@article {1433737,
	title = {Aorta segmentation with a 3D level set approach and quantification of aortic calcifications in non-contrast chest CT},
	journal = {Conf Proc IEEE Eng Med Biol Soc},
	volume = {2012},
	year = {2012},
	month = {2012},
	pages = {2343-6},
	abstract = {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. The centers and radii of circles detected by Hough transform are fitted to smooth cubic spline functions using least-squares fitting. From these center and radius spline functions, we reconstruct an initial aorta surface using the Frenet frame. This reconstructed tubular surface is further refined with 3D level set evolutions. The level set framework we employ optimizes a functional that depends on both edge strength and smoothness terms and evolves the surface to the position of nearby edge location corresponding to the aorta wall. After aorta segmentation, we first detect the aortic calcifications with thresholding applied to the segmented aorta region. We then filter out the false positive regions due to nearby high intensity structures. We tested the algorithm on 45 CT scans and obtained a closest point mean error of 0.52 {\textpm} 0.10 mm between the manually and automatically segmented surfaces. The true positive detection rate of calcification algorithm was 0.96 over all CT scans.},
	keywords = {Aortic Diseases, Aortography, Calcinosis, Contrast Media, Humans, Imaging, Three-Dimensional, Pattern Recognition, Automated, Radiographic Image Interpretation, Computer-Assisted, Radiography, Thoracic, Reproducibility of Results, Sensitivity and Specificity, Tomography, X-Ray Computed},
	issn = {1557-170X},
	doi = {10.1109/EMBC.2012.6346433},
	author = {Kurugol, Sila and Estepar, Raul San Jose and Ross, James and Washko, George R}
}
@article {1433734,
	title = {Association between airway caliber changes with lung inflation and emphysema assessed by volumetric CT scan in subjects with COPD},
	journal = {Chest},
	volume = {141},
	number = {3},
	year = {2012},
	month = {2012 Mar},
	pages = {736-744},
	abstract = {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. Additionally, we compared clinical and CT scan features of subjects with (airway constrictors) and without a decrease in airway caliber.

METHODS: Based on GOLD (Global Initiative for Chronic Obstructive Lung Disease) stages and CT scan subtypes, we created a control group (n = 46) and the following matched COPD groups (n = 23 each): GOLD-2-AP, GOLD-2-EP, GOLD-4-AP, and GOLD-4-EP. From the CT scans of all 138 subjects, we measured emphysema, lung volumes, and caliber changes in the third and fourth airway generations of two bronchi. We expressed airway distensibility (ratio of airway lumen diameter change to lung volume change from end tidal breathing to full inspiration) as a global or lobar measure based on normalization by whole-lung or lobar volume changes.

RESULTS: Global distensibility in the third and fourth airway generations was significantly lower in the GOLD-2-EP and GOLD-4-EP groups than in control subjects. In GOLD-2 subjects, lobar distensibility of the right-upper-lobe fourth airway generation was significantly lower in those with EP than in those with AP. In multivariate analysis, emphysema was an independent determinant of global and lobar airway distensibility. Compared with nonconstrictors, airway constrictors experienced more dyspnea, were more hyperinflated, and had a higher percentage of emphysema.

CONCLUSIONS: Distensibility of large- to medium-sized airways is reduced in subjects with an EP CT scan subtype. Emphysema seems to alter airway-parenchyma interdependence.

TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00608764; URL: www.clinicaltrials.gov.},
	keywords = {Aged, Case-Control Studies, Female, Forced Expiratory Volume, Humans, Lung, Lung Volume Measurements, Male, Middle Aged, Pulmonary Disease, Chronic Obstructive, Pulmonary Emphysema, Respiratory Function Tests, Respiratory System, Severity of Illness Index, Tomography, X-Ray Computed},
	issn = {1931-3543},
	doi = {10.1378/chest.11-1026},
	author = {Diaz, Alejandro A and Come, Carolyn E and Ross, James C and San Jos{\'e} Est{\'e}par, Ra{\'u}l and Han, MeiLan K and Loring, Stephen H and Silverman, Edwin K and Washko, George R}
}
@article {1433738,
	title = {AUTOMATIC AIRWAY ANALYSIS FOR GENOME-WIDE ASSOCIATION STUDIES IN COPD},
	journal = {Proc IEEE Int Symp Biomed Imaging},
	year = {2012},
	month = {2012},
	pages = {1467-1470},
	abstract = {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. Those points are further clustered using connected components filtering to increase their specificity. Finally, we use the particle locations to perform airway wall detection using an edge detector based on the zero-crossing of the second order derivative. Given the airway wall locations, we compute three phenotypes for airway disease: wall thickening (Pi10,WA\%) and luminal remodeling (P\%). We validate the airway extraction technique and present results in 2,500 scans for the association of the extracted phenotypes with clinical outcomes that will be deployed as part of the COPDGene study GWAS analysis.},
	issn = {1945-7928},
	doi = {10.1109/ISBI.2012.6235848},
	author = {San Jos{\'e} Est{\'e}par, Ra{\'u}l and Ross, James C and Kindlmann, Gordon L and Diaz, Alejandro and Okajima, Yuka and Kikinis, Ron and Westin, Carl-Fredrik and Silverman, Edwin K and Washko, George G}
}
@article {1433739,
	title = {COMPUTATIONAL VASCULAR MORPHOMETRY FOR THE ASSESSMENT OF PULMONARY VASCULAR DISEASE BASED ON SCALE-SPACE PARTICLES},
	journal = {Proc IEEE Int Symp Biomed Imaging},
	year = {2012},
	month = {2012},
	pages = {1479-1482},
	abstract = {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{\textquoteright}s scale. The biomarkers are based on the interrelation between vessel cross-section area and blood volume. We validate our vascular extraction method using simulated data with different complexity and we present results in 2,500 CT scans with different degrees of chronic obstructive pulmonary disease (COPD) severity. Results indicate that our CVM pipeline may track vascular remodeling present in COPD and it can be used in further clinical studies to assess the involvement of PVD in patient populations.},
	issn = {1945-7928},
	doi = {10.1109/ISBI.2012.6235851},
	author = {San Jos{\'e} Est{\'e}par, Ra{\'u}l and Ross, James C and Krissian, Karl and Schultz, Thomas and Washko, George R and Kindlmann, Gordon L}
}
@article {1433740,
	title = {Lung deflation and oxygen pulse in COPD: results from the NETT randomized trial},
	journal = {Respir Med},
	volume = {106},
	number = {1},
	year = {2012},
	month = {2012 Jan},
	pages = {109-19},
	abstract = {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. Medical and surgical patients were divided into "deflators" and "non-deflators" based on change in RV/TLC from baseline (∆RV/TLC). We defined deflation as the ∆RV/TLC experienced by 75\% of surgical patients. We examined changes in O(2) pulse at peak and similar (iso-work) exercise. Findings were validated in 718 patients who underwent CPET without ABGs.

