Normalized emphysema scores on low dose CT: Validation as an imaging biomarker for mortality

<div><p>The purpose of this study is to develop a computed tomography (CT) biomarker of emphysema that is robust across reconstruction settings, and evaluate its ability to predict mortality in patients at high risk for lung cancer. Data included baseline CT scans acquired between August 2002 and April 2004 from 1737 deceased subjects and 5740 surviving controls taken from the National Lung Screening Trial. Emphysema scores were computed in the original scans (origES) and after applying resampling, normalization and bullae analysis (normES). We compared the prognostic value of normES versus origES for lung cancer and all-cause mortality by computing the area under the receiver operator characteristic curve (AUC) and the net reclassification improvement (NRI) for follow-up times of 1–7 years. normES was a better predictor of mortality than origES. The 95% confidence intervals for the differences in AUC values indicated a significant difference for all-cause mortality for 2 through 6 years of follow-up, and for lung cancer mortality for 1 through 7 years of follow-up. 95% confidence intervals in NRI values showed a statistically significant improvement in classification for all-cause mortality for 2 through 7 years of follow-up, and for lung cancer mortality for 3 through 7 years of follow-up. Contrary to conventional emphysema score, our normalized emphysema score is a good predictor of all-cause and lung cancer mortality in settings where multiple CT scanners and protocols are used.</p></div

Kaplan-Meier survival estimates by emphysema categories for all-cause mortality when emphysema is quantified by computing origES (left) and normES (right).

<p>Blue, low emphysema category; green, medium emphysema category; orange, high emphysema category. Tick marks on the curves indicate censored data. Vertical dashed lines indicate time points at 730 days (2 years), 1460 days (4 years) and 2190 days (6 years). Number on top of the dashed vertical lines indicate the number of patients being followed up until the corresponding time point. Patients that are no longer followed up may be censored or deceased.</p

Discrimination of origES and normES, and net reclassification improvement for prediction of lung cancer mortality.

<p>Discrimination of origES and normES, and net reclassification improvement for prediction of lung cancer mortality.</p

Illustration of an alive subject that is categorized in the high emphysema group by origES (32.44%) and in the low emphysema group by normES (0.45%).

<p>The subject was followed up for 2595 days. The CT image was acquired using a Siemens Sensation 16 scanner and reconstructed with B70f kernel and 2mm slice thickness. (A) Shows the original CT section, (B) shows the original CT section with an emphysema overlay (origES), (C) shows the normalized CT section, and (D) shows the normalized CT section with a normalized emphysema overlay (normES).</p

Baseline characteristics by mortality status.

<p>Baseline characteristics by mortality status.</p

Illustration of a deceased subject that is categorized in the low emphysema group by origES (1.31%) and in the high emphysema group by normES (5.77%).

<p>The subject died after 1101 days. The CT image was acquired using a GE LightSpeed Pro 16 scanner and reconstructed with STANDARD kernel and 5mm slice thickness. (A) Shows the original CT section, (B) shows the original CT section with an emphysema overlay (origES), (C) shows the normalized CT section, and (D) shows the normalized CT section with a normalized emphysema overlay (normES).</p

Kaplan-Meier survival estimates by emphysema categories for lung cancer mortality when emphysema is quantified by computing origES (left) and normES (right).

<p>Blue, low emphysema category; green, medium emphysema category; orange, high emphysema category. Tick marks on the curves indicate censored data. Vertical dashed lines indicate time points at 730 days (2 years), 1460 days (4 years) and 2190 days (6 years). Number on top of the dashed vertical lines indicate the number of patients being followed up until the corresponding time point. Patients that are no longer followed up may be censored or deceased.</p

Selection of participants flow chart.

<p>Selection of participants flow chart.</p

Degree of structural CT changes (emphysema. airway wall thickening and gas trapping) for the total population and stratified by classification of airflow limitation.

<p>Univariate analysis with the group FEV₁/FVC >70% as reference.^# p<0.001. Log950% =  log-transformed percentage of voxels below HU -950. E/I-ratio%  =  expiratory mean lung density in HU divided by the inspiratory mean lung density in HU expressed as a percentage. Pi10 =  the square root of wall area for a theoretical airway with 10mm lumen perimeter.</p

Baseline demographics, clinical variables and pulmonary function for the total population and stratified by classification of airflow limitation.

<p>Univariate analysis with the group FEV₁/FVC >70% as reference.?p <0.05- >0.001^# p<0.001</p