Testing Of Endovascular Devices Research Articles

Continuous extracorporeal femoral perfusion model for intravascular ultrasound, computed tomography and digital subtraction angiography.

We developed a novel human cadaveric perfusion model with continuous extracorporeal femoral perfusion suitable for performing intra-individual comparison studies, training of interventional procedures and preclinical testing of endovascular devices. Objective of this study was to introduce the techniques and evaluate the feasibility for realistic computed tomography angiography (CTA), digital subtraction angiography (DSA) including vascular interventions, and intravascular ultrasound (IVUS). The establishment of the extracorporeal perfusion was attempted using one formalin-fixed and five fresh-frozen human cadavers. In all specimens, the common femoral and popliteal arteries were prepared, introducer sheaths inserted, and perfusion established by a peristaltic pump. Subsequently, we performed CTA and bilateral DSA in five cadavers and IVUS on both legs of four donors. Examination time without unintentional interruption was measured both with and without non-contrast planning CT. Percutaneous transluminal angioplasty and stenting was performed by two interventional radiologists on nine extremities (five donors) using a broad spectrum of different intravascular devices. The perfusion of the upper leg arteries was successfully established in all fresh-frozen but not in the formalin-fixed cadaver. The experimental setup generated a stable circulation in each procedure (ten upper legs) for a period of more than six hours. Images acquired with CT, DSA and IVUS offered a realistic impression and enabled the sufficient visualization of all examined vessel segments. Arterial cannulating, percutaneous transluminal angioplasty as well as stent deployment were feasible in a way that is comparable to a vascular intervention in vivo. The perfusion model allowed for introduction and testing of previously not used devices. The continuous femoral perfusion model can be established with moderate effort, works stable, and is utilizable for medical imaging of the peripheral arterial system using CTA, DSA and IVUS. Therefore, it appears suitable for research studies, developing skills in interventional procedures and testing of new or unfamiliar vascular devices.

Novel Human Acute Ischemic Stroke Blood Clot Analogs for In Vitro Thrombectomy Testing.

Previous studies have successfully created blood clot analogs for in vitro endovascular device testing using animal blood of various species. Blood components vary greatly among species; therefore, creating clot analogs from human blood is likely a more accurate representation of thrombi formed in the human vasculature. Following approval from the Mayo Clinic institutional review board, human whole-blood and platelet donations were obtained from the blood transfusion service. Twelve clot analogs were created by combining different ratios of red blood cells + buffy coat, plasma, and platelets. Thrombin and calcium chloride were added to stimulate coagulation. Clot composition was assessed using histologic and immunohistochemical staining. To assess the similarities of mechanical properties to patient clots, 3 types of clot analogs (soft, elastic, and stiff) were selected for in vitro thrombectomy testing. The range of histopathologic compositions produced is representative of clots removed during thrombectomy procedures. The red blood cell composition ranged from 8.9% to 91.4%, and fibrin composition ranged from 3.1% to 53.4%. Platelets (CD42b) and von Willebrand Factor ranged from 0.5% to 47.1% and 1.0% to 63.4%, respectively. The soft clots had the highest first-pass effect and successful revascularization rates followed by the elastic and stiff clots. Distal embolization events were observed when clot ingestion could not be achieved, requiring device pullback. The incidence rate of distal embolization was the highest for the stiff clots due to the weak clot/device integration. Red blood cell-rich, fibrin-rich, and platelet-rich clot analogs that mimic clots retrieved from patients with acute ischemic stroke were created in vitro. Differing retrieval outcomes were confirmed using in vitro thrombectomy testing in a subset of clots.

The development and understanding of intracranial aneurysm based on rabbit model.

In modern society, intracranial aneurysms have seriously affected people's life. To better study and treat intracranial aneurysm, animal models are ideal candidates to perform biological research and preclinical endovascular device testing. Rabbit aneurysm model is one of the most commonly used animal models, and the rabbit aneurysms share similarities in histology, morphology, and hemodynamic aspects with human intracranial aneurysms, which is an ideal model for intracranial aneurysm pre-clinical and basic research. In this review, we will summarize the main methods of establishing rabbit aneurysms model and will further discuss the current biological mechanisms of intracranial aneurysms based on rabbit model. Further improvements of rabbit aneurysm model and more deep studies based on this model are needed to provide new insights into studying and clinical treating intracranial aneurysm.

