Micro-CT imaging of tumor angiogenesis: quantitative measures describing micromorphology and vascularization.

Micro-CT imaging of tumor angiogenesis: quantitative measures describing micromorphology and vascularization.
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DOI:
10.1016/j.ajpath.2013.10.014
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发表时间:
2014-02
影响因子:
6
通讯作者:
Lammers, Twan
Lammers, Twan
中科院分区:
医学2区
文献类型:
--
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

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血管生成是癌症的标志,其无创可视化和量化是促进转化抗癌研究的关键因素。使用四种以不同程度的侵袭性和血管生成为特征的肿瘤模型,我们表明,功能性体内和解剖性离体X射线微计算机断层扫描(μCT)的结合可以实现相对血容量(rBV)的高精度量化和肿瘤血管网络的高度详细的三维分析。根据肿瘤模型的不同,使用体内 μCT 测定的 rBV 值范围为 2.6% 至 6.0%,并且与使用 IHC 评估的值很好地对应。使用超高分辨率离体μCT,可以显示小至3.4毫米的血管和高达七级的血管分支,从而能够对肿瘤血管的三维微形态进行高度详细的定量分析。微血管参数如血管大小和血管分支与肿瘤侵袭性和血管生成密切相关。在快速生长和高度血管生成的 A431 肿瘤中,大多数血管都很小,仅分支一次或两次,而在缓慢生长的 A549 肿瘤中,血管要大得多,分支四到七次。因此,我们认为,将高度精确的功能性与高度详细的解剖学 μCT 相结合是促进高通量、定量和转化(抗)血管生成和抗血管生成研究的有用工具。
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 mm 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.
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