ResearchPad - aneurysms https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[A three-dimensional phase-field model for multiscale modeling of thrombus biomechanics in blood vessels]]> https://www.researchpad.co/article/elastic_article_14644 Thromboembolism is associated with detachment of small thrombus pieces from the bulk in the blood vessel. These detached pieces, also known as emboli, travel through the blood flow and may block other vessels downstream, e.g., they may plug the deep veins of the leg, groin or arm, leading to venous thromboembolism (VTE). VTE is a significant cause of morbidity and mortality and it affects more than 900,000 people in the United States and result in approximately 100,000 deaths every year. Mechanical interaction between flowing blood and a thrombus is crucial in determining the deformation of the thrombus and the possibility of releasing emboli. In this study, we develop a phase-field model that is capable of describing the structural properties of a thrombus and its biomechanical properties under different blood flow conditions. Moreover, we combine this thrombus model with a particle-based model which simulates the initiation of the thrombus. This combined framework is the first computational study to simulate the development of a thrombus from platelet aggregation to its subsequent viscoelastic responses to various shear flows. Informed by clinical data, this framework can be used to predict the risk of diverse thromboembolic events under physiological and pathological conditions.

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<![CDATA[Whole exome sequencing identifies MRVI1 as a susceptibility gene for moyamoya syndrome in neurofibromatosis type 1]]> https://www.researchpad.co/article/5b5c0709463d7e28a3e55d74

Background and purpose

Moyamoya angiopathy is a progressive cerebral vasculopathy. The p.R4810K substitution in RNF213 has previously been linked to moyamoya disease in Asian populations. When associated with other medical conditions, such as neurofibromatosis type 1, this vasculopathy is frequently reported as moyamoya syndrome. Intriguingly, most cases of moyamoya-complicated neurofibromatosis type 1 have been described in Caucasians, inverting the population ratio observed in Asians, although prevalence of neurofibromatosis type 1 is constant worldwide. Our aim was to investigate whether, among Caucasians, additive genetic factors may contribute to the occurrence of moyamoya in neurofibromatosis type 1.

Methods

Whole exome sequencing was carried out on an Italian family with moyamoya-complicated neurofibromatosis type 1 to identify putative genetic modifiers independent of the NF1 locus and potentially involved in moyamoya pathogenesis. Results were validated in an unrelated family of German ancestry.

Results

We identified the p.P186S substitution (rs35857561) in MRVI1 that segregated with moyamoya syndrome in both the Italian and German family.

Conclusions

The rs35857561 polymorphism in MRVI1 may be a genetic susceptibility factor for moyamoya in European patients with neurofibromatosis type 1. MRVI1 is a functional partner of ITPR1, PRKG1 and GUCY1A3, which are involved in response to nitric oxide. Mutations in GUCY1A3 have been recently linked to a recessive syndromic form of moyamoya with esophageal achalasia.

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<![CDATA[Morphological and Hemodynamic Discriminators for Rupture Status in Posterior Communicating Artery Aneurysms]]> https://www.researchpad.co/article/5989db3aab0ee8fa60bd4ab7

Background and Purpose

The conflicting findings of previous morphological and hemodynamic studies on intracranial aneurysm rupture may be caused by the relatively small sample sizes and the variation in location of the patient-specific aneurysm models. We aimed to determine the discriminators for aneurysm rupture status by focusing on only posterior communicating artery (PCoA) aneurysms.

Materials and Methods

In 129 PCoA aneurysms (85 ruptured, 44 unruptured), clinical, morphological and hemodynamic characteristics were compared between the ruptured and unruptured cases. Multivariate logistic regression analysis was performed to determine the discriminators for rupture status of PCoA aneurysms.

Results

While univariate analyses showed that the size of aneurysm dome, aspect ratio (AR), size ratio (SR), dome-to-neck ratio (DN), inflow angle (IA), normalized wall shear stress (NWSS) and percentage of low wall shear stress area (LSA) were significantly associated with PCoA aneurysm rupture status. With multivariate analyses, significance was only retained for higher IA (OR = 1.539, p < 0.001) and LSA (OR = 1.393, p = 0.041).

Conclusions

Hemodynamics and morphology were related to rupture status of intracranial aneurysms. Higher IA and LSA were identified as discriminators for rupture status of PCoA aneurysms.

