BACKGROUND: The prevalence of pleural abnormalities in the general population is an epidemiologically important index of asbestos exposure, which has not been investigated since a radiography-based study in 1980. METHODS: We examined 2633 chest CT scans (mean 59.2 years, 50% female) from the Framingham Heart Study (FHS) for the presence and image characteristics of pleural plaques and diffuse pleural thickening. Demographics and pulmonary function were stratified by the presence of pleural abnormalities in association with interstitial lung abnormalities. RESULTS: Pleural abnormalities were present in 1.5% (95% CI 1.1% to 2.1%). Pleural lesions were most commonly bilateral (90.0%), multiple (77.5%), calcified (97.5%) and commonly involved posterior (lower: 92.5%, middle: 87.5%), anterior (upper: 77.5%, middle: 77.5%) and diaphragmatic areas (72.5%). Participants with pleural abnormalities were significantly older (75.7 years, p <0.0001), male (92.5%, p <0.0001), former or current smokers (80.0%, p <0.001) with higher pack-years (33.3, p <0.0001). No significant reduction was noted in pulmonary function measures (p=0.07-0.94) when adjusted for the associated covariates, likely due to small number of cases with pleural abnormalities. Information about prior history of asbestos exposure and occupation was not available. CONCLUSIONS: Pleural plaques and diffuse pleural thickening are present on CT in 1.5% of the FHS cohort. The current prevalence of the pleural abnormalities is smaller than that reported in the previous population-based study using chest radiography, likely representing lower asbestos exposure in recent decades. The posterior portion of the pleura is most frequently involved but the anterior portion is also commonly involved.

The promoter polymorphism (rs35705950) has been associated with interstitial lung abnormalities (ILA) in white participants from the general population; whether these findings are replicated and influenced by the ILA subtype is not known. We evaluated the associations between the genotype and ILA in cohorts with extensive imaging characterisation.We performed ILA phenotyping and promoter genotyping in 5308 and 9292 participants from the AGES-Reykjavik and COPDGene cohorts, respectively.We found that ILA was present in 7% of participants from the AGES-Reykjavik, 8% of non-Hispanic white participants from COPDGene and 7% of African-American participants from COPDGene. Although the genotype was strongly associated (after correction for multiple testing) with ILA (OR 2.1, 95% CI 1.8-2.4, p=1×10), there was evidence of significant heterogeneity between cohorts (I=81%). When narrowed to specific radiologic subtypes, ( subpleural ILA), the genotype remained strongly associated (OR 2.6, 95% CI 2.2-3.1, p=1×10) with minimal heterogeneity (I=0%). Although there was no evidence that the genotype influenced survival, there was evidence that genotype improved risk prediction for possible usual interstitial pneumonia (UIP) or a UIP pattern in non-Hispanic white populations.The promoter polymorphism is strongly associated with ILA and specific radiologic subtypes of ILA, with varying degrees of heterogeneity in the underlying populations.

Pulmonary complications are a significant cause of morbidity, mortality, and resource utilization after hematopoietic stem cell transplantation (HSCT). The objective of this study was to compare antemortem clinical suspicion of pulmonary complications and postmortem findings in a modern HSCT cohort. All patients who underwent allogeneic HSCT at our institution (n = 1854) between January 1, 2000 and June 30, 2010 were reviewed and patients who died of any cause greater than 1 year after HSCT and had an unrestricted autopsy available for analysis were included. Presence of pulmonary graft-versus-host disease (GVHD) was assessed by a pathologist blinded to the autopsy report, as previously described by Yousem (1995). A total of 35 (1.9%) patients had autopsies available for review. Airway disease, vascular disease, and interstitial disease were all clinically under-recognized compared with the pathological findings on autopsy. Varying degrees of pathological changes were detected, including 10 (28.6%) patients having bronchiolitis obliterans (BO) and 12 (34.3%) patients having pulmonary veno-occlusive disease (PVOD). Pulmonary manifestations of chronic GVHD, particularly BO and PVOD, were clinically under-recognized in our cohort. Our results suggest that PVOD, which has traditionally been considered a rare complication, may be clinically and histologically under-recognized.

BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is a clinical manifestation of chronic allograft rejection following lung transplantation. We examined the quantitative measurements of the proximal airway and vessels and pathologic correlations in subjects with BOS. METHODS: Patients who received a lung transplant at the Brigham and Women's Hospital between December 1, 2002 and December 31, 2010 were included in this study. We characterized the quantitative CT measures of proximal airways and vessels and pathological changes. RESULTS: Ninety-four (46.1%) of the 204 subjects were included in the study. There was a significant increase in the airway vessel ratio in subjects who developed progressive BOS compared to controls and non-progressors. There was a significant increase in airway lumen area and decrease in vessel cross-sectional area in patients with BOS compared to controls. Patients with BOS had a significant increase in proximal airway fibrosis compared to controls. CONCLUSIONS: BOS is characterized by central airway dilation and vascular remodeling, the degree of which is correlated to decrements in lung function. Our data suggest that progressive BOS is a pathologic process that affects both the central and distal airways.

BACKGROUND: Bronchiectasis is frequent in smokers with COPD; however, there are only limited data on objective assessments of this process. The objective was to assess bronchovascular morphology, calculate the ratio of the diameters of bronchial lumen and adjacent artery (BA ratio), and identify those measurements able to discriminate bronchiectasis. METHODS: We collected quantitative CT (QCT) measures of BA ratios, peak wall attenuation, wall thickness (WT), wall area, and wall area percent (WA%) at matched fourth through sixth airway generations in 21 ever smokers with bronchiectasis (cases) and 21 never-smoking control patients (control airways). In cases, measurements were collected at both bronchiectatic and nonbronchiectatic airways. Logistic analysis and the area under receiver operating characteristic curve (AUC) were used to assess the predictive ability of QCT measurements for bronchiectasis. RESULTS: The whole-lung and fourth through sixth airway generation BA ratio, WT, and WA% were significantly greater in bronchiectasis cases than control patients. The AUCs for the BA ratio to predict bronchiectasis ranged from 0.90 (whole lung) to 0.79 (fourth-generation). AUCs for WT and WA% ranged from 0.72 to 0.75 and from 0.71 to 0.75. The artery diameters but not bronchial diameters were smaller in bronchiectatic than both nonbronchiectatic and control airways (P < .01 for both). CONCLUSIONS: Smoking-related increases in the BA ratio appear to be driven by reductions in vascular caliber. QCT measures of BA ratio, WT, and WA% may be useful to objectively identify and quantify bronchiectasis in smokers. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00608764; URL: www.clinicaltrials.gov.

PURPOSE OF REVIEW: The present review aims to summarize the most recent evidence related to imaging and severe asthma, both with regard to advances in imaging research and to their current and potential clinical implications. RECENT FINDINGS: Recent work in imaging in severe asthma has principally been using computed tomography (CT) and MRI, as well as the integration of the two. Some of the most notable findings include the use of CT imaging biomarkers to create unique clusters of asthmatics, and the use of co-registration to link CT images of airways with regional variation in ventilation in MRI. In addition, temporal studies have shown that some the ventilation defects found using MRI in asthmatics are intermittent and others are persistent, but both are associated with lower lung function. SUMMARY: The role of imaging in severe asthma currently is primarily in the exclusion of comorbid or other conditions, or in the assessment for complications in the setting of acute decompensation. A rapidly expanding body of literature using CT and MRI suggests that these tools may soon be of utility in the chronic management of the disease.

With the advancement of three-dimensional (3-D) real-time echocardiography in recent years, automatic creation of patient specific geometric models is becoming feasible and important in clinical decision making. However, the vast majority of echocardiographic segmentation methods presented in the literature focus on the left ventricle (LV) endocardial border, leaving segmentation of the right ventricle (RV) a largely unexplored problem, despite the increasing recognition of the RV's role in cardiovascular disease. We present a method for coupled segmentation of the endo- and epicardial borders of both the LV and RV in 3-D ultrasound images. To solve the segmentation problem, we propose an extension of a successful state-estimation segmentation framework with a geometrical representation of coupled surfaces, as well as the introduction of myocardial incompressibility to regularize the segmentation. The method was validated against manual measurements and segmentations in images of 16 patients. Mean absolute distances of [Formula: see text], [Formula: see text], and [Formula: see text] between the proposed and reference segmentations were observed for the LV endocardium, RV endocardium, and LV epicardium surfaces, respectively. The method was computationally efficient, with a computation time of [Formula: see text].

