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Robust, Standardized Quantification of Pulmonary Emphysema in Low Dose CT Exams

Posted Oct 31, 2011 Updated Apr 10, 2023
By Mario Ceresa MSc , Gorka Bastarrika MD PhD , Juan P. de Torres MD PhD , Luis M. Montuenga PhD , Javier J. Zulueta MD , Carlos Ortiz-de-Solorzano PhD , Arrate Muñoz-Barrutia PhD
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Rationale and Objectives

The aim of this study was to present and evaluate a fully automated system for emphysema quantification on low-dose computed tomographic images. The platform standardizes emphysema measurements against changes in the reconstruction algorithm and slice thickness.

Materials and Methods

Emphysema was quantified in 149 patients using a fully automatic, in-house developed software (the Robust Automatic On-Line Pulmonary Helper). The accuracy of the system was evaluated against commercial software, and its reproducibility was assessed using pairs of volume-corrected images taken 1 year apart. Furthermore, to standardize quantifications, the effect of changing the reconstruction parameters was modeled using a nonlinear fit, and the inverse of the model function was then applied to the data. The association between quantifications and pulmonary function testing was also evaluated. The accuracy of the in-house software compared to that of commercial software was measured using Spearman’s rank correlation coefficient, the mean difference, and the intrasubject variability. Agreement between the methods was studied using Bland-Altman plots. To assess the reproducibility of the method, intraclass correlation coefficients and Bland-Altman plots were used. The statistical significance of the differences between the standardized data and the reference data (soft-tissue reconstruction algorithm B40f; slice thickness, 1 mm) was assessed using a paired two-sample t test.

Results

The accuracy of the method, measured as intrasubject variability, was 3.86 mL for pulmonary volume, 0.01% for emphysema index, and 0.39 Hounsfield units for mean lung density. Reproducibility, assessed using the intraclass correlation coefficient, was >0.95 for all measurements. The standardization method applied to compensate for variations in the reconstruction algorithm and slice thickness increased the intraclass correlation coefficients from 0.87 to 0.97 and from 0.99 to 1.00, respectively. The correlation of the standardized measurements with pulmonary function testing parameters was similar to that of the reference (for the emphysema index and the obstructive subgroup: forced expiratory volume in 1 second, −0.647% vs −0.615%; forced expiratory volume in 1 second/forced vital capacity, −0.672% vs −0.654%; and diffusing capacity for carbon monoxide adjusted for hemoglobin concentration, −0.438% vs −0.523%).

Conclusions

The new emphysema quantification method presented in this report is accurate and reproducible and, thanks to its standardization method, robust to changes in the reconstruction parameters.

Chronic obstructive pulmonary disease (COPD) is a respiratory disease with significant extrapulmonary consequences. Its pulmonary component is characterized by airflow limitations, and it is not fully reversible. The airflow limitation is associated with an abnormal inflammatory response of the lung to noxious particles or gases . Traditionally, two phenotypes of COPD have been described: obstructive bronchitis and pulmonary emphysema. The former is defined as an inflammation-driven airway obstruction, while the latter is characterized by parenchymal destruction. Both forms of COPD result in significant systemic comorbidity and premature death. Because of current smoking trends and progressive aging of the world population, an increase in COPD prevalence and related mortality is expected in the coming decades . Furthermore, interest in early detection, follow-up, and distinction between those two phenotypes has been recently boosted by the discovery that patients with COPD with emphysema have increased risk for developing lung cancer compared to those affected by airway obstruction alone .

X-ray computed tomographic (CT) imaging is commonly used to detect and measure the extent of emphysema in the lungs . CT quantification of pulmonary emphysema has been shown to be reproducible, especially when the same acquisition protocol is used in all scans and proper correction methods are used to compensate for differences in air inspiration volumes .

