Ventilation Heterogeneity and Its Association with Nodule Formation Among Participants in the National Lung Screening Trial—A Preliminary Investigation

Rationale and Objectives We have developed a technique to measure ventilation heterogeneity (VH) on low dose chest CT scan that we hypothesize may be associated with the development of lung nodules, and perhaps cancer. If true, such an analysis may improve screening by identifying regional areas of higher risk. Materials and Methods Using the National Lung Screening Trial database, we identified a small subset of those participants who were labeled as having a positive screening test at 1 year (T1) but not at baseline (T0). We isolated the region in which the nodule would form on the T0 scan (“target region”) and measured VH as the standard deviation of the linear dimension of a virtual cubic airspace based on measurement of lung attenuation within the region. Results We analyzed 24 cases, 9 with lung cancer and 15 with a benign nodule. We found that the VH of the target region was nearly statistically greater than that of the corresponding contralateral control region (0.168 [0.110–0.226] vs. 0.112 [0.083–0.203], p = 0.051). The % emphysema within the target region was greater than that of the corresponding contralateral control region (1.339 [0.264–4.367] vs. 1.092 [0.375–4.748], p = 0.037). There was a significant correlation between the % emphysema and the VH of the target region (rho = +0.437, p = 0.026). Conclusion Our study provides the first data in support of increased local VH being associated with subsequent lung nodule formation. Further work is necessary to determine whether this technique can enhance screening for lung cancer by low dose chest CT scan.