Epithelial-mesenchymal transition related genes in unruptured aneurysms identified through weighted gene coexpression network analysis.

Intracranial aneurysm (IA) can cause fatal subarachnoid hemorrhage (SAH) after rupture, and identifying patients with unruptured IAs is essential for reducing SAH fatalities. The epithelial-mesenchymal transition (EMT) may be vital to IA progression. Here, identified key EMT-related genes in aneurysms and their pathogenic mechanisms via bioinformatic analysis. The GSE13353, GSE75436, and GSE54083 datasets from Gene Expression Omnibus were analyzed with limma to identify differentially expressed genes (DEGs) among unruptured aneurysms, ruptured aneurysms, and healthy samples. The results revealed that three EMT-related DEGs (ADIPOQ, WNT11, and CCL21) were shared among all groups. Coexpression modules and hub genes were identified via weighted gene co-expression network analysis, revealing two significant modules (red and green) and 14 EMT-related genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses suggested that cytokine interactions were closely related. Gene set enrichment analysis revealed that unruptured aneurysms were enriched for the terms "inflammatory response" and "vascular endothelial growth". Protein-protein interaction analysis identified seven key genes, which were evaluated with the GSE54083 dataset to determine their sensitivity and specificity. In the external validation set, we verified the differential expression of seven genes in unruptured aneurysms and normal samples. Together, these findings indicate that FN1, and SPARC may help distinguish normal patients from patients with asymptomatic IAs.

Characterizing Tissue Remodeling and Mechanical Heterogeneity in Cerebral Aneurysms.

Accurately assessing the complex tissue mechanics of cerebral aneurysms (CAs) is critical for elucidating how CAs grow and whether that growth will lead to rupture. The factors that have been implicated in CA progression - blood flow dynamics, immune infiltration, and extracellular matrix remodeling - all occur heterogeneously throughout the CA. Thus, it stands to reason that the mechanical properties of CAs are also spatially heterogeneous. Here, we present a new method for characterizing the mechanical heterogeneity of human CAs using generalized anisotropic inverse mechanics, which uses biaxial stretching experiments and inverse analyses to determine the local Kelvin moduli and principal alignments within the tissue. Using this approach, we find that there is significant mechanical heterogeneity within a single acquired human CA. These results were confirmed using second harmonic generation imaging of the CA's fiber architecture and a correlation was observed. This approach provides a single-step method for determining the complex heterogeneous mechanics of CAs, which has important implications for future identification of metrics that can improve accuracy in prediction risk of rupture.

Nitrosative stress induces downregulation of ribosomal protein genes via MYCT1 in vascular smooth muscle cells.

OBJECTIVE: In our previous genomic studies in human intracranial aneurysms, we observed downregulations in the expression of a number of ribosomal protein genes and the c-Myc-related gene MYC target 1 (MYCT1). So far there is no information about the roles of MYCT1 in vascular cells. Our study aims to investigate the functional roles of MYCT1 in vascular smooth muscle cells (SMCs). MATERIALS AND METHODS: Primary SMCs were isolated from rat thoracic aorta and cultured in vitro. The mRNA and protein expressions were determined by real-time PCR and western blot respectively. Apoptosis was detected by measuring caspase 3/7 activity. Collagen production was determined with ELISA. RESULTS: Using PCR, we validated our previous genomic data showing that the expressions of MYCT1 and ribosomal protein genes were decreased in human aneurysm tissues. In vascular SMCs, we showed that nitrosative stress downregulated the expression of both MYCT1 and ribosomal proteins. Knockdown of MYCT1 mimicked the effects of nitrosative stress on ribosomal protein expressions, whereas overexpression of MYCT1 blunted the effects of nitrosative stress. MYCT1-dependent downregulation of ribosomal proteins compromised the protein translational capacity of the cells for collagen production. Moreover, the endogenously expressed MYCT1 in vascular SMCs was involved in maintaining normal cellular functions including survival, proliferation and migration. CONCLUSIONS: MYCT1-dependent gene regulation may, at least partly, explain the downregulated expressions of ribosomal proteins observed in human intracranial aneurysms. It is suggested that MYCT1 may represent a novel molecular target for counteracting the decreased activity of aneurysmal SMCs for tissue repairmen/regeneration.

Hemodynamic and Morphologic Factors Related to Coil Compaction in Basilar Artery Tip Aneurysms.

