Micro-CT Imaging of Tumor Angiogenesis Quantitative Measures Describing Micromorphology and Vascularization

作者:Ehling Josef; Theek Benjamin; Gremse Felix; Baetke Sarah; Moeckel Diana; Maynard Juliana; Ricketts Sally Ann; Gruell Holger; Neeman Michal; Knuechel Ruth; Lederle Wiltrud; Kiessling Fabian; Lammers Twan*
来源:American Journal Of Pathology, 2014, 184(2): 431-441.
DOI:10.1016/j.ajpath.2013.10.014

摘要

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 (p,CT) 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 p.CT ranged from 2.6% to 6.0%, and corresponds well with the values assessed using IHC. Using ultra high-resolution ex vivo p,CT, blood vessels as small as 3.4 p.m 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 p,CT is a useful tool for facilitating high-throughput, quantitative, and translational (anti-) angiogenesis and antiangiogenesis research.

  • 出版日期2014-2