CNS-associated macrophages contribute to intracerebral aneurysm pathophysiology.

Intracerebral aneurysms (IAs) are pathological dilatations of cerebral arteries whose rupture leads to subarachnoid hemorrhage, a significant cause of disability and death. Inflammation is recognized as a critical contributor to the formation, growth, and rupture of IAs; however, its precise actors have not yet been fully elucidated. Here, we report CNS-associated macrophages (CAMs), also known as border-associated macrophages, as one of the key players in IA pathogenesis, acting as critical mediators of inflammatory processes related to IA ruptures. Using a new mouse model of middle cerebral artery (MCA) aneurysms we show that CAMs accumulate in the IA walls. This finding was confirmed in a human MCA aneurysm obtained after surgical clipping, together with other pathological characteristics found in the experimental model including morphological changes and inflammatory cell infiltration. In addition, in vivo longitudinal molecular MRI studies revealed vascular inflammation strongly associated with the aneurysm area, i.e., high expression of VCAM-1 and P-selectin adhesion molecules, which precedes and predicts the bleeding extent in the case of IA rupture. Specific CAM depletion by intracerebroventricular injection of clodronate liposomes prior to IA induction reduced IA formation and rupture rate. Moreover, the absence of CAMs ameliorated the outcome severity of IA ruptures resulting in smaller hemorrhages, accompanied by reduced neutrophil infiltration. Our data shed light on the unexplored role of CAMs as main actors orchestrating the progression of IAs towards a rupture-prone state.

Towards the mechanical characterisation of unruptured intracranial aneurysms: Numerical modelling of interactions between a deformation device and the aneurysm wall.

Intracranial aneurysm is a critical pathology related to the arterial wall deterioration. This work is an essential aspect of a large scale project aimed at providing clinicians with a non-invasive patient-specific decision support tool regarding the rupture risk assessment. A machine learning algorithm links the aneurysm shape observed and a database of UIA clinical images associated with in vivo wall mechanical properties and rupture characterisation. The database constitution is derived from a device prototype coupled with medical imaging. It provides the mechanical characterisation of the aneurysm from the wall deformation obtained by inverse analysis based on the variation of luminal volume. Before performing in vivo tests of the device on small animals, a numerical model was built to quantify the device's impact on the aneurysm wall under natural blood flow conditions. As the clinician will never be able to precisely situate the device, several locations were considered. In preparation for the inverse analysis procedure, artery material laws of increasing complexity were studied (linear elastic, hyper elastic Fung-like). Considering all the device locations and material laws, the device induced relative displacements to the Systole peak (worst case scenario with the highest mechanical stimulus linked to the blood flow) ranging from 375 µm to 1.28 mm. The variation of luminal volume associated with the displacements was between 0.95 % and 4.3 % compared to the initial Systole volume of the aneurysm. Significant increase of the relative displacements and volume variations were found with the study of different cardiac cycle moments between the blood flow alone and the device application. For forthcoming animal model studies, Spectral Photon CT Counting, with a minimum spatial resolution of 250 µm, was selected as the clinical imaging technique. Based on this preliminary study, the displacements and associated volume variations (baseline for inverse analyse), should be observable and exploitable.

Serum Interleukin-1 Levels Are Associated with Intracranial Aneurysm Instability.

