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Successful occlusion of cerebral aneurysms using coil is embolization contingent upon stable thrombus formation, and quality of the thrombus depends upon the biomechanical environment. The goal of this study was to investigate how coil embolization alters the mechanical microenvironment within the aneurysm dome. Inertialess particles were injected in 3-dimensional, computational simulations of flow inside patient aneurysms using patient-specific boundary conditions. Coil embolization was simulated as a homogenous porous medium of known permeability and inertial constant. Lagrangian particle tracking was used to calculate the residence time and shear stress history for particles in the flow before and after treatment. The percentage of particles entering the aneurysm dome correlated with the neck surface area before and after treatment (pretreatment: R2 = 0.831, P < 0.001; posttreatment: R2 = 0.638, P < 0.001). There was an inverse relationship between the change in particles entering the dome and coil packing density (R2 = 0.600, P < 0.001). Following treatment, the particles with the longest residence times tended to remain within the dome even longer while accumulating lower shear stress. A significant correlation was observed between the treatment effect on residence time and the ratio of the neck surface area to porosity (R2 = 0.390, P = 0.007). The results of this study suggest that coil embolization triggers clot formation within the aneurysm dome via a low shear stress-mediated pathway. This hypothesis links independently observed findings from several benchtop and clinical studies, furthering our understanding of this treatment strategy.

Hemodynamic factors have long been associated with clinical outcomes in the treatment of cerebral aneurysms. Computational studies of cerebral aneurysm hemodynamics have provided valuable estimates of the mechanical environment experienced by the endothelium in both the parent vessel and aneurysmal dome walls and have correlated them with disease state. These computational-clinical studies have recently been correlated with the response of endothelial cells using either idealized or patient specific models. Here, we present a robust workflow for generating anatomic-scale aneurysm models, establishing luminal cultures of endothelial cells (ECs) at physiological relevant flow profiles, and comparing EC responses to curvature mediated flow. We show that flow patterns induced by parent vessel curvature produce changes in WSS and WSSG that are correlated with differences in cell morphology and cellular protein localization. Cells in higher WSS regions align better with flow and display strong Notch1-ECD polarization, while, under low WSS, differences in WSSG due to curvature change were associated with less alignment and attenuation of Notch1-ECD polarization in ECs of the corresponding regions. These proof-of-concept results highlight the use of engineered cellularized aneurysm models for connecting computational fluid dynamics to the underlying endothelial biology that mediates disease.

As frequency of endovascular treatments for intracranial aneurysms increases, there is a growing need to understand the mechanisms for coil embolization failure. Computational fluid dynamics (CFD) modeling often simplifies modeling the endovascular coils as a homogeneous porous medium, and focuses on the vascular wall endothelium, not considering the biomechanical environment of platelets. These assumptions limit the accuracy of computations for treatment predictions. We present a rigorous analysis using x-ray microtomographic imaging of the coils and a combination of Lagrangian (platelet) and Eulerian (endothelium) metrics. Four patient-specific, anatomically accurate in vitro flow phantoms of aneurysms are treated with the same patient-specific endovascular coils and Synchrotron tomography scans of the coil mass morphology are obtained. Aneurysmal hemodynamics are computationally simulated before and after coiling, using patient-specific measurements. For each patient, we analyze the trajectories of thousands of platelets during several cardiac cycles, and calculate residence times and shear exposure, relevant to thrombus formation. We quantify the uncertainty of the porous medium approach, comparing them with coil-resolved simulations, showing the under- or overestimation of key hemodynamic metrics used to predict treatment outcomes. We fully characterize aneurysmal hemodynamics with converged statistics of platelet residence time and shear stress history, to augment the traditional wall shear stress on the endothelium. Incorporating microtomographic scans of coil morphology into hemodynamic analysis of intracranial aneurysms, and augmenting traditional analysis with Lagrangian platelet metrics improves CFD predictions, and raises the potential for understanding and clinical translation of computational hemodynamics for intracranial aneurysm treatment outcomes.