RESULTS: In the ABG substudy, surgical and medical deflators improved their RV/TLC and peak O(2) pulse (median ∆RV/TLC -18.0\% vs. -9.3\%, p=0.0003; median ∆O(2) pulse 13.6\% vs. 1.8\%, p=0.12). Surgical deflators also improved iso-work O(2) pulse (0.53 mL/beat, p=0.04 at 20 W). In the validation cohort, surgical deflators experienced a greater improvement in peak O(2) pulse than medical deflators (mean 18.9\% vs. 1.1\%). In surgical deflators improvements in O(2) pulse at rest and during unloaded pedaling (0.32 mL/beat, p,
	keywords = {Aged, Blood Gas Analysis, Cohort Studies, Exercise Test, Female, Forced Expiratory Volume, Humans, Lung, Male, Middle Aged, Multivariate Analysis, Oxygen Consumption, Pneumonectomy, Pulmonary Disease, Chronic Obstructive, Stroke Volume, Total Lung Capacity},
	issn = {1532-3064},
	doi = {10.1016/j.rmed.2011.07.012},
	author = {Come, Carolyn E and Divo, Miguel J and San Jos{\'e} Est{\'e}par, Ra{\'u}l and Sciurba, Frank C and Criner, Gerard J and Marchetti, Nathaniel and Scharf, Steven M and Mosenifar, Zab and Make, Barry J and Keller, Cesar A and Minai, Omar A and Martinez, Fernando J and Han, MeiLan K and Reilly, John J and Celli, Bartolome R and Washko, George R}
}
@article {1433735,
	title = {Parturient Montes},
	journal = {Radiology},
	volume = {262},
	number = {3},
	year = {2012},
	month = {2012 Mar},
	pages = {1042; author reply 1043},
	keywords = {Female, Humans, Male, Pulmonary Disease, Chronic Obstructive, Tomography, X-Ray Computed},
	issn = {1527-1315},
	doi = {10.1148/radiol.11112039},
	author = {Milne, Eric N C and Han, MeiLan K and Washko, George R}
}
@article {1433736,
	title = {Rate of decline in FEV1: is emphysema the culprit?},
	journal = {Am J Respir Crit Care Med},
	volume = {185},
	number = {1},
	year = {2012},
	month = {2012 Jan 01},
	pages = {2-3},
	keywords = {Bronchodilator Agents, Female, Humans, Male, Pulmonary Disease, Chronic Obstructive, Radiography, Respiratory Physiological Phenomena},
	issn = {1535-4970},
	doi = {10.1164/rccm.201111-1938ED},
	author = {Washko, George R}
}
@article {1433733,
	title = {A combined pulmonary-radiology workshop for visual evaluation of COPD: study design, chest CT findings and concordance with quantitative evaluation},
	journal = {COPD},
	volume = {9},
	number = {2},
	year = {2012},
	month = {2012 Apr},
	pages = {151-9},
	abstract = {UNLABELLED: The purposes of this study were: to describe chest CT findings in normal non-smoking controls and cigarette smokers with and without COPD; to compare the prevalence of CT abnormalities with severity of COPD; and to evaluate concordance between visual and quantitative chest CT (QCT) scoring.

METHODS: Volumetric inspiratory and expiratory CT scans of 294 subjects, including normal non-smokers, smokers without COPD, and smokers with GOLD Stage I-IV COPD, were scored at a multi-reader workshop using a standardized worksheet. There were 58 observers (33 pulmonologists, 25 radiologists); each scan was scored by 9-11 observers. Interobserver agreement was calculated using kappa statistic. Median score of visual observations was compared with QCT measurements.

RESULTS: Interobserver agreement was moderate for the presence or absence of emphysema and for the presence of panlobular emphysema; fair for the presence of centrilobular, paraseptal, and bullous emphysema subtypes and for the presence of bronchial wall thickening; and poor for gas trapping, centrilobular nodularity, mosaic attenuation, and bronchial dilation. Agreement was similar for radiologists and pulmonologists. The prevalence on CT readings of most abnormalities (e.g. emphysema, bronchial wall thickening, mosaic attenuation, expiratory gas trapping) increased significantly with greater COPD severity, while the prevalence of centrilobular nodularity decreased. Concordances between visual scoring and quantitative scoring of emphysema, gas trapping and airway wall thickening were 75\%, 87\% and 65\%, respectively.

