Fusiform Aneurysm Models Research Articles

Hemodynamic simulation of abdominal aortic aneurysm on idealised models: Investigation of stress parameters during disease progression

Background and ObjectiveAnalysis and prediction of rupture risk of abdominal aortic aneurysms (AAA) facilitates planning for surgical interventions and assessment of plausible treatment modalities. Present approach of using maximum diameter criterion, is giving way to hemodynamic and bio-mechanical based predictors in conjunction with Computational fluid dynamic (CFD) simulations. Detailed studies on hemodynamic and bio-mechanical parameters at the stage of maximum growth/rupture is of practical importance to the clinical community. However, understanding the changes in these parameters at different stages of growth, will be useful for clinicians, in planning routine monitoring to reduce the risk of sudden rupture. This is particularly useful in medical resource starved nations. Present study investigates the hemodynamic and bio-mechanical changes occurring during the growth stages of aortic aneurysms using fluid structure interaction (FSI) studies. MethodSix idealized fusiform aneurysm models spanning high (shorter) and low (longer) values of the shape index (DHr), have been analysed at three different stages of growth viz, a Dmax of 3.5cm, 4.25cm, 5cm. Pulsatile Newtonian blood flow, passing through an elastic arterial vessel wall with uniform thickness is assumed. Two-way coupled fluid structure interaction have been employed for the numerical simulation of blood flow dynamics and arterial wall mechanics. ResultsWall shear stress (WSS) parameters and vonmises stress indicators, co-relating rupture and thrombus formation, have been extracted and reported, at each growth stage. When the aneurysm progresses in diameter, the areas recording abnormally low TAWSS, as well as areas of high/low OSI were found to increase at different rates for shorter and longer aneurysms. Moreover, drastic increase in the maximum wall stresses (MWS) and wall displacement were observed as the aneurysm approached the critical diameter. ConclusionHemodynamic predictors were found to be highly dependent on the shape index (DHr), when the aneurysm was small, whereas significant influence of DHr on the wall stresses happens, as the aneurysm approaches the critical diameter. Inconsistent variation of these indicators exhibited by shorter aneurysms (high DHr) at different growth stages, demands routine monitoring (using scans), of such aneurysms, to prevent unexpected rupture.

TRANSIENT ANALYSIS OF BLOOD FLOW IN FUSIFORM MODELS OF AORTIC ANEURYSMS

The Computational Fluid Dynamic (CFD) models of idealized fusiform aortic aneurysms and aortic arch with saccular aneurysm were developed to estimate hemodynamic parameters. The transient flow was simulated in aortic aneurysm models with laminar flow condition. The wall of aortic aneurysm was treated as rigid. The hemodynamic parameters flow velocity, wall pressure and wall shear stress (WSS) were estimated from fusiform aneurysm models. These observed hemodynamic parameters shows that, the aneurysms with larger diameter may cause disturbed flow. The variation in peak wall pressure value in all models is minimum. The wall shear stress has attained high value at peak systole in all models. The flow velocity was estimated from saccular aneurysm models. The flow velocity result shows a recirculation of flow in the saccular aneurysm region. The calculated hemodynamic parameters may help to understand the insights of flow in aortic aneurysm models.

Pre-clinical assessment of a prototype non-invasive diagnostic device to detect aortic aneurysms.

