Quantifying heterogeneity in emphysema from high-resolution computed tomography: a lung tissue research consortium study.

RATIONALE AND OBJECTIVES: To quantify spatial distribution of emphysema using high-resolution computed tomography (HRCT), we applied semiautomated analysis with internal attenuation calibration to measure regional air volume, tissue volume, and fractional tissue volume (FTV = tissue/[air + tissue] volume) in well-characterized patients studied by the Lung Tissue Research Consortium (LTRC). METHODS: HRCT was obtained at supine end-inspiration and end-expiration, and prone end-inspiration from 31 patients with mild, moderate, severe, or very severe emphysema (stages II-V, forced expiratory volume at 1 second >75%, 51%-75%, 21%-50% and ≤20% predicted, respectively). Control data were from 20 healthy non-smokers (stage I). Each lobe was analyzed separately. Heterogeneity of FTV was assessed from coefficients of variation (CV) within and among lobes, and the kurtosis and skewness of FTV histograms. RESULTS: In emphysema, lobar air volume increased up to 177% above normal except in the right middle lobe. Lobar tissue volume increased up to 107% in mild-moderate stages then normalized in advanced stages. Normally, FTV was up to 82% higher in lower than upper lobes. In mild-moderate emphysema, lobar FTV increased by up to 74% above normal at supine inspiration. In severe emphysema, FTV declined below normal in all lobes and positions in correlation with pulmonary function (P < .05). Markers of FTV heterogeneity increased steadily with disease stage in correlation with pulmonary function (P < .05); the pattern is distinct from that seen in interstitial lung disease (ILD). CONCLUSION: CT-derived biomarkers differentiate the spatial patterns of emphysema distribution and heterogeneity from that in ILD. Early emphysema is associated with elevated tissue volume and FTV, consistent with hyperemia, inflammation or atelectasis.

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

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.