Departamento de Bioingeniería e Ingeniería Aeroespacial, Universidad Carlos III de Madrid, Leganés, Spain.
Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.
Sci Rep. 2019 Dec 18;9(1):19404. doi: 10.1038/s41598-019-55986-y.
Hollow organs such as the lungs pose a considerable challenge for post-mortem imaging in preclinical research owing to their extremely low contrast and high structural complexity. The aim of our study was to enhance the contrast of tuberculosis lesions for their stratification by 3D x-ray-based virtual slicing. Organ samples were taken from five control and five tuberculosis-infected mice. Micro-Computed Tomography (CT) scans of the subjects were acquired in vivo (without contrast agent) and post-mortem (with contrast agent). The proposed contrast-enhancing technique consists of x-ray contrast agent uptake (silver nitrate and iodine) by immersion. To create the histology ground-truth, the CT scan of the paraffin block guided the sectioning towards specific planes of interest. The digitalized histological slides reveal the presence, extent, and appearance of the contrast agents in lung structures and organized aggregates of immune cells. These findings correlate with the contrast-enhanced micro-CT slice. The abnormal densities in the lungs due to tuberculosis disease are concentrated in the right tail of the lung intensity histograms. The increase in the width of the right tail (~376%) indicates a contrast enhancement of the details of the abnormal densities. Postmortem contrast agents enhance the x-ray attenuation in tuberculosis lesions to allow 3D visualization by polychromatic x-ray CT, providing an advantageous tool for virtual slicing of whole lungs. The proposed contrast-enhancing technique combined with computational methods and the diverse micro-CT modalities will open the doors to the stratification of lesion types associated with infectious diseases.
由于肺部等中空器官对比度极低且结构极其复杂，因此对临床前研究中的死后成像构成了相当大的挑战。我们的研究目的是通过基于 3D X 射线的虚拟切片来增强结核病变的对比度，以对其进行分层。从五只对照鼠和五只感染结核的鼠中采集器官样本。对受试鼠进行体内（无造影剂）和死后（含造影剂）的微计算机断层扫描（CT）。所提出的对比度增强技术包括通过浸泡吸收 X 射线造影剂（硝酸银和碘）。为了创建组织学的真实情况，对石蜡块的 CT 扫描指导着对特定感兴趣平面的切片。数字化的组织学幻灯片揭示了造影剂在肺结构和免疫细胞聚集物中的存在、程度和外观。这些发现与对比度增强的微 CT 切片相关。由于结核病引起的肺部异常密度集中在肺强度直方图的右尾。右尾宽度的增加（~376%）表明异常密度细节的对比度增强。死后造影剂增强了结核病变中的 X 射线衰减，从而可以通过多色 X 射线 CT 进行 3D 可视化，为整个肺部的虚拟切片提供了有利的工具。所提出的对比度增强技术结合计算方法和多种微 CT 模式，将为与传染病相关的病变类型的分层开辟道路。
