title: MicroCT angiography detects vascular formation and regression in skin wound healing.
abstract: Properly regulated angiogenesis and arteriogenesis are essential for effective wound healing. Tissue injury induces robust new vessel formation and subsequent vessel maturation, which involves vessel regression and remodeling. Although formation of functional vasculature is essential for healing, alterations in vascular structure over the time course of skin wound healing are not well understood. Here, using high-resolution ex vivo X-ray micro-computed tomography (microCT), we describe the vascular network during healing of skin excisional wounds with highly detailed three-dimensional (3D) reconstructed images and associated quantitative analysis. We found that relative vessel volume, surface area and branching number are significantly decreased in wounds from day 7 to days 14 and 21. Segmentation and skeletonization analysis of selected branches from high-resolution images as small as 2.5μm voxel size show that branching orders are decreased in the wound vessels during healing. In histological analysis, we found that the contrast agent fills mainly arterioles, but not small capillaries nor large veins. In summary, high-resolution microCT revealed dynamic alterations of vessel structures during wound healing. This technique may be useful as a key tool in the study of the formation and regression of wound vessels.
authors.affiliation: University of Illinois at Chicago, Center for Wound Healing and Tissue Regeneration, Department of Kinesiology and Nutrition, USA. Electronic address: nurao@uic.edu.
authors.forename: Norifumi
authors.initials: N
authors.lastname: Urao
authors.affiliation: University of Illinois at Chicago College of Dentistry, Center for Wound Healing and Tissue Regeneration, Department of Periodontics, USA.
authors.forename: Uzoagu A
authors.initials: UA
authors.lastname: Okonkwo
authors.affiliation: University of Illinois at Chicago, Center for Wound Healing and Tissue Regeneration, Department of Kinesiology and Nutrition, USA.
authors.forename: Milie M
authors.initials: MM
authors.lastname: Fang
authors.affiliation: Yale School of Medicine, Yale University, Yale Translational Research Imaging Center, USA.
authors.forename: Zhen W
authors.initials: ZW
authors.lastname: Zhuang
authors.affiliation: University of Illinois at Chicago, Center for Wound Healing and Tissue Regeneration, Department of Kinesiology and Nutrition, USA.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Koh
authors.affiliation: University of Illinois at Chicago College of Dentistry, Center for Wound Healing and Tissue Regeneration, Department of Periodontics, USA. Electronic address: ldipiet@uic.edu.
authors.forename: Luisa A
authors.initials: LA
authors.lastname: DiPietro
mesh_terms: D000818:Animals; D001160:Arterioles / Q000000981:diagnostic imaging / Q000503:physiopathology; D000072226:Computed Tomography Angiography / Q000379:methods*; D004195:Disease Models, Animal; D021621:Imaging, Three-Dimensional; D008297:Male; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic; D011237:Predictive Value of Tests; D011857:Radiographic Image Interpretation, Computer-Assisted; D012867:Skin / Q000098:blood supply* / Q000000981:diagnostic imaging*; D013997:Time Factors; D014945:Wound Healing; D014947:Wounds and Injuries / Q000000981:diagnostic imaging* / Q000503:physiopathology; D055114:X-Ray Microtomography
keywords: Angiogenesis; Angiography; Micro-computed tomography; Three-dimensional; Wound healing