Application of high-resolution CT imaging data to lung cancer drug development: measuring progress: workshop IX.

Background: Lung cancer is the leading cause of cancer death and a major public health challenge across the entire world. Computed tomography (CT) imaging of the lung is a rapidly improving medical imaging technique. Spiral CT has been reported to not only improve the early detection of lung cancer in screening high-risk tobacco-exposed populations but also to assist in the clinical assessment of new agents for therapy in lung cancer.

Emphysema classification based on embedded probabilistic PCA.

In this article we investigate the suitability of a manifold learning technique to classify different types of emphysema based on embedded Probabilistic PCA (PPCA). Our approach finds the most discriminant linear space for each emphysema pattern against the remaining patterns where lung CT image patches can be embedded. In this embedded space, we train a PPCA model for each pattern.

Distinct quantitative computed tomography emphysema patterns are associated with physiology and function in smokers.

Rationale: Emphysema occurs in distinct pathologic patterns, but little is known about the epidemiologic associations of these patterns. Standard quantitative measures of emphysema from computed tomography (CT) do not distinguish between distinct patterns of parenchymal destruction.

Objectives: To study the epidemiologic associations of distinct emphysema patterns with measures of lung-related physiology, function, and health care use in smokers.

MUC5B promoter polymorphism and interstitial lung abnormalities.

Background: A common promoter polymorphism (rs35705950) in MUC5B, the gene encoding mucin 5B, is associated with idiopathic pulmonary fibrosis. It is not known whether this polymorphism is associated with interstitial lung disease in the general population.

Methods: We performed a blinded assessment of interstitial lung abnormalities detected in 2633 participants in the Framingham Heart Study by means of volumetric chest computed tomography (CT).

Computed tomographic measures of pulmonary vascular morphology in smokers and their clinical implications.

Rationale: Angiographic investigation suggests that pulmonary vascular remodeling in smokers is characterized by distal pruning of the blood vessels.

Objectives: Using volumetric computed tomography scans of the chest we sought to quantitatively evaluate this process and assess its clinical associations.

Methods: Pulmonary vessels were automatically identified, segmented, and measured.

Paired inspiratory-expiratory chest CT scans to assess for small airways disease in COPD.

Background: Gas trapping quantified on chest CT scans has been proposed as a surrogate for small airway disease in COPD. We sought to determine if measurements using paired inspiratory and expiratory CT scans may be better able to separate gas trapping due to emphysema from gas trapping due to small airway disease.

Methods: Smokers with and without COPD from the COPDGene Study underwent inspiratory and expiratory chest CT scans.

Effect of emphysema on CT scan measures of airway dimensions in smokers.

Background: In CT scans of smokers with COPD, the subsegmental airway wall area percent (WA%) is greater and more strongly correlated with FEV1 % predicted than WA% obtained in the segmental airways. Because emphysema is linked to loss of airway tethering and may limit airway expansion, increases in WA% may be related to emphysema and not solely to remodeling. We aimed to first determine whether the stronger association of subsegmental vs segmental WA% with FEV1 % predicted is mitigated by emphysema and, second, to assess the relationships among emphysema, WA%, and total bronchial area (TBA).

Aorta segmentation with a 3D level set approach and quantification of aortic calcifications in non-contrast chest CT.

Automatic aorta segmentation in thoracic computed tomography (CT) scans is important for aortic calcification quantification and to guide the segmentation of other central vessels. We propose an aorta segmentation algorithm consisting of an initial boundary detection step followed by 3D level set segmentation for refinement. Our algorithm exploits aortic cross-sectional circularity: we first detect aorta boundaries with a circular Hough transform on axial slices to detect ascending and descending aorta regions, and we apply the Hough transform on oblique slices to detect the aortic arch.

Comparative study of NOTES alone versus NOTES guided by a new image registration system for navigation in the mediastinum: a study in a porcine model.

Background: Natural orifice transluminal endoscopic surgery (NOTES) mediastinoscopy (MED) through the esophagus has proved to be feasible in the animal model. However, injury of the adjacent pleura and pneumothorax has been reported as a frequent adverse event when using a blind access.