Serum interleukin-1 (IL-1) are possibly indicative of the inflammation in the intracranial aneurysm (IA) wall. This study aimed to investigate whether IL-1 could discriminate the unstable IAs (ruptured intracranial aneurysms (RIAs) and symptomatic unruptured intracranial aneurysms (UIAs)) from stable, asymptomatic UIAs. IA tissues and blood samples from 35 RIA patients and 35 UIA patients were collected between January 2017 and June 2020 as the derivation cohort. Blood samples from 211 patients with UIAs were collected between January 2021 and June 2022 as the validation cohort (including 63 symptomatic UIAs). Blood samples from 35 non-cerebral-edema meningioma patients (non-inflammatory control) and 19 patients with unknown-cause subarachnoid hemorrhage (hemorrhagic control) were also collected. IL-1ß and IL-1.ra (IL-1 receptor antagonist) were measured in serum and IA tissues, and the IL-1 ratio was calculated as log10 (IL-1.ra/IL-1ß). Based on the derivation cohort, multivariate logistic analysis showed that IL-1ß (odds ratio, 1.48, P = 0.001) and IL-1.ra (odds ratio, 0.74, P = 0.005) were associated with RIAs. The IL-1 ratio showed an excellent diagnostic accuracy for RIAs (c-statistic, 0.91). Histological analysis confirmed the significant correlation of IL-1 between serum and aneurysm tissues. IL-1 ratio could discriminate UIAs from non-inflammatory controls (c-statistic, 0.84), and RIAs from hemorrhagic controls (c-statistic, 0.95). Based on the validation cohort, the combination of IL-1 ratio and PHASES score had better diagnostic accuracy for symptomatic UIAs than PHASES score alone (c-statistic, 0.88 vs 0.80, P < 0.001). Serum IL-1 levels correlate with aneurysm tissue IL-1 levels and unstable aneurysm status, and could serve as a potential biomarker for IA instability.

Microsurgical clipping of ruptured supraclinoid internal carotid artery aneurysm with extradural clinoidectomy.

BACKGROUND: Supraclinoid Internal Carotid Artery (ICA) aneurysms require additional access to standard pterional craniotomy via extradural clinoidectomy. Existing texts and surgical videos lack clarity, explanation and a clear step by step process. CASE DESCRIPTION: We present a case of a ruptured supraclinoid ICA aneurysm and extradural clinoidectomy along with 3D reconstructed imaging of the case anatomy to guide its resection. Real-time unedited on table rerupture provides an example of management. CONCLUSION: Extradural Anterior Clinoidectomy is a key maneuver in cerebrovascular surgical armamentarium for clipping of supraclinoid aneurysms. Stereotypical Pathological or Surgical Anatomy, its application, and availability with 3D imaging should be facilitates the framing and learning of normal physiological anatomy.

Wall enhancement as a biomarker of intracranial aneurysm instability: a histo-radiological study.

BACKGROUND: The aim of this is to explore the histological basis of vessel wall enhancement (WE) on magnetic resonance imaging (MRI), which is a strong radiological biomarker of aneurysmal prone to rupture compared to other classical risk predictors (e.g., PHASES score, size, morphology). METHODS: A prospective observational study was performed including all consecutive patients presenting with a saccular intracranial aneurysm at Vall d'Hebron University Hospital between October 2017 and May 2019. The patients underwent high-resolution 3 T MRI, and their aneurysms were classified into asymptomatic, symptomatic, and ruptured. A histological and immunohistochemical study was performed in a subgroup of patients (n = 20, of which 15 presented with WE). Multiple regression analyses were performed to identify predictors of rupture and aneurysm symptoms. RESULTS: A total of 132 patients were enrolled in the study. WE was present in 36.5% of aneurysms: 22.9% asymptomatic, 76.9% symptomatic, and 100% ruptured. Immunohistochemical markers associated with WE were CD3 T cell receptor (p = 0.05) and CD45 leukocyte common antigen (p = 0.05). Moreover, WE is an independent predictor of symptomatic and ruptured aneurysms (p < 0.001). CONCLUSIONS: Aneurysms with WE present multiple histopathological changes that may contribute to wall disruption and represent the pathophysiological basis of radiological WE. Moreover, WE is an independent diagnostic predictor of aneurysm symptoms and rupture.

Molecular Subtypes and Machine Learning-Based Predictive Models for Intracranial Aneurysm Rupture.