Biomechanical simulations and 3D printing for endovascular device testing

Endovascular aortic repair is a minimally invasive procedure to treat aortic diseases such as aneurysms and dissections. Thanks to technological advancements, such procedure has steadily shifted from the abdominal aorta towards the ascending part, i.e., near the heart, calling for an extensive and comprehensive benchmarking of (novel) endografts. Given such considerations, we have exploited porcine aorta with a pulse duplicator to analyse the mechanical interaction between the endovascular device and the native tissue. Our results have implications for using the porcine aorta as a model for human aorta in research. Particularly, the combination of in vitro tests performed using ex-vivo tissue, integrated validated patient-specific numerical simulations, mock arteries manufactured by 3D printing, can offer important insight on biomechanical impact of endograft design on post-operative aortic mechanical response.

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.

High-flow venous pouch aneurysm in the rabbit carotid artery: A model for large aneurysms.

Currently one of the most widely used models for the development of endovascular techniques and coiling devices for treatment of aneurysm is the elastase-induced aneurysm model in the rabbit carotid artery. Microsurgical techniques for creating an aneurysm with a venous pouch have also been established, although both techniques usually result in aneurysms less than 1 cm in diameter. We investigated whether an increase in blood flow toward the neck would produce larger aneurysms in a microsurgical venous pouch model. Microsurgical operations were performed on 11 New Zealand white rabbits. Both carotid arteries and the right jugular vein were dissected, and the right carotid artery was temporarily clipped followed by an arteriotomy. The left carotid artery was also clipped proximally, ligated distally, and sutured onto the proximal half of the arteriotomy in the right carotid artery. The venous graft was sutured onto the distal half of the arteriotomy. Digital subtraction angiography was also performed. Angiography showed patent anastomosed vessels and aneurysms in the seven surviving rabbits. Mean aneurysm measurements among surviving rabbits with patent vessels were: 13.9 mm length, 9.3 mm width, and neck diameter 4.7 mm. The resulting mean aspect ratio was 3.35 and the mean bottleneck ratio was 3.05. A large venous graft and increased blood flow toward the base of the aneurysm seem to be key factors in the creation of large venous pouch aneurysms. These large aneurysms allow testing of endovascular devices designed for large and giant aneurysms.

A multimodality vascular imaging phantom of an abdominal aortic aneurysm with a visible thrombus

With the continuous development of new stent grafts and implantation techniques, it has now become technically feasible to treat abdominal aortic aneurysms (AAA) with challenging anatomy using endovascular repair with standard, fenestrated, or branched stent-grafts. In vitro experimentations are very useful to improve stent-graft design and conformability or imaging guidance for stent-graft delivery or follow-up. Vascular replicas also help to better understand the limitation of endovascular approaches in challenging anatomy and possibly improve surgical planning or training by practicing high risk clinical procedures in the laboratory to improve outcomes in the operating room. Most AAA phantoms available have a very basic anatomy, which is not representative of the clinical reality. This paper presents a method of fabrication of a realistic AAA phantom with a visible thrombus, as well as some mechanical properties characterizing such phantom. A realistic AAA geometry replica of a real patient anatomy taken from a multidetector computed tomography (CT) scan was manufactured. To demonstrate the multimodality imaging capability of this new phantom with a thrombus visible in magnetic resonance (MR) angiography, CT angiography (CTA), digital subtraction angiography (DSA), and ultrasound, image acquisitions with all these modalities were performed by using standard clinical protocols. Potential use of this phantom for stent deployment was also tested. A rheometer allowed defining hyperelastic and viscoelastic properties of phantom materials. MR imaging measurements of SNR and CNR values on T1 and T2-weighted sequences and MR angiography indicated reasonable agreement with published values of AAA thrombus and abdominal components in vivo. X-ray absorption also lay within normal ranges of AAA patients and was representative of findings observed on CTA, fluoroscopy, and DSA. Ultrasound propagation speeds for developed materials were also in concordance with the literature for vascular and abdominal tissues. The mimicked abdominal tissues, AAA wall, and surrounding thrombus were developed to match imaging features of in vivo MR, CT, and ultrasound examinations. This phantom should be of value for image calibration, segmentation, and testing of endovascular devices for AAA endovascular repair.