We have developed a non-invasive diagnostic device for treating thoracic aortic aneurysm that can be applied at a peripheral artery. This study aimed to examine how configuration and size of an aneurysm as well as endoluminal pressure affect our diagnostic device's ability to detect an aneurysm, using a pulsatile mock circulation. We created three different-sized (12, 16, and 20mm) saccular and fusiform aneurysm models using silicone and incorporated them in a pulsatile perfusion circuit to evaluate vertical vessel wall velocity wave form at a location apart from the aneurysm. We also varied the pressure condition to evaluate the changes in the detected wave forms. In both fusiform and saccular aneurysm models, biphasic wave forms indicating the presence of aneurysm within the circuit were observed. Regarding aneurysm diameter, biphasic wave forms were observed in all aneurysm models. However, in the 12-mm model, which is relevant to the minimum diameter of clinical diagnostic criteria for an aneurysm relative to normal size, no biphasic waveform was detected when the endoluminal pressure was relatively low. In the 16- and 20-mm models, biphasic waveform was detected without being affected by the configuration and endoluminal pressure. The detectability of aneurysms within a pulsatile mock circulation using our non-invasive diagnostic device was not affected by the clinically relevant configuration and size of the aneurysm under slightly hypertensive endoluminal pressure condition. Low endoluminal pressure may lower the diagnostic sensitivity for relatively small saccular aneurysm.

A refined experimental model of fusiform aneurysms in a rabbit carotid artery.

Reliable animal models are an important aspect of translational research, especially for relatively uncommon clinical entities such as fusiform aneurysms. While several animal models exist, very few are tailored to cerebral fusiform aneurysms, which have unique attributes compared to abdominal fusiform aneurysms. The authors aimed to build from previous models to create a cerebral fusiform aneurysm model that is simple to use and reliable. Twelve female New Zealand White rabbits were assigned to 3 groups: group E, elastase only; group C, CaCl2 only; group EC, elastase + CaCl2. All rabbits underwent surgical exposure of the right common carotid artery (CCA) and 20 minutes of peri-carotid incubation with their respective chemicals. Angiography was performed 6 weeks later for arterial dilation measurements, with 50% increase in diameter being defined as fusiform aneurysm formation. The arterial segments, along with the contralateral CCAs, were harvested and assessed histologically for wall component measurements and elastin semiquantification. A separate rabbit underwent aneurysm creation per the group EC protocol and was treated with an endovascular flow-diversion device. All of the group EC rabbits developed fusiform aneurysms (mean dilation of 88%), while none of the group E or group C rabbits developed aneurysms (p = 0.001). Histological analysis revealed increased internal elastic lamina fragmentation in the group EC aneurysms, which also had less tunica intima hyperplasia. All aneurysms exhibited thinning of the tunica media and reduction in elastin content. The use of an endovascular flow-diverting stent was successful, with complete parent vessel remodeling, as expected, 4 weeks after deployment. The peri-arterial application of combined elastase and CaCl2 to the CCA appears sufficient to reliably produce fusiform aneurysms after 6 weeks. Exposure to elastase or CaCl2 individually appears insufficient, despite the observed histological changes to the arterial wall. The proposed fusiform aneurysm model is able to accommodate endovascular devices, simulating the tortuous pathway experienced in using such devices in human cerebral aneurysms and thus is a satisfactory model to use in translational research.

A finite element implementation of a growth and remodeling model for soft biological tissues: Verification and application to abdominal aortic aneurysms

The general framework for growth and remodeling (G&R) of soft biological tissues shows a great potential for expanding our current understanding of biochemical and biomechanical processes, and to predict disease progression. Yet, its use is held up by the lack of a reliable and verified 3D finite element (FE) implementation capable of describing G&R processes of soft biological tissues. Thus, in this study we present the implementation of a 3D constrained mixture G&R model in a FE analysis program. In contrast to traditional finite strain FE formulations, we show that the volumetric–isochoric decomposition not only introduces numerical problems and instabilities, it also provides unphysical results. As a verification of the implementation we present adaptations of realistic aorta models to changes in the hemodynamics, i.e. changes in blood flow and pressure. The obtained results show a correspondence with the membrane theory and with clinical expectations. Application to a fusiform aneurysm model provided realistic growth rates, evolution of thickness and stress, whereas changes in the kinetic parameters show good agreement to animal models. Finally, we present simulated expansions of an asymmetric fusiform aneurysm. Non-axisymmetric elastin degradation increased the curvature of the aorta, which is characteristic for abdominal aortic aneurysms.

