A novel in vivo vascular imaging approach for hierarchical quantification of vasculature using contrast enhanced micro-computed tomography.
The vasculature of body tissues is continuously subject to remodeling processes originating at the micro-vascular level. The formation of new blood vessels (angiogenesis) is essential for a number of physiological and pathophysiological processes such as tissue regeneration, tumor development and the integration of artificial tissues. There are currently no time-lapsed in vivo imaging techniques providing information on the vascular network at the capillary level in a non-destructive, three-dimensional and high-resolution fashion. This paper presents a novel imaging framework based on contrast enhanced micro-computed tomography (micro-CT) for hierarchical in vivo quantification of blood vessels in mice, ranging from largest to smallest structures. The framework combines for the first time a standard morphometric approach with densitometric analysis. Validation tests showed that the method is precise and robust. Furthermore, the framework is sensitive in detecting different perfusion levels after the implementation of a murine ischemia-reperfusion model. Correlation with both histological data and micro-CT analysis of vascular corrosion casts confirmed accuracy of the method. The newly developed time-lapsed imaging approach shows high potential for in vivo monitoring of a number of different physiological and pathological conditions in angiogenesis and vascular development.
Institute for Biomechanics, ETH Zurich, Zurich, Switzerland.
Laura
L
Nebuloni
Institute for Biomechanics, ETH Zurich, Zurich, Switzerland.
Gisela A
GA
Kuhn
Institute of Veterinary Physiology and Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland.
Johannes
J
Vogel
Institute for Biomechanics, ETH Zurich, Zurich, Switzerland.
Ralph
R
Müller
D000818:Animals; D016319:Corrosion Casting / Q000379:methods; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D055806:Microvessels / Q000648:ultrastructure*; D015427:Reperfusion Injury / Q000473:pathology*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D059008:Time-Lapse Imaging / Q000379:methods*; D055114:X-Ray Microtomography / Q000379:methods*