Aneurysm Wall Research Articles

Transition of intracranial aneurysmal wall enhancement from high to low wall shear stress mediation with size increase: A hemodynamic study based on 7T magnetic resonance imaging

BackgroundWall shear stress (WSS) has been proved to be related to the formation, development and rupture of intracranial aneurysms. Aneurysm wall enhancement (AWE) on magnetic resonance imaging (MRI) can be caused by inflammation and have confirmed its relationship with low WSS. High WSS can also result in inflammation but the research of its correlation with AWE is lack because of the focus on large aneurysms limited by 3T MRI in most previous studies.This study aimed to assess the potential association between high or low WSS and AWE in different aneuryms. Especially the relationship between high WSS and AWE in small aneurysm. MethodsForty-three unruptured intracranial aneurysms in 42 patients were prospectively included for analysis. 7.0 T MRI was used for imaging. Aneurysm size was measured on three-dimensional time-of-flight (TOF) images. Aneurysm-to-pituitary stalk contrast ratio (CRstalk) was calculated on post-contrast black-blood T1-weighted fast spin echo sequence images. Hemodynamics were assessed by four-dimensional flow MRI. ResultsThe small aneurysms group had more positive WSS–CRstalk correlation coefficient distribution (dome: 78.6 %, p = 0.009; body: 50.0 %, p = 0.025), and large group had more negative coefficient distribution (dome: 44.8 %, p = 0.001; body: 69.0 %, p = 0.002). Aneurysm size was positively correlated with the significant OSI–CRstalk correlation coefficient at the dome (p = 0.012) and body (p = 0.010) but negatively correlated with the significant WSS–CRstalk correlation coefficient at the dome (p < 0.001) and body (p = 0.017). ConclusionAWE can be mediated by both high and low WSS, and translate from high WSS- to low WSS-mediated pathways as size increase. Additionally, AWE may serve as an indicator of the stage of aneurysm development via different correlations with hemodynamic factors.

Hemodynamic study of the ICA aneurysm evolution to attain the cerebral aneurysm rupture risk

The influence of the aneurysm evolution on the hemodynamic characteristic of the blood flow inside the sac region is comprehensively investigated. By using the computational method, the blood flow through the vessel and aneurysm of the sac region is examined to find the role of aneurysm evolution on the wall shear stress, pressure, and risk of aneurysm rupture. Three different models of ICA aneurysms are chosen for the investigation of the aneurysm evolution at risk of rupture. Obtained data shows that the evolution of the aneurysm decreases the wall shear stress and pressure on the sac surface while an oscillatory index of blood increases on the aneurysm wall.

Flow diverters treatment planning of small- and medium-sized intracranial saccular aneurysms on the internal carotid artery via constraint-based virtual deployment.

The internal carotid artery (ICA) is a region with a high incidence for small- and medium-sized saccular aneurysms. However, the treatment relies heavily on the surgeon's experience to achieve optimal outcome. Although the finite element method (FEM) and computational fluid dynamics can predict the postoperative outcomes, due to the computational complexity of traditional methods, there is an urgent need for investigating the fast but versatile approaches related to numerical simulations of flow diverters (FDs) deployment coupled with the hemodynamic analysis to determine the treatment plan. We collected the preoperative and postoperative data from 34 patients (29 females, 5 males; mean age 55.74 ± 9.98 years) who were treated with a single flow diverter for small- to medium-sized intracranial saccular aneurysms on the ICA. The constraint-based virtual deployment (CVD) method is proposed to simulate the FDs expanding outward along the vessel centerline while be constrained by the inner wall of the vessel. The results indicate that there were no significant differences in the reduction rates of wall shear stress and aneurysms neck velocity between the FEM and methods. However, the solution time of CVD was greatly reduced by 98%. In the typical location of small- and medium-sized saccular aneurysms, namely the ICA, our virtual FDs deployment simulation effectively balances the computational accuracy and efficiency. Combined with hemodynamics analysis, our method can accurately represent the blood flow changes within the lesion region to assist surgeons in clinical decision-making.