A new low-profile visualized intraluminal support (LVIS) device, LVIS Blue: laboratory comparison between old and new LVIS

ObjectivesThe Low-profile Visualized Intraluminal Support (LVIS) device is a flexible intracranial stent. The first generation of this system had significant challenges in consistently providing good wall apposition and aneurysm neck coverage. A new modified LVIS, LVIS Blue (Blue), has been developed to address these issues. The purpose of this study is to report a laboratory comparison of wall apposition and aneurysm neck coverage between the original LVIS and Blue.MethodsIn bench-top experiments, we noted the visual appearance of the devices and evaluated changes in stent cell angles, neck coverage surface area (%), and stent cell crossing profile for microcatheters using a fusiform aneurysm model. Our in vitro experiments included evaluation of wall apposition and aneurysm neck coverage of the devices under direct radiographic visualization.ResultsBlue showed three definite different zones (a mid-zone, a high-density zone, and a transitional zone) and higher metal coverage in the straight fusiform aneurysm model compared to LVIS. Two commercially available microcatheters easily crossed the stent cell at the greater curvature for both devices. In in vitro experiments, Blue showed better wall apposition in tortuous arteries and achieved higher neck coverage in the bifurcation aneurysm compared to LVIS.DiscussionBlue achieved better wall apposition in tortuous arteries and higher aneurysm neck coverage (higher metal-to-artery ratio) in bifurcation aneurysms than LVIS. Our results may provide informative physical properties of LVIS and Blue to be expected when those are used for stent-assisted coil embolization of a large-giant fusiform aneurysm or a bifurcation saccular aneurysm clinically.

Hemodynamic Changes Caused by Multiple Stenting in Vertebral Artery Fusiform Aneurysms: A Patient-Specific Computational Fluid Dynamics Study.

The multiple stent placement technique has largely improved the long-term outcomes of intracranial fusiform aneurysms, but the hemodynamic mechanisms remain unclear. In this study, we analyzed the hemodynamic changes caused by different stent-placement strategies in patient-specific models using the computational fluid dynamics technique, aiming to provide evidence for clinical decision-making. Ten vertebral artery fusiform aneurysms were included, and their patient-specific computational fluid dynamics models were reconstructed. A fast virtual stent placement technique was used to simulate sequential multiple stent placements (from a single stent to triple stents) in the vertebral artery fusiform aneurysm models. Hemodynamic parameters, including wall shear stress, pressure, oscillatory shear index, relative residence time, and flow pattern, were calculated and compared among groups with different numbers of stents. Virtual stents were deployed in all 10 cases successfully, consistent with the real stent configuration. Wall shear stress decreased progressively by 7.2%, 20.6%, and 25.8% as the number of stents increased. Meanwhile, relative residence time and pressure increased on average by 11.3%, 15.4%, and 45.0% and by 15.7%, 21.5%, and 28.2%. The oscillatory shear index showed no stable variation trend. Flow patterns improved by weakening the intensity of the vortices and displacing the vortex center from the aneurysmal wall. Stent placement modifies hemodynamic patterns in vertebral artery fusiform aneurysms, which might favor thrombosis formation in the aneurysmal sac. This effect is amplified with the number of stents deployed. However, a potential risk of rupture or recanalization exists and should be considered when planning to use the multiple stent placement technique in vertebral artery fusiform aneurysms.

Development of fusiform aneurysms induced by topical application of elastase in a rabbit model