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<![CDATA[A mathematical model of aortic aneurysm formation]]> https://www.researchpad.co/article/5989db53ab0ee8fa60bdca9d

Abdominal aortic aneurysm (AAA) is a localized enlargement of the abdominal aorta, such that the diameter exceeds 3 cm. The natural history of AAA is progressive growth leading to rupture, an event that carries up to 90% risk of mortality. Hence there is a need to predict the growth of the diameter of the aorta based on the diameter of a patient’s aneurysm at initial screening and aided by non-invasive biomarkers. IL-6 is overexpressed in AAA and was suggested as a prognostic marker for the risk in AAA. The present paper develops a mathematical model which relates the growth of the abdominal aorta to the serum concentration of IL-6. Given the initial diameter of the aorta and the serum concentration of IL-6, the model predicts the growth of the diameter at subsequent times. Such a prediction can provide guidance to how closely the patient’s abdominal aorta should be monitored. The mathematical model is represented by a system of partial differential equations taking place in the aortic wall, where the media is assumed to have the constituency of an hyperelastic material.

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<![CDATA[Fluoroscopy-Free Pulmonary Vein Isolation in Patients with Atrial Fibrillation and a Patent Foramen Ovale Using Solely an Electroanatomic Mapping System]]> https://www.researchpad.co/article/5989da3dab0ee8fa60b88a15

Introduction

The advent of electroanatomical mapping (EAM) systems for pulmonary vein isolation (PVI) has dramatically decreased radiation exposure. However, the need for some fluoroscopy remains for obtaining left atrial (LA) access. The aim was to test the feasibility of fluoroscopy-free PVI in patients with atrial fibrillation (AF) and a patent foramen ovale (PFO) guided solely by an EAM system.

Methods

Consecutive patients with AF undergoing PVI and documented PFO were studied. An EAM-guided approach without fluoroscopy and ultrasound was used. After completing the map of the right atrium, the superior vena cava and the coronary sinus, a catheter pull-down to the PFO was performed allowing LA access. The map of the LA and subsequent PVI was also performed without fluoroscopy.

Results

30 patients [age 61±12 years, 73% male, ejection fraction 0.64 (0.53–0.65), LA size in parasternal long axis 38±7 mm] undergoing PVI were included. The time required for right atrial mapping including transseptal crossing was 9±4 minutes. Total procedure time was 127±37 minutes. Fluoroscopy-free PVI was feasible in 26/30 (87%) patients. In four patients, fluoroscopy was needed to access (n = 3) or to re-access (n = 1) the LA. In these four patients, total fluoroscopy time was 5±3 min and the DAP was 14.9±13.4 Gy*cm2. Single-procedure success rate was 80% (24/30) after a median follow-up of 12 months.

Conclusion

In patients with a documented PFO, completely fluoroscopy-free PVI is feasible in the vast majority of cases.

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<![CDATA[Posterior Cerebral Artery Angle and the Rupture of Basilar Tip Aneurysms]]> https://www.researchpad.co/article/5989dafcab0ee8fa60bc4e68

Since the initial publication of the International Study of Unruptured Intracranial Aneurysms (ISUIA), management of unruptured intracranial aneurysms has been mainly based on the size of the aneurysm. The contribution of morphological characteristics to treatment decisions of unruptured aneurysms has not been well studied in a systematic and location specific manner. We present a large sample of basilar artery tip aneurysms (BTA) that were assessed using a diverse array of morphological variables to determine the parameters associated with ruptured aneurysms. Demographic and clinical risk factors of aneurysm rupture were obtained from chart review. CT angiograms (CTA) were evaluated with Slicer, an open source visualization and image analysis software, to generate 3-D models of the aneurysms and surrounding vascular architecture. Morphological parameters examined in each model included aneurysm volume, aspect ratio, size ratio, aneurysm angle, basilar vessel angle, basilar flow angle, and vessel to vessel angles. Univariate and multivariate analyses were performed to determine statistical significance. From 2008–2013, 54 patients with BTA aneurysms were evaluated in a single institution, and CTAs from 33 patients (15 ruptured, 18 unruptured) were available and analyzed. Aneurysms that underwent reoperation, that were associated with arteriovenous malformations, or that lacked preoperative CTA were excluded. Multivariate logistic regression revealed that a larger angle between the posterior cerebral arteries (P1-P1 angle, p = 0.037) was most strongly associated with aneurysm rupture after adjusting for other morphological variables. In this location specific study of BTA aneurysms, the larger the angle formed between posterior cerebral arteries was found to be a new morphological parameter significantly associated with ruptured BTA aneurysms. This is a physically intuitive parameter that can be measured easily and readily applied in the clinical setting.

