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Purpose: To correlate the ratio of the non-dependent to dependent aspects of the maximal pleural movement vector (MPMVND/D) and gravity-oriented collapse ratio (GCRND/D), and the mean lung field density (MLD) obtained using four-dimensional (4D) dynamic-ventilation computed tomography (DVCT) with airflow limitation parameters and the Brinkman index. Materials and Methods: Forty-seven patients, including 22 patients with COPD, 13 non-COPD smokers, and 12 non-smokers, with no/slight pleural adhesion confirmed using a thoracoscope, underwent 4D-DVCT with 16 cm coverage. Coordinates for the lung field center, as well as ventral and dorsal pleural points, set on the central trans-axial levels in the median and para-median sagittal planes at end-inspiration, were automatically measured (13-17 frame images, 0.35 seconds/frame). MPMVND/D and GCRND/D were calculated based on MPMV and GCR values for all the included points and the lung field center. MLD was automatically measured in each of the time frames, and the maximal change ratio of MLD (MLDCR) was calculated. These measured values were compared among COPD patients, non-COPD smokers, and non-smokers, and were correlated with the Brinkman index, FEV1/FVC, FEV1 predicted, RV/TLC, and FEF25-75% using Spearman's rank coefficients. Results: MPMVND/D was highest in non-smokers (0.819±0.464), followed by non-COPD smokers (0.405±0.131) and patients with COPD (-0.219±0.900). GCRND/D in non-smokers (1.003±1.384) was higher than that in patients with COPD (-0.164±1.199). MLDCR in non-COPD smokers (0.105±0.028) was higher than that in patients with COPD (0.078±0.027). MPMVND/D showed positive correlations with FEV1 predicted (r=0.397, p=0.006), FEV1/FVC (r=0.501, p<0.001), and FEF25-75% (r=0.368, p=0.012). GCRND/D also demonstrated positive correlations with FEV1 (r=0.397, p=0.006), FEV1/FVC (r=0.445, p=0.002), and FEF25-75% (r=0.371, p=0.011). MPMVND/D showed a negative correlation with the Brinkman index (r=-0.398, p=0.006). Conclusion: We demonstrated that reduced MPMVND/D and GCRND/D were associated with respiratory functional indices, in addition to a negative association of MPMVND/D with the Brinkman index, which should be recognized when assessing local pleural adhesion on DVCT, especially for ventral pleural aspects.

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BACKGROUND: Obesity is known to diminish lung volumes and worsen asthma. However, mechanistic understanding is lacking, especially as concerns small-airway responsiveness. The objective of this study was therefore to compare small-airway responsiveness, as represented by the change in expiratory:inspiratory mean lung density ratios (MLDe/i , as determined by computed tomography [CT]) throughout methacholine testing in obese versus non-obese women with asthma. METHODS: Thoracic CT was performed during methacholine bronchoconstriction challenges to produce standardized response curves (SRC: response parameter versus ln[1 + % PD20], where PD20 is the cumulative methacholine dose) for 31 asthma patients (n = 18 non-obese and n = 13 obese patients). Mixed models evaluated obesity effects and interactions on SRCs while adjusting for age and bronchial morphology. Small airway responsiveness as represented by SRC slope was calculated for each third of the MLDe/i response and compared between groups. RESULTS: Obesity-associated effects observed during experimental bronchoconstriction included: (i) a significant baseline effect for forced expiratory volume in 1 second with lower values for the obese (73.11 ± 13.44) versus non-obese (82.19 ± 8.78; p = 0.002) groups prior to methacholine testing and (ii) significantly higher responsiveness in small airways as estimated via differences in MLDe/i slopes (group×ln(1 + % PD20 interaction; p = 0.023). The latter were pinpointed to higher slopes in the obese group at the beginning 2/3 of SRCs (p = 0.004 and p = 0.021). Significant obesity effects (p = 0.035 and p = 0.008) indicating lower forced vital capacity and greater % change in MLDe/I (respectively) throughout methacholine testing, were also observed. CONCLUSION: In addition to baseline differences, small-airway responsiveness (as represented by the change in MLDe/i ) during methacholine challenge is greater in obese women with asthma as compared to the non-obese.

