Improving Cerebral Aneurysm Risk Assessment through Understanding Wall Vulnerability and Failure Modes

通过了解壁的脆弱性和失效模式改进脑动脉瘤风险评估

• 批准号: 10398949
• 负责人: Juan R Cebral
• 金额: $ 63.31万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10398949
• 关键词: Adult; Affect; Aneurysm; Area; Arteries; Biology; Biomechanics; Blood Pressure; Blood flow; Brain; Brain Aneurysms; Bulla; Cerebral Aneurysm; Characteristics; Clinical; Clinical Management; Clinical Treatment; Collagen Fiber; Computer Models; Consensus; Data; Daughter; Dental; Evaluation; Failure; Future; Geometry; Goals; Growth; Health; Human; Intracranial Aneurysm; Investigation; Knowledge; Life; Link; Liquid substance; Measurable; Mechanical Stress; Mechanics; Methodology; Methods; Modeling; Neck; Neurosurgeon; Pathologic; Patients; Periodontal Diseases; Population; Prevalence; Preventive treatment; Protocols documentation; Research; Research Project Grants; Resected; Risk; Risk Assessment; Risk Factors; Rupture; Ruptured Aneurysm; Shapes; Shoulder; Solid; Stents; Stress; Structure; Subcategory; Subgroup; Survivors; Testing; Thrombosis; Tissues; Work; base; bioimaging; brain surgery; clinical practice; clinical risk; dental infection; design; disability; hormone therapy; implantation; improved; in silico; innovation; knowledge of results; mechanical load; modifiable risk; mortality; mortality risk; multidisciplinary; novel strategies; pathogen; personalized decision; prevent; programs; risk selection; soft tissue; sound; targeted treatment; tool; treatment risk; unnecessary treatment

Project Summary and Relevance At least 1 in 50 adults in the US harbor an intracranial aneurysm (IA), a pathological outpouching of a brain artery. Even with improvements in clinical management, IA rupture is fatal for approximately 45% of patients and 50% of survivors suffer from disabilities that prevent them from returning to a normal life. Treatment to prevent rupture strives to shield the wall from blood pressure induced loads by mechanically clipping the IA neck during open brain surgery or by inducing thrombosis using endovascular coiling or stent implantation. These treatments have significant risks of complications that can be higher than the natural rupture risk, including 1-2% risk of mortality. Since the risk of treatment may exceed the natural risk of rupture, there is an urgent need for a reliable method to identify fragile aneurysms at risk of rupture that require immediate treatment and avoid unnecessary treatment in others. The clinical focus of this project is aneurysms that have focal areas of growth (blebs) as these IA have high clinical prevalence (approximately 30%) and are a known risk factor for rupture. Despite this clinical importance, very little is known about why blebs form nor the actual mechanisms by which blebs increase rupture risk. Our prior work demonstrates that aneurysms with blebs can have different wall structures and failure mechanisms than other aneurysms. Even within this subgroup, there are a wide range of wall types and risk factors. Current clinical practice does not distinguish between different types of blebs or their failure modes and treats all blebs equally. The proposed research is innovative because it seeks to change this common clinical approach for aneurysm evaluation where all blebs are treated as a single group. Furthermore, our research is also innovative because it changes the way aneurysms are studied by focusing directly on the vulnerability of the aneurysm wall and its failure modes instead of searching for correlations between different factors and aneurysm rupture. The goal of this project is to improve risk assessment by identifying clinically measurable features that predispose some IAs to bleb formation and then determine which walls features determine rupture risk in these IAs. Specifically, the goals of this project are to i) Identify aneurysms that are at risk for developing blebs, ii) Determine causes for wall vulnerability in aneurysms with blebs, iii) Understand the connection between dental pathogens and IA wall vulnerability. We will achieve these objectives using a multi-faceted approach that combines bioimaging and mechanical testing of human aneurysm tissue with in silico patient specific modeling of the blood flow inside the aneurysms and stresses within the aneurysm wall. We will leverage our multi- disciplinary team of world leaders in the field of cerebral aneurysms which includes seven neurosurgeons and experts in patient specific CFD modeling, computational biomechanics, biology of the IA wall, bioimaging and mechanical testing of soft tissues. The rationale for the proposed research is that by recognizing IAs with blebs as a distinct group with different causes for formation and rupture, we will improve risk assessment and can target patient treatment. Furthermore, by identifying modifiable risk factors that are associated with bleb formation (e.g. dental pathogens), we can initiate preventative treatment for IAs. At the successful completion of this research program we will have i) identified risk factors for bleb formation (an early indication of risk), ii) direct causes for increased rupture risk in blebs, and iii) determined how dental pathogens affect the wall structure and association with measurable patient factors. These results are expected to have a positive impact on human health because they will improve risk assessment in IAs, provide targets for drug therapy and identify preventative approaches for IA treatment.

