Anévrisme de l'aorte abdominale

L' consiste en une dilatation localisée avec perte du parallélisme des parois de l'aorte dans sa portion abdominale. La localisation la plus fréquente se situe en dessous des artères rénales, c'est-à-dire dans la dernière portion de l'aorte. On parle d'anévrisme lorsque le diamètre transversal maximal du vaisseau est supérieur à 1,5 fois la normale ; en deçà, on parle d'ectasie. Son diamètre peut parfois atteindre , la normale étant de à après 65 ans, variable en fonction du sexe et de la morphologie de la personne. Le risque principal en est la rupture. Il dépend de la taille et de la vitesse de croissance (qui est dépendante elle-même de la taille). Épidémiologie Les anévrismes de l'aorte abdominale sont rares avant l'âge de 60 ans. Entre 65 et 80 ans la prévalence est de 5 à 10 % chez l'homme. Elle est beaucoup plus faible chez la femme. L'incidence semble avoir beaucoup augmenté dans la seconde partie du , peut-

The onset of cardiovascular disease in mice: an image-based, computational-experimental approach

Lydia Aslanidou

In a number of cardiovascular diseases, the paucity of longitudinal human data hinders our understanding of disease evolution and forestalls the discovery of new therapeutic strategies. We therefore heavily rely on animal models to elucidate the mechanisms that govern disease development. Nonetheless, the reference mouse arterial physiology and hemodynamics of its systemic circulation have yet to be described. But preclinical research is not limited to healthy mice; it helps decode the elusive etiology of potentially deadly pathologies such as aortic aneurysms and dissections. A key question is: Why are these pathologies so location-specific? In humans, abdominal aortic aneurysms affect the infrarenal aorta and aortic dissections form in the thoracic aorta. Inversely, in the most commonly used mouse model of this field, aortic dissections preferentially form in the suprarenal abdominal aorta but reasons for such localization remain unknown in humans and mice. In Chapter 1 we aimed to fill the knowledge gap of mouse hemodynamics, by translating an existing 1D model of the human arterial circulation to the healthy mouse. The model combines a broad range of literature data with a detailed description of the murine vasculature. Model predictions of pressure and flow were validated against pressure, velocity and diameter measurements from a large independent dataset of mice. This versatile tool can be used to simulate pathology and facilitate the implementation of the 3R's principle in research practice. Our next steps aimed to unravel the origins of site-specific aortic dissections in the mouse model of Angiotensin II infusion. Initially, we imaged the inceptive stage of disease to understand what happens in the suprarenal mouse aorta. Then, we explored why both from a biomechanical and a mechanobiological standpoint. In Chapter 2, we use high-resolution synchrotron imaging to characterize the early morphology of the suprarenal aorta in mice infused with Angiotensin II, prior to overt dissecting events. We found that the primary damage of the wallâs microstructure preferentially occurs around two major side branches of the aorta. After evidence of this direct involvement of side branches in disease onset, we investigated the underlying reasons from two distinct perspectives. In the synchrotron-based computational study of Chapter 3, we hypothesized that biomechanical forces expose branching sites to early vascular injury. We used an in-house framework which enables a. computational structural mechanics of the aortic wall using mouse-specific geometries, and b. mouse-specific validation to indicate whether high mechanical strain spatially coincides with microstructural defects. Branch-related hotspots of strain co-localized with early damaged microstructure, thus pointing towards a mechanically-driven mechanism that nucleates around the aortic branches. In Chapter 4 we explored from a mechanobiological perspective if the suprarenal aorta's vascular function changes prior to dissection. We found a regional variation: both the contractile and the endothelial function were severely compromised in the suprarenal aortaâs dissection-prone segment, but only mildly so in its dissection-protected segments. Surprisingly, vascular function was largely preserved in the adjacent side branches, creating a local discontinuity in the profile of contractile capacity between the (diseased) aorta and the (non-diseased) branches.

EPFL2019

Synchrotron-based phase contrast imaging of cardiovascular tissue in mice-grating interferometry or phase propagation?

Lydia Aslanidou, Mauro Ferraro, Goran Lovric, Patrick Segers, Nikolaos Stergiopulos, Bram Trachet

Synchrotron-based x-ray phase-contrast imaging allows for detailed 3D insight into the microstructure of soft tissue and is increasingly used to improve our understanding of mouse models of cardiovascular disease. Two techniques dominate the field: grating interferometry, with superior density contrast at mid to lower microscopic resolutions, and propagation-based phase contrast, facilitating high-resolution tissue imaging. The choice between these techniques depends on which features one is interested in visualizing and is thus highly sample-dependent. In this manuscript we systematically evaluate the advantages and disadvantages of grating interferometry and propagation-based phase contrast for the specific application of pre-clinical cardiovascular tissue. We scanned samples obtained from 5 different mouse models of cardiovascular disease, ranging from carotid plaques over ascending and abdominal aortic aneurysms to hypertrophic hearts. Based on our findings we discuss in detail how synchrotron-based imaging can be used to increase our understanding of the anatomy and biomechanics of cardiovascular disease in mice. We also present a flowchart that can help future users to select the best synchrotron-based phase contrast technique for their pre-clinical cardiovascular samples.

2019

Angiotensin II infusion into ApoE(-/-) mice: a model for aortic dissection rather than abdominal aortic aneurysm?

Lydia Aslanidou, Alessandra Piersigilli, Patrick Segers, Jessica Sordet-Dessimoz, Nikolaos Stergiopulos, Bram Trachet

Aims Angiotensin II-infused ApoE(-/-) mice are a popular mouse model for preclinical aneurysm research. Here, we provide insight in the often-reported but seldom-explained variability in shape of dissecting aneurysms in these mice. Methods and results N=45 excised aortas were scanned ex vivo with phase-contrast X-ray tomographic microscopy. Micro-ruptures were detected near the ostium of celiac and mesenteric arteries in 8/11 mice that were sacrificed after 3 days of angiotensin II-infusion. At later time points (after 10, 18, and 28 days) the variability in shape of thoraco-abdominal lesions (occurring in 31/34 mice) was classified into 7 different categories based on the presence or absence of a medial tear (31/31), an intramural hematoma (23/31) or a false channel (11/23). Medial tears were detected both in the thoracic and the abdominal aorta and were most prevalent at the left and ventral aspects of celiac and mesenteric arteries. The axial length of the hematoma strongly correlated to the total number of ruptured branch ostia (r(2) = 0.78) and in 22/23 mice with a hematoma the ostium of the left suprarenal artery had ruptured. Supraceliac diameters at baseline were significantly lower for mice that did not develop an intramural hematoma, and the formation of a false channel within that intramural hematoma depended on the location, rather than the length, of the medial tear. Conclusion Based on our observations we propose an elaborate hypothesis that explains how aortic side branches (i) affect the initiation and propagation of medial tears and the subsequent adventitial dissection and (ii) affect the variability in shape of dissecting aneurysms. This hypothesis was partially validated through the live visualization of a dissecting aneurysm that formed during micro-CT imaging, and led us to the conclusion that angiotensin II-infused mice are more clinically relevant for the study of aortic dissections than for the study of abdominal aortic aneurysms.

2017