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BACKGROUND: Recent advancements in computed tomography (CT) scanning and post processing have provided new means of assessing factors affecting respiratory function. For lung cancer patients requiring resection, and especially those with respiratory comorbidities such as chronic obstructive pulmonary disease (COPD), the ability to predict post-operative lung function is a crucial step in the lung cancer operability assessment. The primary objective of the CLIPPCAIR study is to use novel CT data to develop and validate an algorithm for the prediction of lung function remaining after pneumectomy/lobectomy. METHODS: Two sequential cohorts of non-small cell lung cancer patients requiring a pre-resection CT scan will be recruited at the Montpellier University Hospital, France: a test population (N=60) on which predictive models will be developed, and a further model validation population (N=100). Enrolment will occur during routine pre-surgical consults and follow-up visits will occur 1 and 6 months after pneumectomy/lobectomy. The primary outcome to be predicted is forced expiratory volume in 1 second (FEV1) six months after lung resection. The baseline CT variables that will be used to develop the primary multivariable regression model are: expiratory to inspiratory ratios of mean lung density (MLDe/i for the total lung and resected volume), the percentage of voxels attenuating at less than ‒950 HU (PVOX‒950 for the total lung and resected volume) and the ratio of iodine concentrations for the resected volume over that of the total lung. The correlation between predicted and real values will be compared to (and is expected to improve upon) that of previously published methods. Secondary analyses will include the prediction of transfer factor for carbon monoxide (TLCO) and complications in a similar fashion. The option to explore further variables as predictors of post-resection lung function or complications is kept open. DISCUSSION: Current methods for estimating post-resection lung function are imperfect and can add assessments (such as scintigraphy) to the pre-surgical workup. By using CT imaging data in a novel fashion, the results of the CLIPPCAIR study may not only improve such estimates, it may also simplify patient pathways. TRIAL REGISTRATION: Clinicaltrials.gov (NCT03885765).

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OBJECTIVE: Identification of interstitial lung disease (ILD) may be difficult in certain cases using pulmonary function tests (PFTs) or subjective radiological analysis. We evaluated the efficacy of quantitative computed tomography (CT) with 3-dimensional (3D) reconstruction for distinguishing ILD patients from healthy controls. MATERIALS AND METHODS: We retrospectively collected chest CT images of 102 ILD patients and 102 healthy matched controls, and measured the following parameters: lung parenchymal volume, emphysema indices low attenuation area LAA910 volume, LAA950 volume, LAA910%, and LAA950%, and mean lung density (MLD) for whole lung, left lung, right lung, and each lobe, respectively. The Mann-Whitney U test was used to compare quantitative CT parameters between groups. Receiver operating characteristic (ROC) curves, Bayesian stepwise discriminant analysis, and deep neural network analysis were used to test the discriminative performance of quantitative CT parameters. Binary logistic regression was performed to identify ILD markers. RESULTS: Total lung volume was lower in ILD patients than controls, while emphysema and MLD values were higher (P < 0.001) except LAA910 volume in right middle lobe. LAA910 volume, LAA950 volume, LAA910%, LAA950%, and MLD accurately distinguished ILD patients from healthy controls (AUC >0.5, P < 0.05), and high MLD was a significant marker for ILD (OR = 1.047, P < 0.05). CONCLUSIONS: This quantitative CT analysis can effectively identify ILD patients, providing an alternative to subjective image analysis and PFTs.

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ABSTRACT: Objective: To investigate the correlation between the biphasic mean lung density (MLD) measured by a computer-aided method and the pulmonary function test (PFT) in patients with chronic obstructive pulmonary disease (COPD). Methods: Sixty COPD patients diagnosed in The Affiliated Hospital of Yan'an University from June 2017 to June 2018 were retrospectively recruited. CT scans at the end of inspiratory phase and the end of expiratory phase were performed. MLD of the whole lung and individual lobes were measured by a three-dimensional method, and PFT was performed within one week. The correlation between MLD and PFT was analyzed. Results: We found a slight positive correlation between MLDin and PFT of the whole lung and each lung lobe (P<0.05). MLDex, MLDex-MLDin of the whole lung and each lung lobe showed moderate to high positive correlation with PFT (P<0.01), and MLDex/in of the whole lung and each lung lobe showed moderate to high negtive correlation with PFT (P<0.01). Conclusion: Quantitative measurement of mean lung density in COPD patients is correlated with lung function and MLDex/in of the whole lung shows the highest correlation.

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PURPOSE: The purpose of this study was to measure changes in lung density and airway dimension in smokers in the lateral position using four-dimensional dynamic-ventilation computed tomography (CT) during free breathing and to evaluate their correlations with spirometric values. MATERIALS AND METHODS: Preoperative pleural adhesion assessments included dynamic-ventilation CT of 42 smokers (including 22 patients with COPD) in the lateral position, with the unoperated lung beneath (dependent lung). The scanned lungs' mean lung density (MLD) and the bilateral main bronchi's luminal areas (Ai) were measured automatically (13-18 continuous image frames, 0.35 seconds/frame). Calculations included cross-correlation coefficients (CCCs) between the MLD and Ai time curves, and correlations between the quantitative measurements and spirometric values were evaluated by using Spearman's rank coefficient. RESULTS: The ΔMLD1.05 (from the peak inspiration frame to the third expiratory frame, 1.05 seconds later) in the nondependent lung negatively correlated with FEV1/FVC (r=-0.417, P<0.01), suggesting that large expiratory movement of the nondependent lung would compensate limited expiratory movement of the dependent lung due to COPD. The ΔAi1.05 negatively correlated with the FEV1/FVC predicted in both the lungs (r=-0.465 and -0.311, P<0.05), suggesting that early expiratory collapses of the main bronchi indicate severe airflow limitation. The CCC correlated with FEV1/FVC in the dependent lung (r=-0.474, P<0.01), suggesting that reduced synchrony between the proximal airway and lung occurs in patients with severe airflow limitation. CONCLUSION: In COPD patients, in the lateral position, the following abnormal dynamic-ventilation CT findings are associated with airflow limitation: enhanced complementary ventilation in the nondependent lung, early expiratory airway collapses, and reduced synchrony between airway and lung movements in the dependent lung.

