Detection Of Unruptured Intracranial Aneurysms Research Articles

Advancements in opportunistic intracranial aneurysm screening: The impact of a deep learning algorithm on radiologists' analysis of T2-weighted cranial MRI

(1) Background: Unruptured Intracranial Aneurysms (UIAs) are common blood vessel malformations, occurring in up to 3 % of healthy adults. Magnetic Resonance Angiography (MRA) is frequently used for the screening of UIAs due to its high resolution in vascular anatomy. However, T2-Weighted Magnetic Resonance Imaging (T2WI) is a standard sequence utilized for the majority of outpatient head scans. By employing a sequence such as T2WI, there is a possible shift towards early detection of UIAs through opportunistic screening. Here, we assess a Deep Learning Algorithm (DLA) developed to assist radiologists in identifying and reporting UIAs on T2WI in a routine clinical setting. (2) Methods: A DLA was trained on a set of 110 patients undergoing an MR head scan with the gold standard set by two radiology experts. Eight radiologists were given a cohort of 50 cranial T2WI studies and asked for a routine report. After a 10-day washout period, they reviewed the same cases randomized and supported by the DLA predictions. We assessed changes in sensitivity, specificity, accuracy, and false positives. (3) Results: During routine reporting, the models’ assistance improved the sensitivity of the eight participants by an average of 36.19 and the accuracy by 10.00 percentage points. (4) Conclusion: Our results indicate the potential benefit of deep learning to improve radiologists' detection of UIAs during routine reporting. From this, we can infer that the combination of T2WI with our DLA supports opportunistic screening, suggesting potential approaches for future research and application.

Shifts in Diagnostic Testing for Headache in the Emergency Department, 2015 to 2021

Subarachnoid hemorrhage is typically diagnosed by noncontrast head computed tomography (CT); lumbar puncture is recommended if computed tomography is nondiagnostic, although CT cerebral angiography has been promoted as an alternative to lumbar puncture in this diagnostic pathway. The outcomes of this debate in practice have not been studied. To determine whether CT cerebral angiography use has increased in lieu of lumbar puncture among emergency department (ED) patients with headache, with an increase in unruptured intracranial aneurysm detection. This retrospective cohort study took place in 21 community EDs of an integrated health care system in Northern California between 2015 and 2021. Participants were adult (aged >17 years) health plan members with a chief concern of headache. Exclusions were prior diagnoses of subarachnoid hemorrhage, unruptured intracranial aneurysm, cerebral arteriovenous malformation, or cerebrospinal fluid shunt. Data were analyzed from October to November 2023. CT cerebral angiography and/or lumbar puncture during the ED encounter. Primary and secondary outcomes were 14-day and 90-day unruptured intracranial aneurysm detection, respectively. Safety outcomes were missed diagnoses of subarachnoid hemorrhage or bacterial meningitis. The annual incidence of unruptured intracranial aneurysm detection was normalized to the incidence of subarachnoid hemorrhage (UIA:SAH ratio). Average annualized percentage changes were quantified using joinpoint regression analysis. Among 198 109 included ED encounters, the mean (SD) age was 47.5 (18.4) years; 140 001 patients (70.7%) were female; 29 035 (14.7%) were Black or African American, 59 896 (30.2%) were Hispanic or Latino, and 75 602 (38.2%) were White. Per year, CT cerebral angiography use increased (18.8%; 95% CI, 17.7% to 20.3%) and lumbar punctures decreased (-11.1%; 95% CI, -12.0% to -10.4%), with a corresponding increase in the 14-day UIA:SAH ratio (3.5%; 95% CI, 0.9% to 7.4%). Overall, computed tomography cerebral angiography use increased 6-fold relative to lumbar puncture, with a 33% increase in the detection of UIA. Results were similar at 90 days and robust to sensitivity analyses. Subarachnoid hemorrhage (1004 cases) and bacterial meningitis (118 cases) were misdiagnosed in 5% and 18% of cases, respectively, with no annual trends (P = .34; z1003 = .95 and P = .74; z117 = -.34, respectively). In this cohort study of ED patients with headache, increases in CT cerebral angiography use were associated with fewer lumbar punctures and higher detection of unruptured intracranial aneurysms, with no significant change in missed diagnoses of subarachnoid hemorrhage or bacterial meningitis. While this shift in diagnostic strategy appeared safe in the short-term, the long-term consequences remain unclear.

