In the United States, unruptured intracranial aneurysms are present in approximately 4-5% of the general population. Once diagnosed, appropriate therapy may be difficult to recommend with confidence. Surgery is curative, but carries a 17% risk of serious side effects. Endovascular placement of occlusion devices involves lower risk (5-7%), but suboptimal rates of permanent aneurysm closure;subsequent regrowth occurs in many cases. Observation carries a risk of rupture, which is fatal in the majority of cases and neurologically damaging to the majority of survivors. With the objective of altering the grim outlook just described for persons harboring unruptured intracranial aneurysms, work is proposed to build upon a successful research program focused on the study of a realistic model of human aneurysms that is created in rabbits. This model has already undergone extensive validation and been used to better understand the role of altered flow in aneurysms as related to rupture. In the current proposal we will achieve four important aims to further aneurysm research: 1) applying advanced techniques, including genomics and proteomics, to the model;2) correlating aneurysm shape, considered a predictor for rupture by many investigators, with altered flow and disturbed function of the vessel wall within aneurysms;3) applying the model to improve the understanding of why minimally invasive coils fail to occlude aneurysms in many cases;and 4) correlating flow near aneurysms after coil treatment to understand mechanisms of coil failure. Each of these aims will be achieved by creating model aneurysms and then, working with a multidisciplinary, multi-institutional team comprising Radiologists, Mechanical Engineers, Molecular Biologists, and Computer Scientists, applying advanced imaging techniques, molecular biology, genomics, and computational fluid dynamics studies to the model. This program will enhance health by preventing the catastrophic events resulting from spontaneous rupture of intracranial aneurysms.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Medical Imaging Study Section (MEDI)
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Jacobs, Tom P
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Mayo Clinic, Rochester
United States
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Wang, Shunli; Dai, Daying; Kolumam Parameswaran, Praveen et al. (2017) Rabbit aneurysm models mimic histologic wall types identified in human intracranial aneurysms. J Neurointerv Surg :
Morales, Hernán G; Larrabide, Ignacio; Geers, Arjan J et al. (2013) Analysis and quantification of endovascular coil distribution inside saccular aneurysms using histological images. J Neurointerv Surg 5 Suppl 3:iii33-7
Dai, Daying; Ding, Yong Hong; Kadirvel, Ramanathan et al. (2013) Lack of aneurysm formation after carotid artery ligation in rabbits: a polymer MICROFILýý study. Neuroradiology 55:65-70
Kadirvel, R; Ding, Y H; Dai, D et al. (2012) Proteomic analysis of aneurysm healing mechanism after coil embolization: comparison of dense packing with loose packing. AJNR Am J Neuroradiol 33:1177-81
Zeng, Z; Kallmes, D F; Durka, M J et al. (2011) Hemodynamics and anatomy of elastase-induced rabbit aneurysm models: similarity to human cerebral aneurysms? AJNR Am J Neuroradiol 32:595-601
Kadirvel, Ramanathan; Ding, Yong-Hong; Dai, Daying et al. (2011) Gene expression changes: five years after creation of elastase-induced aneurysms. J Vasc Interv Radiol 22:1447-1451.e2
Zeng, Zijing; Durka, Michael J; Kallmes, David F et al. (2011) Can aspect ratio be used to categorize intra-aneurysmal hemodynamics?--A study of elastase induced aneurysms in rabbit. J Biomech 44:2809-16
Kadirvel, R; Ding, Y H; Dai, D et al. (2010) Intrinsic pathway-mediated apoptosis in elastase-induced aneurysms in rabbits. AJNR Am J Neuroradiol 31:165-9
Ding, Y; Dai, D; Kadirvel, R et al. (2010) Creation of large elastase-induced aneurysms: presurgical arterial remodeling using arteriovenous fistulas. AJNR Am J Neuroradiol 31:1935-7
Kadirvel, Ramanathan; Ding, Yong-Hong; Dai, Daying et al. (2010) Differential gene expression in well-healed and poorly healed experimental aneurysms after coil treatment. Radiology 257:418-26

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