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Objective To investigate the changing curve of mean lung density (MLD)in normal preschool children based on CT quantitative measurement.Methods Chest CT data of 409 preschool children were reviewed retrospectively from the "digital lung"database.A computerized algorithm based on the "digital lung"was applied to all examinations in a batch manner.The MLD values of total lung,right lung,left lung and each lobe were obtained automatically.Results There was no correlation between the gender and MLD,however a moderately negative correlation was found between the age of month and MLD (P＜0.05).No significant difference of MLD was found between genders of the same age of month group,except in left lower lobe of 49-60 months of age (P=0.043). The MLD was decreased gradually with age (P＜0.05).Conclusion There is not a statistical difference in MLD between the preschool boys and preschool girls of the same age of month.With the growth of preschool children,the MLD is gradually decreased.

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PURPOSE: Four-dimensional dynamic-ventilation CT imaging demonstrates continuous movement of the lung. The aim of this study was to assess the correlation between interlobar synchrony in lung density and spirometric values in COPD patients and smokers, by measuring the continuous changes in lung density during respiration on the dynamic-ventilation CT. MATERIALS AND METHODS: Thirty-two smokers, including ten with COPD, underwent dynamic-ventilation CT during free breathing. CT data were continuously reconstructed every 0.5 sec. Mean lung density (MLD) of the five lobes (right upper [RU], right middle [RM], right lower [RL], left upper [LU], and left lower [LL]) was continuously measured by commercially available software using a fixed volume of volume of interest which was placed and tracked on a single designated point in each lobe. Concordance between the MLD time curves of six pairs of lung lobes (RU-RL, RU-RM, RM-RL, LU-LL, RU-LU, and RL-LL lobes) was expressed by cross-correlation coefficients. The relationship between these cross-correlation coefficients and the forced expiratory volume in one second/forced vital capacity (FEV1.0/FVC) values was assessed by Spearman rank correlation analysis. RESULTS: In all six pairs of the pulmonary lobes, the cross-correlation coefficients of the two MLD curves were significantly positively correlated with FEV1.0/FVC (ρ =0.60-0.73, P<0.001). The mean value of the six coefficients strongly correlated with FEV1.0/FVC (ρ =0.80, P<0.0001). CONCLUSION: The synchrony of respiratory movements between the pulmonary lobes is limited or lost in patients with more severe airflow limitation.

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RATIONALE: A substantial proportion of subjects without overt airflow obstruction have significant respiratory morbidity and structural abnormalities as visualized by computed tomography. Whether regions of the lung that appear normal using traditional computed tomography criteria have mild disease is not known. OBJECTIVES: To identify subthreshold structural disease in normal-appearing lung regions in smokers. METHODS: We analyzed 8,034 subjects with complete inspiratory and expiratory computed tomographic data participating in the COPDGene Study, including 103 lifetime nonsmokers. The ratio of the mean lung density at end expiration (E) to end inspiration (I) was calculated in lung regions with normal density (ND) by traditional thresholds for mild emphysema (-910 Hounsfield units) and gas trapping (-856 Hounsfield units) to derive the ND-E/I ratio. Multivariable regression analysis was used to measure the associations between ND-E/I, lung function, and respiratory morbidity. MEASUREMENTS AND MAIN RESULTS: The ND-E/I ratio was greater in smokers than in nonsmokers, and it progressively increased from mild to severe chronic obstructive pulmonary disease severity. A proportion of 26.3% of smokers without airflow obstruction had ND-E/I greater than the 90th percentile of normal. ND-E/I was independently associated with FEV1 (adjusted ß = -0.020; 95% confidence interval [CI], -0.032 to -0.007; P = 0.001), St. George's Respiratory Questionnaire scores (adjusted ß = 0.952; 95% CI, 0.529 to 1.374; P < 0.001), 6-minute-walk distance (adjusted ß = -10.412; 95% CI, -12.267 to -8.556; P < 0.001), and body mass index, airflow obstruction, dyspnea, and exercise capacity index (adjusted ß = 0.169; 95% CI, 0.148 to 0.190; P < 0.001), and also with FEV1 change at follow-up (adjusted ß = -3.013; 95% CI, -4.478 to -1.548; P = 0.001). CONCLUSIONS: Subthreshold gas trapping representing mild small airway disease is prevalent in normal-appearing lung regions in smokers without airflow obstruction, and it is associated with respiratory morbidity. Clinical trial registered with www.clinicaltrials.gov (NCT00608764).