Diffusion MRI (dMRI) is the only noninvasive method for mapping white matter connections in the brain. We describe SlicerDMRI, a software suite that enables visualization and analysis of dMRI for neuroscientific studies and patient-specific anatomic assessment. SlicerDMRI has been successfully applied in multiple studies of the human brain in health and disease, and here, we especially focus on its cancer research applications. As an extension module of the 3D Slicer medical image computing platform, the SlicerDMRI suite enables dMRI analysis in a clinically relevant multimodal imaging workflow. Core SlicerDMRI functionality includes diffusion tensor estimation, white matter tractography with single and multi-fiber models, and dMRI quantification. SlicerDMRI supports clinical DICOM and research file formats, is open-source and cross-platform, and can be installed as an extension to 3D Slicer (www.slicer.org). More information, videos, tutorials, and sample data are available at dmri.slicer.org .

Computerized tomography (CT) is a widely adopted modality for analyzing directly or indirectly functional, biological and morphological processes by means of the image characteristics. However, the potential utilization of the information obtained from CT images is often limited when considering the analysis of quantitative information involving different devices, acquisition protocols or reconstruction algorithms. Although CT scanners are calibrated as a part of the imaging workflow, the calibration is circumscribed to global reference values and does not circumvent problems that are inherent to the imaging modality. One of them is the lack of noise stationarity, which makes quantitative biomarkers extracted from the images less robust and stable. Some methodologies have been proposed for the assessment of non-stationary noise in reconstructed CT scans. However, those methods focused on the non-stationarity only due to the reconstruction geometry and are mainly based on the propagation of the variance of noise throughout the whole reconstruction process. Additionally, the philosophy followed in the state-of-the-art methods is based on the reduction of noise, but not in the standardization of it. This means that, even if the noise is reduced, the statistics of the signal remain non-stationary, which is insufficient to enable comparisons between different acquisitions with different statistical characteristics. In this work, we propose a statistical characterization of noise in reconstructed CT scans that leads to a versatile statistical model that effectively characterizes different doses, reconstruction kernels, and devices. The statistical model is generalized to deal with the partial volume effect via a localized mixture model that also describes the non-stationarity of noise. Finally, we propose a stabilization scheme to achieve stationary variance. The validation of the proposed methodology was performed with a physical phantom and clinical CT scans acquired with different configurations (kernels, doses, algorithms including iterative reconstruction). The results confirmed its suitability to enable comparisons with different doses, and acquisition protocols.

AIMS: Non-cystic fibrosis bronchiectasis (NCFB) is a chronic, progressive respiratory disorder characterised by irreversibly and abnormally dilated airways, persistent cough, excessive sputum production and recurrent pulmonary infections. In the last several decades, its prevalence has increased, making it likely to be encountered in the primary care setting. The aim was to review the clinical presentation and diagnosis of NCFB, with an emphasis on the role of computed tomography (CT). METHODS: For this review, trials and reports were identified from PubMed/Medline and ClinicalTrials.gov from the US NIH and the Cochrane Register of Controlled Trials. The search used keywords: bronchiectasis, non-cystic fibrosis bronchiectasis, chronic pulmonary infection and computed tomography. No date/language restrictions were used. RESULTS: Non-cystic fibrosis bronchiectasis often coexists with other respiratory conditions, such as chronic obstructive pulmonary disease. The prevalence of NCFB is increasing, particularly in women and older individuals, possibly as a result of increased physician awareness and widespread use of CT, which is the gold standard for the diagnosis of NCFB. CT can assist in identifying an underlying cause of NCFB and determining the extent and severity of the disease. DISCUSSION: Non-cystic fibrosis bronchiectasis should be suspected in the primary care setting in patients with chronic cough, purulent sputum and frequent respiratory infections that tend to resolve slowly or partially. Early diagnosis and determination of the extent and severity of the disease by CT and other tests are critical to establish therapy to improve quality of life and potentially slow progressive decline of lung function in patients with NCFB.

RATIONALE AND OBJECTIVES: Imaging-based assessment of cardiovascular structure and function provides clinically relevant information in smokers. Non-cardiac-gated thoracic computed tomographic (CT) scanning is increasingly leveraged for clinical care and lung cancer screening. We sought to determine if more comprehensive measures of ventricular geometry could be obtained from CT using an atlas-based surface model of the heart. MATERIALS AND METHODS: Subcohorts of 24 subjects with cardiac magnetic resonance imaging (MRI) and 262 subjects with echocardiography were identified from COPDGene, a longitudinal observational study of smokers. A surface model of the heart was manually initialized, and then automatically optimized to fit the epicardium for each CT. Estimates of right and left ventricular (RV and LV) volume and free-wall curvature were then calculated and compared to structural and functional metrics obtained from MRI and echocardiograms. RESULTS: CT measures of RV dimension and curvature correlated with similar measures obtained using MRI. RV and LV volume obtained from CT inversely correlated with echocardiogram-based estimates of RV systolic pressure using tricuspid regurgitation jet velocity and LV ejection fraction respectively. Patients with evidence of RV or LV dysfunction on echocardiogram had larger RV and LV dimensions on CT. Logistic regression models based on demographics and ventricular measures from CT had an area under the curve of >0.7 for the prediction of elevated right ventricular systolic pressure and ventricular failure. CONCLUSIONS: These data suggest that non-cardiac-gated, non-contrast-enhanced thoracic CT scanning may provide insight into cardiac structure and function in smokers.