OBJECTIVE: Coil compaction is directly related to the degree of cerebral aneurysmal recanalization. The degree of recanalization (DoR) was quantified by measuring the volume vacated by coil deformation. The purpose of this study was to clarify the hemodynamic and morphologic factors associated with coil compaction. METHODS: Computational fluid dynamics simulations were performed on 28 middle-size (5-10 mm) unruptured basilar artery tip aneurysms. The DoR was measured by comparing the coil mass shape obtained from three-dimensional digital subtraction angiography data immediately after coil embolization and again within 1-2 years of follow-up. Deployed coils were modeled using a virtual coiling technique for computational fluid dynamics simulations. Hemodynamic and morphologic factors to predict the DoR were derived using multiple linear regression. RESULTS: Aneurysmal neck area, the maximum pressure generated on the neck surface after coil embolization, and the high-pressure position on the neck surface predicted DoR with statistic significance (P < 0.001, P < 0.001, P = 0.004, respectively). The DoR tended to increase when the neck area was large, the pressure generated on the coils was high, and the high-pressure position was close to the center of the neck surface. The volume embolization ratio was not statistically relevant for the DoR in the cases of this study. CONCLUSIONS: Coil compaction occurs in cerebral aneurysms with a wide neck, high pressure generated on the coils, and high pressure in the center of the neck surface. Establishing the DoR can contribute to the prediction of recanalization after coil embolization.

Wall shear stress gradient is independently associated with middle cerebral artery aneurysm development: a case-control CFD patient-specific study based on 77 patients.

BACKGROUND: Previously published computational fluid dynamics (CFD) studies regarding intracranial aneurysm (IA) formation present conflicting results. Our study analysed the involvement of the combination of high wall shear stress (WSS) and a positive WSS gradient (WSSG) in IA formation. METHODS: We designed a case-control study with a selection of 38 patients with an unruptured middle cerebral artery (MCA) aneurysm and 39 non-aneurysmal controls to determine the involvement of WSS, oscillatory shear index (OSI), the WSSG and its absolute value (absWSSG) in aneurysm formation based on patient-specific CFD simulations using velocity profiles obtained from transcranial colour-coded sonography. RESULTS: Among the analysed parameters, only the WSSG had significantly higher values compared to the controls (11.05 vs - 14.76 [Pa/mm], P = 0.020). The WSS, absWSSG and OSI values were not significantly different between the analysed groups. Logistic regression analysis identified WSS and WSSG as significant co-predictors for MCA aneurysm formation, but only the WSSG turned out to be a significant independent prognosticator (OR: 1.009; 95% CI: 1.001-1.017; P = 0.025). Significantly more patients (23/38) in the case group had haemodynamic regions of high WSS combined with a positive WSSG near the bifurcation apex, while in the control group, high WSS was usually accompanied by a negative WSSG (14/39). From the analysis of the ROC curve for WSSG, the area under the curve (AUC) was 0.654, with the optimal cut-off value -0.37 Pa/mm. The largest AUC was recognised for combined WSS and WSSG (AUC = 0.671). Our data confirmed that aneurysms tend to form near the bifurcation apices in regions of high WSS values accompanied by positive WSSG. CONCLUSIONS: The development of IAs is determined by an independent effect of haemodynamic factors. High WSS impacts MCA aneurysm formation, while a positive WSSG mainly promotes this process.

Involvement of Microglia in the Pathophysiology of Intracranial Aneurysms and Vascular Malformations-A Short Overview.

Aneurysms and vascular malformations of the brain represent an important source of intracranial hemorrhage and subsequent mortality and morbidity. We are only beginning to discern the involvement of microglia, the resident immune cell of the central nervous system, in these pathologies and their outcomes. Recent evidence suggests that activated proinflammatory microglia are implicated in the expansion of brain injury following subarachnoid hemorrhage (SAH) in both the acute and chronic phases, being also a main actor in vasospasm, considerably the most severe complication of SAH. On the other hand, anti-inflammatory microglia may be involved in the resolution of cerebral injury and hemorrhage. These immune cells have also been observed in high numbers in brain arteriovenous malformations (bAVM) and cerebral cavernomas (CCM), although their roles in these lesions are currently incompletely ascertained. The following review aims to shed a light on the most significant findings related to microglia and their roles in intracranial aneurysms and vascular malformations, as well as possibly establish the course for future research.

