Vasilescu Dragoş M, Phillion André B, Kinose Daisuke, Verleden Stijn E, Vanaudenaerde Bart M, Verleden Geert M, Van Raemdonck Dirk, Stevenson Christopher S, Hague Cameron J, Han MeiLan K, Cooper Joel D, Hackett Tillie-Louise, Hogg James C
Centre for Heart Lung Innovation, University of British Columbia, Vancouver, British Columbia, Canada.
Department of Materials Science and Engineering, McMaster University, Hamilton, Ontario, Canada.
J Appl Physiol (1985). 2020 Jun 1;128(6):1604-1616. doi: 10.1152/japplphysiol.00803.2019. Epub 2020 Apr 16.
The application of stereology to lung casts and two-dimensional microscopy images is the gold standard for quantification of the human lung anatomy. However, these techniques are labor intensive, involving fixation, embedding, and histological sectioning of samples and thus have prevented comprehensive studies. Our objective was to demonstrate the application of stereology to volumetric multiresolution computed tomography (CT) to efficiently and extensively quantify the human lung anatomy. Nontransplantable donor lungs from individuals with no evidence of respiratory disease ( = 13) were air inflated, frozen at 10 cmHO, and scanned using CT. Systematic uniform random samples were taken, scanned using micro-CT, and assessed using stereology. The application of stereology to volumetric CT imaging enabled comprehensive quantification of total lung volume, volume fractions of alveolar, alveolar duct, and tissue, mean linear intercept, alveolar surface area, alveolar surface area density, septal wall thickness, alveolar number, number-weighted mean alveolar volume, and the number and morphometry of terminal and transitional bronchioles. With the use of this data set, we found that women and men have the same number of terminal bronchioles (last generation of conducting airways), but men have longer terminal bronchioles, a smaller wall area percentage, and larger lungs due to a greater number of alveoli per acinus. The application of stereology to multiresolution CT imaging enables comprehensive analysis of the human lung parenchyma that identifies differences between men and women. The reported data set of normal donor lungs aged 25-77 yr provides reference data for future studies of chronic lung disease to determine exact changes in tissue pathology. Stereology has been the gold standard to quantify the three-dimensional lung anatomy using two-dimensional microscopy images. However, such techniques are labor intensive. This study provides a method that applies stereology to volumetric computed tomography images of frozen whole human lungs and systematic uniform random samples. The method yielded a comprehensive data set on the small airways and parenchymal lung structures, highlighting morphometric sex differences and providing a reference data set for future pathological studies.
体视学在肺铸型和二维显微镜图像中的应用是定量分析人体肺部解剖结构的金标准。然而，这些技术劳动强度大，涉及样本的固定、包埋和组织切片，因此阻碍了全面的研究。我们的目标是证明体视学在容积多分辨率计算机断层扫描（CT）中的应用，以高效、广泛地定量分析人体肺部解剖结构。对13例无呼吸系统疾病迹象的不可移植供体肺进行充气，在10 cmH₂O压力下冷冻，然后用CT扫描。采集系统均匀随机样本，用微型CT扫描，并采用体视学进行评估。将体视学应用于容积CT成像能够全面定量分析全肺体积、肺泡、肺泡管和组织的体积分数、平均线性截距、肺泡表面积、肺泡表面积密度、间隔壁厚度、肺泡数量、数量加权平均肺泡体积以及终末和过渡细支气管的数量和形态。利用该数据集，我们发现男性和女性的终末细支气管（传导气道的最后一代）数量相同，但男性的终末细支气管更长，壁面积百分比更小，且由于每个腺泡的肺泡数量更多，肺部更大。将体视学应用于多分辨率CT成像能够全面分析人体肺实质，识别男性和女性之间的差异。所报告的25至77岁正常供体肺的数据集为未来慢性肺病研究提供了参考数据，以确定组织病理学的确切变化。体视学一直是使用二维显微镜图像定量三维肺部解剖结构的金标准。然而，此类技术劳动强度大。本研究提供了一种将体视学应用于冷冻全人肺容积计算机断层扫描图像和系统均匀随机样本的方法。该方法产生了关于小气道和肺实质结构的全面数据集，突出了形态计量学上的性别差异，并为未来的病理学研究提供了参考数据集。