BACKGROUND: The determination of biological mechanisms and biomarkers related to intracranial aneurysm (IA) rupture is of utmost significance for the development of effective preventive and therapeutic strategies in the clinical field. METHODS: GSE122897 and GSE13353 datasets were downloaded from Gene Expression Omnibus. Data extracted from GSE122897 were used for analyzing differential gene expression, and consensus clustering was performed to identify stable molecular subtypes. Clinical characteristics were compared between subgroups, and fast gene set enrichment analysis and weighted gene coexpression network analysis were performed. Hub genes were identified via least absolute shrinkage and selection operator analysis. Predictive models were constructed based on hub genes using the Light Gradient Boosting Machine, eXtreme Gradient Boosting, and logistic regression algorithm. Immune cell infiltration in IA samples was analyzed using Microenvironment Cell Population counter, CIBERSORT, and xCell algorithm. The correlation between hub genes and immune cells was analyzed. The predictive model and immune cell infiltration were validated using data from the GSE13353 dataset. RESULTS: A total of 43 IA samples were classified into 2 subgroups based on gene expression profiles. Subgroup I had a higher risk of rupture, while 70% of subgroup II remained unruptured. In subgroup I, specific genes were associated with inflammation and immunity, and weighted gene coexpression network analysis revealed that the black module genes were linked to IA rupture. We identified 4 hub genes (spermine synthase, macrophage receptor with collagenous structure, zymogen granule protein 16B, and LIM and calponin-homology domains 1), which constructed predictive models with good diagnostic performance in differentiating between ruptured and unruptured IA samples. Monocytic lineage was found to be a significant factor in IA rupture, and the 4 hub genes were linked to monocytic lineage (P < 0.05). CONCLUSIONS: We reveal a new molecular subtype that can reflect the actual pathological state of IA rupture, and our predictive models constructed by machine learning algorithms can efficiently predict IA rupture.

Unilateral cerebral arterial tortuosity: Associated with aneurysm occurrence, but potentially inversely associated with aneurysm rupture.

PURPOSE: To investigate the association of tortuosity of the main cerebral arteries with intracranial aneurysm (IA) occurrence and rupture. To investigate the relationship between arterial tortuosity and aneurysm morphology as well as conventional risk factors of vascular diseases. METHODS: Three subject groups were analyzed in this study: Patients with ruptured IAs, patients with unruptured IAs, and healthy subjects. The groups were matched by sex and age using tendency score matching. Their intracranial magnetic resonance angiography (MRA) images were collected retrospectively. The intracranial arterial structures were segmented from the MRA images. Arterial tortuosity was measured and statistically compared between the different subject groups and different vessels. Correlation analysis was conducted between arterial tortuosity and clinical risk factors as well as aneurysm morphology. RESULTS: 120 patients were included in the study (average age: 67.5 years; 60% female), 40 for each group after matching. The tortuosity of the aneurysm-bearing artery was significantly greater than that of the contralateral artery in both the ruptured and unruptured IA groups (p < 0.001). There was no significant association between clinical risk factors (history of hypertension, hyperlipidemia, diabetes, smoking, and alcohol use) and arterial tortuosity. There were significant negative correlations between aneurysm-bearing artery tortuosity and aneurysm morphological features such as maximal diameter (p = 0.0011), neck diameter (p < 0.0001), maximum height (p = 0.0024), and size ratio (p = 0.0269). CONCLUSION: The occurrence of cerebral aneurysms correlates to increased unilateral arterial tortuosity, but the risk of aneurysm enlargement/rupturing decreases with greater arterial tortuosity. Abnormal tortuosity may be congenital as tortuosity has no clear connection with acquired common risk factors of vascular diseases.

Performance of rupture-related morphological parameters in posterior communicating artery aneurysms with fetal-type variant.

BACKGROUND: The aim of the study was to investigate the impact of fetal-type posterior cerebral artery (fPCA) variant on morphological parameters of posterior communicating artery (PComA) aneurysms for rupture risk assessment. MATERIALS AND METHODS: A total of 98 PComA aneurysms (62 ruptured and 36 unruptured) in 98 consecutive patients were reviewed. Morphological parameters were calculated including aneurysm size, aspect ratio (AR), size ratio (SR), dome-to-neck ratio, bottleneck factor and inflow angle. Performances of morphological parameters to discriminate rupture status were compared between aneurysms with or without fPCA. RESULTS: Fetal-type posterior cerebral artery variant was determined in 39 (39.8%, 25 ruptured and 14 unruptured) lesions. The ruptured group revealed a significantly larger size (p = 0.004), AR (p = 0.003), SR (p = 0.001), and inflow angle (p < 0.001). For the aneurysms without fPCA, all morphological parameters were significantly different between ruptured and unruptured aneurysms (p < 0.05); for the aneurysms with fPCA, only inflow angle (p = 0.001) was significantly related with the rupture status. Multivariate analysis showed that SR (p = 0.035 and p = 0.011) and inflow angle (p = 0.001 and p = 0.028) were independent rupture risk factors for the total cohort and the aneurysms without fPCA; while only inflow angle (p = 0.004) revealed to be independently related with rupture status of aneurysms without fPCA. CONCLUSIONS: The performances of morphological parameters to discriminate rupture status were different between PComA aneurysms with and without fPCA variants. Inflow angle might be a reliable predictor for rupture risk of PComA aneurysms.