Treatment for middle cerebral artery bifurcation aneurysms: in silico comparison of the novel Contour device and conventional flow-diverters

Endovascular treatment has become the standard therapy for cerebral aneurysms, while the effective treatment for middle cerebral artery (MCA) bifurcation aneurysms remains a challenge. Current flow-diverting techniques with endovascular coils cover the aneurysm orifice as well as adjacent vessel branches, which may lead to branch occlusion. Novel endovascular flow disruptors, such as the Contour device (Cerus Endovascular), are of great potential to eliminate the risk of branch occlusion. However, there is a lack of valid comparison between novel flow disruptors and conventional (intraluminal) flow-diverters. In this study, two in silico MCA bifurcation aneurysm models were treated by specific Contour devices and flow-diverters using fast-deployment algorithms. Computational fluid dynamic simulations were used to examine the performance and efficiency of deployed devices. Hemodynamic parameters, including aneurysm inflow and wall shear stress, were compared among each Contour device, conventional flow-diverter, and untreated condition. Our results show that the placement of devices can effectively reduce the risk of aneurysm rupture, while the deployment of a Contour device causes more flow reduction than using flow-diverters (e.g. Silk Vista Baby). Besides, the Contour device presents the flow diversion capability of targeting the aneurysm neck without occluding the daughter vessel. In summary, the in silico aneurysm models presented in this study can serve as a powerful pre-planning tool for testing new treatment techniques, optimising device deployment, and predicting the performance in patient-specific aneurysm cases. Contour device is proved to be an effective treatment of MCA bifurcation aneurysms with less daughter vessel occlusion.

392 Validation of a Mathematical Model for Rupture of Spherical Intracranial Aneurysms

INTRODUCTION: An accurate mathematical model of intracranial aneurysm (IA) mechanics is of great value for its potential utility in assessing probability of IA rupture, thus informing the decision to pursue surgical intervention with its associated risks. Such a model for spherical IAs has been proposed which predicts a wall-thickness-to-IA-radius ratio (WTR) of 6.1*10-3 at which IAs rupture (Chaudhry et al. 2006). To our knowledge, no further work has been done to validate this model with clinical data. We assess the accuracy of this model using cases of ruptured and unruptured IAs. METHODS: Aneurysm height, width, neck diameter, and vessel radius were measured on CTAs/MRAs/DSAs of IAs of the basilar tip, anterior communicating, and posterior communicating arteries. Binary logistic regression analysis was performed to determine the WTR where there is a 50% probability of rupture. RESULTS: 52 unruptured and 28 ruptured spherical IAs were included. Binary logistic regression revealed a strong association between decreased WTR and rupture status. The point at which there is a 50% chance of rupture was found to be WTR = 8.6*10-3, from which the proposed 6.1*10-3 differs by only 29%. CONCLUSIONS: The model for IA rupture mechanics proposed by Chaudhry et al. agrees reasonably well with clinical data and could serve as a foundation upon which further investigation may be based. This study was limited primarily by its method of approximating aneurysm wall thickness, which may have over- or under-estimated the actual thickness. Future studies may improve on this by utilizing direct measurements of wall thickness through histological examination.

306 Endothelial Infiltrating Regulatory B Cells and NK T Cells Precipitate Inflammatory Cascade That Leads to Aneurysmal Rupture

INTRODUCTION: Current literature examining the mechanisms delineating intracranial aneurysm development and subsequent rupture is sparse. Studies from decades prior defined the aneurysm model as being one largely driven by flow changes. However, the scope of these models is limited and does not fully explain why only a subset of patients with existing intracranial aneurysms subsequently go on to rupture. METHODS: We obtained aneurysm endothelial lining from 20 patients with ruptured, unruptured, sentinel hemorrhage, and recurrent aneurysms during endovascular coil embolization, which were processed and analyzed using mass spectrometry. RESULTS: Compared to unruptured aneurysms, ruptured aneurysms had significantly increased infiltrating populations of NK cells (5.5% vs 1.4%, p &lt; 0.01), regulatory B cells (27.6% vs 16.0%, p &lt; 0.05), and cytotoxic CD8 T cells (23.7% vs 13.5%, p &lt; 0.05). To understand whether these cells were recruited at the time of rupture or whether they were present prior to the ictus event, we examined aneurysms that were treated after presenting with sentinel hemorrhages – again these patients had that same population of early-NK cells (7.5%, p = 0.2), suggesting that these cells were present at the nexus point immediately prior to rupture. Further, the regulatory B cells were even more prominent in the sentinel population, (45.6%, p &lt; 0.01). CONCLUSIONS: These findings all point to a complex, coordinated immune response that is driving the remodeling of the aneurysm vessel wall. We interpret the results to suggest that regulatory B cell driven destabilization of the aneurysmal wall leads to a series of events; namely the recruitment of NK cells, subsequent inflammatory cascade, and ultimate rupture. While there remains much to be understood about this multi-faceted picture, these findings provide the basis for further studies looking at targets for adjunctive immune therapies in both our unruptured and ruptured patient populations.