CONCLUSIONS: Despite substantial inter-observer variation, visual assessment of chest CT scans in cigarette smokers provides information regarding lung disease severity; visual scoring may be complementary to quantitative evaluation.},
	keywords = {Aged, Case-Control Studies, Education, Emphysema, Female, Humans, Lung, Male, Middle Aged, Observer Variation, Prevalence, Pulmonary Disease, Chronic Obstructive, Research Design, Smoking, Tomography, X-Ray Computed},
	issn = {1541-2563},
	doi = {10.3109/15412555.2012.654923},
	author = {Barr, R Graham and Berkowitz, Eugene A and Bigazzi, Francesca and Bode, Frederick and Bon, Jessica and Bowler, Russell P and Chiles, Caroline and Crapo, James D and Criner, Gerard J and Curtis, Jeffrey L and Dass, Chandra and Dirksen, Asger and Dransfield, Mark T and Edula, Goutham and Erikkson, Leif and Friedlander, Adam and Galperin-Aizenberg, Maya and Gefter, Warren B and Gierada, David S and Grenier, Philippe A and Goldin, Jonathan and Han, MeiLan K and Hanania, Nicola A and Hansel, Nadia N and Jacobson, Francine L and Kauczor, Hans-Ulrich and Kinnula, Vuokko L and Lipson, David A and Lynch, David A and MacNee, William and Make, Barry J and Mamary, A James and Mann, Howard and Marchetti, Nathaniel and Mascalchi, Mario and McLennan, Geoffrey and Murphy, James R and Naidich, David and Nath, Hrudaya and Newell, John D and Pistolesi, Massimo and Regan, Elizabeth A and Reilly, John J and Sandhaus, Robert and Schroeder, Joyce D and Sciurba, Frank and Shaker, Saher and Sharafkhaneh, Amir and Silverman, Edwin K and Steiner, Robert M and Strange, Charlton and Sverzellati, Nicola and Tashjian, Joseph H and van Beek, Edwin J R and Washington, Lacey and Washko, George R and Westney, Gloria and Wood, Susan A and Woodruff, Prescott G}
}
@article {1433732,
	title = {Interstitial lung abnormalities and reduced exercise capacity},
	journal = {Am J Respir Crit Care Med},
	volume = {185},
	number = {7},
	year = {2012},
	month = {2012 Apr 01},
	pages = {756-62},
	abstract = {RATIONALE: The relationship between interstitial lung abnormalities (ILA) and exercise capacity has not been comprehensively evaluated.

OBJECTIVES: To assess the validity of the 6-minute walk test in subjects with ILA, and to examine the association between ILA and 6-minute walk distance (6MWD).

METHODS: Spearman correlation coefficients were used to assess the strength of the relationships between 6MWD and relevant measures of dyspnea, health-related quality of life, and pulmonary function in a cohort of 2,416 people who smoke from the COPDGene study. Unadjusted and adjusted linear and logistic regression models were used to assess the strength of the association between ILA and 6MWD.

MEASUREMENTS AND MAIN RESULTS: In all subjects, and in those with ILA, 6MWD in COPDGene was associated with relevant clinical and physiologic measures. The mean 6MWD in COPDGene subjects with ILA was 386 m (SD, 128 m), and 82\% and 19\% of subjects with ILA had 6MWDs less than or equal to 500 and 250 m, respectively. ILA was associated with a reduced 6MWD in univariate (-30 m; 95\% confidence interval, -50 to -10; P = 0.004) and multivariate models (-19 m; 95\% confidence interval, -33 to -5; P = 0.008). Compared with subjects without ILA, subjects with ILA had an 80\% and 77\% increase in their odds to have a walk distance limited to less than or equal to 500 and 250 m, respectively. Although these findings were dependent on ILA subtype, they were not limited to those with COPD.

CONCLUSIONS: Our study demonstrates that ILA is associated with measurable decrements in the 6MWD of people who smoke. Clinical trial registered with www.clinicaltrials.gov (NCT 00608764).},
	keywords = {Aged, Exercise Test, Exercise Tolerance, Female, Humans, Lung Diseases, Interstitial, Male, Middle Aged, Pulmonary Disease, Chronic Obstructive, Smoking, Walking},
	issn = {1535-4970},
	doi = {10.1164/rccm.201109-1618OC},
	author = {Doyle, Tracy J and Washko, George R and Fernandez, Isis E and Nishino, Mizuki and Okajima, Yuka and Yamashiro, Tsuneo and Divo, Miguel J and Celli, Bartolome R and Sciurba, Frank C and Silverman, Edwin K and Hatabu, Hiroto and Rosas, Ivan O and Hunninghake, Gary M}
}
@article {1433728,
	title = {Long-term comparative immunogenicity of protein conjugate and free polysaccharide pneumococcal vaccines in chronic obstructive pulmonary disease},
	journal = {Clin Infect Dis},
	volume = {55},
	number = {5},
	year = {2012},
	month = {2012 Sep},
	pages = {e35-44},
	abstract = {BACKGROUND: Although the 23-valent pneumococcal polysaccharide vaccine (PPSV23) protects against invasive disease in young healthy persons, randomized controlled trials in chronic obstructive pulmonary disease (COPD) have demonstrated no benefit in the intention-to-treat population. We previously reported that the 7-valent diphtheria-conjugated pneumococcal polysaccharide vaccine (PCV7) is safe and induced greater serotype-specific immunoglobulin G (IgG) and functional antibody than did PPSV23 1 month after vaccination. We hypothesized that these advantages would persist at 1 and 2 years.