Plasma metabolic signatures for intracranial aneurysm and its rupture identified by pseudotargeted metabolomics.

BACKGROUND AND AIMS: The vital metabolic signatures for IA risk stratification and its potential biological underpinnings remain elusive. Our study aimed to develop an early diagnosis model and rupture classification model by analyzing plasma metabolic profiles of IA patients. MATERIALS AND METHODS: Plasma samples from a cohort of 105 participants, including 75 IA patients in unruptured and ruptured status (UIA, RIA) and 30 control participants were collected for comprehensive metabolic evaluation using ultra-high-performance liquid chromatography-mass spectrometry-based pseudotargeted metabolomics method. Furthermore, an integrated machine learning strategy based on LASSO, random forest and logistic regression were used for feature selection and model construction. RESULTS: The metabolic profiling disturbed significantly in UIA and RIA patients. Notably, adenosine content was significantly downregulated in UIA, and various glycine-conjugated secondary bile acids were decreased in RIA patients. Enriched KEGG pathways included glutathione metabolism and bile acid metabolism. Two sets of biomarker panels were defined to discriminate IA and its rupture with the area under receiver operating characteristic curve of 0.843 and 0.929 on the validation sets, respectively. CONCLUSIONS: The present study could contribute to a better understanding of IA etiopathogenesis and facilitate discovery of new therapeutic targets. The metabolite panels may serve as potential non-invasive diagnostic and risk stratification tool for IA.

Increased macrophage M2/M1 ratio is associated with intracranial aneurysm rupture.

PURPOSE: Intracranial aneurysm (IA) rupture results in one of the most severe forms of stroke, with severe neurological sequelae. Inflammation appears to drive aneurysm formation and progression with macrophages playing a key role in this process. However, less is known about their involvement in aneurysm rupture. This study is aimed at demonstrating how relationship between the M1 (pro-inflammatory) and M2 (reparative) macrophage subtypes affect an aneurysm's structure resulting in its rupture. METHODS: Forty-one saccular aneurysm wall samples were collected during surgery including 13 ruptured and 28 unruptured aneurysm sacs. Structural changes were evaluated using histological staining. Macrophages in the aneurysm wall were quantified and defined as M1 and M2 using HLA-DR and CD163 antibodies. Aneurysm samples were divided into four groups according to the structural changes and the M2/1 ratio. Data were analyzed using the Mann-Whitney U test. RESULTS: This study has demonstrated an association between the severity of structural changes of an aneurysm with inflammatory cell infiltration within its wall and subsequent aneurysm rupture. More severe morphological changes and a significantly higher number of inflammatory cells were observed in ruptured IAs (p < 0.001). There was a prevalence of M2 macrophage subtypes within the wall of ruptured aneurysms (p < 0.001). A subgroup of unruptured IAs with morphological and inflammatory changes similar to ruptured IAs was observed. The common feature of this subgroup was the presence of an intraluminal thrombus. CONCLUSIONS: The degree of inflammatory cell infiltration associated with a shift in macrophage phenotype towards M2 macrophages could play an important role in structural changes of the aneurysm wall leading to its rupture.

Double jeopardy - pituitary apoplexy complicated by ruptured aneurysm of the internal carotid artery within an adenoma: a case report.