RATIONALE: Automated analysis of computed tomographic (CT) lung images for epidemiologic and genetic association studies is increasingly common, but little is known about the utility of visual versus semiautomated emphysema and airway assessments for genetic association studies. OBJECTIVES: Assess the relative utility of visual versus semiautomated emphysema and airway assessments for genetic association studies. METHODS: A standardized inspection protocol was used to visually assess chest CT images for 1,540 non-Hispanic white subjects within the COPDGene Study for the presence and severity of radiographic features representing airway wall thickness and emphysema. A genome-wide association study (GWAS) was performed, and two sets of candidate single-nucleotide polymorphisms with a higher prior likelihood of association were specified a priori for separate analysis. For each visual CT examination feature, a corresponding semiautomated CT feature(s) was identified for comparison in the same subjects. MEASUREMENTS AND MAIN RESULTS: GWAS for visual features of chest CT scans identified a genome-wide significant association with visual emphysema at the 15q25 locus (P = 6.3e). In the a priori-specified set of 19 previously identified GWAS loci, 7 and 8 loci were associated with airway measures or emphysema measures, respectively. In the a priori-specified candidate gene set, 13 of 196 candidate genes harbored a nearby single-nucleotide polymorphism significantly associated with an emphysema phenotype. Visual CT examination associations were robust to adjustment for semiautomated correlates in many cases. CONCLUSIONS: Standardized visual assessments of emphysema and airway disease are significantly associated with genetic loci previously associated with chronic obstructive pulmonary disease susceptibility or semiautomated CT examination phenotypes in GWAS. Visual CT measures of emphysema and airways disease offer independent information for genetic association studies in relation to standard semiautomated measures.

Density masking is the de-facto quantitative imaging phenotype for emphysema that is widely used by the clinical community. Density masking defines the burden of emphysema by a fixed threshold, usually between -910 HU and -950 HU, that has been experimentally validated with histology. In this work, we formalized emphysema quantification by means of statistical inference. We show that a non-central Gamma is a good approximation for the local distribution of image intensities for normal and emphysema tissue. We then propose a test statistic in terms of the sample mean of a truncated non-central Gamma random variable. Our results show that this approach is well-suited for the detection of emphysema and superior to standard density masking. The statistical method was tested in a dataset of 1337 samples obtained from 9 different scanner models in subjects with COPD. Results showed an increase of 17% when compared to the density masking approach, and an overall accuracy of 94.09%.

Patients with chronic thromboembolic pulmonary hypertension (CTEPH) have morphologic changes to the pulmonary vasculature. These include pruning of the distal vessels, dilation of the proximal vessels, and increased vascular tortuosity. Advances in image processing and computer vision enable objective detection and quantification of these processes in clinically acquired computed tomographic (CT) scans. Three-dimensional reconstructions of the pulmonary vasculature were created from the CT angiograms of 18 patients with CTEPH diagnosed using imaging and hemodynamics as well as 15 control patients referred to our Dyspnea Clinic and found to have no evidence of pulmonary vascular disease. Compared to controls, CTEPH patients exhibited greater pruning of the distal vasculature (median density of small-vessel volume: 2.7 [interquartile range (IQR): 2.5-3.0] vs. 3.2 [3.0-3.8]; P = 0.008), greater dilation of proximal arteries (median fraction of blood in large arteries: 0.35 [IQR: 0.30-0.41] vs. 0.23 [0.21-0.31]; P = 0.0005), and increased tortuosity in the pulmonary arterial tree (median: 4.92% [IQR: 4.85%-5.21%] vs. 4.63% [4.39%-4.92%]; P = 0.004). CTEPH was not associated with dilation of proximal veins or increased tortuosity in the venous system. Distal pruning of the vasculature was correlated with the cardiac index (R = 0.51, P = 0.04). Quantitative models derived from CT scans can be used to measure changes in vascular morphology previously described subjectively in CTEPH. These measurements are also correlated with invasive metrics of pulmonary hemodynamics, suggesting that they may be used to assess disease severity. Further work in a larger cohort may enable the use of such measures as a biomarker for diagnostic, phenotyping, and prognostic purposes.

