Brain Capillary Networks Across Species: A few Simple Organizational Requirements Are Sufficient to Reproduce Both Structure and Function

Brain Capillary Networks Across Species: A few Simple Organizational Requirements Are Sufficient to Reproduce Both Structure and Function
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DOI:
10.3389/fphys.2019.00233
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发表时间:
2019-03-26
影响因子:
4
通讯作者:
Lorthois, Sylvie
Lorthois, Sylvie
中科院分区:
医学2区
文献类型:
--
作者:
Smith, Amy F.;Doyeux, Vincent;Lorthois, Sylvie

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尽管毛细血管在神经血管功能中起着关键作用,但目前还缺乏对大脑毛细血管网络特性的全面表征。在这里,我们定义了一系列指标(几何、拓扑、流动、质量传递和稳健性),用于量化大脑区域、器官、物种或患者群体之间的结构差异,并并行地以数字方式生成复制解剖网络的关键组织特征(各向同性、连通性、空间填充性质、组织域的凸性、特征大小)的合成网络。为了达到这些目标,我们首先构建了一个定义的健康毛细血管网络指标的数据库,这些指标是通过对小鼠和人脑进行成像获得的。结果表明,两个物种之间的解剖网络在拓扑上是等价的,几何度量只是尺度上的不同。基于这些结果,我们设计了一种使用约束Voronoi图来生成3D模型的合成大脑毛细血管网络的方法,该模型是局部随机的,但在网络尺度上是均匀的。通过对定义的度量进行比较,可以看出,在适当的比例选择下,这些网络具有与解剖数据相同的属性。合成复制大脑毛细血管网络的能力打开了广泛的应用范围,从健康毛细血管网络中结构-功能关系的系统计算研究到病理结构退化的详细分析,甚至到开发嵌入组织工程构建中的3D仿生血管网络的模板。
Despite the key role of the capillaries in neurovascular function, a thorough characterization of cerebral capillary network properties is currently lacking. Here, we define a range of metrics (geometrical, topological, flow, mass transfer, and robustness) for quantification of structural differences between brain areas, organs, species, or patient populations and, in parallel, digitally generate synthetic networks that replicate the key organizational features of anatomical networks (isotropy, connectedness, space-filling nature, convexity of tissue domains, characteristic size). To reach these objectives, we first construct a database of the defined metrics for healthy capillary networks obtained from imaging of mouse and human brains. Results show that anatomical networks are topologically equivalent between the two species and that geometrical metrics only differ in scaling. Based on these results, we then devise a method which employs constrained Voronoi diagrams to generate 3D model synthetic cerebral capillary networks that are locally randomized but homogeneous at the network-scale. With appropriate choice of scaling, these networks have equivalent properties to the anatomical data, demonstrated by comparison of the defined metrics. The ability to synthetically replicate cerebral capillary networks opens a broad range of applications, ranging from systematic computational studies of structure-function relationships in healthy capillary networks to detailed analysis of pathological structural degeneration, or even to the development of templates for fabrication of 3D biomimetic vascular networks embedded in tissue-engineered constructs.