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Exploring neurodegenerative disorders using a novel integrated model of cerebral transport: Initial results
Proceedings of the Institution of Mechanical Engineers, Part H: Journal of Engineering in Medicine ( IF 1.8 ) Pub Date : 2020-10-20 , DOI: 10.1177/0954411920964630
John C Vardakis, Dean Chou, Liwei Guo, Yiannis Ventikos

The neurovascular unit (NVU) underlines the complex and symbiotic relationship between brain cells and the cerebral vasculature, and dictates the need to consider both neurodegenerative and cerebrovascular diseases under the same mechanistic umbrella. Importantly, unlike peripheral organs, the brain was thought not to contain a dedicated lymphatics system. The glymphatic system concept (a portmanteau of glia and lymphatic) has further emphasized the importance of cerebrospinal fluid transport and emphasized its role as a mechanism for waste removal from the central nervous system. In this work, we outline a novel multiporoelastic solver which is embedded within a high precision, subject specific workflow that allows for the co-existence of a multitude of interconnected compartments with varying properties (multiple-network poroelastic theory, or MPET), that allow for the physiologically accurate representation of perfused brain tissue. This novel numerical template is based on a six-compartment MPET system (6-MPET) and is implemented through an in-house finite element code. The latter utilises the specificity of a high throughput imaging pipeline (which has been extended to incorporate the regional variation of mechanical properties) and blood flow variability model developed as part of the [email protected] research platform. To exemplify the capability of this large-scale consolidated pipeline, a cognitively healthy subject is used to acquire novel, biomechanistically inspired biomarkers relating to primary and derivative variables of the 6-MPET system. These biomarkers are shown to capture the sophisticated nature of the NVU and the glymphatic system, paving the way for a potential route in deconvoluting the complexity associated with the likely interdependence of neurodegenerative and cerebrovascular diseases. The present study is the first, to the best of our knowledge, that casts and implements the 6-MPET equations in a 3D anatomically accurate brain geometry.



中文翻译:

使用新的大脑运输集成模型探索神经退行性疾病:初步结果

神经血管单元(NVU)强调脑细胞和脑血管,和指令需要考虑相同的机械伞下两者的神经变性和脑血管疾病之间的复杂和共生关系。重要的是,与外周器官不同,大脑被认为不包含专用的淋巴系统。该glymphatic系统概念(神经胶质和淋巴的混合体)进一步强调了脑脊液运输的重要性,并强调了其作为中枢神经系统废物清除机制的作用。在这项工作中,我们概述了一种新颖的多孔弹性求解器,该求解器嵌入在高精度、特定主题的工作流程中,允许具有不同特性的多个互连隔间共存(多网络多孔弹性理论,或 MPET),允许用于灌注脑组织的生理学准确表示。这种新颖的数值模板基于六室 MPET 系统 (6-MPET),并通过内部有限元代码实现。后者利用高通量成像管道的特异性(已扩展以纳入机械特性的区域变化)和作为 [电子邮件保护] 研究平台的一部分开发的血流变异模型。为了举例说明这种大规模整合管道的能力,使用认知健康的受试者获取与 6-MPET 系统的主要和衍生变量相关的新型生物力学生物标志物。这些生物标志物被证明可以捕捉 NVU 和淋巴系统的复杂性质,为解卷积与神经退行性疾病和脑血管疾病可能相互依赖相关的复杂性铺平了道路。据我们所知,目前的研究是第一个,

更新日期:2020-10-20
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