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: 10621168
• 负责人: Juan R Cebral
• 金额: $ 62.27万
• 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/10621168
• 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; Clip; 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; bioimaging; brain surgery; clinical practice; clinical risk; dental infection; design; disability; hormone therapy; implantation; improved; in silico; innovation; 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，至少五分之一的成年人患有颅内动脉瘤 (IA)，这是一种大脑的病理性突出 动脉。即使临床管理有所改善，IA 破裂对大约 45% 的患者来说仍然是致命的 50% 的幸存者患有残疾，无法恢复正常生活。治疗预防 破裂过程中，通过机械夹住 IA 颈部，努力保护壁免受血压引起的负载的影响。 开颅手术或使用血管内弹簧圈或支架植入诱导血栓形成。这些治疗 有显着的并发症风险，可能高于自然破裂风险，包括 1-2% 的风险 死亡。由于治疗的风险可能超过破裂的自然风险，因此迫切需要可靠的方法 识别有破裂风险的脆弱动脉瘤的方法，需要立即治疗并避免不必要的 在其他人身上进行治疗。 该项目的临床重点是具有局部生长区域（泡）的动脉瘤，因为这些 IA 具有 临床患病率很高（约 30%），是已知的破裂危险因素。尽管这种临床 重要性，但人们对气泡形成的原因以及气泡增加破裂的实际机制知之甚少 风险。我们之前的工作表明，带有气泡的动脉瘤可能具有不同的壁结构和失败 机制优于其他动脉瘤。即使在这个子组中，也存在各种各样的墙类型和风险 因素。目前的临床实践并没有区分不同类型的气泡或其失效模式和 平等对待所有气泡。 拟议的研究具有创新性，因为它试图改变这种常见的动脉瘤临床方法 所有气泡都被视为一个组的评估。此外，我们的研究也具有创新性，因为 它通过直接关注动脉瘤壁的脆弱性及其结构，改变了动脉瘤的研究方式。 失效模式而不是寻找不同因素与动脉瘤破裂之间的相关性。 该项目的目标是通过识别临床可测量的特征来改进风险评估 使一些 IAs 易于形成气泡，然后确定哪些壁特征决定了这些 IAs 的破裂风险 IAs。具体来说，该项目的目标是 i) 识别有形成气泡风险的动脉瘤，ii) 确定带有气泡的动脉瘤壁脆弱的原因，iii) 了解牙科之间的联系 病原体和 IA 壁脆弱性。我们将采用多方面的方法来实现这些目标 将人体动脉瘤组织的生物成像和机械测试与计算机患者特定模型相结合 动脉瘤内的血流和动脉瘤壁内的压力。我们将利用我们的多 由脑动脉瘤领域的世界领先者组成的学科团队，其中包括七名神经外科医生和 患者特定 CFD 建模、计算生物力学、IA 壁生物学、生物成像和 软组织的机械测试。 拟议研究的基本原理是，通过将带有气泡的 IAs 识别为具有不同特征的独特群体， 针对形成和破裂的原因，我们将改进风险评估并可以有针对性地对患者进行治疗。此外， 通过识别与滤泡形成相关的可改变的风险因素（例如牙科病原体），我们可以 启动 IAs 的预防性治疗。成功完成本研究计划后，我们将拥有 i) 确定了气泡形成的风险因素（风险的早期指示），ii) 破裂风险增加的直接原因 气泡，以及 iii) 确定牙科病原体如何影响牙壁结构以及与可测量患者的关联 因素。这些结果预计将对人类健康产生积极影响，因为它们将降低风险 评估 IA，为药物治疗提供目标并确定 IA 治疗的预防方法。

项目成果

Differences Between Ruptured Aneurysms With and Without Blebs: Mechanistic Implications.

• DOI: 10.1007/s13239-022-00640-4
• 发表时间: 2023-02
• 期刊: CARDIOVASCULAR ENGINEERING AND TECHNOLOGY
• 影响因子: 1.8
• 作者: Ashkezari, Seyedeh Fatemeh Salimi;Mut, Fernando;Robertson, Anne M.;Cebral, Juan R.
• 通讯作者: Cebral, Juan R.

Hemodynamic conditions that favor bleb formation in cerebral aneurysms.

• DOI: 10.1136/neurintsurg-2020-016369
• 发表时间: 2021-03
• 期刊: Journal of neurointerventional surgery
• 影响因子: 4.8
• 作者: Salimi Ashkezari SF;Mut F;Chung BJ;Robertson AM;Cebral JR
• 通讯作者: Cebral JR

Prediction of bleb formation in intracranial aneurysms using machine learning models based on aneurysm hemodynamics, geometry, location, and patient population.

• DOI: 10.1136/neurintsurg-2021-017976
• 发表时间: 2022-10
• 期刊: JOURNAL OF NEUROINTERVENTIONAL SURGERY
• 影响因子: 4.8
• 作者: Salimi Ashkezari, Seyedeh Fatemeh;Mut, Fernando;Slawski, Martin;Cheng, Boyle;Yu, Alexander K.;White, Tim G.;Woo, Henry H.;Koch, Matthew J.;Amin-Hanjani, Sepideh;Charbel, Fady T.;Rezai Jahromi, Behnam;Niemela, Mika;Koivisto, Timo;Frosen, Juhana;Tobe, Yasutaka;Maiti, Spandan;Robertson, Anne M.;Cebral, Juan R.
• 通讯作者: Cebral, Juan R.

Phenotyping calcification in vascular tissues using artificial intelligence

使用人工智能对血管组织中的钙化进行表型分析

• 发表时间: 2024
• 期刊: arXiv.org
• 作者: Mehdi Ramezanpour;Anne M. Robertson;Yasutaka Tobe;Xiaowei Jia;J. Cebral
• 通讯作者: J. Cebral

Multimodal exploration of the intracranial aneurysm wall.

• DOI: 10.1007/s11548-023-02850-0
• 发表时间: 2023-12
• 期刊: INTERNATIONAL JOURNAL OF COMPUTER ASSISTED RADIOLOGY AND SURGERY
• 影响因子: 3
• 作者: Niemann, Annika;Tulamo, Riikka;Netti, Eliisa;Preim, Bernhard;Berg, Philipp;Cebral, Juan;Robertson, Anne;Saalfeld, Sylvia
• 通讯作者: Saalfeld, Sylvia