Fleischner Society Visual Emphysema CT Patterns Help Predict Progression of Emphysema in Current and Former Smokers: Results from the COPDGene Study.

Background The correlation between visual emphysema patterns and subsequent progression of disease may provide a way to enrich a study population for treatment trials of emphysema. Purpose To evaluate the potential relationship between emphysema visual subtypes and progression of emphysema and gas trapping. Materials and Methods Current and former smokers with and without chronic obstructive pulmonary disease (COPD) enrolled in the prospective Genetic Epidemiology of COPD (COPDGene) study (ClinicalTrials.gov identifier: NCT02445183) between 2008 and 2011 had their Fleischner Society visual CT scores assessed at baseline, quantitative inspiratory, and expiratory CT and at 5 years. They also underwent pulmonary function testing at baseline CT and at 5 years. The dependent variables were inspiratory lung density at 15th percentile (adjusted for lung volume) as a measure of emphysema and percentage of lung volume with attenuation less than -856 HU at expiratory CT as a measure of air trapping. Statistical analysis used a linear mixed model, adjusted for age, height, sex, race, smoking status, and scanner make. Results A total of 4166 participants (mean age, 60 years ± 9 [standard deviation]; 2091 [50%] men) were evaluated. In participants with COPD (1655 participants, 40%), those with visual presence of mild, moderate, and confluent emphysema at baseline CT showed a mean decline in lung density of 4.6 g/L ± 1.1 (P < .001), 6.7 g/L ± 1.1 (P < .001), and 6.4 g/L ± 1.2 (P < .001), respectively, compared with 2.4 g/L ± 1.3 (P < .001) for those with trace emphysema. For participants without COPD, those with visual presence of mild and moderate emphysema at baseline CT showed a mean decline in lung density of 3.6 g/L ± 1.0 (P < .001) and 3.1 g/L ± 1.6 (P < .001), respectively, compared with 1.8 g/L ± 1.0 (P < .001) for those with trace emphysema. Conclusion The pattern of parenchymal emphysema at baseline CT was an independent predictor of subsequent progression of emphysema in participants who are current or former cigarette smokers with and without chronic obstructive pulmonary disease. © RSNA, 2020 Online supplemental material is available for this article.

Automated Assessment of COVID-19 Reporting and Data System and Chest CT Severity Scores in Patients Suspected of Having COVID-19 Using Artificial Intelligence.

Background The coronavirus disease 2019 (COVID-19) pandemic has spread across the globe with alarming speed, morbidity, and mortality. Immediate triage of patients with chest infections suspected to be caused by COVID-19 using chest CT may be of assistance when results from definitive viral testing are delayed. Purpose To develop and validate an artificial intelligence (AI) system to score the likelihood and extent of pulmonary COVID-19 on chest CT scans using the COVID-19 Reporting and Data System (CO-RADS) and CT severity scoring systems. Materials and Methods The CO-RADS AI system consists of three deep-learning algorithms that automatically segment the five pulmonary lobes, assign a CO-RADS score for the suspicion of COVID-19, and assign a CT severity score for the degree of parenchymal involvement per lobe. This study retrospectively included patients who underwent a nonenhanced chest CT examination because of clinical suspicion of COVID-19 at two medical centers. The system was trained, validated, and tested with data from one of the centers. Data from the second center served as an external test set. Diagnostic performance and agreement with scores assigned by eight independent observers were measured using receiver operating characteristic analysis, linearly weighted κ values, and classification accuracy. Results A total of 105 patients (mean age, 62 years ± 16 [standard deviation]; 61 men) and 262 patients (mean age, 64 years ± 16; 154 men) were evaluated in the internal and external test sets, respectively. The system discriminated between patients with COVID-19 and those without COVID-19, with areas under the receiver operating characteristic curve of 0.95 (95% CI: 0.91, 0.98) and 0.88 (95% CI: 0.84, 0.93), for the internal and external test sets, respectively. Agreement with the eight human observers was moderate to substantial, with mean linearly weighted κ values of 0.60 ± 0.01 for CO-RADS scores and 0.54 ± 0.01 for CT severity scores. Conclusion With high diagnostic performance, the CO-RADS AI system correctly identified patients with COVID-19 using chest CT scans and assigned standardized CO-RADS and CT severity scores that demonstrated good agreement with findings from eight independent observers and generalized well to external data. © RSNA, 2020 Supplemental material is available for this article.