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<![CDATA[Heme Oxygenase-1 Expression Affects Murine Abdominal Aortic Aneurysm Progression]]> https://www.researchpad.co/article/5989da43ab0ee8fa60b8ae9a

Heme oxygenase-1 (HO-1), the rate-limiting enzyme in heme degradation, is a cytoprotective enzyme upregulated in the vasculature by increased flow and inflammatory stimuli. Human genetic data suggest that a diminished HO-1 expression may predispose one to abdominal aortic aneurysm (AAA) development. In addition, heme is known to strongly induce HO-1 expression. Utilizing the porcine pancreatic elastase (PPE) model of AAA induction in HO-1 heterozygous (HO-1+/-, HO-1 Het) mice, we found that a deficiency in HO-1 leads to augmented AAA development. Peritoneal macrophages from HO-1+/- mice showed increased gene expression of pro-inflammatory cytokines, including MCP-1, TNF-alpha, IL-1-beta, and IL-6, but decreased expression of anti-inflammatory cytokines IL-10 and TGF-beta. Furthermore, treatment with heme returned AAA progression in HO-1 Het mice to a wild-type profile. Using a second murine AAA model (Ang II-ApoE-/-), we showed that low doses of the HMG-CoA reductase inhibitor rosuvastatin can induce HO-1 expression in aortic tissue and suppress AAA progression in the absence of lipid lowering. Our results support those studies that suggest that pleiotropic statin effects might be beneficial in AAA, possibly through the upregulation of HO-1. Specific targeted therapies designed to induce HO-1 could become an adjunctive therapeutic strategy for the prevention of AAA disease.

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<![CDATA[Screening for Unruptured Intracranial Aneurysms in Autosomal Dominant Polycystic Kidney Disease: A Survey of 420 Nephrologists]]> https://www.researchpad.co/article/5989d9fcab0ee8fa60b72468

Background

Despite a high prevalence of intracranial aneurysm (ICA) in autosomal dominant polycystic kidney disease (ADPKD), rupture events are rare. The current recommendations for ICA screening are based on expert opinions and studies with low levels of evidence.

Objectives

The aim of our study was to describe the attitudes of practicing nephrologists in Europe towards screening for ICA using magnetic resonance angiography (MRA).

Methods

We conducted a web-based survey among 1315 European French-speaking nephrologists and nephrology residents. An anonymous, electronic questionnaire including 24 independent questions related to ICA screening modalities, indications and participant profiles was sent by email between September and December 2014. Four hundred and twenty nephrologists (mostly from France) participated, including 31 nephrology residents; the response rate was 32%.

Results

Systematic screening for ICA was advocated by 28% of the nephrologists. A family history of ICA rupture, sudden death, stroke and migraine were consensual indications for screening (> 90% of the panel). In other clinical situations largely not covered by the recommendations (pregnancy, nephrectomy, kidney transplantation, cardiac or hepatic surgery, uncontrolled hypertension, lack of familial ADPKD history, at-risk activity, tobacco use), the attitudes towards screening were highly divergent. ICA screening was influenced by nephrologists experience with ADPKD and by their practice setting. The majority of participants (57%) would not repeat a normal ICA screening. Only a few participants (22%) knew that non-contrast MRA was the reference diagnostic tool for ICA screening, whereas most participants thought that contrast enhancement was necessary to screen for ICA. The results from the nephrology residents were analyzed separately and yielded similar results.

Conclusion

This practice survey revealed that most nephrologists follow the current recommendations for the initial screening of ICAs. However, more than a quarter of the panel was in favor of systematic ICA screening, most nephrologists did not know that contrast medium was not necessary to screen for ICA using MRA, and many areas of uncertainty remain.

