Assessment of air space size characteristics by intercept (chord) measurement: an accurate and efficient stereological approach.
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.
Knudsen
Lars
L
Institute of Anatomy, Univ. of Bern, Baltzerstr. 2, CH-3000 Bern, Switzerland.
Weibel
Ewald R
ER
Gundersen
Hans Jørgen G
HJ
Weinstein
Felix V
FV
Ochs
Matthias
M
D000465:Algorithms; D000818:Animals; D004646:Emphysema / Q000235:genetics / Q000503:physiopathology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D066298:In Vitro Techniques; D016014:Linear Models; D008168:Lung / Q000033:anatomy & histology* / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011817:Rabbits; D011994:Recombinant Proteins / Q000627:therapeutic use; D015656:Respiratory Mechanics / Q000502:physiology; D012143:Respiratory Physiological Phenomena; D012137:Respiratory System / Q000033:anatomy & histology*; D013373:Substance P / Q000627:therapeutic use; D014109:Total Lung Capacity
D011994:Recombinant Proteins; D013373:Substance P