A 38-year-old nulliparous woman was admitted with a 24-h history of continuous left iliac fossa pain radiating from the lower back towards the symphysis pubis, which had commenced suddenly after mowing the lawn the previous day. She complained of rigors and had had no relief from paracetamol.She was cardiovascularly stable, with a temperature of 39.58C. Abdominal examination revealed guarding and rebound in the left iliac fossa with the suspicion of a mass arising from the pelvis.White blood cell count was raised at 17.5 with a marked neutrophilia (16.8) and a raised CRP (195). Urine dipstick and pregnancy test were negative. Ultrasound demonstrated a 96667 cm leftsided pelvic mass (Figure 1).At laparotomy she was found to have a 16-week sized fibroid uterus with a normal right tube and ovaries. The left tube was markedly oedematous with a large haematoma filling the entire left broad ligament. This was incised over the anterior margin and the clot evacuated.Postoperative recovery was uneventful. DiscussionTo our knowledge, this is the first case of spontaneous broad ligament haematoma reported in the recent literature.Pregnancy related haematomas are relatively common and range from the complications of early gestation, such as ruptured ectopic pregnancy through to complications surrounding delivery.The majority of cases are associated with childbirth, with the incidence of broad ligament haematoma after vaginal delivery possibly being higher than suspected as demonstrated by Jain and Olcott's study (1999) using MRI to image post-partum pelvic haematomas. Of seven women experiencing pain after difficult vaginal deliveries, three patients had broad ligament haematomas.Broad ligament haematomas are also a recognised complication of caesarean section, either occurring intra-or postoperatively or as a result of scar rupture during labour.Gynaecological cases are rarer but are commonly secondary to surgery (Parulekar 1989; Neely and Elkady 1972).Although not obviously precipitated by any major event, it must be presumed that the activity of mowing the lawn in association with the presence of an enlarged fibroid uterus must have triggered a venous vascular injury. Due to the anatomical nature of the broad ligament, significant bleeding then occurred without much in the way of tamponade, leading to the patient presenting with pain, pyrexia and a mass.Although seemingly a rare occurrence, the differential diagnosis of broad ligament haematoma must be considered in patients Figure 1. Ultrasound showing the 96667 cm left-sided pelvic mass. Gynaecology case reports 449 J Obstet Gynaecol Downloaded from informahealthcare.com by Selcuk Universitesi on 12/26/14For personal use only.

Cerebral aneurysms are a serious clinical challenge, with ∼half resulting in death or disability. Treatment via endovascular coiling significantly reduces the chances of rupture, but the technique has failure rates between 25-40%. This presents a pressing need to develop a method for determining optimal coil deployment strategies. Quantification of aneurysm hemodynamics through computational fluid dynamics (CFD) has the potential to significantly improve the understanding of the mechanics of aneurysm coiling and improve treatment outcomes, but accurately representing the coil mass in CFD simulations remains a challenge. We have used the Finite Element Method (FEM) for simulating patient-specific coil deployment based on mechanical properties and coil geometries provided by the device manufacturer for n=4 ICA aneurysms for which 3D printedin vitromodels were also generated, coiled, and scanned using ultra-high resolution synchrotron micro-CT. The physical and virtual coil geometries were voxelized onto a binary structured grid and porosity maps were generated for geometric comparison. The average binary accuracy score is 0.836 and the average error in porosity map is 6.3%. We then conduct patient-specific CFD simulations of the aneurysm hemodynamics using virtual coils geometries, micro-CT generated oil geometries, and using the porous medium method to represent the coil mass. Hemodynamic parameters of interest including were calculated for each of the CFD simulations. The average error across hemodynamic parameters of interest is ∼19%, a 58% reduction from the average error of the porous media simulations, demonstrating a marked improvement in the accuracy of CFD simulations using FEM generated coil geometries.

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