Five-year Progression of Emphysema and Air Trapping at CT in Smokers with and Those without Chronic Obstructive Pulmonary Disease: Results from the COPDGene Study.

Background CT is used to quantify abnormal changes in the lung parenchyma of smokers that might overlap chronic obstructive pulmonary disease (COPD), but studies on the progression of expiratory air trapping in smokers are scarce. Purpose To evaluate the relationship between longitudinal changes in forced expiratory volume in 1 second (FEV1) and CT-quantified emphysema and air trapping in smokers. Materials and Methods Cigarette smokers with and those without COPD participating in the multicenter observational COPDGene study were evaluated. Subjects underwent inspiratory and expiratory chest CT and spirometry at baseline and 5-year follow-up. Emphysema was quantified by using adjusted lung density (ALD). Air trapping was quantified by using mean lung density at expiratory CT and CT-measured functional residual capacity-to-total lung volume ratio. Linear models were used to regress quantitative CT measurements taken 5 years apart, and models were fit with and without adding FEV1 as a predictor. Analyses were stratified by Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage (GOLD 0, no COPD; GOLD 1, mild COPD; GOLD 2, moderate COPD; GOLD 3, severe COPD; GOLD 4, very severe COPD). Subjects with preserved FEV1-to-forced vital capacity ratio and reduced FEV1 percentage predicted were categorized as having preserved ratio impaired spirometry (PRISm). Results A total of 4211 subjects (503 with PRISm; 2034 with GOLD 0, 388 with GOLD 1, 816 with GOLD 2, 381 with GOLD 3, 89 with GOLD 4) were evaluated. ALD decreased by 1.7 g/L (95% confidence interval [CI]: -2.5, -0.9) in subjects with GOLD 0 at baseline and by 5.3 g/L (95% CI: -6.2, -4.4) in those with GOLD 1-4 (P < .001 for both). When adjusted for changes in FEV1, corresponding numbers were -2.2 (95% CI: -3.0, -1.3) and -4.6 g/L (95% CI: -5.6, -3.4) (P < .001 for both). Progression in air trapping was identified only in GOLD stage 2-4. Approximately 33%-50% of changes in air trapping in GOLD stages 2-4 were accounted for by changes in FEV1. Conclusion CT measures of emphysema and air trapping increased over 5 years in smokers. Forced expiratory volume in one second accounted for less than 10% of emphysema progression and less than 50% of air trapping progression detected at CT. © RSNA, 2020 Online supplemental material is available for this article.

A New Oxygen Uptake Measurement Supporting Target Selection for Endobronchial Valve Treatment.

BACKGROUND: Adequate target lobe selection for endobronchial valve (EBV) treatment in patients with severe emphysema is essential for treatment success and can be based on emphysema destruction, lobar perfusion, lobar volume, and collateral ventilation. As some patients have >1 target lobe for EBV treatment, we were interested whether we could identify the least functional lobe. OBJECTIVES: The objective of this study was to investigate the relationship between endoscopic lobar measurement of oxygen uptake, lobar destruction, and vascular volume, and whether this could help in identifying the least functional lobe and thus optimal target for EBV treatment. METHOD: We prospectively included patients who were scheduled for EBV treatment in our hospital. A customized gas analysis setup was used to measure lobar O2 uptake after lobar balloon occlusion. Quantitative CT analysis was performed to assess the degree of emphysematous destruction and lobar arterial and venous volumes. RESULTS: Twenty-one (5 male/16 female) patients with emphysema (median age 63 years, FEV1 25% of predicted, residual volume 234% of predicted) were included, and 49 endoscopic lobar measurements were performed. A lower O2 uptake significantly correlated with a higher degree of emphysematous lobar destruction (Spearman's ρ: 0.39, p < 0.01), and lower arterial and venous vascular volumes of the lobes (-0.46 and -0.47, respectively; both p < 0.001). CONCLUSIONS: Endoscopic measurement of lobar O2 uptake is feasible in patients with emphysema. Measurement of lobar O2 uptake helped to identify the least functional lobe and can be used as additional tool for EBV target lobe selection.

Endobronchial Valves for Emphysema without Interlobar Collateral Ventilation.