Geometric Deep Learning Using Vascular Surface Meshes for Modality-Independent Unruptured Intracranial Aneurysm Detection.

Early detection of unruptured intracranial aneurysms (UIAs) enables better rupture risk and preventative treatment assessment. UIAs are usually diagnosed on Time-of-Flight Magnetic Resonance Angiographs (TOF-MRA) or contrast-enhanced Computed Tomography Angiographs (CTA). Various automatic voxel-based deep learning UIA detection methods have been developed, but these are limited to a single modality. We propose a modality-independent UIA detection method using a geometric deep learning model with high resolution surface meshes of brain vessels. A mesh convolutional neural network with ResU-Net style architecture was used. UIA detection performance was investigated with different input and pooling mesh resolutions, and including additional edge input features (shape index and curvedness). Both a higher resolution mesh (15,000 edges) and additional curvature edge features improved performance (average sensitivity: 65.6%, false positive count/image (FPC/image): 1.61). UIAs were detected in an independent TOF-MRA test set and a CTA test set with average sensitivity of 52.0% and 48.3% and average FPC/image of 1.04 and 1.05 respectively. We provide modality-independent UIA detection using a deep-learning vascular surface mesh model with comparable performance to state-of-the-art UIA detection methods.

Hemodynamics of anterior circulation intracranial aneurysms with daughter blebs: investigating the multidirectionality of blood flow fields

Recent advances in diagnostic neuroradiological imaging, allowed the detection of unruptured intracranial aneurysms (IAs). The shape – irregular or multilobular – of the aneurysmal dome, is considered as a possible rupture risk factor, independently of the size, the location and patient medical background. Disturbed blood flow fields in particular is thought to play a key role in IAs progression. However, there is an absence of widely-used hemodynamic indices to quantify the extent of a multi-directional disturbed flow. We simulated blood flow in twelve patient-specific anterior circulation unruptured intracranial aneurysms with daughter blebs utilizing the spectral/hp element framework Nektar++. We simulated three cardiac cycles using a volumetric flow rate waveform while we considered blood as a Newtonian fluid. To investigate the multidirectionality of the blood flow fields, besides the time-averaged wall shear stress (TAWSS), we calculated the oscillatory shear index (OSI), the relative residence time (RRT) and the time-averaged cross flow index (TACFI). Our CFD simulations suggest that in the majority of our vascular models there is a formation of complex intrasaccular flow patterns, resulting to low and highly oscillating WSS, especially in the area of the daughter blebs. The existence of disturbed multi-directional blood flow fields is also evident by the distributions of the RRT and the TACFI. These findings further support the theory that IAs with daughter blebs are linked to a potentially increased rupture risk.

Smoking status and unruptured intracranial aneurysm among brain health check-up examinees: a cross-sectional study in Japan.

Objective: Although it is well known that smoking is a risk factor for subarachnoid hemorrhage, the association between smoking and unruptured intracranial aneurysms remains unclear. The aim of the present study was to investigate whether smoking status was associated with unruptured intracranial aneurysms among Japanese brain health check-up examinees.Materials and Methods: We conducted a cross-sectional study of 1,496 adults (aged 26–90 years) undergoing brain health check-ups at a single community medical support hospital in Akita, Japan between 2009 and 2013. In Japan, people can discretionarily undergo a brain health check-up for early detection of unruptured intracranial aneurysms or subarachnoid hemorrhages. Participants responded to a questionnaire on lifestyle, such as smoking status, and were classified into three groups: never, former, and current smoker. The evaluation of unruptured intracranial aneurysms detected by magnetic resonance angiography was performed by an expert physician. Multiple logistic regression models were used to estimate the odds ratio for unruptured intracranial aneurysms. We performed statistical analyses by age, sex, and family history of stroke.Results: The number of participants with unruptured intracranial aneurysms was 43 (2.9%). The mean age (standard deviation) and proportion of males was 55.8 (9.5) years and 53.3%, respectively. The adjusted odds ratios (95% confidence intervals) for unruptured intracranial aneurysms of 1.21 (0.48–3.08) among former smokers and 2.88 (1.10–7.50) among current smokers were compared to those of never smokers (p-trend = 0.041). After stratifying by age, sex, and family history of stroke, no interactions were found.Conclusion: This cross-sectional study conducted in Japan showed that smoking was positively associated with unruptured intracranial aneurysms among brain health check-up examinees.

