Repeatability and Sample Size Assessment Associated with Computed Tomography-Based Lung Density Metrics

Rationale and Objectives: Density-based metrics assess severity of lung disease but vary with lung inflation and method of scanning. The aim of this study was to evaluate the repeatability of single center, computed tomography (CT)-based density metrics of the lung in a normal population and assess study sample sizes needed to detect meaningful changes in lung density metrics when scan parameters and volumes are tightly controlled. Materials and Methods: Thirty-seven participants (normal smokers and non-smokers) gave consent to have randomly assigned repeated, breath-held scans at either inspiration (90% vital capacity: total lung capacity [TLC]) or expiration (20% vital capacity: functional residual capacity [FRC]). Repeated scans were analyzed for: mean lung density (MLD), 15th percentile point of the density histogram (P-15), low attenuation areas (LAA) and alpha (fractal measure of hole size distribution). Using inter-participant differences and previously reported bias, sample size was estimated from change in density metrics obtained from published literature (i.e. meaningful change). Results: Inter-scan difference measurements were small for density metrics (ICC > 0.80) and average intra-class correlation coefficients (ICC) for whole lung alpha-910 and alpha-950 were 0.57 and 0.64, respectively. Power analyses demonstrated that, under the control conditions with minimal extrinsic variation, population sizes needed to detect meaningful changes in density measures for TLC or FRC repeated scans ranged from a few (20-40) to a few hundred participants, respectively. Conclusion: A meaningful sample size was predicted from this study using volume-controlled normal participants in a controlled imaging environment. Under proper breath-hold conditions, high repeatability was obtained in cohorts of normal smokers and non-smokers.