229 Quantitative Imaging Biomarkers for Risk Stratification of Intracranial Aneurysms

INTRODUCTION: Aneurysm wall enhancement (AWE) has emerged as a potential imaging biomarker for risk stratification of Intracranial aneurysms (IAs). Herein, the contrast-enhanced MRI (CE-MRI) exhibits markedly higher intensity on the IA sac as compared to the non-enhanced MRI (NE-MRI). However, currently it is assessed subjectively by clinicians which can introduce subjectivity. METHODS: We retrospectively collected 105 IAs with their NE-MRI, CE-MRI and Time-of-flight angiography images. IAs were classified as high or low risk if they had PHASES &gt;5 or ELAPSS &gt;20. We then identified the significantly different RFs and used them to build a logistic regression model for identifying high-risk IAs. We also compared the performance of this model with traditional AWE metrics like CCRatio (Average intensity on the IA sac normalized by the corpus callosum intensity) and CRStalk (Average intensity on the IA sac normalized by the pituitary stalk intensity). RESULTS: We found 35 high-risk IAs in the cohort and identified 183 RFs that were significantly different between them. After eliminating collinear RFs, we used 52 RFs to build our final model. We observed that the RF based model vastly outperformed the conventional metrics. In the testing set, we observed that the LR model had a higher accuracy as compared to conventional metrics. We observed that non-uniformity in pre-contrast MRI, homogeneity in post-contrast MRI and the difference in gray level non-uniformity had the highest odds ratios in the LR model. CONCLUSIONS: RFs from pre- and post-contrast MRI could identify high-risk IAs better than conventional metrics. This model in combination with 3D visualization could aid in better visualization of VWE and better risk stratification of IAs.

In vivo mechanical characterization of arterial wall using an inverse analysis procedure: application on an animal model of intracranial aneurysm.

Intracranial aneurysm is a pathology related to the deterioration of the arterial wall. This work is an essential part of a large-scale project aimed at providing clinicians with a non-invasive patient-specific decision support tool to facilitate the rupture risk assessment. It will lean on the link between the aneurysm shape clinically observed and a database derived from the in vivo mechanical characterization of aneurysms. To supply this database, a deformation device prototype of the arterial wall was developed. Its use coupled with medical imaging (spectral photon-counting computed tomography providing a spatial resolution down to 250 μm) is used to determine the in vivo mechanical properties of the wall based on the inverse analysis of the quantification of the wall deformation observed experimentally. This study presents the in vivo application of this original procedure to an animal model of aneurysm. The mechanical properties of the aneurysm wall identified were consistent with the literature, and the errors between the numerical and experimental results were less than 10%. Based on these parameters, this study allows the assessment of the aneurysm stress state for a known solicitation and points towards the definition of a rupture criterion.

Chinese guideline for the diagnosis and treatment of Takayasu's arteritis (2023).

Takayasu's arteritis (TAK) is a chronic granulomatous inflammatory disease that involves aorta and its primary branches. It is characterized by wall thickening, stenosis/obliteration or aneurysm formation of the involved arteries. In order to standardize the diagnosis and treatment of TAK in China, a clinical practice guideline with an evidence-based approach is developed under the leadership of National Clinical Medical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID). Eleven recommendations for 11 clinical questions that are important to the diagnosis and treatment of TAK are developed based on the latest evidence and expert opinions combined with real clinical practice in China.

Wall Enhancement of Coiled Intracranial Aneurysms Is Associated with Aneurysm Recanalization: A Cross-Sectional Study.

