Characterization and quantification of angiogenesis in rheumatoid arthritis in a mouse model using μCT.

Characterization and quantification of angiogenesis in rheumatoid arthritis in a mouse model using μCT.
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DOI:
10.1186/1471-2474-15-298
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发表时间:
2014-09-06
影响因子:
2.3
通讯作者:
Engelke K
Engelke K
中科院分区:
医学3区
文献类型:
--
作者:
Gayetskyy S;Museyko O;Käßer J;Hess A;Schett G;Engelke K

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血管生成是慢性炎症,尤其是炎性关节炎的重要病理生理过程。血管化变化的定量测量可以改善关节炎的诊断和监测。这项工作的目的是开发用于量化实验性关节炎血管化的 3D 成像和分析框架。使用高分辨率微型计算机断层扫描 (μCT) 扫描患有关节炎的人肿瘤坏死因子转基因 (hTNFtg) 小鼠和先前灌注含铅造影剂 Microfil MV-122 的非关节炎野生型对照小鼠的膝关节。血管分割是通过结合基于强度(局部自适应阈值)和基于形式(多尺度方法)的分割技术来执行的。以膝关节为中心的四个解剖学定义的同心球壳被用作感兴趣的分析体积。测量血管密度、密度分布以及血管厚度、表面、间距和数量。使用模拟数字血管树模型来验证算法。高分辨率 μCT 可以对关节炎期间膝关节的血管树进行定量评估。分割和分析是高度自动化的,但有时需要手动校正靠近骨表面的血管分割。与野生型对照相比,关节炎 hTNFtg 小鼠的血管化显着增加。操作者内和操作者间分析的形态学参数的精度误差分别小于 3% 和 6%。对于大于扫描仪分辨率两倍的血管,血管厚度的准确度误差约为 20%。关节炎引起的血管树变化,包括血管分支数量、血管段长度和分叉角度的详细和定量描述,可以通过对比增强高分辨率μCT来检测。本文的在线版本 (doi:10.1186/1471-2474-15-298) 包含补充材料,可供授权用户使用。
Angiogenesis is an important pathophysiological process of chronic inflammation, especially in inflammatory arthritis. Quantitative measurement of changes in vascularization may improve the diagnosis and monitoring of arthritis. The aim of this work is the development of a 3D imaging and analysis framework for quantification of vascularization in experimental arthritis. High-resolution micro-computed tomography (μCT) was used to scan knee joints of arthritic human tumor necrosis factor transgenic (hTNFtg) mice and non-arthritic wild-type controls previously perfused with lead-containing contrast agent Microfil MV-122. Vessel segmentation was performed by combination of intensity-based (local adaptive thresholding) and form-based (multi-scale method) segmentation techniques. Four anatomically defined concentric spherical shells centered in the knee joint were used as analysis volumes of interest. Vessel density, density distribution as well as vessel thickness, surface, spacing and number were measured. Simulated digital vessel tree models were used for validation of the algorithms. High-resolution μCT allows the quantitative assessment of the vascular tree in the knee joint during arthritis. Segmentation and analysis were highly automated but occasionally required manual corrections of the vessel segmentation close to the bone surfaces. Vascularization was significantly increased in arthritic hTNFtg mice compared to wild type controls. Precision errors for the morphologic parameters were smaller than 3% and 6% for intra- and interoperator analysis, respectively. Accuracy errors for vessel thickness were around 20% for vessels larger than twice the resolution of the scanner. Arthritis-induced changes of the vascular tree, including detailed and quantitative description of the number of vessel branches, length of vessel segments and the bifurcation angle, can be detected by contrast-enhanced high-resolution μCT. The online version of this article (doi:10.1186/1471-2474-15-298) contains supplementary material, which is available to authorized users.
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