Quantitative computed tomography determined regional lung mechanics in normal nonsmokers, normal smokers and metastatic sarcoma subjects

Abstract

Objectives: Extra-thoracic tumors send out pilot cells that attach to the pulmonary endothelium. We hypothesized that this could alter regional lung mechanics (tissue stiffening or accumulation of fluid and inflammatory cells) through interactions with host cells. We explored this with serial inspiratory computed tomography (CT) and image matching to assess regional changes in lung expansion.

Materials and methods: We retrospectively assessed 44 pairs of two serial CT scans on 21 sarcoma patients: 12 without lung metastases and 9 with lung metastases. For each subject, two or more serial inspiratory clinically-derived CT scans were retrospectively collected. Two research-derived control groups were included: 7 normal nonsmokers and 12 asymptomatic smokers with two inspiratory scans taken the same day or one year apart respectively. We performed image registration for local-to-local matching scans to baseline, and derived local expansion and density changes at an acinar scale. Welch two sample t test was used for comparison between groups. Statistical significance was determined with a p value < 0.05.

Results: Lung regions of metastatic sarcoma patients (but not the normal control group) demonstrated an increased proportion of normalized lung expansion between the first and second CT. These hyper-expanded regions were associated with, but not limited to, visible metastatic lung lesions. Compared with the normal control group, the percent of increased normalized hyper-expanded lung in sarcoma subjects was significantly increased (p < 0.05). There was also evidence of increased lung "tissue" volume (non-air components) in the hyper-expanded regions of the cancer subjects relative to non-hyper-expanded regions. "Tissue" volume increase was present in the hyper-expanded regions of metastatic and non-metastatic sarcoma subjects. This putatively could represent regional inflammation related to the presence of tumor pilot cell-host related interactions.

Conclusions: This new quantitative CT (QCT) method for linking serial acquired inspiratory CT images may provide a diagnostic and prognostic means to objectively characterize regional responses in the lung following oncological treatment and monitoring for lung metastases.

Fig 1. Schematic of flow chart to assess regional lung mechanics based on a pair of serial CT scans.

Fig 2

Schematic of (a) global and local lung volume changes and (b) formulation of normalized fractional volume change.

Fig 3. Regional hyper-expansion signals in serial CT pairs of two control subjects.

(a) Normal non-smoker (Group 1) and (b) Normal smoker (Group 2).

Fig 4. Regional hyper-expansion signals in serial CT pairs of a sarcoma patient (Group 3) with lung metastasis.

(a) Pre1 and Pre2 and (b) Pre2 to Met. Lung metastases were not found at two earlier time points Pre1 and Pre2. A large metastatic nodule was noted on the 3rd scan, Met, indicated by the blue arrow.

Fig 5. Regional hyper-expansion signals in serial CT pairs of a sarcoma patient (Group 3) with no lung metastasis and no therapy or resection.

(a) Time 0 to Time 1 and (b) Time 1 to Time 2. Lung metastases were not found at any of three time points, Time 0, Time 1 and Time 2.

Fig 6. Regional hyper-expansion signals in serial CT pairs of a sarcoma patient (Group 3) with no lung metastasis but with therapy and resection.

(a) Time 0 to Time 1 and (b) Time 1 to Time 2. Lung metastases were not found at any of the three time points, Time 0, Time 1 and Time 2.

Fig 7. Convergence of cost function during image registration of pre-metastatic and metastatic pairs of a sarcoma patient (Group 3) shown in Fig 4.

“Pre1 to Pre2” and “Pre2 to Met” denote for pre-metastatic pair and metastatic pair, respectively.