Objective: To assess the utility and safety of a CT-based image registration system (IRS) for navigation in the mediastinum.

Optimal real-time estimation in diffusion tensor imaging.

Diffusion tensor imaging (DTI) constitutes the most used paradigm among the diffusion-weighted magnetic resonance imaging (DW-MRI) techniques due to its simplicity and application potential. Recently, real-time estimation in DW-MRI has deserved special attention, with several proposals aiming at the estimation of meaningful diffusion parameters during the repetition time of the acquisition sequence. Specifically focusing on DTI, the underlying model of the noise present in the acquired data is not taken into account, leading to a suboptimal estimation of the diffusion tensor.

Statins and pulmonary fibrosis: the potential role of NLRP3 inflammasome activation.

Rationale: The role of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) in the development or progression of interstitial lung disease (ILD) is controversial.

Objectives: To evaluate the association between statin use and ILD.

Methods: We used regression analyses to evaluate the association between statin use and interstitial lung abnormalities (ILA) in a large cohort of smokers from COPDGene.

AUTOMATIC AIRWAY ANALYSIS FOR GENOME-WIDE ASSOCIATION STUDIES IN COPD.

We present an image pipeline for airway phenotype extraction suitable for large-scale genetic and epidemiological studies including genome-wide association studies (GWAS) in Chronic Obstructive Pulmonary Disease (COPD). We use scale-space particles to densely sample intraparenchymal airway locations in a large cohort of high-resolution CT scans. The particle methodology is based on a constrained energy minimization problem that results in a set of candidate airway points situated in both physical space and scale.

COMPUTATIONAL VASCULAR MORPHOMETRY FOR THE ASSESSMENT OF PULMONARY VASCULAR DISEASE BASED ON SCALE-SPACE PARTICLES.

We present a fully automatic computational vascular morphometry (CVM) approach for the clinical assessment of pulmonary vascular disease (PVD). The approach is based on the automatic extraction of the lung intraparenchymal vasculature using scale-space particles. Based on the detected features, we developed a set of image-based biomarkers for the assessment of the disease using the vessel radii estimation provided by the particle's scale.

Association between airway caliber changes with lung inflation and emphysema assessed by volumetric CT scan in subjects with COPD.

Background: An increase in airway caliber (airway distensibility) with lung inflation is attenuated in COPD. Furthermore, some subjects have a decrease in airway caliber with lung inflation. We aimed to test the hypothesis that airway caliber increases are lower in subjects with emphysema-predominant (EP) compared with airway-predominant (AP) CT scan subtypes.

Lung deflation and oxygen pulse in COPD: results from the NETT randomized trial.

Background: In COPD patients, hyperinflation impairs cardiac function. We examined whether lung deflation improves oxygen pulse, a surrogate marker of stroke volume.

Methods: In 129 NETT patients with cardiopulmonary exercise testing (CPET) and arterial blood gases (ABG substudy), hyperinflation was assessed with residual volume to total lung capacity ratio (RV/TLC), and cardiac function with oxygen pulse (O(2) pulse=VO(2)/HR) at baseline and 6 months.

Gender differences of airway dimensions in anatomically matched sites on CT in smokers.

Rationale And Objectives: There are limited data on, and controversies regarding gender differences in the airway dimensions of smokers. Multi-detector CT (MDCT) images were analyzed to examine whether gender could explain differences in airway dimensions of anatomically matched airways in smokers.

Materials And Methods: We used VIDA imaging software to analyze MDCT scans from 2047 smokers (M:F, 1021:1026) from the COPDGene® cohort.

Lung volumes and emphysema in smokers with interstitial lung abnormalities.

Background: Cigarette smoking is associated with emphysema and radiographic interstitial lung abnormalities. The degree to which interstitial lung abnormalities are associated with reduced total lung capacity and the extent of emphysema is not known.

Methods: We looked for interstitial lung abnormalities in 2416 (96%) of 2508 high-resolution computed tomographic (HRCT) scans of the lung obtained from a cohort of smokers.

Kurtosis and skewness of density histograms on inspiratory and expiratory CT scans in smokers.

