Parametric response mapping monitors temporal changes on lung CT scans in the subpopulations and intermediate outcome measures in COPD Study (SPIROMICS)

Abstract

Rationale and objectives: The longitudinal relationship between regional air trapping and emphysema remains unexplored. We have sought to demonstrate the utility of parametric response mapping (PRM), a computed tomography (CT)-based biomarker, for monitoring regional disease progression in chronic obstructive pulmonary disease (COPD) patients, linking expiratory- and inspiratory-based CT metrics over time.

Materials and methods: Inspiratory and expiratory lung CT scans were acquired from 89 COPD subjects with varying Global Initiative for Chronic Obstructive Lung Disease (GOLD) status at 30 days (n = 13) or 1 year (n = 76) from baseline as part of the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) clinical trial. PRMs of CT data were used to quantify the relative volumes of normal parenchyma (PRM(Normal)), emphysema (PRM(Emph)), and functional small airways disease (PRM(fSAD)). PRM measurement variability was assessed using the 30-day interval data. Changes in PRM metrics over a 1-year period were correlated to pulmonary function (forced expiratory volume at 1 second [FEV1]). A theoretical model that simulates PRM changes from COPD was compared to experimental findings.

Results: PRM metrics varied by ∼6.5% of total lung volume for PRM(Normal) and PRM(fSAD) and 1% for PRM(Emph) when testing 30-day repeatability. Over a 1-year interval, only PRM(Emph) in severe COPD subjects produced significant change (19%-21%). However, 11 of 76 subjects showed changes in PRM(fSAD) greater than variations observed from analysis of 30-day data. Mathematical model simulations agreed with experimental PRM results, suggesting fSAD is a transitional phase from normal parenchyma to emphysema.

Conclusions: PRM of lung CT scans in COPD patients provides an opportunity to more precisely characterize underlying disease phenotypes, with the potential to monitor disease status and therapy response.

Keywords: Chronic obstructive pulmonary disease; computed tomography; diagnostic imaging; disease progression; parametric response map; small airways disease; voxel-wise analysis.

Copyright © 2015 AUR. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1

Temporal changes in fSAD as determined by PRM. Representative coronal PRM slice (top) with corresponding Cartesian plot of voxels with paired HU values (bottom) at baseline and 1-year follow-up from cases with (A) increasing and (B) decreasing PRMfSAD. These cases are indicated by (A) * and (B) † in Figure 2. PRMfSAD values are provided in yellow text top-left of PRM image.

Figure 2

PRM as a predictive measure of advancing airflow obstruction. Bar plots of (A) PRMNormal, (B) PRMfSAD and (C) PRMEmph are presented for the one-year interval subject population stratified by increasing (ΔFEV1≥0) and decreasing (ΔFEV1<0) FEV1 and GOLD status. Data is presented as mean ± SEM.

Figure 3

Capture of COPD progression by PRM. Scatter plot of subject PRMfSAD and PRMEmph values over a one-year interval. Arrows indicate subjects with significant changes in PRMfSAD (yellow), PRMEmph (red) or both (orange). Black dots are the mean baseline and follow-up PRM values for subjects with changes in PRM smaller than predetermined thresholds from 30-day interval CT data. Cases with decreasing emphysema are represented as dots (N=5; Table 2). The gray region indicates simulation bounds generated from the compartment model with rate constants [kNormal→fSAD, kfSAD→Normal, kfSAD→Emph] equal to [1, 1, 1] and [1, 0.33, 0.33] for the lower and upper bound, respectively. Emphysema was assumed irreversible for all simulations (i.e. kEmph→fSAD=0) and all rate constants were normalized to kNormal→fSAD. *, † and ‡ indicate the three cases represented in Figures 1A, 1B and 4, respectively.

Figure 4

PRM illustration of small airway disease as a precursor of emphysema. Presented are representative PRM slices at baseline (A: PRMNormal=54, PRMfSAD=33 and PRMEmph=10) and follow-up (B: PRMNormal=53, PRMfSAD=29 and PRMEmph=14). The source of emphysema at follow-up is shown in (C) where follow-up PRMEmph voxels indicated in (D) are colored by their baseline PRM classification. This case is indicated by ‡ in Figure 2.