A Computational Tool for Quantitative Analysis of Vascular Networks

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2011 Nov 24

PMID 22110636

Citations 493

Authors

Enrique Zudaire

Laure Gambardella

Christopher Kurcz

Sonja Vermeren

Affiliations

Soon will be listed here.

Abstract

Angiogenesis is the generation of mature vascular networks from pre-existing vessels. Angiogenesis is crucial during the organism' development, for wound healing and for the female reproductive cycle. Several murine experimental systems are well suited for studying developmental and pathological angiogenesis. They include the embryonic hindbrain, the post-natal retina and allantois explants. In these systems vascular networks are visualised by appropriate staining procedures followed by microscopical analysis. Nevertheless, quantitative assessment of angiogenesis is hampered by the lack of readily available, standardized metrics and software analysis tools. Non-automated protocols are being used widely and they are, in general, time--and labour intensive, prone to human error and do not permit computation of complex spatial metrics. We have developed a light-weight, user friendly software, AngioTool, which allows for quick, hands-off and reproducible quantification of vascular networks in microscopic images. AngioTool computes several morphological and spatial parameters including the area covered by a vascular network, the number of vessels, vessel length, vascular density and lacunarity. In addition, AngioTool calculates the so-called "branching index" (branch points/unit area), providing a measurement of the sprouting activity of a specimen of interest. We have validated AngioTool using images of embryonic murine hindbrains, post-natal retinas and allantois explants. AngioTool is open source and can be downloaded free of charge.

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References

Mavria G, Vercoulen Y, Yeo M, Paterson H, Karasarides M, Marais R . ERK-MAPK signaling opposes Rho-kinase to promote endothelial cell survival and sprouting during angiogenesis. Cancer Cell. 2006; 9(1):33-44. DOI: 10.1016/j.ccr.2005.12.021. View

Guidolin D, Nico B, Mazzocchi G, Vacca A, Nussdorfer G, Ribatti D . Order and disorder in the vascular network. Leukemia. 2004; 18(11):1745-50. DOI: 10.1038/sj.leu.2403526. View

Downs K, Temkin R, GIFFORD S, McHugh J . Study of the murine allantois by allantoic explants. Dev Biol. 2001; 233(2):347-64. DOI: 10.1006/dbio.2001.0227. View

Ruhrberg C, Gerhardt H, Golding M, Watson R, Ioannidou S, Fujisawa H . Spatially restricted patterning cues provided by heparin-binding VEGF-A control blood vessel branching morphogenesis. Genes Dev. 2002; 16(20):2684-98. PMC: 187458. DOI: 10.1101/gad.242002. View

Uehata M, Ishizaki T, Satoh H, Ono T, Kawahara T, Morishita T . Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension. Nature. 1997; 389(6654):990-4. DOI: 10.1038/40187. View

Takakura N, Huang X, Naruse T, Hamaguchi I, Dumont D, Yancopoulos G . Critical role of the TIE2 endothelial cell receptor in the development of definitive hematopoiesis. Immunity. 1998; 9(5):677-86. DOI: 10.1016/s1074-7613(00)80665-2. View

Tanaka M, Okudaira S, Kishi Y, Ohkawa R, Iseki S, Ota M . Autotaxin stabilizes blood vessels and is required for embryonic vasculature by producing lysophosphatidic acid. J Biol Chem. 2006; 281(35):25822-30. DOI: 10.1074/jbc.M605142200. View

Manniesing R, Viergever M, Niessen W . Vessel enhancing diffusion: a scale space representation of vessel structures. Med Image Anal. 2006; 10(6):815-25. DOI: 10.1016/j.media.2006.06.003. View

Croft D, Sahai E, Mavria G, Li S, Tsai J, Lee W . Conditional ROCK activation in vivo induces tumor cell dissemination and angiogenesis. Cancer Res. 2004; 64(24):8994-9001. DOI: 10.1158/0008-5472.CAN-04-2052. View

10.

Kanemura H, Satoh T, Bilasy S, Ueda S, Hirashima M, Kataoka T . Impaired vascular development in the yolk sac and allantois in mice lacking RA-GEF-1. Biochem Biophys Res Commun. 2009; 387(4):754-9. DOI: 10.1016/j.bbrc.2009.07.108. View

11.

Adams R, Alitalo K . Molecular regulation of angiogenesis and lymphangiogenesis. Nat Rev Mol Cell Biol. 2007; 8(6):464-78. DOI: 10.1038/nrm2183. View

12.

Carmeliet P . Angiogenesis in health and disease. Nat Med. 2003; 9(6):653-60. DOI: 10.1038/nm0603-653. View

13.

Pitulescu M, Schmidt I, Benedito R, Adams R . Inducible gene targeting in the neonatal vasculature and analysis of retinal angiogenesis in mice. Nat Protoc. 2010; 5(9):1518-34. DOI: 10.1038/nprot.2010.113. View

14.

Gerhardt H, Golding M, Fruttiger M, Ruhrberg C, Lundkvist A, Abramsson A . VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia. J Cell Biol. 2003; 161(6):1163-77. PMC: 2172999. DOI: 10.1083/jcb.200302047. View

15.

Hoang M, Whelan M, Senger D . Rho activity critically and selectively regulates endothelial cell organization during angiogenesis. Proc Natl Acad Sci U S A. 2004; 101(7):1874-9. PMC: 357020. DOI: 10.1073/pnas.0308525100. View

16.

Vlahos C, Matter W, Hui K, Brown R . A specific inhibitor of phosphatidylinositol 3-kinase, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002). J Biol Chem. 1994; 269(7):5241-8. View

17.

Arganda-Carreras I, Fernandez-Gonzalez R, Munoz-Barrutia A, Ortiz-de-Solorzano C . 3D reconstruction of histological sections: Application to mammary gland tissue. Microsc Res Tech. 2010; 73(11):1019-29. DOI: 10.1002/jemt.20829. View

18.

Uemura A, Kusuhara S, Katsuta H, Nishikawa S . Angiogenesis in the mouse retina: a model system for experimental manipulation. Exp Cell Res. 2005; 312(5):676-83. DOI: 10.1016/j.yexcr.2005.10.030. View

19.

Graupera M, Guillermet-Guibert J, Foukas L, Phng L, Cain R, Salpekar A . Angiogenesis selectively requires the p110alpha isoform of PI3K to control endothelial cell migration. Nature. 2008; 453(7195):662-6. DOI: 10.1038/nature06892. View

20.

Knight Z, Gonzalez B, Feldman M, Zunder E, Goldenberg D, Williams O . A pharmacological map of the PI3-K family defines a role for p110alpha in insulin signaling. Cell. 2006; 125(4):733-47. PMC: 2946820. DOI: 10.1016/j.cell.2006.03.035. View