Voxel-Wise Longitudinal Parametric Response Mapping Analysis of Chest Computed Tomography in Smokers

Abstract

Chronic obstructive pulmonary disease is a heterogeneous disease characterized by small airway abnormality and emphysema. We hypothesized that a voxel-wise computed tomography analytic approach would identify patterns of disease progression in smokers. We analyzed 725 smokers in spirometric GOLD stages 0-4 with two chest CTs 5 years apart. Baseline inspiration, follow-up inspiration and follow-up expiration images were spatially registered to baseline expiration so that each voxel had correspondences across all time points and respiratory phases. Voxel-wise Parametric Response Mapping (PRM) was then generated for the baseline and follow-up scans. PRM classifies lung as normal, functional small airway disease (PRMfSAD), and emphysema (PRMEMPH). Subjects with low baseline PRMfSAD and PRMEMPH predominantly had an increase in PRMfSAD on follow-up; those with higher baseline PRMfSAD and PRMEMPH mostly had increases in PRMEMPH. For GOLD 0 participants (n = 419), mean 5-year increases in PRMfSAD and PRMEMPH were 0.3% for both; for GOLD 1-4 participants (n = 306), they were 0.6% and 1.6%, respectively. Eighty GOLD 0 subjects (19.1%) had overall radiologic progression (30.0% to PRMfSAD, 52.5% to PRMEMPH, and 17.5% to both); 153 GOLD 1-4 subjects (50.0%) experienced progression (17.6% to PRMfSAD, 48.4% to PRMEMPH, and 34.0% to both). In a multivariable model, both baseline PRMfSAD and PRMEMPH were associated with development of PRMEMPH on follow-up, although this relationship was diminished at higher levels of baseline PRMEMPH. A voxel-wise longitudinal PRM analytic approach can identify patterns of disease progression in smokers with and without chronic obstructive pulmonary disease.