Abstract
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.
Highlights
Archaeologists can understand past human economic and sociopolitical behavior, or resilience of ancient societies to strong perturbations such as repeated drought, from the organization of their infrastructures such as roadways, water supply or sewage networks (Dillehay and Kolata, 2004)
We first assess the architecture of mice and humans capillary networks using the simplest morphometrical and topological metrics
Results for the synthetic networks with LC = 90μm and size 264 × 264 × 207μm3 compared to humans were very similar, the agreement was not as good (Figures S6 and S7). This may be partly because fewer human ROIs were extracted (4, rather than 7 for the mouse), metrics were less statistically converged in terms of the number of samples
Summary
Archaeologists can understand past human economic and sociopolitical behavior, or resilience of ancient societies to strong perturbations such as repeated drought, from the organization of their infrastructures such as roadways, water supply or sewage networks (Dillehay and Kolata, 2004). The brain microvascular system is involved in disease, including stroke and neurodegenerative disease, through vascular damage, such as capillary occlusions and progressive rarefaction (Østergaard et al, 2016; Cruz Hernández et al, 2019), and decrease in regulation efficiency (Farkas and Luiten, 2001; Iadecola, 2004) Together, these act to reduce blood flow and the availability of vital nutrients, which, on one hand, plays a key role in disease progression (Zlokovic, 2011; Cruz Hernández et al, 2019) and, on the other hand, makes it difficult to interpret functional imaging data in patient populations (D’Esposito et al, 2003)
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