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Materials and methods

Subjects

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CT Acquisition

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CT Image Analysis

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Lung Segmentation

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Trachea Detection

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Airway Extraction

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Assessment of the Accuracy and Reproducibility of CT Quantification

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Assessment of Sensitivity to Confounding Variables for CT Quantification

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Pulmonary Function Testing

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Correlation Between CT Parameters and Pulmonary Function Testing

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Statistical Analysis

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Results

Assessment of the Accuracy and Reproducibility of Quantification

Accuracy

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Figure 1, Differences of pulmonary volume and emphysema quantification of Robust Automatic On-Line Pulmonary Helper (RALPH) versus Lung Parenchyma Analysis (LUPA; Siemens Medical Systems, Forchheim, Germany). (a) Bland-Altman plot of total lung volume (bias = 136.8 mL, Kendall's τ = 0.237, standard error [SE] = 2.121). (b) Bland-Altman plot of mean lung density (MLD; bias = 17.7 Hounsfield units [HU], Kendall's τ = 0.572, SE = 0.0003). (c) Log-log Bland-Altman plot of emphysema index (EI; bias = −0.209, Kendall's τ = 0.144, SE = 0.006). Bias is shown as a solid line ; the limits of agreement are shown as dashed lines . A value above the upper limit or below the lower limit has 95% likelihood of representing a real difference between the quantifications obtained using the two methods.

Table 1

Comparison of VOL, MLD, and EI Measures for RALPH and LUPA

Variable Spearman’s Coefficient Mean Difference Intrasubject Variability VOL (mL) 0.999 136.82 3.86 MLD (HU) 0.994 17.69 0.39 EI (%) 0.997 −1.09 0.01

EI, emphysema index; HU, Hounsfield units; LUPA, Lung Parenchyma Analysis (Siemens Medical Systems, Forchheim, Germany); MLD, mean lung density; RALPH, Robust Automatic On-Line Pulmonary Helper; VOL, total lung volume.

The differences were not statistically significant except for MLD ( P < .01).

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Reproducibility

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Figure 2, Differences in emphysema quantification between baseline and 12-month follow-up scans. (a) Bland-Altman plot of emphysema index (EI) for SR1 (bias = −0.1, Kendall's τ = −0.105, standard error [SE] = 0.17). (b) Bland-Altman plot of EI for BR1 (bias = 0.6, Kendall's τ = −0.101, SE = 0.38). Bias is shown as a solid line ; the limits of agreement are shown as dashed lines . A value above the upper limit or below the lower limit of agreement has a 95% likelihood of representing a real difference between the quantification of the two exams.

Table 2

ICCs for the Reproducibility of Emphysema Quantification Between Baseline and 12-month Follow-up Scans

Reconstruction Algorithm VOL MLD EI SR 0.97 0.98 0.98 BR 0.96 0.95 0.97

BR, bone reconstruction algorithm; EI, emphysema index; ICC, intraclass correlation coefficient; MLD, mean lung density; SR, soft tissue reconstruction algorithm; VOL, total lung volume.

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Assessment of Sensitivity to Confounding Variables for CT Quantification of Emphysema

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Figure 3, Effect of changing the reconstruction parameters in the quantification of emphysema. (Top row) Three sample transverse computed tomographic slices showing areas of density < −960 Hounsfield units (HU) in yellow . (Bottom row) Front views of the corresponding three-dimensional reconstructions, displaying main airways and lungs in transparent blue and low-density volumes in yellow . The reconstructions were cut with an oblique plane to show the internal distribution of the low-density volumes. All three images correspond to the same acquisition, reconstructed using different parameters (kernel and slice thickness): (left) B40f and 1 mm (total lung volume [VOL], 13,786 mL; mean lung density [MLD], −885 HU; emphysema index [EI], 7.26%); (center) B60f and 1 mm (VOL, 13,778 mL; MLD, −882 HU; EI, 33.20%); (right) B40f and 3 mm (VOL, 1365 mL; MLD, −880 HU; EI, 21.74%).

Figure 4, Effect of confounding variables (reconstruction algorithm and slice thickness) on the quantification of pulmonary emphysema. Box plot (minimum, 25% quartile, median, 75% quartile, maximum) of emphysema index: (a) SR1 versus BR1 and (b) BR1 versus BR3.

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Reduction of the Effect of Changes in the Reconstruction Kernel

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Figure 5, Standardization of the emphysema index (EI) estimates using different reconstruction algorithms. (a) EI of SR1 versus EI of BR1. The model that captures the relationship is drawn solid . (b) Plot of the residuals of the fitted model. (c) EI of SR1 versus standardized EI of BR1. (d) Bland-Altman plot of data on (c) (bias = −0.5, Kendall's τ = −0.43, standard error = 0.46). Bias is shown as a solid line ; the limits of agreement are shown as dashed lines . A value above the upper limit or below the lower limit has a 95% likelihood represent a real difference in the quantification between the SR1 and the standardized BR1 estimates.

