Assessment of air space size characteristics by intercept (chord) measurement: an accurate and efficient stereological approach

Knudsen L, Weibel ER, Gundersen HJ, Weinstein FV, Ochs M. Assessment of air space size characteristics by intercept (chord) measurement: an accurate and efficient stereological approach. J Appl Physiol 108: 412-421, 2010. First published December 3, 2009; doi:10.1152/japplphysiol.01100.2009.-The mean linear intercept (chord) length (L-m) is a useful parameter of peripheral lung structure as it describes the mean free distance in the air spaces. It is often misinterpreted as a measure of alveolar size, and its estimation is fraught with a number of pitfalls. We present two methods for the accurate estimation of L-m: 1) the indirect method, which derives L-m from the volume-to-surface ratio of air spaces estimated by point counting methods, and 2) the direct method, which uses a set of random intercepts and calculates L-m from their frequency distribution, for which we introduce a new and accurate method. Both methods are efficient and, with proper precautions, unbiased. The meaning of L-m is assessed in two different examples. In a physiological study, the effect of different inflation levels is studied, showing that L-m critically depends on lung inflation. In an experimental study on emphysema-like changes in a genetic mouse model, the effect of heterogeneity of air space size is assessed; these results are obtained partly because of differences in lung volume due to altered recoil in the emphysematous lungs. In conclusion, although L-m is not a robust parameter of internal lung structure because it crucially depends on lung volume, it is still a valid measure for which accurate and efficient methods are available that yield additional parameters such as size distribution or alveolar surface area.