Quantitative CT of Normal Lung Parenchyma and Small Airways Disease Topologies are Associated With COPD Severity and Progression

OBJECTIVES: Small airways disease (SAD) is a major cause of airflow obstruction in COPD patients, and has been identified as a precursor to emphysema. Although the amount of SAD in the lungs can be quantified using our Parametric Response Mapping (PRM) approach, the full breadth of this readout as a measure of emphysema and COPD progression has yet to be explored. We evaluated topological features of PRM-derived normal parenchyma and SAD as surrogates of emphysema and predictors of spirometric decline. MATERIALS AND METHODS: PRM metrics of normal lung (PRM(Norm)) and functional SAD (PRM(fSAD)) were generated from CT scans collected as part of the COPDGene study (n=8956). Volume density (V) and Euler-Poincaré Characteristic (χ) image maps, measures of the extent and coalescence of pocket formations (i.e., topologies), respectively, were determined for both PRM(Norm) and PRM(fSAD). Association with COPD severity, emphysema, and spirometric measures were assessed via multivariable regression models. Readouts were evaluated as inputs for predicting FEV(1) decline using a machine learning model. RESULTS: Multivariable cross-sectional analysis of COPD subjects showed that V and χ measures for PRM(fSAD) and PRM(Norm) were independently associated with the amount of emphysema. Readouts χ(fSAD) (β of 0.106, p<0.001) and V(fSAD) (β of 0.065, p=0.004) were also independently associated with FEV(1)% predicted. The machine learning model using PRM topologies as inputs predicted FEV(1) decline over five years with an AUC of 0.69. CONCLUSIONS: We demonstrated that V and χ of fSAD and Norm have independent value when associated with lung function and emphysema. In addition, we demonstrated that these readouts are predictive of spirometric decline when used as inputs in a ML model. Our topological PRM approach using PRM(fSAD) and PRM(Norm) may show promise as an early indicator of emphysema onset and COPD progression.