METHODS: One hundred eighty-one patients with moderate to severe COPD were randomized to receive PPSV23 (n = 90) or PCV7 (1.0 mL; n = 91). We measured IgG by enzyme-linked immunosorbent assay and assessed functional antibody activity by a standardized opsonophagocytosis assay, reported as a killing index (OPK). We determined differences in IgG and OPK between vaccine groups at 1 and 2 years.

RESULTS: Relative to PPSV23, PCV7 induced greater OPK at both 1 and 2 years for 6 of 7 serotypes (not 19F). This response was statistically greater for 5 of 7 serotypes at 1 year and 4 of 7 at 2 years. Comparable differences in IgG were observed but were less often statistically significant. Despite meeting Centers for Disease Control and Prevention criteria for PPSV23 administration, almost 50\% of individuals had never been vaccinated. No differences in the frequency of acute exacerbations, pneumonia, or hospitalization were observed.

CONCLUSIONS: PCV7 induces a greater functional antibody response than PPSV23 in patients with COPD that persists for 2 years after vaccination. This superior functional response supports testing of conjugate vaccination in studies examining clinical end points.

CLINICAL TRIALS REGISTRATION: NCT00457977.},
	keywords = {Aged, Cohort Studies, Female, Heptavalent Pneumococcal Conjugate Vaccine, Humans, Immunoglobulin G, Male, Middle Aged, Phagocytosis, Pneumococcal Infections, Pneumococcal Vaccines, Proportional Hazards Models, Pulmonary Disease, Chronic Obstructive},
	issn = {1537-6591},
	doi = {10.1093/cid/cis513},
	author = {Dransfield, Mark T and Harnden, Sarah and Burton, Robert L and Albert, Richard K and Bailey, William C and Casaburi, Richard and Connett, John and Cooper, J Allen D and Criner, Gerard J and Curtis, Jeffrey L and Han, MeiLan K and Make, Barry and Marchetti, Nathaniel and Martinez, Fernando J and McEvoy, Charlene and Nahm, Moon H and Niewoehner, Dennis E and Porszasz, Janos and Reilly, John and Scanlon, Paul D and Scharf, Steven M and Sciurba, Frank C and Washko, George R and Woodruff, Prescott G and Lazarus, Stephen C}
}
@article {1433730,
	title = {Optimal real-time estimation in diffusion tensor imaging},
	journal = {Magn Reson Imaging},
	volume = {30},
	number = {4},
	year = {2012},
	month = {2012 May},
	pages = {506-17},
	abstract = {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. In this paper, we propose an optimal real-time estimation framework for DTI reconstruction in single-coil acquisitions. By including an online estimation of the time-changing noise variance associated to the acquisition process, the proposed method achieves the sequential best linear unbiased estimator. Results on both synthetic and real data show that our method outperforms those so far proposed, reaching the best performance of the existing proposals by processing a substantially lower number of diffusion images.},
	keywords = {Algorithms, Anisotropy, Brain Mapping, Diffusion Tensor Imaging, Humans, Image Processing, Computer-Assisted},
	issn = {1873-5894},
	doi = {10.1016/j.mri.2011.12.001},
	author = {Casaseca-de-la-Higuera, Pablo and Trist{\'a}n-Vega, Antonio and Aja-Fern{\'a}ndez, Santiago and Alberola-L{\'o}pez, Carlos and Westin, Carl-Fredrik and San Jos{\'e} Est{\'e}par, Ra{\'u}l}
}
@article {1433727,
	title = {Pulmonary arterial enlargement and acute exacerbations of COPD},
	journal = {N Engl J Med},
	volume = {367},
	number = {10},
	year = {2012},
	month = {2012 Sep 06},
	pages = {913-21},
	abstract = {BACKGROUND: Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with accelerated loss of lung function and death. Identification of patients at risk for these events, particularly those requiring hospitalization, is of major importance. Severe pulmonary hypertension is an important complication of advanced COPD and predicts acute exacerbations, though pulmonary vascular abnormalities also occur early in the course of the disease. We hypothesized that a computed tomographic (CT) metric of pulmonary vascular disease (pulmonary artery enlargement, as determined by a ratio of the diameter of the pulmonary artery to the diameter of the aorta [PA:A ratio] of >1) would be associated with severe COPD exacerbations.