Porcine Brachial Artery Tortuosity for In Vivo Evaluation of Neuroendovascular Devices

We report a novel model of arterial tortuosity in the porcine brachial artery for testing of endovascular devices in the flexed forelimb position. This provides an ideal vascular territory for an in vivo assessment of guidewires, microcatheters, and endovascular implants because it closely mimics the challenging curvature at the carotid siphon.

O-023 Pre-clinical model of porcine arterial tortuosity for in vivo testing of neuroendovascular devices

IntroductionPreclinical testing of endovascular devices in an in-vivo environment provides a more realistic simulation of critical vessel viscoelastic and physiologic responses. In comparison, in-vitro and cadaveric models, though indispensible, can...

Mechanical Characterization of Thromboemboli in Acute Ischemic Stroke and Laboratory Embolus Analogs

Mechanical behavior of the thromboembolus is one of the key factors that determine the efficacy of thrombectomy devices for revascularization in AIS. We characterized the mechanical properties and composition of thromboemboli from clinical cases and compared them with commonly used EAs. Thromboemboli were obtained from patients with AIS by using aspiration devices and from carotid atherosclerotic plaques harvested during endarterectomy. In the laboratory, common EAs were created by varying blood donor species (human, porcine, and bovine), thrombin concentration, and presence of barium sulfate. Stiffness and elasticity of the specimens were measured with DMA. Scanning electron microscopy and histology were used to investigate the ultrastructure and composition of all specimens. Red thromboemboli from patients composed mainly of fibrin and erythrocytes were much softer than the calcified and cholesterol-rich material. Of the EAs created in the laboratory, those made from bovine blood presented the highest stiffness that was independent of thrombin concentration. Addition of thrombin increased the stiffness and elasticity of human and porcine EAs (P < .05). The presence of barium sulfate significantly reduced the elasticity of all EAs (P < .05). Endovascular device testing and development requires realistic EAs. The stiffness and elasticity of the cerebral thromboemboli analyzed in this study were closely matched by recalcified porcine EAs and thrombin-induced human EAs. Stiffness of the thrombus extracted from carotid endarterectomy specimens was similar with that of the thrombin-induced bovine and porcine EAs.

Geometric Variability of the Abdominal Aorta and Its Major Peripheral Branches

Vessel geometry determines blood flow dynamics and plays a crucial role in the pathogenesis of vascular disease. In vivo assessment of three-dimensional (3D) vessel anatomy is vital to improve the realism of arterial flow model geometries and investigate factors associated with the localisation of atherosclerosis. The quantification of vascular geometry is also particularly important for the proper design and preclinical testing of endovascular devices used to treat peripheral arterial disease. The purpose of this study was to quantitatively evaluate the intersubject variability of 3D branching and curvature of the abdominal aorta and its major peripheral arteries. Contrast-enhanced renal MRA scans of healthy abdominal vessels obtained in 12 subjects (8 men, 4 women mean age 49 years, range 27-84 years) were segmented, and smoothed centerlines were determined as descriptors of arterial geometry. Robust techniques were employed to characterise non-planar vessel curvature, arterial taper, and 3D branching parameters. Noticeable 3D curvature and tapering were quantified for the proximal anterior visceral and renal branches. Mean 3D branching angles of 63.5+/-10.1 degrees and 73.1+/-6.8 degrees were established for the right and left renal arteries, respectively. Angles describing the ostial position and initial trajectory of the renal arteries confirmed the antero-lateral origin and direction of the right and the more lateral orientation of the left. The anterior visceral branches emerged predominantly from the left side of the anterior aortic wall. Branching parameters determined at the aortic bifurcation demonstrated mild asymmetry and non-planarity at this location. In summary, the results from this study address the scarcity of available in vivo 3D quantitative geometric data relating to the abdominal vasculature and reflect the geometric variability in living subjects.

A New Model of Abdominal Aortic Aneurysm with Gastric Serosa Patch: Surgical Technique and Short-Term Evaluation