Risk Factors for Unruptured Intracranial Aneurysms and Subarachnoid Hemorrhage in a Prospective Population-Based Study.

Background and Purpose- We wanted to evaluate potential risk factors for unruptured intracranial aneurysms (UIAs) and aneurysmal subarachnoid hemorrhage (aSAH) in a large, prospective study of the general population with risk factors collected before the detection of UIA or aSAH. Methods- All residents ≥20 years were invited to the HUNT (The Nord-Trøndelag Health Study). In this study, 89 951 participants were included. The study included standardized measurements of blood pressure and self-administered questionnaires. Cases of UIA and aSAH from 1999 to 2014 were identified using hospital records and the Norwegian Cause of Death Register. Hazard ratios with CIs were estimated using Cox regression analysis. Results- The detection rate of UIA was 8.2 per 100 000 person-years (97 patients). Current smoking (hazard ratio, 4.1; 95% CI, 2.4-7.1) and female sex (hazard ratio, 2.8; 95% CI, 1.7-4.5) were associated with markedly increased risk of UIA, but we found no association with systolic blood pressure (P for trend 0.62). The incidence of aSAH was 9.9 per 100 000 person-years (117 patients). The most important risk factors for aSAH were current smoking, female sex and increasing blood pressure (P for trend 0.006 for systolic blood pressure). Conclusions- In contrast to previous studies on risk factors of UIA, we found no association with systolic blood pressure. However, there was a strong association between systolic blood pressure and aSAH in the same population. Current smoking and female sex were associated with both diseases.

Risk Factors Associated With the Presence of Unruptured Intracranial Aneurysms.

With the increased investigation of cerebral arteries using magnetic resonance angiography in the general population, the detection of unruptured intracranial aneurysms (UIAs) has increased. Understanding the distribution and factors associated with UIAs might be helpful for understanding the pathomechanism. Subjects who underwent magnetic resonance angiography with a health examination at the Health Screening and Promotion Center were enrolled. The incidence and risk factors of UIAs (age, sex, hypertension, diabetes mellitus, smoking, alcohol, and coronary artery disease) were investigated by comparing patients with and without UIAs. These risk factors were also investigated by the UIA location, distal internal carotid artery, anterior cerebral artery and middle cerebral artery (MCA), MCA bifurcation, anterior and posterior communicating artery, and posterior circulation. Among 187 166 subjects who received health examination, 18 954 underwent magnetic resonance angiography. Of them, 367 (1.93%) had UIAs. Age (odds ratio [OR], 1.02; P=0.003), women (OR, 2.00; P<0.001), hypertension (OR, 2.21; P<0.001), smoking (OR, 1.66; P=0.001), and coronary artery disease (OR, 0.23; P<0.001) were independently associated with the presence of UIAs. Hypertension was associated with most UIAs, except for those located at sidewalls (anterior cerebral artery and MCA). MCA aneurysms were associated with old age and smoking. Distal internal carotid artery, posterior communicating artery, and MCA-bifurcation aneurysms were associated with female sex. Anterior communicating artery aneurysms were associated with smoking and alcohol. Posterior circulation UIAs were only associated with hypertension. Coronary artery disease was negatively associated with anterior circulation aneurysms. The risk factors for UIAs differ by their location, compared with the control. Interestingly, the presence of coronary artery disease was protective against the presence of UIAs.

Detection of unruptured intracranial aneurysms on noninvasive imaging. Is there still a role for digital subtraction angiography?

