Strain ultrasound elastography of aneurysm sac content after randomized endoleak embolization with sclerosing and non-sclerosing chitosan-based hydrogels in a preclinical model

Mise en contexte : La réparation endovasculaire des anévrismes de l’aorte abdominale est limitée par le développement des endofuites, qui nécessite un suivi à long terme par imagerie. L’élastographie sonore de déformation a été proposée comme méthode complémentaire pour aider à la détection des endofuites et la caractérisation des propriétés mécaniques des anévrismes. On s’intéresse ici également à la possibilité de suivre l’embolisation des endofuites, qui est indiquée dans certains cas mais dont le succès est variable. Un nouvel agent d’embolisation a été récemment créé en combinant un hydrogel de chitosane radio-opaque (CH) et le sclérosant tetradecyl sulfate de sodium (STS), qui s’appelle CH-STS. Le CH-STS démontre des propriétés mécaniques in vitro favorables, mais son comportement in vivo et son effet sur l’évolution du sac par rapport à un agent non-sclérosant pourraient être mieux caractérisés. L’objectif de cette étude était la caractérisation des propriétés mécaniques des composantes des endofuites embolisées avec CH-STS et CH avec élastographie sonore de déformation. Méthodologie : Des anévrismes bilatéraux avec endofuites de type I ont été créés au niveau des artères iliaques communes chez neuf chiens. Chez chaque sujet, une endofuite a été embolisée avec CH, et l’autre, avec CH-STS, d’une façon aléatoire et aveugle. Des images d’échographie duplex et des cinéloops pour élastographie sonore de déformation ont été acquis à 1 semaine, 1 mois, 3 mois et (chez 3 sujets) 6 mois post-embolisation. La tomodensitométrie a été faite à 3 mois et (si pertinente) 6 mois post-embolisation. L’histopathologie a été faite au sacrifice. Les études radiologiques et les données d’histopathologie ont été co-enregistrées pour définir trois régions d’intérêt sur les cinéloops : l’agent d’embolisation (au sacrifice), le thrombus intraluminal (au sacrifice) et le sac anévrismal (pendant chaque suivi). L’élastographie sonore de déformation a été faite avec les segmentations par deux observateurs indépendants. La déformation axiale maximale (DAM) a été le critère d’évaluation principal. Les analyses statistiques ont été faites avec des modèles mixtes linéaires généralisés et des coefficients de corrélations intraclasses (ICCs). Résultats : Des endofuites résiduelles ont été trouvées dans 7/9 (77.8%) et 4/9 (44.4%) des anévrismes embolisés avec CH et CH-STS, respectivement. Le CH-STS a eu une DAM 66 % plus basse (p < 0.001) que le CH. Le thrombus a eu une DAM 37% plus basse (p = 0.010) que le CH et 77% plus élevée (p = 0.079) que le CH-STS. Il n’y avait aucune différence entre les thrombi associés avec les deux traitements. Les sacs anévrismaux embolisés avec CH-STS ont eu une DAM 29% plus basse (p < 0.001) que ceux embolisés avec CH. Des endofuites résiduelles ont été associées avec une DAM du sac anévrismal 53% plus élevée (p < 0.001). Le ICC pour la DAM a été de 0.807 entre les deux segmentations. Conclusion : Le CH-STS confère des valeurs de déformations plus basses aux anévrismes embolisés. Les endofuites persistantes sont associées avec des déformations plus élevées du sac anévrismal.Background: Endovascular aneurysm repair (EVAR) is the modality of choice for the treatment of abdominal aortic aneurysms (AAAs). EVAR is limited by the development of endoleaks, which necessitate long-term imaging follow-up. Conventional follow-up modalities suffer from unique limitations. Strain ultrasound elastography (SUE) has been recently proposed as an imaging adjunct to detect endoleaks and to characterize aneurysm mechanical properties. Once detected, certain endoleaks may be treated with embolization; however, success is limited. In this context, the embolic agent CH-STS—containing a chitosan hydrogel and the sclerosant sodium tetradecyl sulphate (STS)—was created. CH-STS demonstrates favorable mechanical properties in vitro; however, its behavior in vivo and impact on sac evolution compared to a non-sclerosing chitosan-based embolic agent (CH) merit further characterization. Purpose: To compare the mechanical properties of the constituents of endoleaks embolized with CH and CH-STS—including the agent, the intraluminal thrombus (ILT), and the overall sac—via SUE. Methods: Bilateral common iliac artery aneurysms with type I endoleaks were created in nine dogs. In each animal, one endoleak was randomly embolized with CH, and the other with CH-STS. Duplex ultrasound (DUS) and radiofrequency cine loops were acquired at 1 week, 1 month, 3 months, and—in 3 subjects—6 months post-embolization. Contrast-enhanced CT was performed at 3 months and—where applicable—6 months post-embolization. Histopathological analysis was performed at time of sacrifice. Radiological studies and histopathological slides were co-registered to identify three regions of interest (ROIs) on the cine loops: embolic agent (at sacrifice), ILT (at sacrifice), and aneurysm sac (at all follow-up times). SUE was performed using segmentations from two independent observers on the cine loops. Maximum axial deformation (MAD) was the main outcome. Statistical analysis was performed using general linear mixed models and intraclass correlation coefficients (ICCs). Results: Residual endoleaks were identified in 7/9 (77.8%) and 4/9 (44.4%) aneurysms embolized with CH and CH-STS, respectively. CH-STS had a 66 % lower MAD (p < 0.001) than CH. The ILT had a 37% lower MAD (p = 0.010) than CH and a 77% greater MAD (p = 0.079; trending towards significance) than CH-STS. There was no difference in the ILT between treatment groups. Aneurysm sacs embolized with CH-STS had a 29% lower MAD (p < 0.001) than those with CH. Residual endoleak increased MAD of the aneurysm sac by 53% (p < 0.001), regardless of the agent used. The ICC for MAD was 0.807 between readers’ segmentations. Conclusion: CH-STS confers lower strain values to embolized aneurysms. Persistent endoleaks result are associated with increased sac strain, which may be useful for clinical follow-up