BACKGROUND: Sudden onset of severe headache is the most common presentation of a ruptured intracranial aneurysm. Similar symptoms can be caused by pituitary apoplexy, and radiological examination is needed to distinguish between the two. Development of infarction and/or haemorrhage of the hypophysis with concomitant unruptured cerebral aneurysm has been described. However, intratumoural aneurysm within a pituitary adenoma presenting with the ictus of both pathologies is extremely rare. CASE PRESENTATION: A 64-year-old man presented with classic symptoms of pituitary apoplexy. His symptoms improved after a few days, and he was discharged. However, he subsequently developed further episodes of sudden and severe headache together with visual decline and ophthalmoplegia. Radiographs demonstrated an enlarging sellar mass with suspicion of a ruptured internal carotid artery aneurysm, within the apoplectic pituitary macroadenoma. Although an endovascular procedure was planned, the patient developed massive subarachnoid haemorrhage resulting in brain death. CONCLUSION: This case report describes an intratumoural aneurysm of the cavernous internal carotid artery as a potential cause or result of pituitary apoplexy. Despite its rarity, this possible life-threatening complication of pituitary apoplexy should be recognised for prompt diagnosis and early management.

Lymphatic vessels are present in human saccular intracranial aneurysms.

Saccular intracranial aneurysm (sIA) rupture leads to subarachnoid haemorrhage and is preceded by chronic inflammation and atherosclerotic changes of the sIA wall. Increased lymphangiogenesis has been detected in atherosclerotic extracranial arteries and in abdominal aortic aneurysms, but the presence of lymphatic vessels in sIAs has remained unexplored. Here we studied the presence of lymphatic vessels in 36 intraoperatively resected sIAs (16 unruptured and 20 ruptured), using immunohistochemical and immunofluorescence stainings for lymphatic endothelial cell (LEC) markers. Of these LEC-markers, both extracellular and intracellular LYVE-1-, podoplanin-, VEGFR-3-, and Prox1-positive stainings were detected in 83%, 94%, 100%, and 72% of the 36 sIA walls, respectively. Lymphatic vessels were identified as ring-shaped structures positive for one or more of the LEC markers. Of the sIAs, 78% contained lymphatic vessels positive for at least one LEC marker. The presence of LECs and lymphatic vessels were associated with the number of CD68+ and CD163+ cells in the sIA walls, and with the expression of inflammation indicators such as serum amyloid A, myeloperoxidase, and cyclo-oxygenase 2, with the presence of a thrombus, and with the sIA wall rupture. Large areas of VEGFR-3 and α-smooth muscle actin (αSMA) double-positive cells were detected in medial parts of the sIA walls. Also, a few podoplanin and αSMA double-positive cells were discovered. In addition, LYVE-1 and CD68 double-positive cells were detected in the sIA walls and in the thrombus revealing that certain CD68+ macrophages are capable of expressing LEC markers. This study demonstrates for the first time the presence of lymphatic vessels in human sIA walls. Further studies are needed to understand the role of lymphatic vessels in the pathogenesis of sIA.

The prognosis and treatment effectiveness of de novo aneurysm formation after radiation therapy for brain tumor.

Radiation therapy is a well-established, minimally invasive method of treating brain tumors. In recent years, the number of post-radiotherapy patients has increased, and delayed side effects are evident. De novo aneurysm formation after radiation often manifests as fatal subarachnoid hemorrhage (SAH), resulting in severe clinical outcomes. Nevertheless, the prognosis and therapeutic efficacy of radiation-induced aneurysms (RIAs) remain unclear. Using the PubMed database from 1980 to 2021, we screened 45 articles (53 individual cases) on RIAs; approximately 70% of RIAs were diagnosed after rupture. Of 38 ruptured RIAs, 12 (31.6%) had modified Rankin scale (mRS) 5-6. On the other hand, all unruptured RIAs (15 cases) recovered without neurological deficits (p = 0.012). Ten of the 39 ruptured RIAs were treated surgically, and 22 were treated endovascularly. There was no significant difference in mRS between treatment modalities (p = 0.393), but conservative therapy was significantly related to unfavorable outcomes (p = 0.025). To improve clinical outcomes, RIAs need to be diagnosed before rupture. Surgeons should be aware of de novo aneurysm formation in patients long after radiation therapy.