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PURPOSE: Four-dimensional dynamic-ventilation computed tomography (CT) imaging demonstrates continuous movement of the airways and lungs, which cannot be depicted with conventional CT. We aimed to investigate continuous changes in lung density and airway dimensions and to assess the correlation with spirometric values in smokers. MATERIALS AND METHODS: This retrospective study was approved by the Institutional Review Board, and informed consent was waived. Twenty-one smokers including six patients with COPD underwent four-dimensional dynamic-ventilation CT during free breathing (160 mm in length). The mean lung density (MLD) of the scanned lung and luminal areas (Ai) of fixed points in the trachea and the right proximal bronchi (main bronchus, upper bronchus, bronchus intermedius, and lower bronchus) were continuously measured. Concordance between the time curve of the MLD and that of the airway Ai values was expressed by cross-correlation coefficients. The associations between these quantitative measurements and the forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) values were assessed by Spearman's rank correlation analysis. RESULTS: On the time curve for the MLD, the Δ-MLD1.05 values between the peak inspiratory frame to the later third frame (1.05 seconds later) were strongly correlated with the FEV1/FVC (ρ=0.76, P<0.0001). The cross-correlation coefficients between the airway Ai and MLD values were significantly correlated with the FEV1/FVC (ρ=-0.56 to -0.66, P<0.01), except for the right upper bronchus. This suggested that the synchrony between the airway and lung movement was lost in patients with severe airflow limitation. CONCLUSION: Respiratory changes in the MLD and synchrony between the airway Ai and the MLD measured with dynamic-ventilation CT were correlated with patient's spirometric values.

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OBJECTIVES: To determine the improvement of emphysema quantification with density correction and to determine the optimal site to use for air density correction on volumetric computed tomography (CT). METHODS: Seventy-eight CT scans of COPD patients (GOLD II-IV, smoking history 39.2±25.3 pack-years) were obtained from several single-vendor 16-MDCT scanners. After density measurement of aorta, tracheal- and external air, volumetric CT density correction was conducted (two reference values: air, -1,000 HU/blood, +50 HU). Using in-house software, emphysema index (EI) and mean lung density (MLD) were calculated. Differences in air densities, MLD and EI prior to and after density correction were evaluated (paired t-test). Correlation between those parameters and FEV1 and FEV1/FVC were compared (age- and sex adjusted partial correlation analysis). RESULTS: Measured densities (HU) of tracheal- and external air differed significantly (-990 ± 14, -1016 ± 9, P<0.001). MLD and EI on original CT data, after density correction using tracheal- and external air also differed significantly (MLD: -874.9 ± 27.6 vs. -882.3 ± 24.9 vs. -860.5 ± 26.6; EI: 16.8 ± 13.4 vs. 21.1 ± 14.5 vs. 9.7 ± 10.5, respectively, P<0.001). The correlation coefficients between CT quantification indices and FEV1, and FEV1/FVC increased after density correction. The tracheal air correction showed better results than the external air correction. CONCLUSION: Density correction of volumetric CT data can improve correlations of emphysema quantification and PFT.

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OBJECTIVE: To assess whether high-resolution computed tomography (HRCT) variables are as good as other known clinical variables in grading emphysema patients. METHODS: A detailed clinical history was taken and physical examination performed. We performed serum study, lung function testing, and HRCT scanning to assess emphysema. Mean lung density, the attenuation value separating the least 15% of pixels (PERC15), the percentage of the relative area of the lungs with attenuation values < -950 Hounsfield units (HU) (RA950), and histogram analysis were calculated from computerized data. RESULTS: The final analysis was based on data from 92 subjects, and they were moderately emphysematous (mean lung density was -877 ± 23 HU, PERC15 was -953 ± 21 HU, and RA950 was 16 ± 5%). There was a significant difference regarding subjective emphysema severity in the St George's Respiratory Questionnaire, smoking history, FEV1, C-reactive protein, age, and body mass index (P < .001). There was a significant correlation between the 3 objective image variables and the 6 objective clinical variables (St George's Respiratory Questionnaire, smoking history, FEV1, C-reactive protein, age, and body mass index) (P < .001). CONCLUSIONS: This study shows the possible important role of HRCT in the diagnosis and quantification of pulmonary emphysema.

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