Background:To determine the utility of digital subtraction angiography (DSA) in patients with unruptured intracranial aneurysms (UIA) detected on noninvasive imaging, such as magnetic resonance angiography (MRA) and computed tomography angiography (CTA). The follow-up of patients with untreated UIAs involves serial imaging; however, this diagnosis may be based on false positive (FP) results. We examined the incidence of FPs in our institutional series.Methods:DSAs performed at our institution from January 2011 to June 2014 were retrospectively reviewed and patients referred with UIA detected on noninvasive imaging were selected. Clinical presentation as well as aneurysm location, size, and number reported on DSA and noninvasive imaging were assessed.Results:Two hundred and eighty six patients (mean age 56.8 years, female 74.8%) with a total of 355 UIA were included. Thirty-one patients had a symptomatic presentation. Analysis per patient showed the pooled FP rate of noninvasive imaging was 15%. MRA FP was 13% (22/171) and CTA FP was 18% (22/120). FP increased significantly with aneurysm size < 3.5 mm on MRA (P < 0.001) and <4.0 mm on CTA (P = 0.01). Mean aneurysm size among symptomatic patients was significantly larger (P < 0.001) as compared to the incidental group (17.8 vs. 7.7 mm). No location was significantly susceptible to false detection of aneurysms.Conclusion:DSA detection of FP UIA diagnosed on noninvasive imaging is significantly higher for aneurysms <4.0 mm. Accurate diagnosis with DSA may eliminate the need for further follow-up and its associated negative psychological and economic effects. Within the limitations of this retrospective study, we conclude that DSA has a diagnostic role in small aneurysms detected on noninvasive imaging.

Cognitive function, depression, anxiety and quality of life in Chinese patients with untreated unruptured intracranial aneurysms

Detected unruptured intracranial aneurysms (UIA) are becoming more common with the increased utilization of CT angiography, MR angiography and digital subtraction angiography. A proportion of patients with UIA remain untreated. We investigated to assess cognitive function, depression, anxiety and quality of life (QoL) in Chinese patients with untreated UIA. Thirty one Chinese patients with untreated UIA and 25 healthy controls were identified and matched for variables including age, sex, and living area. Cognitive function was evaluated with the Montreal Cognitive Assessment (MoCA). Depression, anxiety and QoL were screened with the Self-Rating Depression Scale, Self-Rating Anxiety Scale, and Short Form-36, respectively. Non-parametric tests were used for comparisons between groups. No patient had cognitive dysfunction at 1month or 1year after detection of UIA. However, a significant decrease of overall MoCA subscores was found in 30 (97%) of 31 patients 5years after UIA discovery, suggestive of mild cognitive impairment. A significant decrease in depression and anxiety was found in patients over time. QoL in patients was reduced most prominently in psychosocial function and social activities 1year after detection of UIA, but these improved to within normal limits at the end of the follow-up period. For Chinese patients with untreated UIA, depression, anxiety and reduced QoL may be short-term complications. Mild cognitive impairment may be a long-term complication.

Long-term behavioral and cognitive outcomes following clipping for incidental unruptured intracranial aneurysms.

Recent advances in neuroimaging techniques have resulted in more frequent detection of unruptured intracranial aneurysms. Regardless of the method employed, most interventions to treat lesions have low morbidity and mortality rates. Recently, some studies have suggested that changes in cognitive status are one complication of microsurgical treatments. However, no study to date has performed any behavioral analysis. Moreover, cognitive assessment beyond 12 months after surgical intervention is missing. The current study sought to evaluate the long-term impact of clipping on the behavioral and cognitive functions of patients with unruptured intracranial aneurysms. A within-subjects prospective clinical trial was performed to evaluate 40 patients who underwent microsurgical clipping for incidental unruptured intracranial aneurysms. The participants underwent a full neuropsychological evaluation during the preoperative period, at 3 months after surgery and at 3 years after surgery. Paired Student's t tests and an ANOVA, followed by a Bonferroni post hoc test, were used to examine group differences. The cognitive and behavioral test performance of the patients did not deteriorate during either the short or the long term following intervention. Moreover, the patients' clinical and demographic characteristics did not predict behavioral or cognitive changes, and neither the surgical approach nor the topography, multiplicity, or size of the aneurysms affected the results. In either the short or the long term following clipping for patients with incidental unruptured intracranial aneurysms, behavioral and cognitive functions had no significant change from baseline. The intervention demonstrated high efficacy and was associated with a low morbidity rate.

