A review of recent developments and applications of morphometry/stereology in lung research

Abstract

Here, we analyze the current use of morphometric and stereological methods in lung research and provide an overview on recent methodological developments and biological observations made by the use of stereology. Based on this analysis we hope to provide useful recommendations for a good stereological practice to further the use of advanced and unbiased stereological methods.design-based stereology; fibrosis; serial block face scanning electron microscopy; morphometry; emphysema DESIGN-BASED STEREOLOGY HAS been widely accepted as the gold standard of quantitative morphology in lung research. Approximately 50 yr after the beginning of Weibel's research on the structure-function relationships of the lung (160, 162), the American Thoracic Society and the European Respiratory Society published a joint research policy statement on the use of stereology for the quantitative assessment of lung structure (51), thereby providing a coherent framework for quantitative morphology in lung research. Still, the implementation of this theoretical framework into a practical research question remained challenging. This led us to provide a more practically and problem-oriented approach to lung stereology recently by addressing the pathology of various lung diseases and by making practical recommendations of useful stereological parameters for these diseases (101, 111).The current review article intends to provide an update on lung stereology over the last 2 yr, first by analyzing the use of stereological methods in the two basic lung research journals with the highest impact factor in recent years. Here, we discuss what stereological methods are currently most widely used and where there is still space for further improving the quality of quantitative morphology in lung research. In the second part of this article, we address recent methodological developments and advances, and we highlight new biological observations made by the use of stereology. Analysis of the Current Use of Stereology in Lung Research Selection of journals and articles. Among the journals dedicated to pulmonary research, we chose the American Journal of Physiology Lung Cellular and Molecular Physiology and the American Journal of Respiratory Cell and Molecular Biologyfor a literature review. The two journals were selected because they have the highest impact factor of those journals publishing basic lung science and because their impact factor has proven to be in the same range over the last years (87). Another important reason is the fact that both journals or their corresponding societies have made substantial efforts to increase the quality of morphometry in lung research by publishing research guidelines (51) and review articles (10, 101, 111) as well as editorials (47,89,162) dedicated to this topic. To identify target articles, all articles (except reviews) published in the print issues in 2013 and 2014 were searched for the terms "morphometry/morphometric" and "stereology/stereological." The selection of articles was then closely looked at to analyze w...

mTOR pathway activation drives lung cell senescence and emphysema

“…One limitation in our assessment of lung emphysema is that lung volume was not measured. This point may have led to overestimation of the results (43). However, the close association between the development of lung emphysema and pulmonary hypertension in our models is consistent with the pathophysiological mechanisms occurring during cigarette smoke exposure.…”

Estimation of absolute number of alveolar epithelial type 2 cells in mouse lungs: a comparison between stereology and flow cytometry

“…The stereological analysis of lung structure has gained much momentum over the past years (Weibel, ), where stereology is increasingly appreciated as a means to study pathological disturbances to lung structure that accompany disease (Mühlfeld & Ochs, ; Ochs & Mühlfeld, ; Mühlfeld et al ., ; Surate Solaligue et al ., ; Weibel, ). Similarly, stereology is appreciated as a means to quantify the parenchymal (Hyde et al ., ; Ochs et al ., , Knust et al ., ; Wulfsohn et al ., ; Herring et al ., ; Pozarska et al ., ; Hoang et al ., ) and vascular (Knust et al ., ; Willführ et al ., ; Mühlfeld et al ., ) structure of healthy immature, as well as adult lungs.…”

Influence of prenatal hypoxia and postnatal hyperoxia on morphologic lung maturation in mice

“…Characterizing the capillary network with accuracy, bias and precision without systematic error using stereological methods requires that the profiles of capillaries are clearly recognizable. Therefore, perfusion fixation would be the method of choice [84,85]. Regrettably all lungs in the present study were fixed by instillation.…”