BackgroundResearch on the etiology and pathophysiology of fusiform aneurysm has been impeded due to the inability to collect fusiform aneurysm specimens. We aim to resolve this through the development of a novel fusiform aneurysm model in rabbits.MethodsSixty New Zealand White rabbits were divided into ten groups (n = 6 per group): groups A, B, C, D, E and groups a, b, c, d, e. Elastase, at a concentration of 0, 0.5, 1, 2.5 and 5 U/μL respectively was administered to each rabbit to incubate their carotid arteries. Three weeks later, angiography, histomorphometry, immunohistochemistry and immunofluorescent were performed.ResultsHeparin administration is indispensable. No thrombosis was observed in groups A, B, C, D and E, whereas, increased thromboembolism occurred in groups a, b, c, d and e. Based on the size and wall thickness of aneurysms specimens, 5 U/μL was the optimal concentration of elastase to induce fusiform aneurysms. At 5 U/μL, the intraluminal carotid diameter increased significantly from 2.50 ± 0.32 mm to 3.11 ± 0.55 mm (p < 0.01). The wall thickness significantly reduced from 176.0 ± 39.8 μm to 39.7 ± 14.6 μm (p < 0.01) post aneurysm induction. The histolopathological evaluation revealed the elastic lamina and the smooth muscle cell’s lamina were markedly attenuated and the intimal endothelial lamina became thin or even absent.ConclusionsOur research demonstrates that intracranial fusiform aneurysm could be modeled in rabbit carotid artery adventitia incubation by porcine pancreatic elastase.

Testing Stenting and Flow Diversion Using a Surgical Elastase-Induced Complex Fusiform Aneurysm Model.

Rabbit elastase-induced saccular aneurysms have been commonly used for preclinical testing of endovascular devices, including flow diverters. However, all tested devices have been shown to be capable of aneurysm occlusion with this model. We aimed to create a more challenging model to test and discriminate among neurovascular devices of varying efficacies. With a surgical approach that included elastase infusion and balloon dilation, we attempted the creation of complex fusiform aneurysms in 16 rabbits, with standard saccular carotid aneurysms created in 15 other animals. Aneurysms were randomly allocated to one of the following treatments: flow diversion (n = 8), high-porosity stent (n = 6), double high-porosity stent (n = 5), and control (n = 6). Angiographic assessment and pathologic analyses were performed at 3 months. Creation of complex fusiform and standard saccular aneurysms was successful in 12/16 and 13/15 attempts, respectively. All saccular (n = 4) or complex fusiform (n = 4) aneurysms treated with flow diverters were successfully occluded. Three of 3 saccular compared with 0/2 complex fusiform aneurysms were occluded by double high-porosity stents. One of 3 saccular and 0/3 complex fusiform aneurysms were occluded by a single high-porosity stent. Both aneurysm types shared the same pathologic findings when untreated: The aneurysm wall lacked an elastic layer and smooth muscle cells, while the lumen was lined with neointima of varying thickness. Neointimal coverage of the devices was complete when aneurysms were occluded, while leaks were always associated with aneurysm remnants. Challenging fusiform aneurysms can be created in rabbits by using a surgical modification of the elastase method.

A novel fusiform aneurysmal model in a rabbit carotid: a combination of pericarotid calcium chloride and elastase incubation

Background: The purpose of this study was to develop a novel, simple and effective model of fusiform artery aneurysms in rabbits using a combination of periaortic calcium chloride (CaCl2) and elastase incubation. Methods: Fusiform aneurysms were developed in three New Zealand White rabbits by exposing a 2 cm segment of the right carotid artery to CaCl2 (0.5 mol/L) and pancreatic porcine elastase (75 U) for 20 minutes. The left carotid was used as a control. Vessel diameter was measured by serial digital subtraction angiography imaging at weeks 2, 4 and 6. Animals were sacrificed on week 6 and histopathological studies were performed. Results: All rabbits developed a fusiform aneurysm, with an average dilation ratio of 105%±10% by week 6. No mortality was reported. Histopathological studies revealed pathological features consistent with fusiform aneurysms. Conclusions: This novel rabbit model of fusiform carotid aneurysms is the first in the literature by using a combination of periaortic CaCl2 and elastase incubation. This is a simple, reliable, and effective technique and results in a potentially valuable model for the study of fusiform aneurysms and possible therapeutic interventions, such as flow diversion.

