From whole-organ imaging to in-silico blood flow modeling: A new multi-scale network analysis for revisiting tissue functional anatomy

• Published in: PLoS computational biology Vol. 16; no. 2; p. e1007322
• Main Authors: Kennel, Pol, Dichamp, Jules, Barreau, Corinne, Guissard, Christophe, Teyssedre, Lise, Rouquette, Jacques, Colombelli, Julien, Lorsignol, Anne, Casteilla, Louis, Plouraboué, Franck
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 14.02.2020; PLOS; Public Library of Science (PLoS)
• Subjects: Adipose tissue; Animals; Biology and Life Sciences; Blood; Blood Circulation; Blood flow; Blood vessels; Cluster analysis; Clustering; Community involvement; Computer Simulation; Digitization; Ecology and Environmental Sciences; Engineering Sciences; Flow (Dynamics); Fluid mechanics; Fluids mechanics; Fluorescence; Fluorescence microscopy; Functional anatomy; Functional morphology; Image reconstruction; Laser microscopy; Male; Mechanics; Medicine and Health Sciences; Mesoscale phenomena; Metabolism; Mice; Mice, Inbred C57BL; Microscopy; Modelling; Models, Biological; Multiscale analysis; Network analysis; Perfusion; Research and Analysis Methods; Software; Structure-function relationships; Time; Tissue analysis; Tissues; Veins & arteries; Workflow; Workflow software; France; Fat pad; Micro-vascular clusters; Microscopy; Fluorescence; In-silico modeling; Light-Sheet; Tissue micro-environment
• ISSN: 1553-7358; 1553-734X; 1553-7358
• DOI: 10.1371/journal.pcbi.1007322

We present a multi-disciplinary image-based blood flow perfusion modeling of a whole organ vascular network for analyzing both its structural and functional properties. We show how the use of Light-Sheet Fluorescence Microscopy (LSFM) permits whole-organ micro-vascular imaging, analysis and modelling. By using adapted image post-treatment workflow, we could segment, vectorize and reconstruct the entire micro-vascular network composed of 1.7 million vessels, from the tissue-scale, inside a ∼ 25 × 5 × 1 = 125mm3 volume of the mouse fat pad, hundreds of times larger than previous studies, down to the cellular scale at micron resolution, with the entire blood perfusion modeled. Adapted network analysis revealed the structural and functional organization of meso-scale tissue as strongly connected communities of vessels. These communities share a distinct heterogeneous core region and a more homogeneous peripheral region, consistently with known biological functions of fat tissue. Graph clustering analysis also revealed two distinct robust meso-scale typical sizes (from 10 to several hundred times the cellular size), revealing, for the first time, strongly connected functional vascular communities. These community networks support heterogeneous micro-environments. This work provides the proof of concept that in-silico all-tissue perfusion modeling can reveal new structural and functional exchanges between micro-regions in tissues, found from community clusters in the vascular graph.