IMPORTANCE: Central airway collapse greater than 50% of luminal area during exhalation (expiratory central airway collapse [ECAC]) is associated with cigarette smoking and chronic obstructive pulmonary disease (COPD). However, its prevalence and clinical significance are unknown. OBJECTIVE: To determine whether ECAC is associated with respiratory morbidity in smokers independent of underlying lung disease. DESIGN, SETTING, AND PARTICIPANTS: Analysis of paired inspiratory-expiratory computed tomography images from a large multicenter study (COPDGene) of current and former smokers from 21 clinical centers across the United States. Participants were enrolled from January 2008 to June 2011 and followed up longitudinally until October 2014. Images were initially screened using a quantitative method to detect at least a 30% reduction in minor axis tracheal diameter from inspiration to end-expiration. From this sample of screen-positive scans, cross-sectional area of the trachea was measured manually at 3 predetermined levels (aortic arch, carina, and bronchus intermedius) to confirm ECAC (>50% reduction in cross-sectional area). EXPOSURES: Expiratory central airway collapse. MAIN OUTCOMES AND MEASURES: The primary outcome was baseline respiratory quality of life (St George's Respiratory Questionnaire [SGRQ] scale 0 to 100; 100 represents worst health status; minimum clinically important difference [MCID], 4 units). Secondary outcomes were baseline measures of dyspnea (modified Medical Research Council [mMRC] scale 0 to 4; 4 represents worse dyspnea; MCID, 0.7 units), baseline 6-minute walk distance (MCID, 30 m), and exacerbation frequency (events per 100 person-years) on longitudinal follow-up. RESULTS: The study included 8820 participants with and without COPD (mean age, 59.7 [SD, 6.9] years; 4667 [56.7%] men; 4559 [51.7%] active smokers). The prevalence of ECAC was 5% (443 cases). Patients with ECAC compared with those without ECAC had worse SGRQ scores (30.9 vs 26.5 units; P < .001; absolute difference, 4.4 [95% CI, 2.2-6.6]) and mMRC scale scores (median, 2 [interquartile range [IQR], 0-3]) vs 1 [IQR, 0-3]; P < .001]), but no significant difference in 6-minute walk distance (399 vs 417 m; absolute difference, 18 m [95% CI, 6-30]; P = .30), after adjustment for age, sex, race, body mass index, forced expiratory volume in the first second, pack-years of smoking, and emphysema. On follow-up (median, 4.3 [IQR, 3.2-4.9] years), participants with ECAC had increased frequency of total exacerbations (58 vs 35 events per 100 person-years; incidence rate ratio [IRR], 1.49 [95% CI, 1.29-1.72]; P < .001) and severe exacerbations requiring hospitalization (17 vs 10 events per 100 person-years; IRR, 1.83 [95% CI, 1.51-2.21]; P < .001). CONCLUSIONS AND RELEVANCE: In a cross-sectional analysis of current and former smokers, the presence of ECAC was associated with worse respiratory quality of life. Further studies are needed to assess long-term associations with clinical outcomes.