The aim of this study is to evaluate the relationship between lung function and kurtosis or skewness of lung density histograms on computed tomography (CT) in smokers. Forty-six smokers (age range 46?81 years), enrolled in the Lung Tissue Research Consortium, underwent pulmonary function tests (PFT) and chest CT at full inspiration and full expiration. On both inspiratory and expiratory scans, kurtosis and skewness of the density histograms were automatically measured by open-source software.

Intrathoracic tracheal volume and collapsibility on inspiratory and end-expiratory ct scans correlations with lung volume and pulmonary function in 85 smokers.

Rationale And Objectives: To evaluate the correlations of tracheal volume and collapsibility on inspiratory and end-expiratory computed tomography (CT) with lung volume and with lung function in smokers.

Materials And Methods: The institutional review board approved this study at each institution. 85 smokers (mean age 68, range 45-87 years; 40 females and 45 males) underwent pulmonary function tests and chest CT at full inspiration and end-expiration.

Evaluation of colonoscopy technical skill levels by use of an objective kinematic-based system.

Background: Colonoscopy requires training and experience to ensure accuracy and safety. Currently, no objective, validated process exists to determine when an endoscopist has attained technical competence. Kinematics data describing movements of laparoscopic instruments have been used in surgical skill assessment to define expert surgical technique.

The relationship between small pulmonary vascular alteration and aortic atherosclerosis in chronic obstructive pulmonary disease: quantitative CT analysis.

Rationale And Objectives: The relationship between chronic obstructive pulmonary disease (COPD) and atherosclerosis has been suggested; this association may relate to systemic inflammation and endothelial dysfunction, which can lead to alteration of small pulmonary vessels. The relationship between atherosclerosis and small pulmonary vessel alteration, however, has not been assessed in COPD patients. We tested the hypothesis that the severity of thoracic aortic calcification measured by computed tomography (CT) would be associated with the total cross-sectional area of small pulmonary vessels (CSA) on CT images.

Quantitative assessment of bronchial wall attenuation with thin-section CT: An indicator of airflow limitation in chronic obstructive pulmonary disease.

Objective: The purpose of this study was to evaluate the relation between bronchial wall attenuation on thin-section CT images and airflow limitation in persons with chronic obstructive pulmonary disease.

Subjects And Methods: One hundred fourteen subjects (65 men, 49 women; age range, 56-74 years) enrolled in the National Lung Screening Trial underwent chest CT and prebronchodilation spirometry at a single institution. At CT, mean peak wall attenuation, wall area percentage, and luminal area were measured in the third, fourth, and fifth generations of the right B(1) and B(10) segmental bronchi.

Airway count and emphysema assessed by chest CT imaging predicts clinical outcome in smokers.

Background: Recently, it has been shown that emphysematous destruction of the lung is associated with a decrease in the total number of terminal bronchioles. It is unknown whether a similar decrease is visible in the more proximal airways. We aimed to assess the relationships between proximal airway count, CT imaging measures of emphysema, and clinical prognostic factors in smokers, and to determine whether airway count predicts the BMI, airflow obstruction, dyspnea, and exercise capacity (BODE) index.

Relationship of emphysema and airway disease assessed by CT to exercise capacity in COPD.

Objective: To assess the association of emphysema and airway disease assessed by volumetric computed tomography (CT) with exercise capacity in subjects with chronic obstructive pulmonary disease (COPD).

Methods: We studied 93 subjects with COPD (Forced Expiratory Volume in 1 s [FEV(1)] %predicted mean +/- SD 57.1 +/- 24.

Collapsibility of lung volume by paired inspiratory and expiratory CT scans: correlations with lung function and mean lung density.

Rationale And Objectives: To evaluate the relationship between measurements of lung volume (LV) on inspiratory/expiratory computed tomography (CT) scans, pulmonary function tests (PFT), and CT measurements of emphysema in individuals with chronic obstructive pulmonary disease.

Materials And Methods: Forty-six smokers (20 females and 26 males; age range 46-81 years), enrolled in the Lung Tissue Research Consortium, underwent PFT and chest CT at full inspiration and expiration. Inspiratory and expiratory LV values were automatically measured by open-source software, and the expiratory/inspiratory (E/I) ratio of LV was calculated.