An in situ forming biodegradable hydrogel-based embolic agent for interventional therapies

We present here the characteristics of an in situ forming hydrogel prepared from carboxymethyl chitosan and oxidized carboxymethyl cellulose for interventional therapies. Gelation, owing to the formation of Schiff bases, occurred both with and without the presence of a radiographic contrast agent. The hydrogel exhibited a highly porous internal structure (pore diameter 17±4μm), no cytotoxicity to human umbilical vein endothelial cells, hemocompatibility with human blood, and degradability in lysozyme solutions. Drug release from hydrogels loaded with a sclerosant, tetracycline, was measured at pH 7.4, 6 and 2 at 37°C. The results showed that tetracycline was more stable under acidic conditions, with a lower release rate observed at pH 6. An anticancer drug, doxorubicin, was loaded into the hydrogel and a cumulative release of 30% was observed over 78h in phosphate-buffered saline at 37°C. Injection of the hydrogel precursor through a 5-F catheter into a fusiform aneurysm model was feasible, leading to complete filling of the aneurysmal sac, which was visualized by fluoroscopy. The levels of occlusion by hydrogel precursors (1.8% and 2.1%) and calibrated microspheres (100–300μm) in a rabbit renal model were compared. Embolization with hydrogel precursors was performed without clogging and the hydrogel achieved effective occlusion in more distal arteries than calibrated microspheres. In conclusion, this hydrogel possesses promising characteristics potentially beneficial for a wide range of vascular intervention procedures that involve embolization and drug delivery.

Application of the Willis covered stent using the telescopic technique for the treatment of fusiform aneurysm in a canine model

The covered stent is one of the most promising tools for the treatment of intracranial fusiform aneurysms. We developed an in vivo model of fusiform aneurysms and evaluated the effectiveness of double telescoping Willis covered stents for their treatment. An external jugular vein graft was anastomosed with the common carotid artery (CCA) to construct the fusiform aneurysm model. After at least 4 weeks, two Willis covered stents were implanted in a telescopic fashion. Angiography follow-up was performed at 2 weeks and 1 and 3 months to examine the grafts. The animals were sacrificed at 1 or 3 months of the follow-up period, and the stents were examined histologically. A total of eight fusiform aneurysms in four canines were created and 16 covered stents were implanted successfully. No technical or device-related difficulties occurred. The angiographic follow-up results showed that six fusiform aneurysms were completely occluded, and a minimal endoleak occurred in two fusiform aneurysms. Histological examination revealed endothelial progress and all aneurysm sacs were filled with thrombi. Vein graft anastomosis with CCA to construct a model of fusiform aneurysm may reproduce the clinical conditions. This study demonstrated that the implantation of two Willis covered stents in a telescoping fashion is an effective way to treat an experimental model of fusiform aneurysm.

Intra-aneurysmal flow reductions in a thin film nitinol flow diverter

A novel hyper-elastic thin film nitinol (HE-TFN) covered stent has been developed topromote aneurysm occlusion by diminishing flow in the aneurysm. Laboratory aneurysmmodels were used to assess the flow changes produced by stents covered with differentpatterns of HE-TFN placed across the aneurysm neck in the parent vessel. The flowdiverters were constructed by covering Wingspan stents (Boston Scientific) withdifferent HE-TFNs (i.e., of 82% and 77% porosity) and deployed in both in vitrowide-neck and fusiform glass aneurysm models. In wide-neck aneurysms, the 82%porous HE-TFN stent reduced mean flow velocity in the middle of the sac by86 ± 1%, while the 77% porous stent reduced the velocity by93 ± 5% (n = 3). Local wall shear rates were also significantly reduced by about 98%in this model after device placement. Tests conducted on the fusiformaneurysm revealed smaller intra-aneurysmal flow velocity reduction by48 ± 3% for the 82% porousstent and by 59 ± 7% for the 77% porous stent. The wall shear was reduced by approximately 50% by HE-TFNstents in fusiform models. These results suggest that HE-TFN covered stents have thepotential to promote thrombosis in both wide-neck and fusiform aneurysm sacs.

