A Patient-Specific Analysis Framework for Assessing Stroke Risk in Pediatric Moyamoya Disease

用于评估小儿烟雾病中风风险的患者特异性分析框架

• 批准号: 9789985
• 负责人: Shaolie Samira Hossain
• 金额: $ 8.15万
• 依托单位: TEXAS HEART INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-30 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9789985
• 关键词: 3-Dimensional; Affect; Angiography; Appearance; Arteries; Behavior; Blood Vessels; Blood flow; Brain hemorrhage; Cardiac; Cerebrovascular Disorders; Characteristics; Childhood; Circle of Willis; Clinical; Clinical Data; Coagulation Process; Complex; Computer Analysis; Computer Simulation; Convection; Data; Databases; Diffusion; Disease Progression; Early Intervention; Elements; Environment; Future; Geometry; Goals; Human; Image; Impairment; Infection; Intervention; Intracranial Hemorrhages; Investigation; Ischemic Stroke; Japanese Population; Knockout Mice; Liquid substance; Location; Medical; Modeling; Morbidity - disease rate; Moyamoya Disease; Mutation; Names; Operative Surgical Procedures; Pathologic; Patient Care; Patients; Perioperative; Phenotype; Pilot Projects; Population; Prevention strategy; Preventive Intervention; Recording of previous events; Recurrence; Research; Risk; Role; Severity of illness; Smoke; Spatial Distribution; Stenosis; Stroke; Technology; Therapeutic Intervention; Wild Type Mouse; cerebrovascular; cohort; follow-up; hemodynamics; human model; improved; insight; mouse model; pediatric patients; prevent; shear stress; simulation; stroke event; stroke risk; three-dimensional modeling; trend

PROJECT SUMMARY: Pediatric MoyaMoya Disease (MMD) is a cerebrovascular disease characterized by progressive narrowing of the major arteries in the Circle of Willis (CoW), leading to recurring ischemic and hemorrhagic stroke. Clinical strategies to prevent or reverse vessel occlusion through medical management are not available. Neurosurgical interventions are used to augment blood flow to the affected region and avert future stroke events; but carry the risk of perioperative stroke, infection and intracranial hemorrhage. Treatment is an absolute necessity however, since a morbidity rate of > 70% in untreated patients is currently realized. While atypical vessel straightening, narrowing and collateralizations are commonly observed on the CT- angiograms, there is a lack of understanding how these characteristic vascular alterations affect local hemodynamics and disease progression, and there has been no study of the effect of surgical interventions on future stroke events. Computational simulations, adjusted with patient-specific attributes, have been successfully used in other pathological conditions to predict local hemodynamics, potentially informing therapy and interventional strategies. The long-term objective is therefore to develop a predictive patient-specific analysis framework to assess stroke risk in pediatric MMD patients treated by surgical intervention, and delineate scenarios affecting disease severity. In a pilot study involving ACTA2(-/-) knockout mouse models, which develop many of the phenotypic features of MMD, computational fluid dynamic analysis of the authentic CoW vasculature was performed applying state-of-the-art isogeometric analysis technology. Locations of critical wall shear rate (above the coagulation limit) that were at a greater risk of clot formation were predicted. Results show that occlusion in one of the major arteries in the CoW increases stroke risk in mouse models of MMD. If a similar or equivalent behavior is realized in the human condition, it could have profound implications for patient care. The goal for the proposed research is to perform 3D patient-specific analysis on a pilot cohort (n=6) of human CoW to identify susceptible regions that could evolve into severe stenosis or complete vessel occlusion, leading to stroke in pediatric MMD patients, and compare the predictions to follow up clinical observations. The central hypothesis is that the simulations will accurately predict the occurrence and location of the stroke. Once the analysis framework is established and the predictive capability assessed in this pilot; a comprehensive study on a population of at least 50 cases will be performed to reliably assess the utility of computational predictions of stroke risk in pediatric MMD patients. The proposed research is significant, as it will provide predictive insight into complex interplay between vascular geometry and hemodynamic environment altered by MMD in a patient-specific sense. If confirmed in a larger cohort, the presented analysis framework could enable clinicians to predict patients at risk of stroke prior to the imaging assessments of severe hemodynamic impairment/collaterization that is used currently, potentially leading to earlier intervention.

项目摘要：小儿莫亚马亚病（MMD）是一种脑血管疾病，其为特征 威利斯（牛）圈子中主要动脉的逐渐狭窄，导致了不断性的缺血性和 出血中风。通过医疗管理预防或反向容器阻塞的临床策略 不可用。神经外科干预措施用于增强流向受影响区域的血流并避免 未来的中风事件；但承担围手术期中风，感染和颅内出血的风险。治疗 但是，这是绝对的必要性，因为目前未经治疗的患者的发病率> 70％。 在非典型血管拉直的同时，通常在CT-上观察到狭窄和抵押品 血管造影，缺乏了解这些特征性血管变化如何影响局部 血液动力学和疾病进展，没有研究手术干预对 未来的中风事件。用特定于患者的属性调整的计算模拟已经 在其他病理状况中成功使用以预测局部血液动力学，可能会告知治疗 和介入策略。因此，长期目标是开发一种预测性患者特异性的 分析框架评估通过手术干预治疗的小儿MMD患者的中风风险， 描述影响疾病严重程度的情况。在涉及ACTA2（ - / - ）敲除鼠标模型的试验研究中， 它发展了MMD的许多表型特征，对真实的计算流体动态分析 采用最先进的同几幅分析技术进行了牛管脉管系统。位置 预测临界壁剪切速率（高于凝血极限），该临界剪切速率预测了凝块形成的风险更大。 结果表明，牛的主要动脉之一的闭塞增加了鼠标模型中的中风风险 MMD。如果在人类条件下实现类似或同等的行为，则可能具有深刻的含义 用于患者护理。拟议的研究的目的是对飞行员队列进行3D特定于患者的分析 （n = 6）人牛，以识别可能演变成严重狭窄或完整血管的易感区域 闭塞，导致小儿MMD患者中风，并比较跟踪临床的预测 观察。中心假设是模拟将准确预测出现和位置 中风。一旦建立了分析框架并在该飞行员中评估了预测能力；一个 将对至少50例案件的人群进行全面研究，以可靠地评估 小儿MMD患者中风风险的计算预测。拟议的研究很重要，因为 将提供有关血管几何和血液动力学之间复杂相互作用的预测性洞察力 在特定于患者的意义上，MMD改变了环境。如果在较大的队列中确认，则进行了分析 框架可以使临床医生能够在成像评估之前预测有中风风险的患者 当前使用的严重血液动力学障碍/副作用可能导致较早的干预。