METHODS: We conducted a multicenter, observational trial that enrolled current and former smokers with COPD. We determined the association between a PA:A ratio of more than 1 and a history at enrollment of severe exacerbations requiring hospitalization and then examined the usefulness of the ratio as a predictor of these events in a longitudinal follow-up of this cohort, as well as in an external validation cohort. We used logistic-regression and zero-inflated negative binomial regression analyses and adjusted for known risk factors for exacerbation.

RESULTS: Multivariate logistic-regression analysis showed a significant association between a PA:A ratio of more than 1 and a history of severe exacerbations at the time of enrollment in the trial (odds ratio, 4.78; 95\% confidence interval [CI], 3.43 to 6.65; P,
	keywords = {Acute Disease, Aged, Aorta, Aortography, Female, Humans, Logistic Models, Male, Middle Aged, Observation, Pulmonary Artery, Pulmonary Disease, Chronic Obstructive, Recurrence, Risk Factors, Smoking, Tomography, X-Ray Computed},
	issn = {1533-4406},
	doi = {10.1056/NEJMoa1203830},
	author = {Wells, J Michael and Washko, George R and Han, MeiLan K and Abbas, Naseer and Nath, Hrudaya and Mamary, A James and Regan, Elizabeth and Bailey, William C and Martinez, Fernando J and Westfall, Elizabeth and Beaty, Terri H and Curran-Everett, Douglas and Curtis, Jeffrey L and Hokanson, John E and Lynch, David A and Make, Barry J and Crapo, James D and Silverman, Edwin K and Bowler, Russell P and Dransfield, Mark T}
}
@article {1433731,
	title = {Relationship between quantitative CT metrics and health status and BODE in chronic obstructive pulmonary disease},
	journal = {Thorax},
	volume = {67},
	number = {5},
	year = {2012},
	month = {2012 May},
	pages = {399-406},
	abstract = {BACKGROUND: The value of quantitative CT (QCT) to identify chronic obstructive pulmonary disease (COPD) phenotypes is increasingly appreciated. The authors hypothesised that QCT-defined emphysema and airway abnormalities relate to St George{\textquoteright}s Respiratory Questionnaire (SGRQ) and Body-Mass Index, Airflow Obstruction, Dyspnea and Exercise Capacity Index (BODE).

METHODS: 1200 COPDGene subjects meeting Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria for COPD with QCT analysis were included. Total lung emphysema was measured using the density mask technique with a -950 Hounsfield unit threshold. An automated programme measured mean wall thickness (WT), wall area percentage (WA\%) and 10 mm lumenal perimeter (pi10) in six segmental bronchi. Separate multivariate analyses examined the relative influence of airway measures and emphysema on SGRQ and BODE.

