Targeted stereology: sampling heterogeneously distributed structures and lesions in the lung

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Stereology, the gold standard of lung morphometry, critically depends on sampling of tissue for analysis. Random sampling approaches guarantee each part of the organ an equal chance of being included in the analysis; hence, they guarantee a representative sample of the whole. However, when biological or pathological structures of interest are rare and/or heterogeneously distributed over the whole lung, the random sampling approach can be inefficient or even result in meaningless data. In such cases, a targeted sampling approach can be useful, which helps to relate the analytical items to an appropriate reference space. Targeted stereology greatly benefits from the increasing availability of multiresolution imaging techniques at macroscopic and microscopic levels as well as digital tools of segmentation. As such, this article outlines two basic sampling scenarios: 1) In the first scenario, computed tomography and microscopy are subsequently used to segment the airway/arterial tree and perform stereological measurements on specific branches of the tree. 2) The second scenario deals with the heterogeneous distribution of pathological lesions. This type of analysis can be divided into two stages: assessment of lesions of interest (LOIs) within the lung and assessment of subcompartments within LOIs. Taken together, targeted stereology has a thorough foundation in stereological theory and is able to not only significantly increase the efficiency of the analysis but also yield new types of information that would be lost with the classical random sampling approach.