An imbalance between RAGE/MR/HMGB1 and ATP1α3 is associated with inflammatory changes in rat brain harboring cerebral aneurysms prone to rupture.

BACKGROUND AND PURPOSE: An aneurysmal subarachnoid hemorrhage is a devastating event. To establish an effective therapeutic strategy, its pathogenesis must be clarified, particularly the pathophysiology of brain harboring intracranial aneurysms (IAs). To elucidate the pathology in brain harboring IAs, we examined the significance of the receptor for advanced glycation end-products (RAGE)/mineralocorticoid receptor (MR) pathway and Na+/K+-ATPase (ATP1α3). METHODS: Ten-week-old female rats were subjected to oophorectomy as well as hypertension and hemodynamic changes to induce IAs, and were fed a high-salt diet. Brain damage in these rats was assessed by inflammatory changes in comparison to sham-operated rats fed a standard diet. RESULTS: Six weeks after IA induction (n = 30), irregular morphological changes, i.e., an enlarged vessel diameter and vascular wall, were observed in all of the left posterior cerebral arteries (Lt PCAs) prone to rupture. Approximately 20% of rats had ruptured IAs within 6 weeks. In brain harboring unruptured IAs at the PCA, the mRNA levels of RAGE and MR were higher, and that of ATP1α3 was lower than those in the sham-operated rats (p < 0.05, each). Immunohistochemically, elevated expression of RAGE and MR, and decreased expression of ATP1α3 were observed in the brain parenchyma adjacent to the Lt PCA, resulting in increased Iba-1 and S100B expression that reflected the inflammatory changes. There was no difference between the unruptured and ruptured aneurysm rat groups. Treatment with the MR antagonist esaxerenone abrogated these changes, and led to cerebral and vascular normalization and prolonged subarachnoid hemorrhage-free survival (p < 0.05). CONCLUSIONS: Regulation of the imbalance between the RAGE/MR pathway and ATP1α3 may help attenuate the damage in brain harboring IAs, and further studies are warranted to clarify the significance of the down-regulation of the MR/RAGE pathway and the up-regulation of ATP1α3 for attenuating the pathological changes in brain harboring IAs.

Association of bleb formation with peri-aneurysmal contact in unruptured intracranial aneurysms.

The mechanism of bleb formation in unruptured intracranial aneurysms (UIAs) remains unclear. This study aimed to investigate the association between peri-aneurysmal contact (PAC) and bleb formation. Forty-five aneurysms were classified depending on the presence of blebs and PAC using computed tomographic angiography and magnetic resonance imaging. Aneurysmal hemodynamics were assessed using computational fluid dynamics. The independent variables associated with bleb formation were statistically assessed. Fourteen aneurysms (31.1%) had blebs, all of which were located at the site of PAC (group A). Thirty-one aneurysms (68.9%) had no bleb, of which 13 had a PAC (group B) and 18 had no PAC (group C). PAC was the only independent variable associated with bleb formation (p < 0.05). Aneurysmal volumes were significantly higher in group A, followed by groups B and C in series. Aneurysmal wall shear stress (WSS) tended to be lowest in group A, followed by groups B and C in series. The maximum WSS at the blebs was only 17% of the maximum WSS at the aneurysmal domes. This study demonstrated that bleb formation in UIAs was associated with the establishment of PAC during their growth, which may have more detrimental effects on bleb formation than hemodynamics.

Impact of inflammation-related degenerative changes on the wall strength of unruptured intracranial aneurysms: a pilot study.

