ABSTRACT
BACKGROUND: Rupture of brain aneurysms is associated with high fatality and morbidity rates. Through remodeling of the collagen matrix, many aneurysms can remain unruptured for decades, despite an enlarging and evolving geometry. OBJECTIVE: Our objective was to explore this adaptive remodeling for the first time in an elastase induced aneurysm model in rabbits. METHODS: Saccular aneurysms were created in 22 New Zealand white rabbits and remodeling was assessed in tissue harvested 2, 4, 8 and 12 weeks after creation. RESULTS: The intramural principal stress ratio doubled after aneurysm creation due to increased longitudinal loads, triggering a remodeling response. A distinct wall layer with multi-directional collagen fibers developed between the media and adventitia as early as 2 weeks, and in all cases by 4 weeks with an average thickness of 50.6 ± 14.3 µm. Collagen fibers in this layer were multi-directional (AI = 0.56 ± 0.15) with low tortuosity (1.08 ± 0.02) compared with adjacent circumferentially aligned medial fibers (AI = 0.78 ± 0.12) and highly tortuous adventitial fibers (1.22 ± 0.03). A second phase of remodeling replaced circumferentially aligned fibers in the inner media with longitudinal fibers. A structurally motivated constitutive model with both remodeling modes was introduced along with methodology for determining material parameters from mechanical testing and multiphoton imaging. CONCLUSIONS: A new mechanism was identified by which aneurysm walls can rapidly adapt to changes in load, ensuring the structural integrity of the aneurysm until a slower process of medial reorganization occurs. The rabbit model can be used to evaluate therapies to increase aneurysm wall stability.
ABSTRACT
BACKGROUND AND PURPOSE: Animal models provide a mechanism for fundamental studies of the coupling between hemodynamics and pathophysiology in diseases such as saccular aneurysms. In this work, we evaluated the capability of an elastase-induced saccular aneurysm model in rabbits to reproduce the anatomic and hemodynamic features typical for human intracranial aneurysms. MATERIALS AND METHODS: Saccular aneurysms were created in 51 rabbits at the origin of the RCCA. Twelve weeks' postcreation, the lumen geometry of the aneurysm and surrounding vasculature was acquired by using 3DRA. Geometric features of these models were measured. Pulsatile 3D CFD studies were performed with rabbit-specific inlet profiles. RESULTS: Geometric features, including aneurysm height, width, neck diameter, aspect ratio, and NSI of all 51 rabbit aneurysm models fell within the range reported for human IAs. The distribution and range in values of pressure, WSS, and OSI were also typical for human IAs. A single recirculation region was observed in 33 (65%) of 51 cases, whereas a second transient recirculation zone was observed in 18 (35%) cases. Both of these flow types are commonly observed in human IAs. CONCLUSIONS: Most hemodynamic and geometric features in a commonly used elastase-induced rabbit saccular aneurysm model are qualitatively and quantitatively similar to those seen in large numbers of human cerebral aneurysms.