Wall enhancement of untreated intracranial aneurysms on MR imaging is thought to predict aneurysm instability. Wall enhancement or enhancement of the aneurysm cavity in coiled intracranial aneurysms is discussed controversially in the literature regarding potential healing mechanisms or adverse inflammatory reactions. Our aim was to compare the occurrence of aneurysm wall enhancement and cavity enhancement between completely occluded intracranial aneurysms and recanalized aneurysms after initially complete coil embolization. In this single-center cross-sectional study, we evaluated intracranial aneurysms after successful coil embolization for aneurysm recanalization, wall enhancement, and cavity enhancement with 3T MR imaging. We then compared the incidence of wall enhancement and cavity enhancement of completely occluded aneurysms with aneurysms with recanalization using the χ2 test and performed a multivariate linear regression analysis with recanalization size as an independent variable. We evaluated 59 patients (mean age, 54.7 [SD, 12.4] years; 48 women) with 60 intracranial aneurysms and found a significantly higher incidence of wall enhancement in coiled aneurysms with recanalization (n=38) compared with completely occluded aneurysms (n = 22, P = .036). In addition, there was a significantly higher incidence of wall enhancement in aneurysms with recanalization of >3 mm (P = .003). In a multivariate linear regression analysis, wall enhancement (P = .010) and an increase of overall aneurysm size after embolization (P < .001) were significant predictors of recanalization size (corrected R 2= 0.430, CI 95%). The incidence of aneurysm wall enhancement is increased in coiled intracranial aneurysms with recanalization and is associated with recanalization size.

Relationships between irregular pulsation and variations in morphological characteristics during the cardiac cycle in unruptured intracranial aneurysms by 4D-CTA.

Irregular pulsation of the aneurysmal wall has been suggested as a novel predictor for aneurysm rupture. Aneurysm volume variations during the cardiac cycle and the association between irregular pulsation and morphological features have been discussed, but the clinical significance remains unclear. The purpose of this study was to quantify changes in morphological characteristics over the cardiac cycle and examine their correlation with irregular pulsation to facilitate comprehension of aneurysm dynamics. Fourteen unruptured intracranial aneurysms (UIAs) from 11 patients were included in this study, and each of them underwent 4D-CTA after diagnosis by DSA. The R-R intervals were divided into 20-time phases at 5% intervals to determine whether an aneurysm had irregular pulsation throughout the cardiac cycle. CT images from the 20-time phases were used to reconstruct 3D aneurysm models, measure 14 morphological parameters, and quantify each parameter's absolute change and relative rates of change during the cardiac cycle. Seven of 14 UIAs exhibited irregular pulsation over the cardiac cycle by 4D-CTA, 5 of which were small aneurysms ( 7 mm). The UIAs with irregular pulsation exhibited greater changes in morphological characteristics. As aneurysm size increased, the absolute change in aneurysm volume increased (p = 0.035), but the relative rates of change in aneurysm size (p = 0.013), height (p = 0.014), width (p = 0.008), height-to-width ratio (p = 0.009), dome-to-neck ratio (p = 0.019) and bottleneck factor (p = 0.012) decreased. Although the larger the aneurysm, the greater the amplitude of its volumetric variation, small aneurysms are prone to irregular pulsation during the cardiac cycle and have more pronounced and dramatic morphological changes during the cardiac cycle that may increase the risk of rupture. This proof-of-concept study could help to explain the importance of dynamic changes using 4D-CTA in assessing the rupture risk of UIAs.

Profiling of immune infiltration landscape of ruptured intracranial aneurysm.

Previous research has indicated that the rupture of intracranial aneurysm (IA) is a significant contributor to mortality from stroke. The objective of this present study was to examine the infiltration patterns in ruptured intracranial aneurysm (RIA), with the aim of generating insights that could inform the development of effective immunotherapeutic approaches. To achieve this, we obtained Gene Expression Omnibus datasets pertaining to ruptured aneurysms, encompassing a total of 19 unruptured intracranial aneurysms (UIA) and 27 RIA. Subsequently, we conducted differential gene analysis and immune cell analysis specifically for the RIA. According to the conducted studies, the analysis has identified 10 hub genes within key modules. Through the utilization of Kyoto Encyclopedia of Genes and Genomes pathway and gene ontology terms analyses, it has been established that genes exhibiting differential expression are associated with immune cell infiltration in the aneurysm wall. Furthermore, the implementation of the CIBERSORT algorithm has revealed that there are 22 distinct immune cells between RIA and tissues of UIA. IA samples contained a higher proportion of macrophages M1, mast cells resting, and CD4 naive T cells, while macrophages M0 and neutrophils were relatively lower in RIA compared with those in UIA. The current study initially identified highly conservative hub genes and immune cell infiltration patterns in IA. Data presented in the current study improved understanding of immune genes that drive IA which can be exploited in development of effective immunotherapies.