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<![CDATA[The Impact of Surgical Experience on Major Intraoperative Aneurysm Rupture and Their Consequences on Outcome: A Multivariate Analysis of 538 Microsurgical Clipping Cases]]> https://www.researchpad.co/article/5989da0dab0ee8fa60b78411

The incidence and associated mortality of major intraoperative rupture (MIOR) in intracranial aneurysm surgery is diverse. One possible reason is that many studies failed to consider and properly adjust the factor of surgical experience in the context. We conducted this study to clarify the role of surgical experience on MIOR and associated outcome. 538 consecutive intracranial aneurysm surgeries performed on 501 patients were enrolled in this study. Various potential predictors of MIOR were evaluated with stratified analysis and multivariate logistic regression. The impact of surgical experience and MIOR on outcome was further studied in a logistic regression model with adjustment of each other. The outcome was evaluated using the Glasgow Outcome Scale one year after the surgery. Surgical experience and preoperative Glasgow Coma Scale (GCS) were identified as independent predictors of MIOR. Experienced neurovascular surgeons encountered fewer cases of MIOR compared to novice neurosurgeons (MIOR, 18/225, 8.0% vs. 50/313, 16.0%, P = 0.009). Inexperience and MIOR were both associated with a worse outcome. Compared to experienced neurovascular surgeons, inexperienced neurosurgeons had a 1.90-fold risk of poor outcome. On the other hand, MIOR resulted in a 3.21-fold risk of unfavorable outcome compared to those without it. Those MIOR cases managed by experienced neurovascular surgeons had a better prognosis compared with those managed by inexperienced neurosurgeons (poor outcome, 4/18, 22% vs. 30/50, 60%, P = 0.013).

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<![CDATA[ADAMTS-1 in abdominal aortic aneurysm]]> https://www.researchpad.co/article/5989db5cab0ee8fa60be0203

Introduction

Extracellular matrix degradation is a hallmark of abdominal aortic aneurysm (AAA). Among proteases that are capable of degrading extracellular matrix are a disintegrin and metalloproteases with thrombospondin motifs (ADAMTS). Pathogenesis of these proteases in AAA has not been investigated until date.

Methods and results

Human aneurysmal and control aortas were collected and analyzed with RT-PCR measuring the ADAMTS-1, 4,5,6,8,9,10,13,17 and ADAMTSL-1. Expression of a majority of the investigated ADAMTS members on mRNA level was decreased in aneurysm compared to control aorta. ADAMTS-1 was one of the members that was reduced most. Protein analysis using immunohistochemistry and western blot for localization and expression of ADAMTS-1 revealed that ADAMTS-1 was present predominantly in areas of SMCs and macrophages in aneurysmal aorta and higher expressed in AAA compared to control aortas. The role of ADAMTS-1 in AAA disease was further examined using ADAMTS-1 transgenic/apoE-/- mice with the experimental angiotensin II induced aneurysmal model. Transgenic mice overexpressing ADAMTS-1 showed to be similar to ADAMTS-1 wild type mice pertaining collagen, elastin content and aortic diameter.

Conclusion

Several of the ADAMTS members, and especially ADAMTS-1, are down regulated at mRNA level in AAA, due to unknown mechanisms, at the same time ADAMTS-1 protein is induced. The cleavage of its substrates, don’t seem to be crucial for the pathogenesis of AAA but rather more important in the development of thoracic aortic aneurysm and atherosclerosis as shown in previous studies.

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<![CDATA[Recurrent Rare Genomic Copy Number Variants and Bicuspid Aortic Valve Are Enriched in Early Onset Thoracic Aortic Aneurysms and Dissections]]> https://www.researchpad.co/article/5989d9eeab0ee8fa60b6d721

Thoracic Aortic Aneurysms and Dissections (TAAD) are a major cause of death in the United States. The spectrum of TAAD ranges from genetic disorders, such as Marfan syndrome, to sporadic isolated disease of unknown cause. We hypothesized that genomic copy number variants (CNVs) contribute causally to early onset TAAD (ETAAD). We conducted a genome-wide SNP array analysis of ETAAD patients of European descent who were enrolled in the National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions (GenTAC). Genotyping was performed on the Illumina Omni-Express platform, using PennCNV, Nexus and CNVPartition for CNV detection. ETAAD patients (n = 108, 100% European American, 28% female, average age 20 years, 55% with bicuspid aortic valves) were compared to 7013 dbGAP controls without a history of vascular disease using downsampled Omni 2.5 data. For comparison, 805 sporadic TAAD patients with late onset aortic disease (STAAD cohort) and 192 affected probands from families with at least two affected relatives (FTAAD cohort) from our institution were screened for additional CNVs at these loci with SNP arrays. We identified 47 recurrent CNV regions in the ETAAD, FTAAD and STAAD groups that were absent or extremely rare in controls. Nine rare CNVs that were either very large (>1 Mb) or shared by ETAAD and STAAD or FTAAD patients were also identified. Four rare CNVs involved genes that cause arterial aneurysms when mutated. The largest and most prevalent of the recurrent CNVs were at Xq28 (two duplications and two deletions) and 17q25.1 (three duplications). The percentage of individuals harboring rare CNVs was significantly greater in the ETAAD cohort (32%) than in the FTAAD (23%) or STAAD (17%) cohorts. We identified multiple loci affected by rare CNVs in one-third of ETAAD patients, confirming the genetic heterogeneity of TAAD. Alterations of candidate genes at these loci may contribute to the pathogenesis of TAAD.

