Fractal analysis of vascular networks: Insights from morphogenesis

Considering their extremely complicated and hierarchical structure, a long standing question in vascular physio-pathology is how to characterize blood vessels patterns, including which parameters to use. Another question is how to define a pertinent taxonomy, with applications to normal development and to diagnosis and/or staging of diseases.To address these issues, fractal analysis has been applied by previous investigators to a large variety of healthy or pathologic vascular networks whose fractal dimensions have been sought. A review of the results obtained on healthy vascular networks first shows that no consensus has emerged about whether normal networks must be considered as fractals or not.Based on a review of previous theoretical work on vascular morphogenesis, we argue that these divergences are the signature of a two-step morphogenesis process, where vascular networks form via progressive penetration of arterial and venous quasi-fractal arborescences into a pre-existing homogeneous capillary mesh. Adopting this perspective, we study the multi-scale behavior of generic patterns (model structures constructed as the superposition of homogeneous meshes and quasi-fractal trees) and of healthy intracortical networks in order to determine the artifactual and true components of their multi-scale behavior. We demonstrate that, at least in the brain, healthy vascular structures are a superposition of two components: at low scale, a mesh-like capillary component which becomes homogeneous and space-filling over a cut-off length of order of its characteristic length; at larger scale, quasi-fractal branched (tree-like) structures. Such complex structures are consistent with all previous studies on the multi-scale behavior of vascular structures at different scales, resolving the apparent contradiction about their fractal nature.Consequences regarding the way fractal analysis of vascular networks should be conducted to provide meaningful results are presented. Finally, consequences for vascular morphogenesis or hemodynamics are discussed, as well as implications in case of pathological conditions, such as cancer.