Targeting myeloperoxidase to stabilize unruptured aneurysm: an imaging-guided approach

Inflammation plays a key role in pathogenesis and rupture of aneurysms. Non-invasively and dynamically monitoring aneurysm inflammation is critical. This study evaluated myeloperoxidase (MPO) as an imaging biomarker and therapeutic target for aneurysm inflammation using an elastase-induced rabbit model treated with or without 4-aminobenzoic acid hydrazide (ABAH), an irreversible inhibitor of MPO. Myeloperoxidase-sensitive magnetic resonance imaging (MRI) using Mn-TyrEDTA, a peroxidase activity-dependent contrast agent, revealed weak contrast enhancement in contralateral arteries and decreased contrast enhancement in aneurysm walls with ABAH treatment, indicating MPO activity decreased and inflammation mitigated. This was supported by reduced immune cell infiltration, matrix metalloproteinases (MMP-2 and − 9) activity, ROS production and arterial wall destruction on histology. Finally, the aneurysm expansion rate remained < 50% throughout the study in the ABAH(+) group, but increased gradually in the ABAH(-) group. Our results suggest that inhibition of MPO attenuated inflammation and expansion of experimental aneurysm and MPO-sensitive MRI showed promise as a noninvasive tool for monitoring aneurysm inflammation.

Three-dimensional wall-thickness distributions of unruptured intracranial aneurysms characterized by micro-computed tomography

Aneurysmal rupture is associated with wall thinning, but the mechanism is poorly understood. This study aimed to characterize the three-dimensional wall-thickness distributions of unruptured intracranial aneurysms. Five aneurysmal tissues were investigated using micro-computed tomography. First, the wall thickness was related to the aneurysmal wall appearances during surgery. The median wall thicknesses of the translucent and non-translucent walls were 50.56 and 155.93 µm, respectively (p < 0.05) with significant variation in the non-translucent wall thicknesses (p < 0.05). The three-dimensional observations characterized the spatial variation of wall thicknesses. Thin walls showed a uniform thickness profile ranging from 10 to 40 µm, whereas thick walls presented a peaked thickness profile ranging from 300 to 500 µm. In transition walls, the profile undulated due to the formation of focal thin/thick spots. Overall, the aneurysmal wall thicknesses were strongly site-dependent and spatially varied by 10 to 40 times within individual cases. Aneurysmal walls are exposed to wall stress driven by blood pressure. In theory, the magnitude of wall stress is inversely proportional to wall thickness. Thus, the observed spatial variation of wall thickness may increase the spatial variation of wall stress to a similar extent. The irregular wall thickness may yield stress concentration. The observed thin walls and focal thin spots may be caused by excessive wall stresses at the range of mechanical failure inducing wall injuries, such as microscopic tears, during aneurysmal enlargement. The present results suggested that blood pressure (wall stress) may have a potential of acting as a trigger of aneurysmal wall injury.

A Case of Posterior Communicating Artery Aneurysm Combined With an Atypical Origin of the Ipsilateral Ophthalmic Artery