Acute Stenting and Concomitant Tirofiban Administration for the Endovascular Treatment of Acute Ischemic Stroke Related to Intracranial Artery Dissections: A Single Center Experience and Systematic Review of the Literature.

BACKGROUND: Intracranial artery dissection is an uncommon cause of acute ischemic stroke. Although acute stenting of the dissected arterial segment is a therapeutic option, the associated antiplatelet regimen remains a matter of debate. OBJECTIVES: To evaluate the efficacy and safety of acute intracranial stenting together with concomitant intravenous administration of tirofiban and to perform a systematic review of the literature. MATERIALS AND METHODS: A single-center, retrospective study of the clinical and radiological records of all patients treated at our center by intracranial stenting in the setting of acute ischemic stroke between January 2010 and December 2020. A systematic review of the literature was conducted according to the PRISMA-P guidelines for relevant publications from January 1976 to December 2020 on intracranial artery dissection treated by stent. RESULTS: Seven patients with intracranial artery dissections underwent acute stenting with concomitant tirofiban during the study period. Mid-term follow-up showed parent artery patency in 6/7 cases (85.7%). The modified Rankin Score was ≤ 0-2 at 3 months in 5/7 cases (71.4%). The literature review identified 22 patients with intracranial artery dissection treated with acute stenting in association with different antithrombotic therapies. Complete revascularization was obtained in 86.3% of cases with a modified Rankin Score of ≤ 0-2 in 68% of patients at 3-month follow-up. CONCLUSIONS: Acute intracranial stenting together with intravenous tirofiban administration could be a therapeutic option in patients with intracranial artery dissection and a small ischemic core.

Newly Identified Hemodynamic Parameter to Predict Thin-Walled Regions of Unruptured Cerebral Aneurysms Using Computational Fluid Dynamics Analysis.

BACKGROUND: The thin-walled regions (TIWRs) of intracranial aneurysms have a high risk of rupture during surgical manipulation. They have been reported to be predicted by wall shear stress and pressure (PS) based on computational fluid dynamics analysis, although this remains controversial. In this study, we investigated whether the oscillatory shear index (OSI) can predict TIWRs. METHODS: Twenty-five unruptured aneurysms were retrospectively analyzed; the position and orientation of the computational fluid dynamics color maps were adjusted to match the intraoperative micrographs. The red area on the aneurysm wall was defined as TIWR, and if most of the regions on the color map corresponding to TIWR were OSI low (lower quartile range), time-averaged wall shear stress (TAWSS) high, or PS high (upper quartile range), each region was defined as a matched region and divided by the total number of TIWRs to calculate the match rate. In addition, the mean values of OSI, TAWSS, and PS corresponding to TIWRs were quantitatively compared with those in adjacent thick-walled regions. RESULTS: Among 27 TIWRs of 25 aneurysms, 23, 10, and 14 regions had low OSI, high TAWSS, and high PS regions (match rate: 85.2%, 37.0%, and 51.9%), respectively. Receiver operating characteristic curve analysis demonstrated that OSI was the most effective hemodynamic parameter (area under the curve, 0.881), followed by TAWSS (0.798). Multivariate analysis showed that OSI was a significant independent predictor of TIWRs (odds ratio, 18.30 [95% CI, 3.2800-102.00], P < 0.001). CONCLUSIONS: OSI may be a unique predictor for TIWRs. Low OSI strongly corresponds with TIWRs of intracranial aneurysms.

In-silico trial of intracranial flow diverters replicates and expands insights from conventional clinical trials.

The cost of clinical trials is ever-increasing. In-silico trials rely on virtual populations and interventions simulated using patient-specific models and may offer a solution to lower these costs. We present the flow diverter performance assessment (FD-PASS) in-silico trial, which models the treatment of intracranial aneurysms in 164 virtual patients with 82 distinct anatomies with a flow-diverting stent, using computational fluid dynamics to quantify post-treatment flow reduction. The predicted FD-PASS flow-diversion success rates replicate the values previously reported in three clinical trials. The in-silico approach allows broader investigation of factors associated with insufficient flow reduction than feasible in a conventional trial. Our findings demonstrate that in-silico trials of endovascular medical devices can: (i) replicate findings of conventional clinical trials, and (ii) perform virtual experiments and sub-group analyses that are difficult or impossible in conventional trials to discover new insights on treatment failure, e.g. in the presence of side-branches or hypertension.

