Improved Animal Modeling of Saccular Aneurysms

改进的囊状动脉瘤动物模型

基本信息

批准号：
7738476
负责人：
DAVID F KALLMES
金额：
$ 48.76万
依托单位：
MAYO CLINIC ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-09-21 至 2011-05-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7738476
关键词：
Address Adverse effects Aftercare Aneurysm Animal Model Apoptosis Area Arteries Berry Aneurysm Biological Candidate Disease Gene Cell Survival Clinical Research Communities Computers Custom Devices Diagnosis Endothelial Cells Engineering Event Extracellular Matrix Degradation Face Failure Functional disorder Funding Gene Proteins General Population Genetic Transcription Genomics Goals Grant Health Height Hemorrhage Human Human Resources Imaging Techniques Inflammation Intracranial Aneurysm Lead Liquid substance Mechanics Medical Medicine Modeling Molecular Molecular Biology Morbidity - disease rate Morphology Neck Neurosciences New Zealand Operative Surgical Procedures Oryctolagus cuniculus Parents Patient Care Patients Persons Positioning Attribute Preclinical Testing Process Protein Biosynthesis Proteomics Recurrence Research Research Personnel Research Project Grants Resources Risk Role Rupture Ruptured Aneurysm Scientist Shapes Spontaneous Rupture Study models Survivors Targeted Research Techniques Technology Testing Trust United States Validation Width Work base bioimaging clinical care design hemodynamics improved innovation insight interest minimally invasive molecular dynamics multidisciplinary prevent programs radiologist research study response shear stress success tool vascular inflammation

项目摘要

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：在美国，大约 4-5% 的普通人群存在未破裂颅内动脉瘤。一旦确诊，可能很难自信地推荐适当的治疗方法。手术可以治愈，但有 17% 的风险出现严重副作用。血管内放置封堵器的风险较低（5-7%），但动脉瘤永久闭合率不理想；在许多情况下会发生随后的再生。观察存在破裂的风险，这在大多数情况下是致命的，并对大多数幸存者造成神经损伤。为了改变刚刚描述的未破裂颅内动脉瘤患者的严峻前景，建议在一项成功的研究计划的基础上开展工作，该计划的重点是研究在兔子中创建的人类动脉瘤的现实模型。该模型已经经过广泛的验证，并用于更好地理解动脉瘤中血流改变与破裂相关的作用。在当前的提案中，我们将实现进一步动脉瘤研究的四个重要目标：1）将包括基因组学和蛋白质组学在内的先进技术应用于模型； 2）将动脉瘤形状与动脉瘤内血流改变和血管壁功能紊乱相关联，许多研究者认为动脉瘤形状是破裂的预测因素； 3）应用该模型来加深对为什么微创弹簧圈在许多情况下无法闭塞动脉瘤的理解； 4) 关联弹簧圈治疗后动脉瘤附近的血流，以了解弹簧圈失效的机制。这些目标中的每一个都将通过创建动脉瘤模型来实现，然后与由放射科医生、机械工程师、分子生物学家和计算机科学家组成的多学科、多机构团队合作，应用先进的成像技术、分子生物学、基因组学和计算流体动力学来实现对模型进行研究。该计划将通过预防颅内动脉瘤自发破裂引起的灾难性事件来增强健康。

项目成果

期刊论文数量（32）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Gene expression changes: five years after creation of elastase-induced aneurysms.

DOI：
10.1016/j.jvir.2011.01.447
发表时间：
2011-10
期刊：
JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY
影响因子：
2.9
作者：
Kadirvel, Ramanathan;Ding, Yong-Hong;Dai, Daying;Lewis, Debra A.;Kallmes, David F.
通讯作者：
Kallmes, David F.

A proposed ordinal scale for grading histology in elastase-induced, saccular aneurysms.