Statistical analysis of lung nodule volume measurements with CT in a large-scale phantom study

Purpose: To determine inter-related factors that contribute substantially to measurement error of pulmonary nodule measurements with CT by assessing a large-scale dataset of phantom scans and to quantitatively validate the repeatability and reproducibility of a subset containing nodules and CT acquisitions consistent with the Quantitative Imaging Biomarker Alliance (QIBA) metrology recommendations. Methods: The dataset has about 40 000 volume measurements of 48 nodules (5-20 mm, four shapes, three radiodensities) estimated by a matched-filter estimator from CT images involving 72 imaging protocols. Technical assessment was performed under a framework suggested by QIBA, which aimed to minimize the inconsistency of terminologies and techniques used in the literature. Accuracy and precision of lung nodule volume measurements were examined by analyzing the linearity, bias, variance, root mean square error (RMSE), repeatability, reproducibility, and significant and substantial factors that contribute to the measurement error. Statistical methodologies including linear regression, analysis of variance, and restricted maximum likelihood were applied to estimate the aforementioned metrics. The analysis was performed on both the whole dataset and a subset meeting the criteria proposed in the QIBA Profile document. Results: Strong linearity was observed for all data. Size, slice thickness x collimation, and randomness in attachment to vessels or chest wall were the main sources of measurement error. Grouping the data by nodule size and slice thickness x collimation, the standard deviation (3.9%-28%), and RMSE (4.4%-68%) tended to increase with smaller nodule size and larger slice thickness. For 5, 8, 10, and 20 mm nodules with reconstruction slice thickness <= 0.8, 3, 3, and 5 mm, respectively, the measurements were almost unbiased (-3.0% to 3.0%). Repeatability coefficients (RCs) were from 6.2% to 40%. Pitch of 0.9, detail kernel, and smaller slice thicknesses yielded better (smaller) RCs than those from pitch of 1.2, medium kernel, and larger slice thicknesses. Exposure showed no impact on RC. The overall reproducibility coefficient (RDC) was 45%, and reduced to about 20%-30% when the slice thickness and collimation were fixed. For nodules and CT imaging complying with the QIBA Profile (QIBA Profile subset), the measurements were highly repeatable and reproducible in spite of variations in nodule characteristics and imaging protocols. The overall measurement error was small and mostly due to the randomness in attachment. The bias, standard deviation, and RMSE grouped by nodule size and slice thickness x collimation in the QIBA Profile subset were within +/-3%, 4%, and 5%, respectively. RCs are within 11% and the overall RDC is equal to 11%. Conclusions: The authors have performed a comprehensive technical assessment of lung nodule volumetry with a matched-filter estimator from CT scans of synthetic nodules and identified the main sources of measurement error among various nodule characteristics and imaging parameters. The results confirm that the QIBA Profile set is highly repeatable and reproducible. These phantom study results can serve as a bound on the clinical performance achievable with volumetric CT measurements of pulmonary nodules.