Objective: Anatomy of the ophthalmic artery (OA) is of great practical importance in surgery for anterior circulation aneurysms. In most cases, the OA arises from the supraclinoid segment of the internal carotid artery (ICA) and enters the orbit through the optic canal inferolaterally to the optic nerve. The OA arising from the anterior cerebral artery (ACA) and entering the optic canal above the optic nerve is extremely rare.Clinical case: We report a case of a 29-year-old female patient admitted to Scientific Research Institute – Ochapovsky Regional Clinical Hospital No. 1 (Krasnodar, Russian Federation) with a ruptured true aneurysm of the left posterior communicating artery (PCoA) and an abnormal origin of the OA from the ACA. The disease manifested itself as ischemic stroke in the basal ganglia on the left causing diagnostic difficulties during initial hospitalization. Cerebral angiography confirmed a PCoA aneurysm and origin of the OA from the ipsilateral ACA. During surgery the neck of the aneurysm was clipped, and the aneurysm dome was opened to control the extent of clipping and remove thrombotic masses. During their removal, hemorrhage appeared from the posterior pole of the aneurysm. During the exploration it was found that the aneurysm was a dilated PCoA connecting the right ICA with the right posterior cerebral artery (PCA). A thrombosed anterior thalamoperforating artery emerged from the superior surface of the dome, and its junction with the precommunicating segment of the right PCA was detected in the region of the posterior pole of the aneurysm. The second clip was placed at the communication site between the aneurysm and the right PCA. The patient was discharged in satisfactory condition with a stable neurological status.Conclusions: The combination of abnormal anatomy of arteries at the base of the brain and cerebral aneurysms increases the risk of tactical errors and perioperative complications. Each such case requires a careful comparison of the clinical, imaging, and intraoperative findings. In the presented case of the patient with the ruptured rare PCoA aneurysm, the disease manifested atypically due to the partial thrombosis of the aneurysm and hemorrhage into the aneurysmal wall. The imaging findings revealed lacunar stroke in the thalamoperforating artery basin and an ICA aneurysm with no signs of subarachnoid hemorrhage. During the surgery the aneurysm was initially regarded as typical saccular. The opening of the dome and removal of all thrombotic masses made it possible to determine the eccentric fusiform nature of the aneurysm, perform its radical exclusion, and prevent fatal hemorrhage in the postoperative period.

Low shear stress induces macrophage infiltration and aggravates aneurysm wall inflammation via CCL7/CCR1/TAK1/ NF-κB axis

BackgroundThis study aimed to elucidate the mechanism by which wall shear stress (WSS) influences vascular walls, accounting for the susceptibility of intracranial aneurysms (IAs) to rupture. MethodWe collected blood samples from the sacs of 24 ruptured and 28 unruptured IAs and analyzed the expression of chemokine CCL7 using enzyme-linked immunosorbent assay (ELISA). Univariate and multivariate logistic regression analyses were employed to assess clinical data, aneurysm morphology, and hemodynamics in both groups. Pearson correlation analysis investigated the relationship between CCL7 expression in aneurysm sac blood and WSS. Additionally, we established a bionic cell parallel plate co-culture shear stress model and a mouse low shear stress (LSS) model. The model was modulated using CCL7 recombinant protein, CCR1 inhibitor, and TAK1 inhibitor. We further evaluated CCL7 expression in endothelial cells and the levels of TAK1, NF-κB, IL-1β, and TNF-α in macrophages. Subsequently, the intergroup differences in expression were calculated. ResultsCCL7 expression was significantly higher in the ruptured group compared to the unruptured group. Hemodynamic analysis indicated that WSS was an independent predictor of the risk of aneurysm rupture. A negative linear correlation was observed between CCL7 expression and WSS. Upon addition of CCL7 recombinant protein, upregulation of CCR1 expression and increased levels of p-TAK1 and p-p65 were observed. Treatment with CCR1 and TAK1 inhibitors reduced inflammatory cytokine expression in macrophages under LSS conditions. Overexpression of TAK1 significantly alleviated the inhibitory effects of CCR1 inhibitors on p-p65 and inflammatory cytokines. ConclusionLSS prompts endothelial cells to secrete CCL7, which, upon binding to the macrophage surface receptor CCR1, stimulates the release of macrophage inflammatory factors via the TAK1/NF-κB signaling pathway. This process exacerbates aneurysm wall inflammation and increases the risk of aneurysm rupture.

A Systematic Review and Meta-Analysis of the Pathology Underlying Aneurysm Enhancement on Vessel Wall Imaging.

