Functionalized synchrotron in-line phase-contrast computed tomography: a novel approach for simultaneous quantification of structural alterations and localization of barium-labelled alveolar macrophages within mouse lung samples.
Functionalized synchrotron in-line phase-contrast computed tomography: a novel approach for simultaneous quantification of structural alterations and localization of barium-labelled alveolar macrophages within mouse lung samples.
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DOI：
10.1107/s1600577514021730
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发表时间：
2015-01
影响因子：
2.5
通讯作者：
Tromba G
中科院分区：
文献类型：
--
作者：
Dullin C;dal Monego S;Larsson E;Mohammadi S;Krenkel M;Garrovo C;Biffi S;Lorenzon A;Markus A;Napp J;Salditt T;Accardo A;Alves F;Tromba G
本研究提出了一种方法，以增加肺部计算机断层扫描（CT）成像的灵敏度，利用线相衬CT结合单距离相位检索算法和专用的图像处理制度。如本文所示，与健康对照组相比，功能性CT成像可用于评估哮喘小鼠肺组织的结构改变和滴注硫酸钡标记的巨噬细胞的积聚模式。由于基于X射线吸收的成像的有限灵敏度，功能化计算机断层扫描（CT）与标记细胞的组合几乎不存在，但对于实现整个生物体中的细胞跟踪研究是非常理想的。在这项研究中，我们应用在线自由传播X射线相衬CT（XPCT）在过敏性哮喘小鼠模型，以评估结构的变化以及生物分布的钡标记的巨噬细胞在肺组织。肺泡巨噬细胞，硫酸钡负载和荧光标记的气管内滴入哮喘和对照小鼠。24小时后处死小鼠，将肺保持在原位，用空气充气，并在SYRMEP光束线（Elettra Synchrotron Light Source，意大利）处使用XPCT扫描。 单距离相位检索用于生成比基于吸收的CT（在我们的设置中）高十倍的对比度噪声比的数据集，从而允许描绘和量化哮喘肺的结构特征，例如减少的空气量、气道阻塞和增加的软组织含量。此外，我们还发现哮喘肺组织中钡标记的巨噬细胞的浓度较高，并具有特异性积聚。认为XPCT将有益于临床前哮喘研究，用于评估治疗反应以及分析巨噬细胞募集至炎症部位的作用。
This study presents an approach to increase the sensitivity of lung computed tomography (CT) imaging by utilizing in-line phase contrast CT in combination with single-distance phase-retrieval algorithms and a dedicated image-processing regime. As demonstrated here, functional CT imaging can be achieved for the assessment of both structural alterations in asthmatic mouse lung tissue and the accumulation pattern of instilled barium-sulfate-labelled macrophages in comparison with healthy controls. Functionalized computed tomography (CT) in combination with labelled cells is virtually non-existent due to the limited sensitivity of X-ray-absorption-based imaging, but would be highly desirable to realise cell tracking studies in entire organisms. In this study we applied in-line free propagation X-ray phase-contrast CT (XPCT) in an allergic asthma mouse model to assess structural changes as well as the biodistribution of barium-labelled macrophages in lung tissue. Alveolar macrophages that were barium-sulfate-loaded and fluorescent-labelled were instilled intratracheally into asthmatic and control mice. Mice were sacrificed after 24 h, lungs were kept in situ, inflated with air and scanned utilizing XPCT at the SYRMEP beamline (Elettra Synchrotron Light Source, Italy). Single-distance phase retrieval was used to generate data sets with ten times greater contrast-to-noise ratio than absorption-based CT (in our setup), thus allowing to depict and quantify structural hallmarks of asthmatic lungs such as reduced air volume, obstruction of airways and increased soft-tissue content. Furthermore, we found a higher concentration as well as a specific accumulation of the barium-labelled macrophages in asthmatic lung tissue. It is believe that XPCT will be beneficial in preclinical asthma research for both the assessment of therapeutic response as well as the analysis of the role of the recruitment of macrophages to inflammatory sites.