BACKGROUND: Bronchoscopic lung-volume reduction with the use of one-way endobronchial valves is a potential treatment for patients with severe emphysema. To date, the benefits have been modest but have been hypothesized to be much larger in patients without interlobar collateral ventilation than in those with collateral ventilation. METHODS: We randomly assigned patients with severe emphysema and a confirmed absence of collateral ventilation to bronchoscopic endobronchial-valve treatment (EBV group) or to continued standard medical care (control group). Primary outcomes were changes from baseline to 6 months in forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and 6-minute walk distance. RESULTS: Eighty-four patients were recruited, of whom 16 were excluded because they had collateral ventilation (13 patients) or because lobar segments were inaccessible to the endobronchial valves (3 patients). The remaining 68 patients (mean [±SD] age, 59±9 years; 46 were women) were randomly assigned to the EBV group (34 patients) or the control group (34). At baseline, the FEV1 and FVC were 29±7% and 77±18% of the predicted values, respectively, and the 6-minute walk distance was 374±86 m. Intention-to-treat analyses showed significantly greater improvements in the EBV group than in the control group from baseline to 6 months: the increase in FEV1 was greater in the EBV group than in the control group by 140 ml (95% confidence interval [CI], 55 to 225), the increase in FVC was greater by 347 ml (95% CI, 107 to 588), and the increase in the 6-minute walk distance was greater by 74 m (95% CI, 47 to 100) (P<0.01 for all comparisons). By 6 months, 23 serious adverse events had been reported in the EBV group, as compared with 5 in the control group (P<0.001). One patient in the EBV group died. Serious treatment-related adverse events in this group included pneumothorax (18% of patients) and events requiring valve replacement (12%) or removal (15%). CONCLUSIONS: Endobronchial-valve treatment significantly improved pulmonary function and exercise capacity in patients with severe emphysema characterized by an absence of interlobar collateral ventilation. (Funded by the Netherlands Organization for Health Research and Development and the University Medical Center Groningen; Netherlands Trial Register number, NTR2876.).

Minimal important difference of target lobar volume reduction after endobronchial valve treatment for emphysema.

BACKGROUND AND OBJECTIVE: Target lobar volume reduction (TLVR) is an important efficacy outcome measure for bronchoscopic lung volume reduction (BLVR) treatment using one-way endobronchial valves (EBV) in patients with severe emphysema. The commonly used cut-off value for TLVR that expresses a perceivable clinical benefit is -350 mL. However, a scientifically determined minimal important difference (MID) for TLVR never has been published. The objective of the present study was to determine the MID for TLVR on HRCT in patients who were treated with EBV. METHODS: A total of 318 patients with severe emphysema from two BLVR trials were analysed. Anchor-based methods were used to define the TLVR MID at 6 months follow-up. Forced expiratory volume in 1 s (FEV1 ), residual volume (RV) and St. George's Respiratory Questionnaire (SGRQ) were used as anchors. RESULTS: The calculated TLVR MID with each anchor was: FEV1 -587 mL, RV -534 mL and SGRQ -560 mL. The combined MID (average of the three anchor-based MIDs) was -563 mL. CONCLUSION: Using the anchor-based method, we established a TLVR MID of -563 mL in patients with severe emphysema at 6 months follow-up after EBV treatment. This value can be useful for both interpreting the results from trials and clinical practice, as well as for designing future studies on lung volume reduction.

Chartis Measurement of Collateral Ventilation: Conscious Sedation versus General Anesthesia - A Retrospective Comparison.

BACKGROUND: Absence of interlobar collateral ventilation using the Chartis measurement is the key predictor for successful endobronchial valve treatment in severe emphysema. Chartis was originally validated in spontaneous breathing patients under conscious sedation (CS); however, this can be challenging due to cough, mucus secretion, mucosal swelling, and bronchoconstriction. Performing Chartis under general anesthesia (GA) avoids these problems and may result in an easier procedure with a higher success rate. However, using Chartis under GA with positive pressure ventilation has not been validated. OBJECTIVES: In this study we investigated the impact of anesthesia technique, CS versus GA, on the feasibility and outcomes of Chartis measurement. METHODS: We retrospectively analyzed all Chartis measurements performed at our hospital from October 2010 until December 2017. RESULTS: We analyzed 250 emphysema patients (median forced expiratory volume in 1 s 26%, range 12-52% predicted). In 121 patients (48%) the measurement was performed using CS, in 124 (50%) using GA, and in 5 (2%) both anesthesia techniques were used. In total, 746 Chartis readings were analyzed (432 CS, 277 GA, and 37 combination). Testing under CS took significantly longer than GA (median 19 min [range 5-65] vs. 11 min [3-35], p < 0.001) and required more measurements (3 [1-13] vs. 2 [1-6], p < 0.001). There was no significant difference in target lobe volume reduction after treatment (-1,123 mL [-3,604 to 332] in CS vs. -1,251 mL [-3,333 to -1] in GA, p = 0.35). CONCLUSIONS: In conclusion, Chartis measurement under CS took significantly longer and required more measurements than under GA, without a difference in treatment outcome. We recommend a prospective trial comparing both techniques within the same patients to validate this approach.