Analysis of Blood Flow in Patient-specific Models of Type B Aortic Dissection

Aortic dissection is the most common acute catastrophic event affecting the aorta. The majority of patients presenting with an uncomplicated type B dissection are treated medically, but 25% of these patients develop subsequent dilatation and aortic aneurysm formation. The reasons behind the long‐term outcomes of type B aortic dissection are poorly understood. As haemodynamic factors have been involved in the development and progression of a variety of cardiovascular diseases, the flow phenomena and environment in patient‐specific models of type B aortic dissection have been studied in this thesis by applying computational fluid dynamics (CFD) to in vivo data. The present study aims to gain more detailed knowledge of the links between morphology, flow characteristics and clinical outcomes in type B dissection patients. The thesis includes two parts of patient‐specific study: a multiple case cross‐sectional study and a single case longitudinal study. The multiple cases study involved a group of ten patients with classic type B aortic dissection with a focus on examining the flow characteristics as well as the role of morphological factors in determining the flow patterns and haemodynamic parameters. The single case study was based on a series of follow‐up scans of a patient who has a stable dissection, with an aim to identify the specified haemodynamic factors that are associated with the progression of aortic dissection. Both studies were carried out based on computed tomography images acquired from the patients. 4D Phase‐contrast magnetic resonance imaging was performed on a typical type B aortic dissection patient to provide detailed flow data for validation purpose. This was achieved by qualitative and quantitative comparisons of velocity‐encoded images with simulation results of the CFD model. The analysis of simulation results, including velocity, wall shear stress and turbulence intensity profiles, demonstrates certain correlations between the morphological features and haemodynamic factors, and also their effects on long‐term outcomes of type B aortic dissections. The simulation results were in good agreement with in vivo MR flow data in the patient‐specific validation case, giving credence to the application of the computational model to the study of flow conditions in aortic dissection. This study made an important contribution by identifying the role of certain morphological and haemodynamic factors in the development of type B aortic dissection, which may help provide a better guideline to assist surgeons in choosing optimal treatment protocol for individual patient

Scanning protocol optimisation for dual-energy computed tomography angiography in peripheral artery stenting

In this thesis, a novel approach has been proposed to evaluate the optimal scanning protocol for dual energy computed tomography angiography in peripheral arterial stents. This new approach includes evaluation of different protocols and image reconstructions at different energy level, development of the optimal protocol based on lowest radiation dose and acceptable image quality. Furthermore, an optimal contrast medium protocol has been identified in imaging peripheral arterial disease

Design of a testing device for an anatomical part of the ascending aorta

Aortic aneurysms are life-threatening pathologies that cause thousands of deaths worldwide. The current main clinical criteria for surgical intervention is aortic diameter, although a large percentage of patients with dissection or rupture has a normal diameter. Computation methods have been adopted to model the biomechanical behaviour of biological tissue in view of adding in the diagnosis of this pathology. Furthermore, experimental testing on aneurismatic aortic tissue has been performed to validate these models. The objective of this study is to integrate com- putational mechanical methods into an innovative experimental test with a specifically designed device where material parameters are obtained by inverse methods assisted by Digital Image Correlation (DIC). Axiomatic Design (AD) is taken into consideration to develop the testing device in a clear, methodical, and efficient way. A case study is analysed, and a patient-specific 3D geometry of an Ascending Thoracic Aortic Aneurysm (ATAA) is obtained by segmenting Computed Tomography Angiography (CTA) images. A methodology is presented by attribut- ing a hyperelastic constitutive model to the geometry and executing Finite Element Analysis (FEA). Future work should rely on real experimental tests where Finite Element Model Up- dating (FEMU) should be adopted to fit the constitutive model more accurately to the actual specimen material.O aneurisma da aorta é uma patologia de risco que provoca milhares de mortes mundialmente. O critério atual para intervenção cirúrgica é o diâmetro da aorta, no entanto, uma grande percentagem de pacientes com dissecção ou rutura da aorta apresenta um diâmetro normal. Métodos computacionais têm sido adotados para modelar o comportamento biomecânico de tecido biológico e auxiliar no diagnóstico desta patologia. Testes experimentais nestes tecidos são executados para validar os modelos. O objetivo deste estudo é um contributo para uma plataforma digital integrando métodos computacionais para o desenvolvimento de um mecan- ismo de ensaio experimental, cuja identificação de parâmetros material deve ser auxiliada pela técnica de correlação digital de imagem 3D. Esta abordagem segue um desenvolvimento de pro- duto orientado por simulação numérica, em que a análise computacional é totalmente integrada como parte do projeto mecânico. Teoria Axiomática de Projeto é tida em consideração para desenvolver o dispositivo de uma forma clara, metódica e eficiente. Um caso de estudo é anal- isado e uma geometria da peça anatómica 3D, específica de um paciente, é obtida através da segmentação de imagens de uma angiotomografia. Uma metodologia é apresentada atribuindo um modelo constitutivo hiperelástico ao material e executando análise de elementos finitos. Como trabalho futuro a identificação dos parametros constitutivos deve ser obtida com recurso a métodos inversos avançados baseados em campos de deformação obtidos por correlação digital de imagem