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<![CDATA[Risk Factors for the Rupture of Middle Cerebral Artery Bifurcation Aneurysms Using CT Angiography]]> https://www.researchpad.co/article/5989dab8ab0ee8fa60bad796

Background and Purpose

To investigate the clinical and morphological characteristics associated with risk factors for the rupture of bifurcation-type middle cerebral artery aneurysms (MCAAs).

Methods

A total of 169 consecutive patients with 177 bifurcation-type MCAAs were reviewed from August 2011 to January 2016. Based on the clinical and morphologic characteristics findings, the risk factors of aneurysm rupture were assessed using statistical methods.

Results

Age, cerebral atherosclerosis, no hypertension, hypertension grade 2 and coronary artery disease (CAD) were negatively correlated with aneurysm rupture. The mean diameter (MD) of the parent and two daughter arteries was negatively correlated with rupture. Aneurysms with irregularity, depth, width, maximum size, aspect ratio, depth-to-width ratio, bottleneck factor, and size ratio were positively correlated with rupture. The multivariate logistic regression model revealed that irregular shape (odds ratio (OR) 2.697) and aspect ratio (OR 3.723) were significantly and positively correlated with rupture, while cerebral atherosclerosis (OR 0.033), CAD (OR 0.080), and MD (OR 0.201) were negatively correlated with rupture. Receiver operating characteristic analysis revealed that the threshold value of the aspect ratio and MD were 0.96 and 2.43 mm, respectively.

Conclusions

Cerebral atherosclerosis and CAD are protective factors against rupture. Morphological characteristics such as an aneurysm with an irregular shape, a high aspect ratio (>0.96) and a small MD (<2.43 mm) are likely better predictors of rupture.

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<![CDATA[Large Residual Volume, Not Low Packing Density, Is the Most Influential Risk Factor for Recanalization after Coil Embolization of Cerebral Aneurysms]]> https://www.researchpad.co/article/5989da62ab0ee8fa60b912f4

Background

Tight coil packing with density of at least 20%–25% is known to be important for preventing recanalization after embolization of cerebral aneurysms. However, large aneurysms sometimes recanalize regardless of the packing density, suggesting that the absolute residual volume which is determined by aneurysm volume and packing density may be more important risk factor for recanalization. To validate this hypothesis, we analyzed the factors affecting the outcomes of treated aneurysms at our institute.

Methods and Findings

We included 355 small and large aneurysms. The following six factors were obtained from every case: aneurysm volume (mL), neck size (mm), packing density (%), residual volume (mL), rupture status at presentation, and stent assistance (with or without stent). The data were then subjected to multivariate logistic regression analysis to identify significant risk factors for recanalization. Recanalization occurred in 61 aneurysms (17.2%). Significant predictors for recanalization were aneurysm volume (odds ratio, 15.3; P < 0.001) and residual volume (odds ratio, 30.9; P < 0.001), but not packing density (odds ratio, 0.98; P = 0.341). These results showed that for each 0.1-mL increase in aneurysm volume and residual volume, the risk of recanalization increased by 1.3 times and 1.4 times, respectively.

Conclusions

The most influential risk factor for recanalization after coil embolization was residual volume, not packing density. The larger the aneurysm volume, the greater the packing density has to be to minimize the residual volume and risk of recanalization. Since tight coil packing has already been aimed, further innovation of coil property or embolization technique may be needed. Otherwise, different treatment modality such as flow diverter or parent artery occlusion may have to be considered.

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<![CDATA[Hemodynamic Effects of Stent Struts versus Straightening of Vessels in Stent-Assisted Coil Embolization for Sidewall Cerebral Aneurysms]]> https://www.researchpad.co/article/5989daa3ab0ee8fa60ba6833

Background

Recent clinical studies have shown that recanalization rates are lower in stent-assisted coil embolization than in coiling alone in the treatment of cerebral aneurysms.

