title: Micro-CT imaging of tumor angiogenesis: quantitative measures describing micromorphology and vascularization.
abstract: Angiogenesis is a hallmark of cancer, and its noninvasive visualization and quantification are key factors for facilitating translational anticancer research. Using four tumor models characterized by different degrees of aggressiveness and angiogenesis, we show that the combination of functional in vivo and anatomical ex vivo X-ray micro-computed tomography (μCT) allows highly accurate quantification of relative blood volume (rBV) and highly detailed three-dimensional analysis of the vascular network in tumors. Depending on the tumor model, rBV values determined using in vivo μCT ranged from 2.6% to 6.0%, and corresponds well with the values assessed using IHC. Using ultra-high-resolution ex vivo μCT, blood vessels as small as 3.4 μm and vessel branches up to the seventh order could be visualized, enabling a highly detailed and quantitative analysis of the three-dimensional micromorphology of tumor vessels. Microvascular parameters such as vessel size and vessel branching correlated very well with tumor aggressiveness and angiogenesis. In rapidly growing and highly angiogenic A431 tumors, the majority of vessels were small and branched only once or twice, whereas in slowly growing A549 tumors, the vessels were much larger and branched four to seven times. Thus, we consider that combining highly accurate functional with highly detailed anatomical μCT is a useful tool for facilitating high-throughput, quantitative, and translational (anti-) angiogenesis and antiangiogenesis research.
authors.affiliation: Department of Experimental Molecular Imaging, University Clinic and Helmholtz Institute for Biomedical Engineering, RWTH-Aachen University, Aachen, Germany; Institute of Pathology, Medical Faculty, RWTH-Aachen University, Aachen, Germany.
authors.forename: Josef
authors.initials: J
authors.lastname: Ehling
authors.affiliation: Department of Experimental Molecular Imaging, University Clinic and Helmholtz Institute for Biomedical Engineering, RWTH-Aachen University, Aachen, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Theek
authors.affiliation: Department of Experimental Molecular Imaging, University Clinic and Helmholtz Institute for Biomedical Engineering, RWTH-Aachen University, Aachen, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Gremse
authors.affiliation: Department of Experimental Molecular Imaging, University Clinic and Helmholtz Institute for Biomedical Engineering, RWTH-Aachen University, Aachen, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Baetke
authors.affiliation: Department of Experimental Molecular Imaging, University Clinic and Helmholtz Institute for Biomedical Engineering, RWTH-Aachen University, Aachen, Germany.
authors.forename: Diana
authors.initials: D
authors.lastname: Möckel
authors.affiliation: Personalized Healthcare & Biomarkers, AstraZeneca, Alderley Park, Macclesfield, United Kingdom.
authors.forename: Juliana
authors.initials: J
authors.lastname: Maynard
authors.affiliation: Personalized Healthcare & Biomarkers, AstraZeneca, Alderley Park, Macclesfield, United Kingdom.
authors.forename: Sally-Ann
authors.initials: SA
authors.lastname: Ricketts
authors.affiliation: Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands.
authors.forename: Holger
authors.initials: H
authors.lastname: Grüll
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Neeman
authors.affiliation: Institute of Pathology, Medical Faculty, RWTH-Aachen University, Aachen, Germany.
authors.forename: Ruth
authors.initials: R
authors.lastname: Knuechel
authors.affiliation: Department of Experimental Molecular Imaging, University Clinic and Helmholtz Institute for Biomedical Engineering, RWTH-Aachen University, Aachen, Germany.
authors.forename: Wiltrud
authors.initials: W
authors.lastname: Lederle
authors.affiliation: Department of Experimental Molecular Imaging, University Clinic and Helmholtz Institute for Biomedical Engineering, RWTH-Aachen University, Aachen, Germany. Electronic address: fkiessling@ukaachen.de.
authors.forename: Fabian
authors.initials: F
authors.lastname: Kiessling
authors.affiliation: Department of Experimental Molecular Imaging, University Clinic and Helmholtz Institute for Biomedical Engineering, RWTH-Aachen University, Aachen, Germany; Department of Targeted Therapeutics, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, the Netherlands; Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands. Electronic address: tlammers@ukaachen.de.
authors.forename: Twan
authors.initials: T
authors.lastname: Lammers
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D009369:Neoplasms / Q000098:blood supply* / Q000000981:diagnostic imaging* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging* / Q000473:pathology; D055114:X-Ray Microtomography; D023041:Xenograft Model Antitumor Assays