Fusiform Aneurysm Model in Rabbit Carotid Artery

Aims: To develop a reproducible and accessible model of elastase-induced fusiform aneurysm in carotid rabbit arteries. Methods: Elastase, at a concentration of 1–30 U, was incubated into the lumen of carotid rabbit arteries. Four weeks later, angiography, histomorphometry, immunohistochemistry and zymography were performed. Results: The optimal concentration of elastase in this model was 3 U according to the balance between mortality and thrombosis rates. Indeed, at 3 U, external carotid diameter increased from 1.9 ± 0.1 to 3.1 ± 0.4 mm (p < 0.0001) associated with degradation of elastic fibers, matrix metalloproteinase-9 secretion, apoptosis and macrophage infiltration. Conclusions: Our study underlines that abdominal aortic aneurysm can be reliably duplicated in an elastase-induced aneurysm in carotid artery, a much more accessible vessel.

In Vitro Assessment of EmboGel and UltraGel Radiopaque Hydrogels for the Endovascular Treatment of Aneurysms

To describe two hydrogel embolic materials, the alginate-based EmboGel and the polyethylene glycol diacrylate-based UltraGel and examine their use as embolic agents in in vitro models of abdominal aortic aneurysm (AAA) endoleak and saccular aneurysms. EmboGel is a mixture of iohexol and alginate, with a calcium chloride solution used to induce polymerization. UltraGel is a mixture of igracure, iohexol, and polyethylene glycol diacrylate and polymerizes in the presence of ultraviolet (UV) light. Modified microcatheter delivery systems were used in both cases to demonstrate use of the hydrogels in fusiform and saccular aneurysm models. Preliminary in vitro results suggest that EmboGel and UltraGel provide effective embolization in fusiform and saccular aneurysm models, respectively. Due to the rapid polymerization of EmboGel, the agent was delivered in a strand-like form. When used in conjunction with a stent in an AAA endoleak model, this form was able to effectively fill the aneurysmal cavity and occlude it from the central blood flow. UltraGel, conversely, was delivered as a liquid and slowly polymerized in the presence of UV light. This system in a saccular aneurysm model was able to form a solid cast inside the aneurysm wall, again showing complete occlusion from the parent flow. Preliminary results indicate these two novel hydrogel applications may prove effective for the treatment of saccular and fusiform aneurysms.

The authors have produced an experimental model of fusiform aneurysms in rats

The authors have produced an experimental model of fusiform aneurysms in rats

Hemodynamic phenomena in fusiform aneurysms--II: pulsatile flow conditions.

Pressure and flow distributions are reported at different pulsatile flows for four latex fusiform aneurysm models. The accuracy of results by Pitot-static techniques is examined in terms of experimental evidence and theoretical considerations. Pressure distributions within the aneurysm are associated with the Reynolds number, the degree of wall divergence, and the degree of sac dilation, and these parameters are interactive. The Bernoulli principle was usually inapplicable, and higher peak pressures may be seen where measured velocities may lead one to predict lower pressures. The presence of such localized high pressures depends on whether disturbed flow occurs at that location. There may be little qualitative difference in the patterns of velocity and pressure within an aneurysm between pulsatile and steady flow conditions. However, with pulsatile flow, the presence of distributed flow may be more obvious and commence closer to the proximal end of the aneurysm.

Hemodynamic Phenomena in Fusiform Aneurysms - I: Steady Flow Conditions

Pressure and flow distributions are reported at different steady flows for four latex fusiform aneurysm models. The accuracy of results by pitot-static techniques is examined in terms of experimental evidence and theoretical considerations. Results indicate that pressure distributions are associated with the Reynolds number, the degree of wall divergence and the degree of dilation of the sac, and that these parameters are interactive. The Reynolds number was found to have some predictive value for pressure distribution in the aneurysm, but the Bernoulli principle, based on geometrical variation and laminar flow, was usually inapplicable. Also, disturbed flow (eddies, reversal, turbulence) can occur as functions of the interactive parameters.