Objective

This study aimed to assess and compare the hemodynamic effect of stent struts and straightening of vessels by stent placement on reducing flow velocity in sidewall aneurysms, with the goal of reducing recanalization rates.

Methods

We evaluated 16 sidewall aneurysms treated with Enterprise stents. We performed computational fluid dynamics simulations using patient-specific geometries before and after treatment, with or without stent struts.

Results

Stent placement straightened vessels by a mean (±standard deviation) of 12.9°±13.1° 6 months after treatment. Placement of stent struts in the initial vessel geometries reduced flow velocity in aneurysms by 23.1%±6.3%. Straightening of vessels without stent struts reduced flow velocity by 9.6%±12.6%. Stent struts had significantly stronger effects on reducing flow velocity than straightening (P = 0.004, Wilcoxon test). Deviation of the effects was larger by straightening than by stent struts (P = 0.01, F-test). The combination of stent struts and straightening reduced flow velocity by 32.6%±12.2%. There was a trend that larger inflow angles produced a larger reduction in flow velocity by straightening of vessels (P = 0.16).

Conclusion

In sidewall aneurysms, stent struts have stronger effects (approximately 2 times) on reduction in flow velocity than straightening of vessels. Hemodynamic effects by straightening vary in each case and can be predicted by inflow angles of pre-operative vessel geometry. These results may be useful to design a treatment strategy for reducing recanalization rates.

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<![CDATA[Magnetic Resonance Imaging of Cerebral Aspergillosis: Imaging and Pathological Correlations]]> https://www.researchpad.co/article/5989da2aab0ee8fa60b82457

Cerebral aspergillosis is associated with a significant morbidity and mortality rate. The imaging data present different patterns and no full consensus exists on typical imaging characteristics of the cerebral lesions. We reviewed MRI findings in 21 patients with cerebral aspergillosis and correlated them to the immune status of the patients and to neuropathological findings when tissue was available. The lesions were characterized by their number, topography, and MRI signal. Dissemination to the brain resulted from direct spread from paranasal sinuses in 8 patients, 6 of them being immunocompetent. Hematogenous dissemination was observed in 13 patients, all were immunosuppressed. In this later group we identified a total of 329 parenchymal abscesses involving the whole brain with a predilection for the corticomedullary junction. More than half the patients had a corpus callosum lesion. Hemorrhagic lesions accounted for 13% and contrast enhancement was observed in 61% of the lesions. Patients with hematogenous dissemination were younger (p = 0.003), had more intracranial lesions (p = 0.0004) and had a higher 12-week mortality rate (p = 0.046) than patients with direct spread from paranasal sinuses. Analysis of 12 aneurysms allowed us to highlight two distinct situations. In case of direct spread from the paranasal sinuses, aneurysms are saccular and located on the proximal artery portions, while the hematogenous dissemination in immunocompromised patients is more frequently associated with distal and fusiform aneurysms. MRI is the exam of choice for cerebral aspergillosis. Number and type of lesions are different according to the mode of dissemination of the infection.

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<![CDATA[Magnetic Particle Imaging for High Temporal Resolution Assessment of Aneurysm Hemodynamics]]> https://www.researchpad.co/article/5989d9d8ab0ee8fa60b66c00

Purpose

The purpose of this work was to demonstrate the capability of magnetic particle imaging (MPI) to assess the hemodynamics in a realistic 3D aneurysm model obtained by additive manufacturing. MPI was compared with magnetic resonance imaging (MRI) and dynamic digital subtraction angiography (DSA).

Materials and Methods

The aneurysm model was of saccular morphology (7 mm dome height, 5 mm cross-section, 3–4 mm neck, 3.5 mm parent artery diameter) and connected to a peristaltic pump delivering a physiological flow (250 mL/min) and pulsation rate (70/min). High-resolution (4 h long) 4D phase contrast flow quantification (4D pc-fq) MRI was used to directly assess the hemodynamics of the model. Dynamic MPI, MRI, and DSA were performed with contrast agent injections (3 mL volume in 3 s) through a proximally placed catheter.

Results and Discussion

4D pc-fq measurements showed distinct pulsatile flow velocities (20–80 cm/s) as well as lower flow velocities and a vortex inside the aneurysm. All three dynamic methods (MPI, MRI, and DSA) also showed a clear pulsation pattern as well as delayed contrast agent dynamics within the aneurysm, which is most likely caused by the vortex within the aneurysm. Due to the high temporal resolution of MPI and DSA, it was possible to track the contrast agent bolus through the model and to estimate the average flow velocity (about 60 cm/s), which is in accordance with the 4D pc-fq measurements.