Computer-aided detection of pulmonary nodules: a comparative study using the public LIDC/IDRI database.

OBJECTIVES: To benchmark the performance of state-of-the-art computer-aided detection (CAD) of pulmonary nodules using the largest publicly available annotated CT database (LIDC/IDRI), and to show that CAD finds lesions not identified by the LIDC's four-fold double reading process. METHODS: The LIDC/IDRI database contains 888 thoracic CT scans with a section thickness of 2.5 mm or lower. We report performance of two commercial and one academic CAD system. The influence of presence of contrast, section thickness, and reconstruction kernel on CAD performance was assessed. Four radiologists independently analyzed the false positive CAD marks of the best CAD system. RESULTS: The updated commercial CAD system showed the best performance with a sensitivity of 82 % at an average of 3.1 false positive detections per scan. Forty-five false positive CAD marks were scored as nodules by all four radiologists in our study. CONCLUSIONS: On the largest publicly available reference database for lung nodule detection in chest CT, the updated commercial CAD system locates the vast majority of pulmonary nodules at a low false positive rate. Potential for CAD is substantiated by the fact that it identifies pulmonary nodules that were not marked during the extensive four-fold LIDC annotation process. KEY POINTS: • CAD systems should be validated on public, heterogeneous databases. • The LIDC/IDRI database is an excellent database for benchmarking nodule CAD. • CAD can identify the majority of pulmonary nodules at a low false positive rate. • CAD can identify nodules missed by an extensive two-stage annotation process.

Normalizing computed tomography data reconstructed with different filter kernels: effect on emphysema quantification.

OBJECTIVES: To propose and evaluate a method to reduce variability in emphysema quantification among different computed tomography (CT) reconstructions by normalizing CT data reconstructed with varying kernels. METHODS: We included 369 subjects from the COPDGene study. For each subject, spirometry and a chest CT reconstructed with two kernels were obtained using two different scanners. Normalization was performed by frequency band decomposition with hierarchical unsharp masking to standardize the energy in each band to a reference value. Emphysema scores (ES), the percentage of lung voxels below -950 HU, were computed before and after normalization. Bland-Altman analysis and correlation between ES and spirometry before and after normalization were compared. Two mixed cohorts, containing data from all scanners and kernels, were created to simulate heterogeneous acquisition parameters. RESULTS: The average difference in ES between kernels decreased for the scans obtained with both scanners after normalization (7.7 ± 2.7 to 0.3 ± 0.7; 7.2 ± 3.8 to -0.1 ± 0.5). Correlation coefficients between ES and FEV1, and FEV1/FVC increased significantly for the mixed cohorts. CONCLUSIONS: Normalization of chest CT data reduces variation in emphysema quantification due to reconstruction filters and improves correlation between ES and spirometry. KEY POINTS: • Emphysema quantification is sensitive to the reconstruction kernel used. • Normalization allows comparison of emphysema quantification from images reconstructed with varying kernels. • Normalization allows comparison of emphysema quantification obtained with scanners from different manufacturers. • Normalization improves correlation of emphysema quantification with spirometry. • Normalization can be used to compare data from different studies and centers.

Predicting Lung Volume Reduction after Endobronchial Valve Therapy Is Maximized Using a Combination of Diagnostic Tools.

