Abstract:
Electron microscopy is the primary approach to study ultrastructural features of the cerebrovasculature. However, 2D snapshots of a vascular bed capture only a small fraction of its complexity. Recent efforts to synaptically map neuronal circuitry using volume electron microscopy have also sampled the brain microvasculature in 3D. Here, we perform a meta-analysis of 7 data sets spanning different species and brain regions, including two data sets from the MICrONS consortium that have made efforts to segment vasculature in addition to all parenchymal cell types in mouse visual cortex. Exploration of these data have revealed rich information for detailed investigation of the cerebrovasculature. Neurovascular unit cell types (including, but not limited to, endothelial cells, mural cells, perivascular fibroblasts, microglia, and astrocytes) could be discerned across broad microvascular zones. Image contrast was sufficient to identify subcellular details, including endothelial junctions, caveolae, peg-and-socket interactions, mitochondria, Golgi cisternae, microvilli and other cellular protrusions of potential significance to vascular signaling. Additionally, non-cellular structures including the basement membrane and perivascular spaces were visible and could be traced between arterio-venous zones along the vascular wall. These explorations revealed structural features that may be important for vascular functions, such as blood-brain barrier integrity, blood flow control, brain clearance, and bioenergetics. They also identified limitations where accuracy and consistency of segmentation could be further honed by future efforts. The purpose of this article is to introduce these valuable community resources within the framework of cerebrovascular research. We do so by providing an assessment of their vascular contents, identifying features of significance for further study, and discussing next step ideas for refining vascular segmentation and analysis.
摘要:
电子显微镜是研究脑血管超微结构特征的主要方法。然而,血管床的2D快照仅捕获其复杂性的一小部分。最近使用体积电子显微镜对神经元电路进行突触映射的努力也以3D方式对脑微脉管系统进行了采样。这里,我们对跨越不同物种和大脑区域的7个数据集进行荟萃分析,包括来自MICRONS联盟的两个数据集,这些数据集除了在小鼠视觉皮层中的所有实质细胞类型之外,还致力于分割脉管系统。对这些数据的探索揭示了丰富的信息,可用于详细调查脑血管系统。神经血管单位细胞类型(包括,但不限于,内皮细胞,壁细胞,血管周围成纤维细胞,小胶质细胞,和星形胶质细胞)可以在广阔的微血管区识别。图像对比度足以识别亚细胞细节,包括内皮连接,Caveolae,peg-and-socket交互,线粒体,高尔基蓄水池,对血管信号传导具有潜在意义的微绒毛和其他细胞突起。此外,可见包括基底膜和血管周围间隙在内的非细胞结构,并且可以在沿血管壁的动静脉区之间追踪。这些探索揭示了可能对血管功能很重要的结构特征,如血脑屏障的完整性,血流控制,大脑清除,和生物能学。他们还确定了限制,可以通过未来的努力进一步磨练分割的准确性和一致性。本文的目的是在脑血管研究的框架内介绍这些宝贵的社区资源。我们通过评估它们的血管含量来做到这一点,确定具有进一步研究意义的特征,并讨论了细化血管分割和分析的下一步思路。