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

Rationale and Objectives 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. Materials and Methods 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 (PRM fSAD ), and emphysema (PRM EMPH ). Results Subjects with low baseline PRM fSAD and PRM EMPH predominantly had an increase in PRM fSAD on follow-up; those with higher baseline PRM fSAD and PRM EMPH mostly had increases in PRM EMPH . For GOLD 0 participants ( n  = 419), mean 5-year increases in PRM fSAD and PRM EMPH 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 PRM fSAD , 52.5% to PRM EMPH , and 17.5% to both); 153 GOLD 1–4 subjects (50.0%) experienced progression (17.6% to PRM fSAD , 48.4% to PRM EMPH , and 34.0% to both). In a multivariable model, both baseline PRM fSAD and PRM EMPH were associated with development of PRM EMPH on follow-up, although this relationship was diminished at higher levels of baseline PRM EMPH . Conclusion A voxel-wise longitudinal PRM analytic approach can identify patterns of disease progression in smokers with and without chronic obstructive pulmonary disease.