Conclusions

The ionizing radiation free, 4D high resolution MPI method is a very promising tool for imaging and characterization of hemodynamics in human. It carries the possibility of overcoming certain disadvantages of other modalities like considerably lower temporal resolution of dynamic MRI and limited 2D characteristics of DSA. Furthermore, additive manufacturing is the key for translating powerful pre-clinical techniques into the clinic.

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<![CDATA[Incidence and Mortality of Spontaneous Subarachnoid Hemorrhage in Martinique]]> https://www.researchpad.co/article/5989d9d8ab0ee8fa60b66b6d

Background

Incidence of spontaneous subarachnoid hemorrhages (SAH) varies wildly across the world and seems to be low in Central and South America (4.2 per 100 000 person-years; CI 95%; 3.1–5.7). The objective of our study was to describe the characteristics of SAH and to estimate its incidence and severity in Martinique, a small French island located in the Caribbean Sea.

Methods

Due to its insular nature and small captive population, Martinique is ideal for the setting up of population-based epidemiological studies with good exhaustiveness. Our study, spanning a 7 year period (2007–2013), consisted of retrospective case ascertainment with multiple overlapping methods. Crude incidence and 30 day case-fatality rates for SAH among the Martinican population were computed for the study period. Incidence and disease severity was also analyzed according to age, gender and aneurysm presence. World age-standardized incidence rates were also calculated.

Results

A total of 121 patients had a SAH during the study period, with a higher frequency of female cases (71.1% versus 28.9%, p<0.001). Patient mean age was 57.1 years (median = 55 [46–66]). An aneurysmal origin was found in 96 SAH cases (79.3%). Crude annual incidence was 4.36 per 100 000 person-years (CI 95% 2.30–6.42). World age-standardized incidence was 3.29 per 100 000 person-years (CI 95% 1.74–4.84). During the 30 days following SAH diagnosis, 29 patients died (case fatality rate: 24% (CI 95% 16.4–31.6)).

Conclusions

The incidence of spontaneous subarachnoid hemorrhage in Martinique is much lower than in other parts of the world and similar to countries in Central and South America. These results are possibly related to environmental factors and most particularly to a low rate of smoking in the Martinican population. Thirty-day case-fatality rate is similar to what is observed in developed countries.

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<![CDATA[Three-Dimensional Visualization and Imaging of the Entry Tear and Intimal Flap of Aortic Dissection Using CT Virtual Intravascular Endoscopy]]> https://www.researchpad.co/article/5989d9f0ab0ee8fa60b6e2d9

Aims

Conventional computed tomography (CT) approaches provides limited visualization of the entire endoluminal changes of aortic dissection (AD), which is essential for its treatment. As an important supplement, three-dimensional CT virtual intravascular endoscopy (VIE) can show relevant details. This study aims to determine the value of VIE in displaying the entry tear and intimal flap of AD.

Methods and Results

Among 127 consecutive symptomatic patients with suspected AD who underwent CT angiography (CTA), 84 subjects were confirmed to have AD and were included in the study. Conventional CT and VIE images were observed and evaluated. From the 92 entry tears revealed via conventional CT, 88 (95.7%) tears appeared on VIE with round (n = 26), slit-shaped (n = 9), or irregular (n = 53) shapes, whereas the intimal flaps were sheetlike (n = 34), tubular (n = 34), wavelike (n = 13), or irregular (n = 7) in shape. The VIE also showed the spatial relationship between the torn flap and adjacent structures. Among 58 entry tears with multiple-line type flap shown on conventional CT, 41 (70.7%) appeared with an irregular shape on VIE, whereas among 30 tears with single-line type flap, 17 (56.7%) appeared as round or slit-shaped on VIE. These results demonstrated a significant difference (P < 0.05). The poor display of tears on VIE was related to the low CT attenuation values in lumen or in neighboring artifacts (P < 0.01).

Conclusion

CT VIE presents the complete configurations and details of the intimal tears and flaps of AD better than conventional CT approaches. Accordingly, it should be recommended as a necessary assessment tool for endovascular therapy and as part of strategy planning in pre-surgical patients.