BACKGROUND: Bronchoscopic lung volume reduction using one-way endobronchial valves (EBVs) has been proven to be effective in patients with severe emphysema. However, the selection of patients without collateral ventilation prior to treatment is critical for procedural success. Collateral ventilation can be assessed directly with the Chartis system or indirectly using computed tomography (CT) fissure analysis. OBJECTIVES: We retrospectively evaluated the diagnostic value of a combination of the quantitative CT interlobar fissure completeness score (FCS) and Chartis in predicting responders to EBV therapy. METHODS: CT data from four prospective studies were pooled and analyzed using semiautomated software to quantify the completeness of interlobar fissures. These FCSs were compared to a reference standard of achieving ≥350 ml of target lobe volume reduction after EBV treatment. Using a receiver operating characteristic curve, optimal thresholds predictive of complete fissures (responders) and incomplete fissures (non-responders) were determined. A subgroup of patients with partially complete fissures was identified, where software had lower accuracy. The complementary value of Chartis was investigated in this group. RESULTS: A fissure was defined as complete (FCS >95%), incomplete (FCS <80%), or partially complete (80% < FCS < 95%). The positive predictive value (PPV) of complete fissures is 88.1%, and the negative predictive value (NPV) is 92.9%, with an overall accuracy of 89.2%. Chartis was utilized in patients with partially complete fissures, with a PPV of 82.3%, an NPV of 84.6%, and an accuracy of 83.3%. CONCLUSION: Combining diagnostic tools could reduce the burden on patients and the healthcare system while providing clinicians with a better means for patient selection for EBV therapy.

Airway wall thickness associated with forced expiratory volume in 1 second decline and development of airflow limitation.

Airway wall thickness and emphysema contribute to airflow limitation. We examined their association with lung function decline and development of airflow limitation in 2021 male smokers with and without airflow limitation. Airway wall thickness and emphysema were quantified on chest computed tomography and expressed as the square root of wall area of a 10-mm lumen perimeter (Pi10) and the 15th percentile method (Perc15), respectively. Baseline and follow-up (median (interquartile range) 3 (2.9-3.1) years) spirometry was available. Pi10 and Perc15 correlated with baseline forced expiratory volume in 1 s (FEV1) (r= -0.49 and 0.11, respectively (p<0.001)). Multiple linear regression showed that Pi10 and Perc15 at baseline were associated with a lower FEV1 after follow-up (p<0.05). For each sd increase in Pi10 and decrease in Perc15 the FEV1 decreased by 20 mL and 30.2 mL, respectively. The odds ratio for developing airflow limitation after 3 years was 2.45 for a 1-mm higher Pi10 and 1.46 for a 10-HU lower Perc15 (p<0.001). A greater degree of airway wall thickness and emphysema was associated with a higher FEV1 decline and development of airflow limitation after 3 years of follow-up.

Pulmonary function and CT biomarkers as risk factors for cardiovascular events in male lung cancer screening participants: the NELSON study.

OBJECTIVE: The objective of this study was to investigate the association of spirometry and pulmonary CT biomarkers with cardiovascular events. METHODS: In this lung cancer screening trial 3,080 male participants without a prior cardiovascular event were analysed. Fatal and non-fatal cardiovascular events were included. Spirometry included forced expiratory volume measured in units of one-second percent predicted (FEV1%predicted) and FEV1 divided by forced vital capacity (FVC; FEV1/FVC). CT examinations were quantified for coronary artery calcium volume, pulmonary emphysema (perc15) and bronchial wall thickness (pi10). Data were analysed via a Cox proportional hazard analysis, net reclassification improvement (NRI) and C-indices. RESULTS: 184 participants experienced a cardiovascular event during a median follow-up of 2.9 years. Age, pack-years and smoking status adjusted hazard ratios were 0.992 (95% confidence interval (CI) 0.985-0.999) for FEV1%predicted, 1.000 (95%CI 0.986-1.015) for FEV1/FVC, 1.014 (95%CI 1.005-1.023) for perc15 per 10 HU, and 1.269 (95%CI 1.024-1.573) for pi10 per 1 mm. The incremental C-index (<0.015) and NRI (<2.8%) were minimal. Coronary artery calcium volume had a hazard ratio of 1.046 (95%CI 1.034-1.058) per 100 mm(3), an increase in C-index of 0.076 and an NRI of 16.9% (P < 0.0001). CONCLUSIONS: Pulmonary CT biomarkers and spirometry measurements were significantly associated with cardiovascular events, but did not contain clinically relevant independent prognostic information for cardiovascular events. KEY POINTS: • Pulmonary CT biomarkers and spirometry are associated with cardiovascular events • These pulmonary measurements do not contain clinically relevant independent prognostic information • Only coronary calcium score improved cardiovascular risk prediction above age and smoking.