INTRODUCTION: Saccular intracranial aneurysm (sIA) rupture is a serious cerebrovascular event associated with inflammatory destructive processes leading to gradual weakening of the sIA wall. The aim of the present study was to identify the morphological and histological determinants for low wall strength in unruptured sIAs harvested from autopsy subjects. MATERIAL AND METHODS: A total of eight single unruptured sIAs were identified and excised with adjacent cerebral arteries during 8 of 184 postmortem examinations. The dome morphology was assessed for each sIA at a constant pressure of 100 mmHg. Then, after 5 preconditioning cycles which assured muscle fibre relaxation, sIA specimens were subjected to gradually increasing intraluminal pressure at a rate of 20 mmHg/s until rupture of the sIA or cerebral artery was achieved. Micro-structural degenerative changes and inflammatory cell infiltration within the sIA wall were quantitatively analysed after pressurization of the sIA specimens. The microscopic analysis of the slides stained with histological methods (HE, Mallory trichrome, Masson trichrome, orcein) and immunohistochemical methods (LCA, CD3, CD68) was performed. RESULTS: The wall of the sIA ruptured in three specimens, while in the other cases, rupture occurred at the arterial wall. The mean maximal dome size was significantly larger in sIAs with low wall strength, that is, in sIAs that ruptured during pressurization, than in sIAs with high wall strength (6.46 mm vs. 2.43 mm, p = 0.034). Moreover, a significantly higher average percentage of wall hyalinization in sIAs that ruptured than in sIAs that did not rupture was observed (30% vs. 0%, p = 0.006). In contrast, the degree of inflammatory cell infiltration did not differ between the wall strength categories. CONCLUSIONS: Our results support the observations that larger sIAs may be at a higher risk of rupture. Histological analysis revealed that hyalinization corresponds to the weakened regions of the wall of unruptured sIAs.

Moments of Intra-Dome Velocity Distribution as Robust Predictors of Rupture Status in Cerebral Aneurysms.

BACKGROUND: Wall shear stress (WSS), the spatial gradient of flow velocity at luminal surface, has been employed for aneurysmal hemodynamic analysis, but it is sensitive to surface irregularities and noise. We devised a volumetric approach to evaluate discriminant power of intra-dome flow velocity distribution and modal analysis in rupture status determination compared with previously described WSS analysis. METHODS: Catheter three-dimensional rotational angiographic datasets matched for volume were segmented in 20 sidewall aneurysms (10 ruptured), computational fluid dynamics simulations were performed, and velocity distributions were extracted from mesh-independent isometric sampling followed by moment analysis (mean, variance, skewness, and kurtosis). Univariate and multivariate analysis was used to evaluate discriminant performance of velocity moments. Sensitivity of velocity moments and WSS was evaluated to bleb presence and surface irregularity using digital bleb removal and surface noise addition. RESULTS: Velocity moments of ruptured aneurysms showed higher skewness (2.45 ± 0.57 vs. 1.36 ± 0.82, P = 0.003) and kurtosis (11.83 ± 4.77 vs. 6.05 ± 4.65, P = 0.01) with lower mean (0.019 ± 0.01 vs. 0.038 ± 0.02, P = 0.03) compared with unruptured lesions; in multivariate modeling, skewness alone emerged as best predictor (area under the curve = 0.88). Bleb removal increased low WSS by 548%, and surface noise decreased it by 85.8% while having a smaller (<7%) effect on velocity skewness and kurtosis. CONCLUSIONS: High aneurysm dome flow velocity skewness and kurtosis suggest an exponential distribution in ruptured lesions, with high peaks at low velocities, consistent with areas of slow flow. In contrast to WSS-based techniques, this approach is robust against surface variations, with promising improved rupture status discriminant performance that requires further validation in expanded future studies.

Intracranial aneurysm wall (in)stability-current state of knowledge and clinical perspectives.

Intracranial aneurysm (IA), a local outpouching of cerebral arteries, is present in 3 to 5% of the population. Once formed, an IA can remain stable, grow, or rupture. Determining the evolution of IAs is almost impossible. Rupture of an IA leads to subarachnoid hemorrhage and affects mostly young people with heavy consequences in terms of death, disabilities, and socioeconomic burden. Even if the large majority of IAs will never rupture, it is critical to determine which IA might be at risk of rupture. IA (in)stability is dependent on the composition of its wall and on its ability to repair. The biology of the IA wall is complex and not completely understood. Nowadays, the risk of rupture of an IA is estimated in clinics by using scores based on the characteristics of the IA itself and on the anamnesis of the patient. Classification and prediction using these scores are not satisfying and decisions whether a patient should be observed or treated need to be better informed by more reliable biomarkers. In the present review, the effects of known risk factors for rupture, as well as the effects of biomechanical forces on the IA wall composition, will be summarized. Moreover, recent advances in high-resolution vessel wall magnetic resonance imaging, which are promising tools to discriminate between stable and unstable IAs, will be described. Common data elements recently defined to improve IA disease knowledge and disease management will be presented. Finally, recent findings in genetics will be introduced and future directions in the field of IA will be exposed.