Role of MRA in the detection of intracranial aneurysm in the acute phase of subarachnoid hemorrhage

Magnetic resonance angiography (MRA) has been evaluated for the detection of unruptured intracranial aneurysms with favorable results at 3 Tesla (3T) and with similar diagnostic accuracy as both 3D time-of-flight (3D-TOF) and contrast-enhanced (CE-MRA) MRA. However, the diagnostic value and place of MRA in the detection of ruptured aneurysms has been little evaluated. Thus, the goal of this prospective single-center series was to assess the feasibility and diagnostic value of 3T 3D-TOF MRA and CE-MRA for aneurysm detection in acute non-traumatic subarachnoid hemorrhage (SAH). From March 2006 to December 2007, all consecutive patients admitted to our hospital with acute non-traumatic SAH (≤10 days) were prospectively included in this study evaluating MRA in the diagnostic workup of SAH. Feasibility of MRA and sensitivity/specificity of 3D-TOF and CE-MRA were assessed compared with gold standard DSA. In all, 84 consecutive patients (45 women, 39 men; age 23-86 years) were included. The feasibility of MRA was low (43/84, 51.2%). The reasons given for patients not undergoing magnetic resonance imaging (MRI) examination were clinical status (27 patients), potential delay in aneurysm treatment (11 patients) and contraindications to MRI (three patients). In patients explored by MRA, the sensitivity of CE-MRA (95%) was higher compared with 3D-TOF (86%) with similar specificity (80%). Also, 3D-TOF missed five aneurysms while CE-MRA missed two. The value of MRA in the diagnostic workup of ruptured aneurysms is limited due to its low feasibility during the acute phase of bleeding. Sensitivity for aneurysm detection was good for both MRA techniques, but tended to be better with CE-MRA.

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

Increasing detection of unruptured intracranial aneurysms, catastrophic outcomes from subarachnoid hemorrhage, and risks and cost of treatment necessitate defining objective predictive parameters of aneurysm rupture risk. Image-based computational fluid dynamics models have suggested associations between hemodynamics and intracranial aneurysm rupture, albeit with conflicting findings regarding wall shear stress. We propose that the "high-versus-low wall shear stress" controversy is a manifestation of the complexity of aneurysm pathophysiology, and both high and low wall shear stress can drive intracranial aneurysm growth and rupture. Low wall shear stress and high oscillatory shear index trigger an inflammatory-cell-mediated pathway, which could be associated with the growth and rupture of large, atherosclerotic aneurysm phenotypes, while high wall shear stress combined with a positive wall shear stress gradient trigger a mural-cell-mediated pathway, which could be associated with the growth and rupture of small or secondary bleb aneurysm phenotypes. This hypothesis correlates disparate intracranial aneurysm pathophysiology with the results of computational fluid dynamics in search of more reliable risk predictors.

Intracranial Aneurysms in Patients With Carotid Disease

Before the routine use of computed tomography (CT) angiography, decisions for carotid artery treatment were mostly based on ultrasound findings and conventional angiography. Implementation and increasing use of CT angiography provided better visualization of the carotid and vertebrobasilar arteries system leading to an unexpected more frequent detection of unruptured intracranial aneurysms (UIAs). Concomitant presence of intracranial aneurysms in patients with severe carotid stenosis is a potential cause of significant mortality and morbidity. Due to the possible higher risk of aneurysm rupture after carotid procedures and ischemic events after aneurysm repair, the simultaneous presence of both lesions creates several therapeutic dilemmas. We review the prevalence of UIAs in patients with carotid occlusive disease and management difficulties and the current treatment strategies for handling the concomitant presence of these life-threatening diseases.

Detection of unruptured cerebral artery aneurysms by MRA at 3.0 tesla: comparison with multislice helical computed tomographic angiography

Computed tomographic angiography (CTA) has become the primary non-invasive method for detection of cerebral artery aneurysms in many neurovascular centers. To compare MR-angiography at a 3.0 tesla (3T) scanner to CTA in the detection of unruptured intracranial aneurysms. CTA and 3T MRA data from 60 patients were evaluated. CTA was obtained with a 4-16-row helical CT-scanner after administration of 120 cc intravenous contrast agent, MRA was performed by a 3T MR-scanner using time-of-flight pulse sequence. Fifty-five cerebral artery aneurysms were detected by MRA and 47 aneurysms by CTA. Most of the aneurysms detected by MRA but not by CTA were small internal carotid artery (ICA) aneurysms. Bone structures and venous enhancement deteriorated CTA accuracy, especially in skull base. In one patient a fairly large anterior communicating artery aneurysm was not visible in MRA due to spin saturation, although it was clearly visualized in CTA. After contrast injection the aneurysm was also seen in MRA. Although the overall image quality of MRA and CTA were comparable, MRA was more susceptible to artifacts and thus re-formatted surface-shaded volume rendered 3-dimensional images of aneurysms from MRA were inferior compared to those from CTA. MRA at 3T appears to be at least as sensitive as CTA in the detection of unruptured cerebral artery aneurysms, however image quality control is crucial and contrast agent enhances visualization of complex and large aneurysms.