Lung volume reduction coil treatment for patients with severe emphysema: a European multicentre trial.

BACKGROUND: The lung volume reduction (LVR) coil is a minimally invasive bronchoscopic nitinol device designed to reduce hyperinflation and improve elastic recoil in severe emphysema. We investigated the feasibility, safety and efficacy of LVR coil treatment in a prospective multicentre cohort trial in patients with severe emphysema. METHODS: Patients were treated in 11 centres. Safety was evaluated by recording all adverse events, efficacy by the St George's Respiratory Questionnaire (SGRQ) as primary endpoint, and pulmonary function testing, modified Medical Research Council dyspnoea score (mMRC) and 6-min walk distance (6MWD) up to 12 months after the final treatment. RESULTS: Sixty patients (60.9 ± 7.5 years, forced expiratory volume in 1 s (FEV(1)) 30.2 ± 6.3% pred) were bronchoscopically treated with coils (55 bilateral, 5 unilateral), with a median of 10 (range 5-15) coils per lobe. Within 30 days post-treatment, seven chronic obstructive pulmonary disease exacerbations (6.1%), six pneumonias (5.2%), four pneumothoraces (3.5%) and one haemoptysis (0.9%) occurred as serious adverse events. At 6 and 12 months, respectively, ΔSGRQ was -12.1±12.9 and -11.1±13.3 points, Δ6MWD was +29.7±74.1 m and +51.4±76 m, ΔFEV(1) was +0.11±0.20 L and +0.11±0.30 L, and ΔRV (residual volume) was -0.65±0.90 L and -0.71±0.81 L (all p<0.01). Post hoc analyses showed significant responses for SGRQ, 6MWD and RV in patients with both heterogeneous and homogeneous emphysema. CONCLUSIONS: LVR coil treatment results in significant clinical improvements in patients with severe emphysema, with a good safety profile and sustained results for up to 1 year. TRIAL REGISTRATION NUMBER: NCT01328899.

Lung volume reduction coil treatment in chronic obstructive pulmonary disease patients with homogeneous emphysema: a prospective feasibility trial.

BACKGROUND: In patients with heterogeneous emphysema, surgical and bronchoscopic lung volume reduction (LVR) treatments are available. However, for patients with homogeneous emphysema these treatments are hardly investigated and seem less effective. Bronchoscopic LVR coil treatment has been shown to be effective in patients with heterogeneous emphysema, but this treatment has not been exclusively investigated in homogeneous emphysema. OBJECTIVES: The aim of this study was to investigate the safety and efficacy of LVR coil treatment in patients with homogeneous emphysema. METHODS: In this single-arm, open-label study, patients received a maximum of 12 LVR coils (PneumRx Inc., Mountain View, Calif., USA) in each upper lobe in two sequential procedures. Tests were performed at baseline and at 6 months. The primary endpoint was the improvement from baseline in 6-min walking distance (6MWD) after treatment. RESULTS: Ten patients with severe airway obstruction and hyperinflation were treated. A median of 11 (range 10-12) coils were placed in each lung. Two chronic obstructive pulmonary disease exacerbations and one small pneumothorax were recorded as serious adverse events. At 6 months, 6MWD had improved from 289 to 350 m (p = 0.005); forced vital capacity from 2.17 to 2.55 liters (p = 0.047); residual volume from 5.04 to 4.44 liters (p = 0.007) and St. George's Respiratory Questionnaire from 63 to 48 points (p = 0.028). CONCLUSION: LVR coil treatment in homogeneous patients improves hyperinflation, airway resistance, exercise capacity and quality of life with an acceptable safety profile. The benefit of LVR coil treatment is not limited to patients with heterogeneous emphysema, and patients with homogenous emphysema can benefit as well.

Contribution of CT quantified emphysema, air trapping and airway wall thickness on pulmonary function in male smokers with and without COPD.