RESULTS: In separate models predicting SGRQ score, a 1 unit SD increase in each airway measure predicted higher SGRQ scores (for WT, 1.90 points higher, p=0.002; for WA\%, 1.52 points higher, p=0.02; for pi10, 2.83 points higher p,
	keywords = {Aged, Aged, 80 and over, Body Mass Index, Dyspnea, Emphysema, Female, Health Status, Humans, Lung, Male, Middle Aged, Multivariate Analysis, Pulmonary Disease, Chronic Obstructive, Regression Analysis, Spirometry, Surveys and Questionnaires, Tomography, X-Ray Computed},
	issn = {1468-3296},
	doi = {10.1136/thoraxjnl-2011-201185},
	author = {Martinez, Carlos H and Chen, Ya-Hong and Westgate, Phillip M and Liu, Lyrica X and Murray, Susan and Curtis, Jeffrey L and Make, Barry J and Kazerooni, Ella A and Lynch, David A and Marchetti, Nathaniel and Washko, George R and Martinez, Fernando J and Han, MeiLan K}
}
@article {1433729,
	title = {The role and potential of imaging in COPD},
	journal = {Med Clin North Am},
	volume = {96},
	number = {4},
	year = {2012},
	month = {2012 Jul},
	pages = {729-43},
	abstract = {Chronic obstructive pulmonary disease is a heterogeneous condition of the lungs and body. Techniques in chest imaging and quantitative image analysis provide novel in vivo insight into the disease and potentially examine divergent responses to therapy. This article reviews the strengths and limitations of the leading imaging techniques: computed tomography, magnetic resonance imaging, positron emission tomography, and optical coherence tomography. Following an explanation of the technique, each section details some of the useful information obtained with these examinations. Future clinical care and investigation will likely include some combination of these imaging modalities and more standard assessments of disease severity.},
	keywords = {Airway Remodeling, Humans, Magnetic Resonance Imaging, Phenotype, Positron-Emission Tomography, Pulmonary Disease, Chronic Obstructive, Tomography, Optical Coherence, Tomography, X-Ray Computed},
	issn = {1557-9859},
	doi = {10.1016/j.mcna.2012.05.003},
	author = {Washko, George R}
}
@article {1433726,
	title = {TLR4 deficiency promotes autophagy during cigarette smoke-induced pulmonary emphysema},
	journal = {Am J Physiol Lung Cell Mol Physiol},
	volume = {303},
	number = {9},
	year = {2012},
	month = {2012 Nov 01},
	pages = {L748-57},
	abstract = {Toll-like receptors (TLRs) exert important nonimmune functions in lung homeostasis. TLR4 deficiency promotes pulmonary emphysema. We examined the role of TLR4 in regulating cigarette smoke (CS)-induced autophagy, apoptosis, and emphysema. Lung tissue was obtained from chronic obstructive lung disease (COPD) patients. C3H/HeJ (Tlr4-mutated) mice and C57BL/10ScNJ (Tlr4-deficient) mice and their respective control strains were exposed to chronic CS or air. Human or mouse epithelial cells (wild-type, Tlr4-knockdown, and Tlr4-deficient) were exposed to CS-extract (CSE). Samples were analyzed for TLR4 expression, and for autophagic or apoptotic proteins by Western blot analysis or confocal imaging. Chronic obstructive lung disease lung tissues and human pulmonary epithelial cells exposed to CSE displayed increased TLR4 expression, and increased autophagic [microtubule-associated protein-1 light-chain-3B (LC3B)] and apoptotic (cleaved caspase-3) markers. Beas-2B cells transfected with TLR4 siRNA displayed increased expression of LC3B relative to control cells, basally and after exposure to CSE. The basal and CSE-inducible expression of LC3B and cleaved caspase-3 were elevated in pulmonary alveolar type II cells from Tlr4-deficient mice. Wild-type mice subjected to chronic CS-exposure displayed airspace enlargement;, however, the Tlr4-mutated or Tlr4-deficient mice exhibited a marked increase in airspace relative to wild-type mice after CS-exposure. The Tlr4-mutated or Tlr4-deficient mice showed higher levels of LC3B under basal conditions and after CS exposure. The expression of cleaved caspase-3 was markedly increased in Tlr4-deficient mice exposed to CS. We describe a protective regulatory function of TLR4 against emphysematous changes of the lung in response to CS.},
	keywords = {Aged, Aged, 80 and over, Animals, Apoptosis, Autophagy, Case-Control Studies, Caspase 3, Cells, Cultured, Female, Gene Expression, Humans, Lung, Male, Mice, Mice, Inbred C3H, Mice, Inbred C57BL, Microtubule-Associated Proteins, Middle Aged, Oxidative Stress, Primary Cell Culture, Pulmonary Disease, Chronic Obstructive, Pulmonary Emphysema, Smoking, Toll-Like Receptor 4},
	issn = {1522-1504},
	doi = {10.1152/ajplung.00102.2012},
