Quantification of regional interstitial lung disease from CT-derived fractional tissue volume: a lung tissue research consortium study

Abstract

Rationale and objectives: Evaluation of chest computed tomography (CT) is usually qualitative or semiquantitative, resulting in subjective descriptions often by different observers over time and imprecise determinations of disease severity within distorted lobes. There is a need for standardized imaging biomarkers to quantify regional disease, maximize diagnostic yield, and facilitate multicenter comparisons. We applied lobe-based voxelwise image analysis to derive regional air (Vair) and tissue (Vtissue) volumes and fractional tissue volume (FTV = tissue/[tissue+air] volume) as internally standardized parameter for assessing interstitial lung disease (ILD).

Materials and methods: High-resolution CT was obtained at supine and prone end-inspiration and supine end-expiration in 29 patients with ILD and 20 normal subjects. Lobar Vair, Vtissue, and FTV were expressed along standard coordinate axes.

Results: In normal subjects from end-inspiration to end-expiration, total Vair declined ~43%, FTV increased ~80%, but Vtissue remained unchanged. With increasing ILD, Vair declined and Vtissue rose in all lobes; FTV increased with a peripheral-to-central progression inversely correlated to spirometry and lung diffusing capacity (r(2) = 0.57-0.75, prone end-inspiration). Inter- and intralobar coefficients of variation of FTV increased 84-148% in mild-to-moderate ILD, indicating greater spatial heterogeneity, then normalized in severe ILD. Analysis of discontinuous images incurs <3% error compared to consecutive images.

Conclusions: These regional attenuation-based biomarkers could quantify heterogeneous parenchymal disease in distorted lobes, detect mild ILD involvement in all lobes and describe the pattern of disease progression. The next step would be to study a larger series, examine reproducibility and follow longitudinal changes in correlation with clinical and functional indices.

Figure 1

Representative axial HRCT images (top panels), color maps of FTV (middle panels), and the three-dimensional surface color maps of FTV (bottom panels in two orientations) from one normal subject and one subject each with mild, moderate, severe and more severe ILD (groups I through V respectively).

Figure 2

Lobar air and tissue volumes and FTV are shown at prone end-inspiration, supine end-inspiration and supine end-expiration for each ILD group: normal, mild, moderate, severe and more severe (groups I through V, respectively). Mean ± SD. P<0.05 * vs. I (normal); § vs. II (mild); † vs. III (moderate); a vs. RML; b vs. RLL; c vs. LUL; and d vs. LLL, by repeated measures ANOVA.

Figure 3

A) Total air volume, total tissue volume, and average whole lung FTV are shown with respect to ILD severity: normal, mild, moderate, severe and more severe (groups I through V, respectively). Dashed lines denote upper and lower 95% confidence intervals (omitted for Group V due to the small number of subjects). * p<0.05 vs. I (normal); § vs. II (mild), † vs. III (moderate) by repeated measures ANOVA. B) The same data are shown with respect to posture and respiratory phase in each group. Air volume was significantly lower and FTV higher at supine-expiration than prone-inspiration or supine-inspiration (mean ± SD, p<0.0001 by repeated measures ANOVA). Total tissue volume did not change significantly with posture or respiratory phase.

Figure 3

A) Total air volume, total tissue volume, and average whole lung FTV are shown with respect to ILD severity: normal, mild, moderate, severe and more severe (groups I through V, respectively). Dashed lines denote upper and lower 95% confidence intervals (omitted for Group V due to the small number of subjects). * p<0.05 vs. I (normal); § vs. II (mild), † vs. III (moderate) by repeated measures ANOVA. B) The same data are shown with respect to posture and respiratory phase in each group. Air volume was significantly lower and FTV higher at supine-expiration than prone-inspiration or supine-inspiration (mean ± SD, p<0.0001 by repeated measures ANOVA). Total tissue volume did not change significantly with posture or respiratory phase.

Figure 4

Intra-lobar distribution of FTV at prone end-inspiration is shown with respect to the position (% of the total span) along a given axis in each lobe. Mean ± SD. * p<0.05 vs. I (normal); § vs. II (mild), † vs. III (moderate); ‡ vs. IV (severe) by repeated measures ANOVA.

Figure 5

Mean lobar FTV correlated inversely with FEV₁, FVC and DL_CO (% predicted) at prone end-inspiration, supine end-inspiration, and supine end-expiration (shown for the right lower lobe only, all p<0.001).

Figure 6

Coefficients of variation (CV’s) of FTV among lobes (left panel) and within lobes (right panel) at prone end-inspiration are shown with respect to ILD severity groups. Mean ± SD. * p<0.05 vs. I (normal); § p<0.05 and # p=0.06 vs. II (mild) by factorial ANOVA.