Emphysema, airway wall thickening and air trapping are associated with chronic obstructive pulmonary disease (COPD). All three can be quantified by computed tomography (CT) of the chest. The goal of the current study is to determine the relative contribution of CT derived parameters on spirometry, lung volume and lung diffusion testing. Emphysema, airway wall thickening and air trapping were quantified automatically on CT in 1,138 male smokers with and without COPD. Emphysema was quantified by the percentage of voxels below -950 Hounsfield Units (HU), airway wall thickness by the square root of wall area for a theoretical airway with 10 mm lumen perimeter (Pi10) and air trapping by the ratio of mean lung density at expiration and inspiration (E/I-ratio). Spirometry, residual volume to total lung capacity (RV/TLC) and diffusion capacity (Kco) were obtained. Standardized regression coefficients (ß) were used to analyze the relative contribution of CT changes to pulmonary function measures. The independent contribution of the three CT measures differed per lung function parameter. For the FEV1 airway wall thickness was the most contributing structural lung change (ß = -0.46), while for the FEV1/FVC this was emphysema (ß = -0.55). For the residual volume (RV) air trapping was most contributing (ß = -0.35). Lung diffusion capacity was most influenced by emphysema (ß = -0.42). In a cohort of smokers with and without COPD the effect of different CT changes varies per lung function measure and therefore emphysema, airway wall thickness and air trapping need to be taken in account.

Diagnosis of chronic obstructive pulmonary disease in lung cancer screening Computed Tomography scans: independent contribution of emphysema, air trapping and bronchial wall thickening.

BACKGROUND: Beyond lung cancer, screening CT contains additional information on other smoking related diseases (e.g. chronic obstructive pulmonary disease, COPD). Since pulmonary function testing is not regularly incorporated in lung cancer screening, imaging biomarkers for COPD are likely to provide important surrogate measures for disease evaluation. Therefore, this study aims to determine the independent diagnostic value of CT emphysema, CT air trapping and CT bronchial wall thickness for COPD in low-dose screening CT scans. METHODS: Prebronchodilator spirometry and volumetric inspiratory and expiratory chest CT were obtained on the same day in 1140 male lung cancer screening participants. Emphysema, air trapping and bronchial wall thickness were automatically quantified in the CT scans. Logistic regression analysis was performed to derivate a model to diagnose COPD. The model was internally validated using bootstrapping techniques. RESULTS: Each of the three CT biomarkers independently contributed diagnostic value for COPD, additional to age, body mass index, smoking history and smoking status. The diagnostic model that included all three CT biomarkers had a sensitivity and specificity of 73.2% and 88.%, respectively. The positive and negative predictive value were 80.2% and 84.2%, respectively. Of all participants, 82.8% was assigned the correct status. The C-statistic was 0.87, and the Net Reclassification Index compared to a model without any CT biomarkers was 44.4%. However, the added value of the expiratory CT data was limited, with an increase in Net Reclassification Index of 4.5% compared to a model with only inspiratory CT data. CONCLUSION: Quantitatively assessed CT emphysema, air trapping and bronchial wall thickness each contain independent diagnostic information for COPD, and these imaging biomarkers might prove useful in the absence of lung function testing and may influence lung cancer screening strategy. Inspiratory CT biomarkers alone may be sufficient to identify patients with COPD in lung cancer screening setting.

Reproducibility of volume and densitometric measures of emphysema on repeat computed tomography with an interval of 1 week.

OBJECTIVES: The reproducibilities of CT lung volume and densitometric measures of emphysema were assessed over 1 week. The influence of breathhold on reproducibility was assessed. METHODS: HRCT was performed on 44 subjects at inspiration on two visits with a 7-day interval. CT lung volume, relative area below -950HU (RA950-raw), and 15th percentile density (PD15-raw) were computed. Volume correction was used to obtain RA950-adj and PD15-adj. Reproducibilities between visits were assessed using concordance correlation coefficient (CCC) and repeatability coefficient (RC). Reproducibilities were compared between raw and adjusted measures. Differences between visits were computed for volume and density measures. Correlations were computed for density differences versus volume difference. Subgroup analysis was performed using a 0.25 L volume difference threshold. RESULTS: High CCC were observed for all measures in full group (CCC > 0.97). Reproducibilities of volume (RC = 0.67 L), RA950-raw (RC = 2.3%), and PD15-raw (RC = 10.6HU) were observed. Volume correction significantly improved PD15 (RC = 3.6HU) but not RA950 (RC = 1.7%). RA950-raw and PD15-raw had significantly better RC in <0.25 L subgroup than ≥0.25 L. Significant correlations with volume were observed for RA950-raw and PD15-raw (R (2) > 0.71), but not RA950-adj or PD15-adj (R (2) < 0.11). CONCLUSIONS: Good breathhold and RA950 reproducibilities were achieved. PD15 was less reproducible but improved with volume correction or superior breathhold reproduction. KEY POINTS: • Good breath-hold reproducibility is achievable between multiple CT examinations. • Reproducibility of densitometric measures may be improved by statistical volume correction. • Volume correction may result in decreased signal. • Densitometric reproducibility may also be improved by achieving good breath-hold reproduction. • Careful consideration of signal and noise is necessary in reproducibility assessment.