Roles of Phytoestrogen in the Pathophysiology of Intracranial Aneurysm.

Background and Purpose: The incidences of intracranial aneurysm and aneurysmal subarachnoid hemorrhage are high in postmenopausal women. Although population-based studies suggest that hormone replacement therapy is beneficial for postmenopausal women with intracranial aneurysms, estrogen replacement may no longer be recommended for the prevention of chronic diseases given its association with adverse outcomes, such as cancer and ischemic stroke. The isoflavone daidzein and its intestinal metabolite equol are bioactive phytoestrogens and potent agonists of estrogen receptors. Given their estrogenic properties, we investigated whether the isoflavones daidzein and equol are protective against the formation and rupture of intracranial aneurysms in a mouse model of the postmenopausal state. Methods: We induced intracranial aneurysms in ovariectomized adult female mice using a combination of induced systemic hypertension and a single injection of elastase into the cerebrospinal fluid. We fed the mice with an isoflavone-free diet with/without daidzein supplementation, or in a combination of intraperitoneal equol, or oral vancomycin treatment. We also used estrogen receptor beta knockout mice. Results: Both dietary daidzein and supplementation with its metabolite, equol, were protective against aneurysm formation in ovariectomized mice. The protective effects of daidzein and equol required estrogen receptor-ß. The disruption of the intestinal microbial conversion of daidzein to equol abolished daidzein's protective effect against aneurysm formation. Mice treated with equol had lower inflammatory cytokines in the cerebral arteries, suggesting that phytoestrogens modulate inflammatory processes important to intracranial aneurysm pathogenesis. Conclusions: Our study establishes that both dietary daidzein and its metabolite, equol, protect against aneurysm formation in ovariectomized female mice through the activation of estrogen receptor-ß and subsequent suppression of inflammation. Dietary daidzein's protective effect required the intestinal conversion to equol. Our results indicate the potential therapeutic value of dietary daidzein and its metabolite, equol, for the prevention of the formation of intracranial aneurysms and related subarachnoid hemorrhage.

Flow Diversion in Acute Sub Arachnoid Haemorrhage: A Single Centre Five Year Experience.

OBJECTIVES: The role of flow-diversion in acute sub-arachnoid haemorrhage (SAH) is controversial. Many of the published data warns of high rates of procedure-related complications and aneurysmal rebleed. This study evaluates the safety, efficacy, clinical and angiographic outcomes of acute flow-diversion at our institute. METHODS: The institutional database from June 2015 to June 2020 was retrospectively reviewed for aneurysmal SAH (aSAH) treated with flow diversion. Clinical presentation, procedural details, complications, anti-platelet usage, rebleeding and aneurysm occlusion rates and outcomes were recorded. RESULTS: 22 (59% females; median age 56 years) consecutive patients were identified. None of them were on regular antiplatelets/anticoagulation in the 15-days preceding the treatment. The mean aneurysm diameter was 5.4 mm and the median delay to flow-diversion was 2 days. Almost 73% (16/22) of patients had adjunctive coiling in the same session. There was no aneurysmal rebleed at a median follow up of 8.5 months and 86.3% (19/22 patients) had good clinical outcomes (3-month MRS 0-2). Adverse events related to the flow diversion procedure were seen in 3 patients; none of them had a medium to long-term clinical consequence. Three patients died from complications of SAH, unrelated to the procedure. Vascular imaging follow-up was available for 20 patients and the complete aneurysm occlusion rate was 95%. CONCLUSION: Flow-diversion could be a reasonably safe and effective technique for treating ruptured aneurysms in appropriately selected patients when conventional options of surgical clipping and coiling are considered challenging.

Enhancement of cerebrovascular 4D flow MRI velocity fields using machine learning and computational fluid dynamics simulation data.

Blood flow metrics obtained with four-dimensional (4D) flow phase contrast (PC) magnetic resonance imaging (MRI) can be of great value in clinical and experimental cerebrovascular analysis. However, limitations in both quantitative and qualitative analyses can result from errors inherent to PC MRI. One method that excels in creating low-error, physics-based, velocity fields is computational fluid dynamics (CFD). Augmentation of cerebral 4D flow MRI data with CFD-informed neural networks may provide a method to produce highly accurate physiological flow fields. In this preliminary study, the potential utility of such a method was demonstrated by using high resolution patient-specific CFD data to train a convolutional neural network, and then using the trained network to enhance MRI-derived velocity fields in cerebral blood vessel data sets. Through testing on simulated images, phantom data, and cerebrovascular 4D flow data from 20 patients, the trained network successfully de-noised flow images, decreased velocity error, and enhanced near-vessel-wall velocity quantification and visualization. Such image enhancement can improve experimental and clinical qualitative and quantitative cerebrovascular PC MRI analysis.