IMPORTANCE: Interstitial lung abnormalities have been associated with lower 6-minute walk distance, diffusion capacity for carbon monoxide, and total lung capacity. However, to our knowledge, an association with mortality has not been previously investigated. OBJECTIVE: To investigate whether interstitial lung abnormalities are associated with increased mortality. DESIGN, SETTING, AND POPULATION: Prospective cohort studies of 2633 participants from the FHS (Framingham Heart Study; computed tomographic [CT] scans obtained September 2008-March 2011), 5320 from the AGES-Reykjavik Study (Age Gene/Environment Susceptibility; recruited January 2002-February 2006), 2068 from the COPDGene Study (Chronic Obstructive Pulmonary Disease; recruited November 2007-April 2010), and 1670 from ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints; between December 2005-December 2006). EXPOSURES: Interstitial lung abnormality status as determined by chest CT evaluation. MAIN OUTCOMES AND MEASURES: All-cause mortality over an approximate 3- to 9-year median follow-up time. Cause-of-death information was also examined in the AGES-Reykjavik cohort. RESULTS: Interstitial lung abnormalities were present in 177 (7%) of the 2633 participants from FHS, 378 (7%) of 5320 from AGES-Reykjavik, 156 (8%) of 2068 from COPDGene, and in 157 (9%) of 1670 from ECLIPSE. Over median follow-up times of approximately 3 to 9 years, there were more deaths (and a greater absolute rate of mortality) among participants with interstitial lung abnormalities when compared with those who did not have interstitial lung abnormalities in the following cohorts: 7% vs 1% in FHS (6% difference [95% CI, 2% to 10%]), 56% vs 33% in AGES-Reykjavik (23% difference [95% CI, 18% to 28%]), and 11% vs 5% in ECLIPSE (6% difference [95% CI, 1% to 11%]). After adjustment for covariates, interstitial lung abnormalities were associated with a higher risk of death in the FHS (hazard ratio [HR], 2.7 [95% CI, 1.1 to 6.5]; P = .03), AGES-Reykjavik (HR, 1.3 [95% CI, 1.2 to 1.4]; P < .001), COPDGene (HR, 1.8 [95% CI, 1.1 to 2.8]; P = .01), and ECLIPSE (HR, 1.4 [95% CI, 1.1 to 2.0]; P = .02) cohorts. In the AGES-Reykjavik cohort, the higher rate of mortality could be explained by a higher rate of death due to respiratory disease, specifically pulmonary fibrosis. CONCLUSIONS AND RELEVANCE: In 4 separate research cohorts, interstitial lung abnormalities were associated with a greater risk of all-cause mortality. The clinical implications of this association require further investigation.

The Agatston score, computed from ECG-gated computed tomography (CT), is a well established metric of coronary artery disease. It has been recently shown that the Agatston score computed from chest CT (non ECG-gated) studies is highly correlated with the Agatston score computed from cardiac CT scans. In this work we present an automated method to compute the Agatston score from chest CT images. Coronary arteries calcifications (CACs) are defined as voxels contained within the coronary arteries with a value greater or equal to 130 Hounsfield Units (HU). CACs are automatically detected in chest CT studies by locating the heart, generating a region of interest around it, thresholding the image in such region and applying a set of rules to discriminate CACs from calcifications in the main vessels or from metallic implants. We evaluate the methodology in a large cohort of 1500 patients for whom manual reference standard is available. Our results show that the Pearson correlation coefficient between manual and automated Agatston score is ρ = 0.86 ( < 0.0001).

The great density and structural complexity of pulmonary vessels and airways impose limitations on the generation of accurate reference standards, which are critical in training and in the validation of image processing methods for features such as pulmonary vessel segmentation or artery-vein (AV) separations. The design of synthetic computed tomography (CT) images of the lung could overcome these difficulties by providing a database of pseudorealistic cases in a constrained and controlled scenario where each part of the image is differentiated unequivocally. This work demonstrates a complete framework to generate computational anthropomorphic CT phantoms of the human lung automatically. Starting from biological and image-based knowledge about the topology and relationships between structures, the system is able to generate synthetic pulmonary arteries, veins, and airways using iterative growth methods that can be merged into a final simulated lung with realistic features. A dataset of 24 labeled anthropomorphic pulmonary CT phantoms were synthesized with the proposed system. Visual examination and quantitative measurements of intensity distributions, dispersion of structures and relationships between pulmonary air and blood flow systems show good correspondence between real and synthetic lungs (p > 0.05 with low Cohen's d effect size and AUC values), supporting the potentiality of the tool and the usefulness of the generated phantoms in the biomedical image processing field.

Computed tomographic measures of central airway morphology have been used in clinical, epidemiologic, and genetic investigation as an inference of the presence and severity of small-airway disease in smokers. Although several association studies have brought us to believe that these computed tomographic measures reflect airway remodeling, a careful review of such data and more recent evidence may reveal underappreciated complexity to these measures and limitations that prompt us to question that belief. This Perspective offers a review of seminal papers and alternative explanations of their data in the light of more recent evidence. The relationships between airway morphology and lung function are observed in subjects who never smoked, implying that native airway structure indeed contributes to lung function; computed tomographic measures of central airways such as wall area, lumen area, and total bronchial area are smaller in smokers with chronic obstructive pulmonary disease versus those without chronic obstructive pulmonary disease; and the airways are smaller as disease severity increases. The observations suggest that (1) native airway morphology likely contributes to the relationships between computed tomographic measures of airways and lung function; and (2) the presence of smaller airways in those with chronic obstructive pulmonary disease versus those without chronic obstructive pulmonary disease as well as their decrease with disease severity suggests that smokers with chronic obstructive pulmonary disease may simply have smaller airways to begin with, which put them at greater risk for the development of smoking-related disease.