A method for the automatic quantification of the completeness of pulmonary fissures: evaluation in a database of subjects with severe emphysema.

OBJECTIVES: To propose and evaluate a technique for automatic quantification of fissural completeness from chest computed tomography (CT) in a database of subjects with severe emphysema. METHODS: Ninety-six CT studies of patients with severe emphysema were included. The lungs, fissures and lobes were automatically segmented. The completeness of the fissures was calculated as the percentage of the lobar border defined by a fissure. The completeness score of the automatic method was compared with a visual consensus read by three radiologists using boxplots, rank sum tests and ROC analysis. RESULTS: The consensus read found 49% (47/96), 15% (14/96) and 67% (64/96) of the right major, right minor and left major fissures to be complete. For all fissures visually assessed as being complete the automatic method resulted in significantly higher completeness scores (mean 92.78%) than for those assessed as being partial or absent (mean 77.16%; all p values <0.001). The areas under the curves for the automatic fissural completeness were 0.88, 0.91 and 0.83 for the right major, right minor and left major fissures respectively. CONCLUSIONS: An automatic method is able to quantify fissural completeness in a cohort of subjects with severe emphysema consistent with a visual consensus read of three radiologists. KEY POINTS: • Lobar fissures are important for assessing the extent and distribution of lung disease • Modern CT allows automatic lobar segmentation and assessment of the fissures • This segmentation can also assess the completeness of the fissures. • Such assessment is important for decisions about novel therapies (eg for emphysema).

Toward automatic regional analysis of pulmonary function using inspiration and expiration thoracic CT.

PURPOSE: To analyze pulmonary function using a fully automatic technique which processes pairs of thoracic CT scans acquired at breath-hold inspiration and expiration, respectively. The following research objectives are identified to: (a) describe and systematically analyze the processing pipeline and its results; (b) verify that the quantitative, regional ventilation measurements acquired through CT are meaningful for pulmonary function analysis; (c) identify the most effective of the calculated measurements in predicting pulmonary function; and (d) demonstrate the potential of the system to deliver clinically important information not available through conventional spirometry. METHODS: A pipeline of automatic segmentation and registration techniques is presented and demonstrated on a database of 216 subjects well distributed over the various stages of COPD (chronic obstructive pulmonary disorder). Lungs, fissures, airways, lobes, and vessels are automatically segmented in both scans and the expiration scan is registered with the inspiration scan using a fully automatic nonrigid registration algorithm. Segmentations and registrations are examined and scored by expert observers to analyze the accuracy of the automatic methods. Quantitative measures representing ventilation are computed at every image voxel and analyzed to provide information about pulmonary function, both globally and on a regional basis. These CT derived measurements are correlated with results from spirometry tests and used as features in a kNN classifier to assign COPD global initiative for obstructive lung disease (GOLD) stage. RESULTS: The steps of anatomical segmentation (of lungs, lobes, and vessels) and registration in the workflow were shown to perform very well on an individual basis. All CT-derived measures were found to have good correlation with spirometry results, with several having correlation coefficients, r, in the range of 0.85-0.90. The best performing kNN classifier succeeded in classifying 67% of subjects into the correct COPD GOLD stage, with a further 29% assigned to a class neighboring the correct one. CONCLUSIONS: Pulmonary function information can be obtained from thoracic CT scans using the automatic pipeline described in this work. This preliminary demonstration of the system already highlights a number of points of clinical importance such as the fact that an inspiration scan alone is not optimal for predicting pulmonary function. It also permits measurement of ventilation on a per lobe basis which reveals, for example, that the condition of the lower lobes contributes most to the pulmonary function of the subject. It is expected that this type of regional analysis will be instrumental in advancing the understanding of multiple pulmonary diseases in the future.