Incidence of Neo-Intimal Hyperplasia in Anterior Circulation Aneurysms Following Pipeline Flow Diversion.

INTRODUCTION: Flow diversion of the distal anterior circulation cerebral vasculature may be used for management of wide necked aneurysms not amenable to other endovascular approaches. Follow-up angiography sometimes demonstrates neo-intimal hyperplasia within or adjacent to the stent, however there is limited evidence in the literature examining the incidence in MCA and ACA aneurysms. We present our experience with flow diversion of the distal vasculature and evaluate the incidence of neo-intimal hyperplasia. MATERIALS AND METHODS: Retrospective review of patients who underwent Pipeline embolization device (PED) treatment for ruptured and unruptured anterior circulation aneurysms. RESULTS: A total of 251 anterior circulation aneurysms were treated by pipeline flow diversion, of which 175 were ICA aneurysms, 14 were ACA aneurysms and 18 were MCA aneurysms. 6-month follow-up angiography was available in 207 patients. The incidence of neo-intimal hyperplasia was 15.9%, 21.4%, and 61.1% in ICA, ACA, and MCA aneurysms, respectively. MCA-territory aneurysms developed neo-intimal hyperplasia at a significantly higher rate than aneurysms in other vessel territories. Rates of aneurysmal occlusion did not significantly differ from those patients who did not exhibit intimal hyperplasia on follow-up angiography. CONCLUSION: In our experience, flow diversion of distal wide-necked MCA and ACA aneurysms is a safe and effective treatment strategy. The presence of neo-intimal hyperplasia at 6-month angiography is typically clinically asymptomatic. Given the statistically higher rate of neo-intimal hyperplasia in MCA aneurysms at 6-month angiography, we propose delaying initial follow-up angiography to 12-months and maintaining dual antiplatelet therapy during that time.

Enigma of what is Known about Intracranial Aneurysm Occlusion with Endovascular Devices.

Aneurysmal subarachnoid Hemorrhage is a major cause of neurological morbidity and mortality. Over the years vascular neurosurgery has witnessed technological advances aimed to reduce the morbidity and mortality. Several endovascular devices have been used in clinical practice to achieve this goal in the management of ruptured and unruptured cerebral aneurysms. Recurrence due to recanalization is encountered in all of these endovascular devices as well as illustrated by Barrow Ruptured Aneurysm Trial. Histological and molecular characterization of the aneurysms treated with endovascular devices is an area of active animal and human research studies. Yet, the pathobiology illustrating the mechanisms of aneurysmal occlusion and healing lacks evidence. The enigma of aneurysmal healing following treatment with endovascular devices needs to be de-mystified to understand the biological interaction of endovascular device and aneurysm and thereby guide the future development of endovascular devices aimed at better aneurysm occlusion. We performed a comprehensive and detailed literature review to bring all the known facts of the pathobiology of intracranial aneurysm healing, the knowledge of which is of paramount importance to neurosurgeons, an interventional neuroradiologist, molecular biologist, geneticists, and experts in animal studies. This review serves as a benchmark of what is known and platform for future studies basic science research related to intracranial aneurysms.

Inflow Hemodynamics of Intracranial Aneurysms: A Comparison of Computational Fluid Dynamics and 4D Flow Magnetic Resonance Imaging.

