Automated mean linear intercept measurement: quantifying bias and parameter sensitivity in lung morphometry.

Objective.The mean linear intercept (MLI) is often used in lung morphometry; however, its assessment is labor-intensive, time-consuming, and prone to systematic biases when using the conventional indirect method. This study examines the inherent systematic biases in the indirect method, and explores the differences between the two methods, including how methodological parameters, such as the number of accepted field-of-view (FOV) images and guideline length, affect the measurement.Approach.We developed an automated MLI measurement system that uses a multiresolution semantic segmentation model. The system enables both indirect and direct MLI methods and allows for controlled variation of measurement parameters. The number of accepted FOVs was varied from 10 to 1000, and the guideline length from 39 to 702 pixels (19.4-349.5µm).Main results.The indirect method consistently overestimated MLI due to Septa Bias and Partial Chord Bias. The standard error of MLI decreases with more accepted FOV images, and the direct method consistently yielded a lower standard error than the indirect method. Short guideline lengths (<135.9µm) have a large impact on the indirect method, whereas the direct method is relatively insensitive to this parameter.Significance.The automated MLI measurement system improves the efficiency over human raters and enables higher precision by leveraging the advantages of the direct method (e.g. lower standard error, low sensitivity to guideline length) and the analysis of a larger number of FOV images. Moreover, the segmentation model used in the system is demonstrated to be accurate, which can facilitate the development of advanced morphometry techniques.