aneurysm (IA) causes devastating hemorrhagic strokes. Yet, most IAs remain asymptomatic and undetected until they rupture. In the search for circulating biomarkers of unruptured IAs, we previously performed transcriptome profiling on whole blood and identified an IA-associated panel of 18 genes. In this study, we seek to determine if these genes are also differentially expressed within the IA lumen, which could provide a mechanistic link between the disease and the observed circulating gene expression patterns. To this end, we collected blood from the lumen of 37 IAs and their proximal parent vessels in 31 patients. The expression levels of 18 genes in the lumen and proximal vessel were then measured by quantitative polymerase chain reaction. This analysis revealed that the expression of 6/18 genes (CBWD6, MT2A, MZT2B, PIM3, SLC37A3, and TNFRSF4) was significantly higher in intraluminal blood, while the expression of 3/18 genes (ST6GALNAC1, TCN2, and UFSP1) was significantly lower. There was a significant, positive correlation between intraluminal and proximal expression of CXCL10, MT2A, and MZT2B, suggesting local increases of these genes is reflected in the periphery. Expression of ST6GALNAC1 and TIFAB was significantly positively correlated with IA size, while expression of CCDC85B was significantly positively correlated with IA enhancement on post-contrast MRI, a metric of IA instability and risk. In conclusion, intraluminal expression differences in half of the IA-associated genes observed in this study provide evidence for IA tissue-mediated transcriptional changes in whole blood. Additionally, some genes may be informative in assessing IA risk, as their intraluminal expression was correlated to IA size and aneurysmal wall enhancement.

The relationship between staying up late and risk of intracranial aneurysm rupture: A single-center study

ObjectiveTo evaluate the impact of staying up late (SUL) on the risk of intracranial aneurysm (IA) rupture. MethodsThis case-control study included 452 patients diagnosed with IA. They were divided into ruptured and unruptured groups. Staying up late was categorized in three levels (11–12 o’clock, 12-1 o’clock, after 1 o’clock) according to the time of falling asleep. To explore the relationship between staying up late and risk of IA rupture, univariate and multivariate logistic regression analyses were performed. ResultsMultivariate analysis found a significant difference in the percentage of patients falling asleep at 12-1 o’clock (OR, 2.25; 95% CI, 1.10–4.59) or after 1 o’clock (OR, 4.68; 95% CI, 1.74–12.55) between the ruptured and unruptured groups. The following risk factors differed significantly between the two groups: hypertension (OR, 2.05; 95% CI, 1.33–3.17), current smoking (OR, 1.72; 95% CI, 1.09–2.71), irregular IA (OR, 1.85; 95% CI, 1.15–3.00), IA size ≥8mm (OR, 1.92; 95% CI, 1.22–3.02), MCA location (OR, 2.45; 95% CI, 1.19–5.02), and aspect ratio (OR, 1.33; 95% CI, 1.02–1.73). ConclusionPatients who fell asleep later than 12 midnight on average showed higher risk of IA rupture. The reasons for this are not very clear. A review of the literature suggests that this association may be related to a series of physiological, pathophysiological, endocrine and metabolic changes.