Automated computerized scheme for detection of unruptured intracranial aneurysms in three-dimensional magnetic resonance angiography 1

A computerized scheme for automated detection of unruptured intracranial aneurysms in magnetic resonance angiography was developed based on the use of a three-dimensional selective enhancement filter for dots (aneurysms). Twenty-nine cases with 36 unruptured aneurysms (diameter, 3 to 26 mm; mean, 6.6 mm) and 31 non-aneurysm cases were used in this study. The isotropic 3-dimensional magnetic resonance angiography images with 400 x 400 x 128 voxels (voxel size, 0.5 mm) were processed by use of the selective enhancement filter. The initial candidates were identified by use of a multiple gray-level thresholding technique on the dot-enhanced images and a region-growing technique with monitoring some image features. All candidates were classified into four types of candidates according to the size and local structures based on the effective diameter and skeleton image of each candidate (ie, large candidates and three types of small candidates including short-branch type, single-vessel type, and bifurcation type). In each group, a number of false-positives were removed by use of different rules on localized image features related to gray levels and morphology. Linear discriminant analysis was used for further removal of false-positives. With this computer-aided diagnostic scheme, all of 36 aneurysms were correctly detected with 2.4 false-positives per patient based on a leave-one-out-by-patient test method. This computer-aided diagnostic system would be useful in assisting radiologists for the detection of intracranial aneurysms in magnetic resonance angiography.

破裂および未破裂脳動脈瘤のMRA診断

Most previous reports have explored the efficacy of magnetic resonance angiography (MRA) as a noninvasive screening method for the detection of unruptured intracranial aneurysms and occlusive vascular disease. The purpose of this study was to assess the accuracy of three-dimensional (3D) time-of-flight (TOF) MRA in the identification of ruptured aneurysms presenting subarachnoid hemorrhage (SAH) as well as unruptured aneurysms. Sixty-two consecutive patients with 36 ruptured and 32 unruptured aneurysms were examined. MR angiograms and conventional contrast angiograms were retrospectively reviewed with regard to the relation between the detectability on MRA and size of aneurysm, location, and influence of subarachnoid hematoma. The size of ruptured aneurysms was significantly larger than that of unruptured aneurysms. Twenty-seven of 29 ruptured aneurysms in acute stage (93%) was detected on MRA, whereas 29 of 36 unruptured aneurysms (81%) and none of 4 ruptured aneurysms in subacute stage (0%) were detectable. Individual vessel visualization and image quality of MRA in patients with acute SAH were satisfactory, although in patients with subacute SAH, MRA showed poor visualization of vessels due to T1-shortening of subacute surrounding hematoma and presence of delayed vasospasm. Main causes of failure to detect aneurysms on MRA included limitation of spatial resolution, limited projections obtainable with maximum-intensity-projection (MIP) techniques and subacute hematoma simulating flow signal on MIP reconstructions. Improvement of present limitation of MRA requires higher spatial resolution, higher contrast resolution and a more adequate reconstruction method. MRA was considered to be a safe and useful examination for intracranial aneurysms especially in patients with acute SAH.

Respiratory monitoring

<h3>Summary:</h3> Increasing detection of unruptured intracranial aneurysms, catastrophic outcomes from subarachnoid hemorrhage, and risks and cost of treatment necessitate defining objective predictive parameters of aneurysm rupture risk. Image-based computational fluid dynamics models have suggested associations between hemodynamics and intracranial aneurysm rupture, albeit with conflicting findings regarding wall shear stress. We propose that the “high-versus-low wall shear stress” controversy is a manifestation of the complexity of aneurysm pathophysiology, and both high and low wall shear stress can drive intracranial aneurysm growth and rupture. Low wall shear stress and high oscillatory shear index trigger an inflammatory-cell-mediated pathway, which could be associated with the growth and rupture of large, atherosclerotic aneurysm phenotypes, while high wall shear stress combined with a positive wall shear stress gradient trigger a mural-cell-mediated pathway, which could be associated with the growth and rupture of small or secondary bleb aneurysm phenotypes. This hypothesis correlates disparate intracranial aneurysm pathophysiology with the results of computational fluid dynamics in search of more reliable risk predictors.