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

Abstract

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.

Keywords: Linear airspace dimension; Low dose chest CT; Lung cancer; National Lung Screening Trial; Ventilation heterogeneity.

Figure 1.

Representative axial CT images of a nodule in the right upper lobe at T1 (right), compared to the same axial level image 1 year prior at T0 (left), in which no nodule is seen, but the region of interest in which the nodule would form is highlighted (solid circle).

Figure 2.

Illustration of CT regions of interest (ROI) analyzed. At Time 1 (T1, right), we identified the nodule (T1 Nodule ROI, solid circle). We then coregistered the scan from baseline (1 year prior, T0, left) and identified the ROI where the T1 nodule would subsequently form (Target ROI, hashed circle). We analyzed the attenuation within this region and used the data to calculate the standard deviation of the linear airspace dimension as a measure of ventilation heterogeneity, as explained in the text. Next, we identified and analyzed a similar sized region at the same horizontal level on the axial view in the contralateral lung at T0 to serve as the T0 Contralateral Control ROI (wavy circle). We also analyzed two other control ROIs at T0 (stippled), one being the ipsilateral slice of lung in which the Target ROI was contained (T0-Ipsilateral Slice Control ROI), and the other being the slice on the contralateral side (T0-Contralateral Slice Control ROI).

Figure 3.

p Values for key comparisons between differences in ventilation heterogeneity of different regions (left) and percent emphysema of different regions (right) on the baseline T0 CT scan. See text for details.