The purpose of this work was to develop an abdominal aortic aneurysm (AAA) model that resembles human aneurysms with potential for further growth, patent collateral vessels, and a predictable tendency to rupture, and that can be used in the development of new endoprostheses and implant training. An infrarenal AAA model was created in five domestic swine using an autologous gastric serosal patch. Pre- and postsurgical digital substraction aortograms (DSA) were obtained to document the appearance and dimensions of the aneurysm. Animals were followed up with DSA and ultrasonography on days 7, 14, 30, 45, 60, and 90 after model creation. Aneurysmal diameters were measured with both techniques in all examinations. On day 90, animals were euthanized, target arteries were harvested, and pathological evaluation was performed. The nonparametric Wilcoxon test was used to assess any differences in measured diameters. All the animals survived the surgical procedure. The aneurysmal diameters increased from 8.14± 2.15 to 13.28± 1.18 mm immediately after surgery (p <. 05), but no subsequent significant growth of the aneurysmal sac was seen during follow-up. In this experimental setting, measurements obtained with DSA were slightly larger than those obtained with ultrasound. Two animals died of AAA rupture on days 6 and 10 (40% rupture rate). Pathological examination showed lack of elastic laminae and increased collagen content in the aortic patch. Thus, model showed a tendency to rupture, but no significant potential for further aneurysmal growth. It might be useful for training in endovascular therapies, but its usefulness for preclinical endovascular device testing is limited by its lack of growth potential.

A rabbit model of abdominal aortic aneurysms (AAA)

Abstract Introduction: The rat elastase model of AAA is well established and useful for studying the early events in AAA formation. Development of a physiologic large animal model that reliably produces AAA expansion will allow in vivo testing of endovascular devices. Methods: Adult male New Zealand white rabbits (3.0–3.5 kg) were anesthetized and the terminal aorta exposed through a midline incision. Nine animals were divided into three groups: (I) saline controls, (II) elastase (100u/ml), or (III) elastase (100 μ/mL) and collagenase (50 μ/mL). A 2 cm segment of infrarenal aorta was isolated and was infused with one of the solutions for 5 minutes. Peak pressures were maintained between 300–400 mmHg. The aortic diameter was measured directly and by angiography before infusion, after infusion and at 8 weeks, when the animals were humanly killed. Results: Both treatment groups had significant increases in the size of the aorta at the end of the experiment compared to controls (p = 0.013). Animals treated with elastase and collagenase had a significantly greater change in mean aortic diameter, 2.7mm increased to 6.1mm, at 8-weeks compared to elastase alone, 2.8mm increased to 4.3 mm (p = 0.018). Conclusions: Infusion of an isolated segment of rabbit aorta with elastase and collagenase may provide a reproducible large animal model of AAA. Further work is required to determine if this could lead to a physiologic model with reproducible rupture that will allow in vivo testing of endovascular devices.

Are the configuration and neck morphology of experimental aneurysms predictable? A technical approach.

Aneurysm configuration and neck morphology are important factors in the decision for cerebral aneurysm therapy, i.e., clipping versus coiling. The aim of our study was to create various aneurysm configurations in a predictable and reproducible way in an animal model. In our recently proposed endovascular approach to produce bifurcation aneurysms in the rabbit, the right common carotid artery (CCA) is surgically exposed and distally ligated, and a sheath is advanced retrogradely into the CCA, the base of which is proximally occluded using a Fogarty balloon. Subsequently, elastase is injected via a microcatheter that is placed directly distal to the balloon and allowed to incubate for 20 min. After removal of the sheath, saccular aneurysms begin to form within 2 weeks. For greater variability in aneurysm size and neck morphology, we modified two parameters of this formerly established elastase-induced aneurysm model--the distance between the balloon and sheath and the level of balloon position--before the elastase was endoluminally incubated in 15 rabbits. Three weeks after aneurysm induction, the size and configuration of the aneurysms were controlled using DSA. Our results confirm that balloon occlusion in the brachiocephalic trunk results in broad-based aneurysms, whereas balloon occlusion in the CCA gives rise to circumscribed aneurysm necks. By increasing the distance between the balloon and sheath, the rabbits developed significantly larger aneurysms. The balloon-sheath distance and the level of balloon occlusion proved to be parameters whose modifications result in predictable and reproducible aneurysm variants that can be used for the testing of endovascular devices.

A human cadaveric circulation model

Although endovascular techniques have achieved widespread acceptance, a suitable model for device development and physician training has not been available. Plastic models of the arterial tree and live animal models have significant limitations. Arterial-to-arterial flow is established in fresh frozen human cadavers after a simple thrombolytic process to achieve a more realistic model for endovascular device testing and training. Circulation can be established through most of the arterial system, including the cerebral, aortoiliac, and extremity vessels. This model offers antegrade flow in human arterial anatomy and has been used successfully for physician training and device development. (J Vasc Surg 2001;33:1128-30.)