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Table 3

Correlations Between Emphysema Indicators Computed from CT Images Reconstructed with a Soft Tissue Reconstruction and Functional Respiratory Tests (n = 65)

Variable Entire Sample ( n = 65) Obstructive ( n = 22) Control ( n = 43) CC_P_ CC_P_ CC_P_ EI FEV 1 (%) −0.469 .00106 −0.615 .004 0.131 .496 FEV 1 /FVC (%) −0.658 <.0001 −0.654 .00217 −0.298 .115 DLCOadj (%) −0.288 .044 −0.523 .018 0.346 .065 MLD FEV 1 (%) 0.251 .081 0.467 .037 −0.182 .344 FEV 1 /FVC (%) 0.528 <.0001 0.630 .002 0.259 .174 DLCOadj (%) −0.023 .871 0.348 .131 −0.430 .019

CC, correlation coefficient; CT, computed tomographic; DLCOadj, diffusing capacity for carbon monoxide after adjusting for concentration of hemoglobin; EI, emphysema index; FEV 1 , forced expiratory volume in 1 second; FVC, forced vital capacity; MLD, mean lung density.

Table 4

Correlation Between Emphysema Indicators Computed from CT Images Reconstructed with a Bone Reconstruction Algorithm and Functional Respiratory Tests

Variable Entire Sample ( n = 65) Obstructive ( n = 22) Control ( n = 43) CC_P_ CC_P_ CC_P_ EI FEV 1 (%) −0.291 .041 −0.574 .008 0.122 .528 FEV 1 /FVC (%) −0.473 .00105 −0.446 .049 −0.288 .129 DLCOadj (%) −0.012 .934 −0.338 .144 0.393 .035 MLD FEV 1 (%) 0.194 .180 0.377 .100 −0.205 .287 FEV 1 /FVC (%) 0.476 .005 0.568 .009 0.237 .213 DLCOadj (%) −0.017 .904 0.364 .114 −0.425 .021

CC, correlation coefficient; CT, computed tomographic; DLCOadj, diffusing capacity for carbon monoxide after adjusting for concentration of hemoglobin; EI, emphysema index; FEV 1 , forced expiratory volume in 1 second; FVC, forced vital capacity; MLD, mean lung density.

Table 5

Correlation Between Emphysema Indicators Computed from CT Images Reconstructed with a Bone Reconstruction Algorithm After Standardization and Functional Respiratory Tests

Variable Entire Sample ( n = 65) Obstructive ( n = 22) Control ( n = 43) CC_P_ CC_P_ CC_P_ EI FEV 1 (%) −0.443 .001 −0.647 .002 0.116 .548 FEV 1 /FVC (%) −0.592 <.0001 −0.672 .001 −0.255 .182 DLCOadj (%) −0.250 .082 −0.438 .05 0.289 .127

CC, correlation coefficient; CT, computed tomographic; DLCOadj, diffusing capacity for carbon monoxide after adjusting for concentration of hemoglobin; EI, emphysema index; FEV 1 , forced expiratory volume in 1 second; FVC, forced vital capacity; MLD, mean lung density.

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Reduction of the Effect of a Change in Slice Thickness

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Figure 6, Standardization of the emphysema index (EI) estimates using different slice thickness. (a) EI quantification on BR1 versus BR3. The exponential and linear least squares models are drawn solid and dashed , respectively. (b) Residual plot for the exponential fit. (c) EI of BR1 versus standardized EI of BR3. (d) Bland-Altman plot of data on (c) (bias = 1.96, Kendall's τ = −0.08, standard error = 0.001). Bias is shown as a solid line ; the limits of agreement are shown as dashed lines . A value above the upper limit or below the lower limit has a 95% likelihood to represent a real difference in the EI quantification between the BR1 and the standardized BR3 estimates.

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Discussion

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Conclusions

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Acknowledgments

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Academic Radiology, Volume 18, Issue 11
Journals General Radiology
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