Intracranial aneurysms are common, but only a minority rupture and cause subarachnoid haemorrhage, presenting a dilemma regarding which to treat. Vessel wall imaging (VWI) is a contrast-enhanced magnetic resonance imaging (MRI) technique used to identify unstable aneurysms. The pathological basis of MR enhancement of aneurysms is the subject of debate. This review synthesises the literature to determine the pathological basis of VWI enhancement. PubMed and Embase searches were performed for studies reporting VWI of intracranial aneurysms and their correlated histological analysis. The risk of bias was assessed. Calculations of interdependence, univariate and multivariate analysis were performed. Of 228 publications identified, 7 met the eligibility criteria. Individual aneurysm data were extracted for 72 out of a total of 81 aneurysms. Univariate analysis showed macrophage markers (CD68 and MPO, p = 0.001 and p = 0.002), endothelial cell markers (CD34 and CD31, p = 0.007 and p = 0.003), glycans (Alcian blue, p = 0.003) and wall thickness (p = 0.030) were positively associated with enhancement. Aneurysm enhancement therefore appears to be associated with inflammatory infiltrate and neovascularisation. However, all these markers are correlated with each other, and the literature is limited in terms of the numbers of aneurysms analysed and the parameters considered. The data are therefore insufficient to determine if these associations are independent of each other or of aneurysm size, wall thickness and rupture status. Thus, the cause of aneurysm-wall enhancement currently remains unknown.

Decoding the Cell Atlas and Inflammatory Features of Human Intracranial Aneurysm Wall by Single-Cell RNA Sequencing.

Intracranial aneurysm (IA) is common and occasionally results in life-threatening hemorrhagic strokes. However, the cell architecture and inflammation in the IA dome remain less understood. Single-cell RNA sequencing was performed on ruptured and unruptured human IA domes for delineating the cell atlas, gene expression perturbations, and inflammation features. Two external bulk mRNA sequencing-based data sets and serological results of 126 patients were collected for validation. As a result, a total of 21 332 qualified cells were captured. Vascular cells, including endothelial cells, smooth muscle cells, fibroblasts, and pericytes, were assigned in extremely sparse numbers (4.84%), and were confirmed by immunofluorescence staining. Pericytes, characterized by ABCC9 and HIGD1B, were identified in the IA dome for the first time. Abundant immune cells were identified, with the proportion of monocytes/macrophages and neutrophils being remarkably higher in ruptured IA. The lymphocyte compartment was also thoroughly categorized. By leveraging external data sets and machine learning algorithms, macrophages were robustly associated with IA rupture, irrespective of their polarization status. The single nucleotide polymorphism rs2280543, which is identified in East Asian populations, was associated with macrophage metabolic reprogramming through regulating TALDO1 expression. This study provides insights into the cellular architecture and inflammatory features in the IA dome and may enlighten novel therapeutics for unruptured IA.

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.

Hemodynamic Insights into Abdominal Aortic Aneurysms: Bridging the Knowledge Gap for Improved Patient Care

Background: Abdominal aortic aneurysms (AAAs) present a formidable public health concern due to their propensity for localized, anomalous expansion of the abdominal aorta. These insidious dilations, often in their early stages, mask the life-threatening potential for rupture, which carries a grave prognosis. Understanding the hemodynamic intricacies governing AAAs is paramount for predicting aneurysmal growth and the imminent risk of rupture. Objective: Our extensive investigation delves into this complex hemodynamic environment intrinsic to AAAs, utilizing comprehensive numerical analyses of the physiological pulsatile blood flow and realistic boundary conditions to explore the multifaceted dynamics influencing aneurysm rupture risk. Our study introduces novel elements by integrating these parameters into the overall context of aneurysm pathophysiology, thus advancing our understanding of the intricate mechanics governing their evolution and rupture. Methods: Conservation of mass and momentum equations are used to model the blood flow in an AAAs, and these equations are solved using a finite volume-based ANSYS Fluent solver. Resistance pressure outlets following a three-element Windkessel model were imposed at each outlet to accurately model the blood flow and the AAAs’ shear stress. Results: Our results uncover elevated blood flow velocities within an aneurysm, suggesting an augmented risk of future rupture due to increased stress in the aneurysm wall. During the systole phase, high wall shear stress (WSS) was observed, typically associated with a lower risk of rupture, while a low oscillatory shear index (OSI) was noted, correlating with a decreased risk of aneurysm expansion. Conversely, during the diastole phase, low WSS and a high OSI were identified, potentially weakening the aneurysm wall, thereby promoting expansion and rupture. Conclusion: Our study underscores the indispensable role of computational fluid dynamic (CFD) techniques in the diagnostic, therapeutic, and monitoring realms of AAAs. This body of research significantly advances our understanding of aneurysm pathophysiology, thus offering pivotal insights into the intricate mechanics underpinning their progression and rupture, informing clinical interventions and enhancing patient care.