Enhanced Radiomics for Prediction of Rupture Status in Cerebral Aneurysms.

BACKGROUND: Radiomics is a powerful tool for automatic extraction of morphological features, but when applied to cerebral aneurysms, it is inferior to established descriptors in classifying rupture status. We sought a strategy to recover neck orientation and parent vessel caliber to enhance Radiomics performance and facilitate its adoption for aneurysm risk stratification. METHODS: We analyzed 135 sidewall (32 ruptured) and 216 bifurcation (90 ruptured) aneurysms from three-dimensional rotational catheter angiography datasets. Clinical three-dimensional rotational catheter angiography defined in arbitrary orientation underwent affine transformations enabling aneurysm neck alignment to XY plane before analysis in PyRadiomics, facilitating automatic extraction of aneurysm height and width, previously not possible with random alignment. Additionally, parent vessel size was estimated from aneurysm location and incorporated into enhanced Radiomics (height, width, height/width, size ratio). Rupture status classification was compared across methodologies for 31 automatically computed conventional Radiomics, enhanced Radiomics, and established size/shape descriptors using univariate, multivariate, and area under the curve (AUC) statistics. RESULTS: Enhanced Radiomics-derived height/width and size ratio were significantly higher in both ruptured subsets. Using multivariate analysis in sidewall lesions, enhanced Radiomics (AUC = 0.85) matched established features (AUC = 0.86) and outperformed conventional Radiomics (AUC = 0.82); in bifurcation lesions, enhanced Radiomics (AUC = 0.78) outperformed both established features (AUC = 0.76) and conventional Radiomics (AUC = 0.74). CONCLUSIONS: Enhanced Radiomics incorporating neck orientation and parent vessel estimate is an efficient operator-independent methodology that offers superior rupture status classification for both sidewall and bifurcation aneurysms and should be considered a strong candidate for larger-scale multicenter and multimodality validation.

Risk factors for intracranial aneurysm rupture in pediatric patients.

BACKGROUND: Intracranial aneurysm (IA) rupture in pediatric patients is a rare but fatal condition. Although risk factors for aneurysm rupture in adults have been well documented, they remain unknown in pediatric patients. METHODS: Data for 94 pediatric patients with IAs were retrospectively analyzed. The patients were divided into ruptured and unruptured groups. Risk factors for aneurysm rupture were analyzed through univariable and multiple logistic regression analyses. Typical patients with risk factors were described. RESULTS: Univariable analyses showed that the unruptured group had significantly higher percentages of giant aneurysms (43.2% vs 12.3%, P = 0.002), wide-neck aneurysms (67.6% vs 29.8%, P = 0.001), and aneurysms located in the internal carotid artery (40.5% vs 3.5%, P < 0.001), while the ruptured group had significantly higher percentages of patients younger than 5 years old (28.1% vs 5.4%, P = 0.013) and aneurysms located in the anterior cerebral artery (24.6% vs 5.4%, P = 0.032), posterior cerebral artery (14.0% vs 0%, P = 0.045), and distal arterial region (DAR) (46.8% vs 27.0%, P < 0.001). Multiple logistic regression analysis confirmed that age 0-5 years (OR = 6.844, P = 0.042) and IAs located in the DAR (OR = 4.162, P = 0.029) were independently related to an increased risk of rupture. Wide-necked aneurysms (OR = 0.235, P = 0.047) were independently associated with a lower risk of rupture. CONCLUSIONS: Among pediatric patients, age younger than 5 years and lesions located in the DAR are independent risk factors for IA rupture, while an IA with a wide neck acts as a protective factor.