PURPOSE: Although the inflow hemodynamics of cerebral aneurysms are key factors in their rupture and recurrence after endovascular treatments, the most available method for inflow hemodynamics evaluation remains unestablished. We compared the efficacy of inflow hemodynamics evaluation using computational fluid dynamics (CFD) analysis and that using four-dimensional (4D) flow magnetic resonance imaging (MRI). METHODS: In 23 unruptured cerebral aneurysms, the inflow hemodynamics was evaluated using both CFD and 4D flow MRI. The evaluated parameters included visually classified inflow jet patterns, the inflow rate ratio (the ratio of the inflow rate at the aneurysmal orifice to the flow rate in the proximal parent artery), and the velocity ratio (the ratio of the inflow velocity to the velocity in the proximal parent artery). The Shapiro-Wilk test was used to assess the normality of variable data, and logarithmic transformation was performed for variables with non-normal distributions. Data analysis was performed using Pearson correlation analyses and the chi-square test. RESULTS: There was a significant correlation between inflow jet patterns evaluated by CFD and 4D flow MRI (p = 0.008). Moreover, there was a strong correlation between the inflow rate ratios evaluated by CFD and 4D flow MRI (r = 0.801; p <0.001). Furthermore, there was a moderate correlation between the velocity ratios measured by CFD and 4D flow MRI (r = 0.559; p = 0.008). CONCLUSION: Inflow hemodynamics evaluated by CFD analysis and 4D flow MRI showed good correlations in inflow jet pattern, inflow rate ratio, and velocity ratio.

Numerical study on the energy cascade of pulsatile Newtonian and power-law flow models in an ICA bifurcation.

The complex physics and biology underlying intracranial hemodynamics are yet to be fully revealed. A fully resolved direct numerical simulation (DNS) study has been performed to identify the intrinsic flow dynamics in an idealized carotid bifurcation model. To shed the light on the significance of considering blood shear-thinning properties, the power-law model is compared to the commonly used Newtonian viscosity hypothesis. We scrutinize the kinetic energy cascade (KEC) rates in the Fourier domain and the vortex structure of both fluid models and examine the impact of the power-law viscosity model. The flow intrinsically contains coherent structures which has frequencies corresponding to the boundary frequency, which could be associated with the regulation of endothelial cells. From the proposed comparative study, it is found that KEC rates and the vortex-identification are significantly influenced by the shear-thinning blood properties. Conclusively, from the obtained results, it is found that neglecting the non-Newtonian behavior could lead to underestimation of the hemodynamic parameters at low Reynolds number and overestimation of the hemodynamic parameters by increasing the Reynolds number. In addition, we provide physical insight and discussion onto the hemodynamics associated with endothelial dysfunction which plays significant role in the pathogenesis of intracranial aneurysms.

Histone deacetylase 9 inhibition upregulates microRNA-92a to repress the progression of intracranial aneurysm via silencing Bcl-2-like protein 11.

OBJECTIVE: Histone deacetylases (HDACs) have been revealed to be involved in cerebrovascular diseases, while the role of HDAC9 in intracranial aneurysm (IA) remains seldom studied. We aim to explore the role of the HDAC9/microRNA-92a (miR-92a)/Bcl-2-like protein 11 (BCL2L11) axis in IA progression. METHODS: Expression of HDAC9, miR-92a and BCL2L11 in IA tissues was assessed. IA rat models were established by ligation of left renal artery and common carotid artery, and the rats were respectively injected with relative plasmid vectors and/or oligonucleotides. The blood pressure was measured to estimate the IA degree, and the pathological changes were observed. The expression of matrix metalloproteinase (MMP)-2, MMP-9 and vascular endothelial growth factor (VEGF) was detected, and the levels of inflammatory factors were evaluated. Expression of apoptosis-related proteins, HDAC9, miR-92a and BCL2L11 was assessed. RESULTS: HDAC9 and BCL2L11 were upregulated while miR-92a was downregulated in IA clinical samples and rat models. HDAC9 inhibition or miR-92a elevation improved pathological changes and repressed apoptosis and expression of MMP-2, MMP-9, VEGF and inflammatory factors in vascular tissues from IA rats. Oppositely, HDAC9 overexpression or miR-92a reduction had contrary effects. miR-92a downregulation reversed the effect of silenced HDAC9 on IA rats. CONCLUSION: HDAC9 inhibition upregulates miR-92a to repress the progression of IA via silencing BCL2L11.

Clinical and radiological outcomes in relation with the anatomical orientation of clipped middle cerebral artery bifurcation aneurysms.