项目摘要和相关性 在美国，至少有50名成年人中有1个胸腔内动脉瘤（IA），一种病理学的脑部 动脉。即使临床管理有所改善，IA破裂对于约45％的患者而致命，并且 50％的幸存者患有残疾，阻止他们恢复正常生活。预防治疗 破裂努力通过机械地剪断IA颈，以使墙壁免受血压引起的载荷。 开放式脑部手术或使用血管内卷曲或支架植入诱导血栓形成。这些治疗方法 具有明显的并发症风险，可能高于自然破裂风险，包括1-2％的风险 死亡。由于治疗风险可能超过破裂的自然风险，因此迫切需要可靠 识别需要立即治疗并避免不必要的破裂风险的脆弱动脉瘤的方法 其他治疗。 该项目的临床重点是具有增长焦点（BLEB）的动脉瘤，因为这些IA具有 高临床患病率（约30％），是已知破裂的危险因素。尽管有这种临床 重要的是，关于为什么要形成泡沫的原因或泡泡增加破裂的实际机制知之甚少 风险。我们先前的工作表明，带有BLEB的动脉瘤可能具有不同的墙壁结构和故障 机制比其他动脉瘤。即使在该亚组中，也有多种墙类型和风险 因素。当前的临床实践不能区分不同类型的泡沫或其故障模式和 平等地对待所有泡沫。 拟议的研究具有创新性，因为它试图改变这种动脉瘤的常见临床方法 评估所有BLEB都被视为单个组。此外，我们的研究也是创新的，因为 它通过直接关注动脉瘤壁的脆弱性及其，它改变了动脉瘤的研究方式 故障模式而不是寻找不同因素与动脉瘤破裂之间的相关性。 该项目的目的是通过识别临床可测量的功能来改善风险评估 使一些IAS倾向于形成BLEB，然后确定哪些壁特征决定了破裂的风险 IAS。具体而言，该项目的目标是i）确定有开发泡沫风险的动脉瘤，ii） 确定带有泡沫的动脉瘤中墙壁脆弱性的原因，iii）了解牙齿之间的联系 病原体和IA墙脆弱性。我们将使用多方面的方法实现这些目标 将人动脉瘤组织的生物成像和机械测试与硅特异性建模中 动脉瘤内动脉瘤内的血液流动和动脉瘤壁内的压力。我们将利用我们的多 在脑动脉瘤领域的世界领导人纪律团队，其中包括七个神经外科医生 患者特定CFD建模，计算生物力学，IA墙生物学的专家，生物成像和 软组织的机械测试。 拟议的研究的理由是，通过将BLEB的IAS识别为一个不同的群体， 形成和破裂的原因，我们将改善风险评估，并可以针对患者治疗。此外， 通过确定与形成BLEB相关的可修改风险因素（例如牙科病原体），我们可以 对IAS进行预防治疗。成功完成该研究计划时，我们将拥有I） 确定了BLEB形成的风险因素（风险的早期迹象），ii）直接原因导致增加破裂风险的原因 Blebs，iii）确定牙齿病原体如何影响墙壁结构并与可测量的患者联系 因素。预计这些结果将对人类健康产生积极影响，因为它们将改善风险 IAS评估，提供药物治疗的靶标，并确定IA治疗的预防方法。