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: 9651745
• 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 2020-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9651745
• 关键词: 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.

项目概述：儿童烟雾病（MMD）是一种脑血管疾病， Willis环（CoW）中主要动脉的进行性狭窄，导致复发性缺血和 出血性中风通过医疗管理预防或逆转血管闭塞的临床策略 不可用。神经外科干预用于增加受影响区域的血流， 未来卒中事件;但存在围手术期卒中、感染和颅内出血的风险。治疗 然而，这是绝对必要的，因为目前认识到未经治疗的患者的发病率> 70%。 虽然在CT上通常观察到非典型血管变直、变窄和侧支化， 血管造影，缺乏了解这些特征性血管改变如何影响局部 血流动力学和疾病进展，并且还没有研究手术干预对 未来的中风事件。计算模拟，调整与患者的具体属性，已被 成功用于其他病理状况，以预测局部血流动力学，可能为治疗提供信息 干预策略。因此，长期目标是开发预测性患者特异性 评估接受外科干预治疗的儿童MMD患者卒中风险的分析框架，以及 描述影响疾病严重程度的情景。在涉及ACTA 2（-/-）敲除小鼠模型的初步研究中， 开发MMD的许多表型特征，真实的计算流体动力学分析 采用最先进的等几何分析技术进行CoW脉管系统。位置 临界壁剪切速率（高于凝血极限）是在更大的凝块形成的风险进行了预测。 结果表明，在小鼠模型中，牛脑中一条主要动脉的闭塞增加了中风的风险。 MMD。如果在人类的条件下实现类似或等效的行为，它可能会产生深远的影响 用于病人护理拟议研究的目标是对试点队列进行3D患者特异性分析 （n=6）人类CoW，以识别可能演变为严重狭窄或完整血管的易感区域 闭塞，导致儿童MMD患者中风，并比较预测随访临床 意见。中心假设是，模拟将准确预测的发生和位置 的中风。一旦建立了分析框架，并在该试点中评估了预测能力; a 将对至少50例病例的人群进行综合研究，以可靠地评估 儿童MMD患者中风风险的计算预测。这项研究意义重大，因为它 将为血管几何结构和血流动力学之间的复杂相互作用提供预测性见解 MMD在患者特异性意义上改变了环境。如果在更大的队列中得到证实， 该框架可以使临床医生在对脑卒中进行成像评估之前预测患者的卒中风险， 目前使用的重度血流动力学损伤/胶原化，可能导致早期干预。