BACKGROUND: The middle cerebral artery (MCA) bifurcation represents the most frequent location for intracranial aneurysms. Often, the aneurysmal dome can hide the origin of perforating arteries from the M1 segment during the surgical clipping causing ischemic lesions and worse clinical outcome. The aim of this paper is to analyze the association between the orientation of the aneurysm sac and the clinical and radiological outcomes after surgical clipping. METHODS: Data from 50 MCA bifurcation clipped aneurysms in 47 patients were collected retrospectively. Three different groups were identified according to the aneurysmal sac orientation: anterior-inferior, posterior and superior. A possible association between the aneurysmal sac projection and the outcome was searched through a univariable logistic regression analysis. RESULTS: Statistical analysis showed significant correlation between the radiologic evidence of post-operative ischemia in the posterior group (p = 0.046, RR = 1.65) and an increased risk in the superior orientation group (p = 0.145, RR = 1.38). The anterior-inferior group was, instead, significantly associated with no evidence of radiologic ischemia (p = 0.0019, RR = 0.58). CONCLUSION: The orientation of the aneurysmal dome and sac represents a fundamental feature to be considered during the surgical clipping of the MCA aneurysms. Indeed, its posterior and superior projection is associated with a higher incidence of radiologic ischemic lesions due to the origin of perforating arteries from M1 segment behind the aneurysmal sac. The anterior-inferior orientation, on the contrary, is associated with a lower risk.

Traumatic Distal Anterior Cerebral Artery Aneurysms - Pathomechanism and Revascularisation Strategies.

Traumatic intracranial aneurysms (TICA) of the distal anterior cerebral artery (dACA) are exceptionally rare and display therapeutic challenges due to their angioanatomical characteristics. The objective of this work was to discuss the mechanisms of TICA formation of the dACA and to elucidate the best treatment and revascularization strategies in these patients based on two illustrative cases. Case 1: 20-year-old patient with a traumatic, partially thrombosed 14 × 10 mm aneurysm of the right pericallosal artery (rPericA), distal to the origin of the right callosomarginal artery (rCMA). Complete trapping of the right dissection A3 aneurysm and flow replacement extra-to-intracranial (EC-IC) bypass (STA - radial artery - A4) was performed. Case 2: 16-year-old patient with a traumatic polylobulated, partially thrombosed 16 × 10 mm aneurysm of the rPericA. Microsurgical excision of the A3- segment harboring the aneurysm and flow replacement intra-to-intracranial (IC-IC) bypass via reimplantation of the right remaining PericA on the contralateral PericA (end-to-side anastomosis) was performed (in situ bypass). TICA of the dACA are exceptionally rare. Mechanical vessel wall injury and aneurysm formation of the dACA in blunt head trauma is very likely due to the proximity of the dACA with the rigid free edge of the falx. Given their nature as dissecting (complex) aneurysm, trapping and revascularization is a very important strategy. The interhemispheric cistern offers multiple revascularization options with its numerous donor vessels. The IC-IC bypass is often the simplest revascularization construct.

How patient-specific do internal carotid artery inflow rates need to be for computational fluid dynamics of cerebral aneurysms?

BACKGROUND: Computational fluid dynamics (CFD) has become a popular tool for studying 'patient-specific' blood flow dynamics in cerebral aneurysms; however, rarely are the inflow boundary conditions patient-specific. We aimed to test the impact of widespread reliance on generalized inflow rates. METHODS: Internal carotid artery (ICA) flow rates were measured via 2D cine phase-contrast MRI for 24 patients scheduled for endovascular therapy of an ICA aneurysm. CFD models were constructed from 3D rotational angiography, and pulsatile inflow rates imposed as measured by MRI or estimated using an average older-adult ICA flow waveform shape scaled by a cycle-average flow rate (Qavg) derived from the patient's ICA cross-sectional area via an assumed inlet velocity. RESULTS: There was good overall qualitative agreement in the magnitudes and spatial distributions of time-averaged wall shear stress (TAWSS), oscillatory shear index (OSI), and spectral power index (SPI) using generalized versus patient-specific inflows. Sac-averaged quantities showed moderate to good correlations: R2=0.54 (TAWSS), 0.80 (OSI), and 0.68 (SPI). Using patient-specific Qavg to scale the generalized waveform shape resulted in near-perfect agreement for TAWSS, and reduced bias, but not scatter, for SPI. Patient-specific waveform had an impact only on OSI correlations, which improved to R2=0.93. CONCLUSIONS: Aneurysm CFD demonstrates the ability to stratify cases by nominal hemodynamic 'risk' factors when employing an age- and vascular-territory-specific recipe for generalized inflow rates. Qavg has a greater influence than waveform shape, suggesting some improvement could be achieved by including measurement of patient-specific Qavg into aneurysm imaging protocols.