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<![CDATA[Inhibition of endoplasmic reticulum stress signaling pathway: A new mechanism of statins to suppress the development of abdominal aortic aneurysm]]> https://www.researchpad.co/article/5989db51ab0ee8fa60bdc235

Background

Abdominal aortic aneurysm (AAA) is a potentially lethal disease with extremely poor survival rates once the aneurysm ruptures. Statins may exert beneficial effects on the progression of AAA. However, the underlying mechanism is still not known. The purpose of the present study is to investigate whether statin could inhibit AAA formation by inhibiting the endoplasmic reticulum (ER) stress signal pathway.

Methods

A clinically relevant AAA model was induced in Apolipoprotein E-deficient (ApoE−/−) mice, which were infused with angiotensin II (Ang II) for 28 days. These mice were randomly divided into following 4 groups: saline infusion alone; Ang II infusion alone; Ang II infusion plus Atorvastatin (20mg/kg/d); and Ang II infusion plus Atorvastatin (30mg/kg/d). Besides, another AAA model was induced in C57 mice with extraluminal CaCl2, which were divided into 3 groups: sham group, CaCl2-induced AAA group, and CaCl2-induced AAA plus atorvastatin (20mg/kg/d) group. Then, aortic tissue was excised for further examinations, respectively. In vitro studies, Ang II with or without simvastatin treatment were applied to the vascular smooth muscle cells (VSMCS) and Raw 264.7 cells. The ER stress signal pathway, apoptosis and inflammatory response were evaluated by in vivo and in vitro assays.

Results

We found that higher dose of atorvastatin can effectively suppress the development and progression of AAA induced by Ang II or CaCl2. Mechanistically, the activation of ER stress and inflammatory response were found involved in Ang II-induced AAA formation. The atorvastatin infusion significantly reduced ER stress signaling proteins, the number of apoptotic cells, and the activation of Caspase12 and Bax in the Ang II-induced ApoE−/− mice, compared with mice treated by Ang II alone. Furthermore, proinflammatory cytokines such as IL-6, IL-8, IL-1β were all remarkably inhibited after atorvastatin treatment. In vitro, the inhibitory effect of simvastatin on the ER stress signal pathway could be observed in both vascular smooth muscle cells and macrophages, and these inhibitory effects of statin were in a dose-dependent manner. In addition, apoptosis was induced with Ang II treatment. The maximal inhibitory effect of simvastatin on apoptosis was observed at 10 μmol/l.

Conclusions

We conclude that higher dose of statin can effectively suppress the development of AAA, and reduce ER stress, ER stress-associated apoptosis signaling pathways, and inflammatory response. These findings reveal a new mechanism underlying the inhibitory effect of statin on AAA formation/progression.

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<![CDATA[Aortic and Cardiac Structure and Function Using High-Resolution Echocardiography and Optical Coherence Tomography in a Mouse Model of Marfan Syndrome]]> https://www.researchpad.co/article/5989db40ab0ee8fa60bd6620

Marfan syndrome (MFS) is an autosomal-dominant disorder of connective tissue caused by mutations in the fibrillin-1 (FBN1) gene. Mortality is often due to aortic dissection and rupture. We investigated the structural and functional properties of the heart and aorta in a [Fbn1C1039G/+] MFS mouse using high-resolution ultrasound (echo) and optical coherence tomography (OCT). Echo was performed on 6- and 12-month old wild type (WT) and MFS mice (n = 8). In vivo pulse wave velocity (PWV), aortic root diameter, ejection fraction, stroke volume, left ventricular (LV) wall thickness, LV mass and mitral valve early and atrial velocities (E/A) ratio were measured by high resolution echocardiography. OCT was performed on 12-month old WT and MFS fixed mouse hearts to measure ventricular volume and mass. The PWV was significantly increased in 6-mo MFS vs. WT (366.6 ± 19.9 vs. 205.2 ± 18.1 cm/s; p = 0.003) and 12-mo MFS vs. WT (459.5 ± 42.3 vs. 205.3 ± 30.3 cm/s; p< 0.0001). PWV increased with age in MFS mice only. We also found a significantly enlarged aortic root and decreased E/A ratio in MFS mice compared with WT for both age groups. The [Fbn1C1039G/+] mouse model of MFS replicates many of the anomalies of Marfan patients including significant aortic dilation, central aortic stiffness, LV systolic and diastolic dysfunction. This is the first demonstration of the direct measurement in vivo of pulse wave velocity non-invasively in the aortic arch of MFS mice, a robust measure of aortic stiffness and a critical clinical parameter for the assessment of pathology in the Marfan syndrome.

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