title: Quantitative Micro-Computed Tomography Imaging of Vascular Dysfunction in Progressive Kidney Diseases.
abstract: Progressive kidney diseases and renal fibrosis are associated with endothelial injury and capillary rarefaction. However, our understanding of these processes has been hampered by the lack of tools enabling the quantitative and noninvasive monitoring of vessel functionality. Here, we used micro-computed tomography (µCT) for anatomical and functional imaging of vascular alterations in three murine models with distinct mechanisms of progressive kidney injury: ischemia-reperfusion (I/R, days 1-56), unilateral ureteral obstruction (UUO, days 1-10), and Alport mice (6-8 weeks old). Contrast-enhanced in vivo µCT enabled robust, noninvasive, and longitudinal monitoring of vessel functionality and revealed a progressive decline of the renal relative blood volume in all models. This reduction ranged from -20% in early disease stages to -61% in late disease stages and preceded fibrosis. Upon Microfil perfusion, high-resolution ex vivo µCT allowed quantitative analyses of three-dimensional vascular networks in all three models. These analyses revealed significant and previously unrecognized alterations of preglomerular arteries: a reduction in vessel diameter, a prominent reduction in vessel branching, and increased vessel tortuosity. In summary, using µCT methodology, we revealed insights into macro-to-microvascular alterations in progressive renal disease and provide a platform that may serve as the basis to evaluate vascular therapeutics in renal disease.
authors.affiliation: Institute for Experimental Molecular Imaging, Helmholtz Institute for Biomedical Engineering, Medical Faculty, Rheinisch-Westfälische Technische Hochschule (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: Institute of Pathology, Medical Faculty, RWTH Aachen University, Aachen, Germany; Institute of Molecular Biomedicine, Comenius University, Bratislava, Slovakia;
authors.forename: Janka
authors.initials: J
authors.lastname: Bábíčková
authors.affiliation: Institute for Experimental Molecular Imaging, Helmholtz Institute for Biomedical Engineering, Medical Faculty, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University, Aachen, Germany;
authors.forename: Felix
authors.initials: F
authors.lastname: Gremse
authors.affiliation: Institute of Pathology, Medical Faculty, RWTH Aachen University, Aachen, Germany;
authors.forename: Barbara M
authors.initials: BM
authors.lastname: Klinkhammer
authors.affiliation: Institute for Experimental Molecular Imaging, Helmholtz Institute for Biomedical Engineering, Medical Faculty, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University, Aachen, Germany;
authors.forename: Sarah
authors.initials: S
authors.lastname: Baetke
authors.affiliation: Institute of Pathology, Medical Faculty, RWTH Aachen University, Aachen, Germany;
authors.forename: Ruth
authors.initials: R
authors.lastname: Knuechel
authors.affiliation: Institute for Experimental Molecular Imaging, Helmholtz Institute for Biomedical Engineering, Medical Faculty, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University, Aachen, Germany;
authors.forename: Fabian
authors.initials: F
authors.lastname: Kiessling
authors.affiliation: Department of Nephrology, Medical Faculty, RWTH Aachen University, Aachen, Germany;
authors.forename: Jürgen
authors.initials: J
authors.lastname: Floege
authors.affiliation: Institute for Experimental Molecular Imaging, Helmholtz Institute for Biomedical Engineering, Medical Faculty, Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University, Aachen, Germany; Department of Targeted Therapeutics, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands; and Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands pboor@ukaachen.de tlammers@ukaachen.de.
authors.forename: Twan
authors.initials: T
authors.lastname: Lammers
authors.affiliation: Institute of Pathology, Medical Faculty, RWTH Aachen University, Aachen, Germany; Institute of Molecular Biomedicine, Comenius University, Bratislava, Slovakia; Department of Nephrology, Medical Faculty, RWTH Aachen University, Aachen, Germany; pboor@ukaachen.de tlammers@ukaachen.de.
authors.forename: Peter
authors.initials: P
authors.lastname: Boor
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000503:physiopathology*; D018450:Disease Progression; D007668:Kidney / Q000098:blood supply*; D007674:Kidney Diseases / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D051379:Mice; D055114:X-Ray Microtomography
keywords: capillary rarefaction; chronic kidney disease; computed tomography; fibrosis; imaging; noninvasive