Figures & data
Figure 1. CONSORT Flow diagram. Of the 266 participants enrolled in the TINCan study, 33 were enrolled in a sub-study, 61 either canceled or did not complete all required tests during visit 1, and five had CT or MRI artifacts which precluded analysis. Of the 167 participants who completed Visit 1, five were not yet within their 10-year follow-up timeframe. At follow-up, there were 52 deceased participants, of whom 14 were ex-smokers and 38 were ex-smokers with COPD.
Figure 2. Participant enrollment and follow-up timeframe. Arrows showing the timeline of participant enrollment and follow-up period for mortality data collection within 10-years from the initial visit in all ex-smoker participants. Of the 162 ex-smokers analyzed, the first participant completed the baseline visit on December 1st, 2009 and the last participant completed their baseline visit on December 12th, 2012.
Table 1. Participant demographics, pulmonary function and imaging measurements in survivors and deceased ex-smokers.
Figure 3. Chest CT for representative surviving and deceased ex-smokers with and without COPD. Coronal center-slice of chest CT and the corresponding qualitative CT texture heterogeneity. Top panel: A 63 yo male ex-smoker with COPD: FEV1=72% pred, FEV1/FVC = 50, BMI =27 kg/m2, DLCO=79%pred, ADC = 0.38 cm2/s, VDP = 10%, RA950=10.8%, GLCM-Imc2=.77, Wavelet-HH-GLDM-DV=.812; And a 66 yo female ex-smoker: FEV1=80%pred, FEV1/FVC = 76, BMI =36 kg/m2, DLCO=80%pred, ADC = 0.24 cm2/s, VDP = 5.4%, RA950=2.3%, GLCM-Imc2=.76, Wavelet-HH-GLDM-DV=.766; Bottom panel: A 78 yo male ex-smoker with COPD that died: FEV1=38%pred, FEV1/FVC = 39, BMI =20 kg/m2, DLCO=30%pred, ADC = 0.55 cm2/s, VDP = 28%, RA950=24.9%, GLCM-Imc2=.84, Wavelet-HH-GLDM-DV = 1.14; And a 64 yo female ex-smoker that died: FEV1=111%pred, FEV1/FVC = 82, BMI = 36 kg/m2, DLCO=68%pred, ADC = 0.26 cm2/s, VDP = 4.5%, RA950=1.2%, GLCM-Imc2=.82, Wavelet-HH-GLDM-DV = 1.02.
Figure 4. Hyperpolarized gas MRI for representative surviving and deceased ex-smokers with and without COPD. Coronal center-slice of MRI ADC and ventilation with corresponding qualitative and quantitative MRI texture heterogeneity. Top panel: A 63 yo male ex-smoker with COPD: FEV1=72%pred, FEV1/FVC = 50, BMI = 27 kg/m2, DLCO=79%pred, ADC = 0.38 cm2/s, VDP = 10%, RA950=10.8%, Shape-SVR=.43, Wavelet-LL-Skewness = 0.58; And a 66 yo female ex-smoker: FEV1=80%pred, FEV1/FVC = 76, BMI = 36 kg/m2, DLCO=80%pred, ADC = 0.24 cm2/s, VDP = 5.4%, RA950=2.3%, Shape-SVR=.45, Wavelet-LL-Skewness=.81; Bottom panel: A 78 yo male ex-smoker with COPD that died: FEV1=38%pred, FEV1/FVC = 39, BMI = 20 kg/m2, DLCO=30%pred, ADC = 0.55 cm2/s, VDP = 28%, RA950=24.9%, Shape-SVR=.62, Wavelet-LL-Skewness = 2.1; And a 64 yo female ex-smoker that died: FEV1=111%pred, FEV1/FVC = 82, BMI = 36 kg/m2, DLCO=68%pred, ADC = 0.26 cm2/s, VDP = 4.5%, RA950=1.2%, Shape-SVR=.48, Wavelet-LL-Skewness = 1.25.
Table 2. MRI and CT texture features in survivors and deceased ex-smokers.
Table 3. Machine-learning performance at predicting all-cause mortality after 10-years.
Figure 5. Receiver-operator characteristic curves of texture features and clinical variables. Top Panel: Logistic regression analysis of individual clinical variables at predicting 10-year all-cause mortality in ex-smoker participants. DLCO had the best AUC=.736. Middle Panel: Logistic regression analysis of standard imaging measurements at predicting 10-year all-cause mortality in ex-smoker participants. 3He ADC had the best AUC=.738. Bottom Panel: Logistic regression analysis of imaging texture features at predicting 10-year all-cause mortality in ex-smoker participants. CT Wavelet-LL-GLCM-Imc1 had best AUC=.787.
Figure 6. Logistic regression models for associations between all-cause mortality and clinical, imaging and textural measurements. All-cause mortality assessment was conducted in 162 ex-smokers, of whom 52 deceased across the longitudinal study duration (10-years). Bolded values indicate categories where 95% CI did not include 1.0 (P < 0.05). *All odds ratios were adjusted for age, BMI, sex, and pack-years. GLCM = gray level co-occurrence matrix; 6MWD = six minute walk distance; ADC = apparent diffusion coefficients; DLCO =diffusing capacity of the lung for carbon monoxide; GLDM = gray level dependence matrix; HH = high-high pass filter; LL = low-low pass filter; SVR = Surface volume ratio; DV = dependence variance; RV = run variance; FEV1=forced expiratory volume in 1 second; FVC = forced vital capacity; SGRQ = St. George’s respiratory questionnaire; LAC = lowest attenuating cluster; RA950=relative area of lung less than -950 Hounsfield Units; All texture feature abbreviations and descriptions can be found in supplementary Table S2.
Figure 7. Kaplan-Meier survival curves of 10-year all-cause mortality in ex-smokers. Orange: All-cause mortality analysis in ex-smokers with normal vs abnormal MRI ADC (ADC < 0.25cm2/s). Log-rank (Mantel-Cox) test χ2=6.38; P=.01. Black: All-cause mortality analysis in ex-smokers with normal vs abnormal DLCO (DLCO<75%pred). Log-rank (Mantel-Cox) test χ2=11.95; P <.001. Green: All-cause mortality analysis in ex-smokers with tertiles of the MRI Wavelet-LL-FO-Skewness texture feature. Log-rank (Mantel-Cox) test across all tertiles: χ2=22.43; P <.001. Log-rank test between tertile-Low and tertile-Medium: χ2=7.86; P=.005. Log-rank test between tertile-Medium and tertile-High: χ2=4.99; P=.02. Log-rank test between tertile-Low and tertile-High: χ2=21.81; P <.001.
Table 4. Summary of top performing measurements for the key statistical analyses.
Supplemental Material
Download PDF (257.6 KB)Data availability statement
Data generated or analyzed during the study are available from the corresponding author upon request.