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

项目简介：儿童烟雾病(MMD)是一种脑血管疾病，其特征是 Willis环内主要动脉进行性狭窄(COW)，导致复发的缺血和 出血性中风。通过药物治疗预防或逆转血管闭塞的临床策略 都不可用。神经外科干预被用来增加到受影响区域的血流量，并避免 未来的中风事件；但有围术期中风、感染和颅内出血的风险。治疗 然而，这是绝对必要的，因为目前在未经治疗的患者中实现了70%的发病率。 而不典型的血管伸直、狭窄和侧支循环在CT上是常见的。 血管造影术，缺乏对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，目前还没有关于手术干预对 未来的中风事件。根据患者特定的属性进行调整的计算模拟已经被 成功地用于其他病理条件下预测局部血流动力学，潜在地为治疗提供参考 和干预性策略。因此，长期目标是开发一种针对特定患者的预测性 评估接受手术治疗的儿童MMD患者中风风险的分析框架，以及 描述影响疾病严重程度的情景。在一项涉及ACTA2(-/-)基因敲除小鼠模型的试点研究中， 其中发展了MMD的许多表型特征，计算流体动力学分析的正宗 应用最先进的等距分析技术进行奶牛血管成像。地点： 预测了血栓形成风险较大的临界壁面剪切率(高于凝血极限)。 结果表明，阻断奶牛的一条主要动脉增加了小鼠中风的风险。 MMD。如果类似或等同的行为在人类的情况下发生，可能会产生深远的影响 用来照顾病人。这项拟议研究的目标是对飞行员队列进行3D患者特定分析 (n=6)人牛，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患者发生卒中，并比较其预测，以用于临床随访 观察。中心假设是模拟将准确地预测事件的发生和地点 中风的症状。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例患者进行全面研究，以可靠地评估 儿童MMD患者卒中风险的计算预测。拟议的研究具有重要意义，因为它 将提供对血管几何和血流动力学之间复杂相互作用的预测性洞察 MMD在患者特有的意义上改变了环境。如果在更大的队列中得到证实，所提供的分析 框架可以使临床医生在对中风的成像评估之前预测中风风险的患者 目前使用的严重血流动力学损害/侧支循环，可能导致更早的干预。

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.