	author = {An, Chang Hyeok and Wang, Xiao Mei and Lam, Hilaire C and Ifedigbo, Emeka and Washko, George R and Ryter, Stefan W and Choi, Augustine M K}
}
@article {473251,
	title = {Toward Optimum Resection Margins: Preliminary Studies in Soft-Tissue Sarcoma Surgery},
	journal = {International journal of computer assisted radiology and surgeryInternational journal of computer assisted radiology and surgery},
	volume = {7},
	year = {2012},
	pages = {436-437},
	publisher = {Springer-Verlag},
	author = {Garc{\'\i}a-V{\'a}zquez, Veronica and San Jose Est{\'e}par, Ra{\'u}l and Colen, Rivka R and Jayender, Jagadeesan and Walsh, Connor R and Lapidus, M and Pascua, Javier and Desco, Manuel and Raut, C P and Kirby G. Vosburgh}
}
@report {473211,
	title = {Providing Guidance on Lung Cancer Screening To Patients and Physicians },
	year = {2012},
	month = {May},
	institution = {American Lung Association},
	author = {Samet, Jonathan and Crowell, Richard and San Jose Est{\'e}par, Ra{\'u}l and Powe, Neil and Rand, Cynthia and Rizzo, Albert and Yung, Rex}
}
@article {473221,
	title = {Aorta segmentation with a 3D level set approach and quantification of aortic calcifications in non-contrast chest CT.},
	journal = {Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. ConferenceConference proceedings : ... Annual International Conference of the IEEE Engi},
	volume = {2012},
	year = {2012},
	month = {Feb 01},
	pages = {2343-2346},
	abstract = {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. The centers and radii of circles detected by Hough transform are fitted to smooth cubic spline functions using least-squares fitting. From these center and radius spline functions, we reconstruct an initial aorta surface using the Frenet frame. This reconstructed tubular surface is further refined with 3D level set evolutions. The level set framework we employ optimizes a functional that depends on both edge strength and smoothness terms and evolves the surface to the position of nearby edge location corresponding to the aorta wall. After aorta segmentation, we first detect the aortic calcifications with thresholding applied to the segmented aorta region. We then filter out the false positive regions due to nearby high intensity structures. We tested the algorithm on 45 CT scans and obtained a closest point mean error of 0.52 {\textpm} 0.10 mm between the manually and automatically segmented surfaces. The true positive detection rate of calcification algorithm was 0.96 over all CT scans. View full abstract},
	author = {Kurugol, Sila and San Jose Est{\'e}par, Ra{\'u}l and Ross, James and Washko, George R}
}
@article {473216,
	title = {Association Between Airway Caliber Changes With Lung Inflation and Emphysema Assessed by Volumetric CT Scan in Subjects With COPD.},
	journal = {ChestChest},
	volume = {141},
	year = {2012},
	month = {Apr},
	pages = {736-744},
	abstract = {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. Additionally, we compared clinical and CT scan features of subjects with (airway constrictors) and without a decrease in airway caliber. METHODS: Based on GOLD (Global Initiative for Chronic Obstructive Lung Disease) stages and CT scan subtypes, we created a control group (n = 46) and the following matched COPD groups (n = 23 each): GOLD-2-AP, GOLD-2-EP, GOLD-4-AP, and GOLD-4-EP. From the CT scans of all 138 subjects, we measured emphysema, lung volumes, and caliber changes in the third and fourth airway generations of two bronchi. We expressed airway distensibility (ratio of airway lumen diameter change to lung volume change from end tidal breathing to full inspiration) as a global or lobar measure based on normalization by whole-lung or lobar volume changes. RESULTS: Global distensibility in the third and fourth airway generations was significantly lower in the GOLD-2-EP and GOLD-4-EP groups than in control subjects. In GOLD-2 subjects, lobar distensibility of the right-upper-lobe fourth airway generation was significantly lower in those with EP than in those with AP. In multivariate analysis, emphysema was an independent determinant of global and lobar airway distensibility. Compared with nonconstrictors, airway constrictors experienced more dyspnea, were more hyperinflated, and had a higher percentage of emphysema. CONCLUSIONS: Distensibility of large- to medium-sized airways is reduced in subjects with an EP CT scan subtype. Emphysema seems to alter airway-parenchyma interdependence. Trial registry: ClinicalTrials.gov; No.: NCT00608764; URL: www.clinicaltrials.gov.},
	author = {Diaz, Alejandro A and Come, Carolyn E and Ross, James C and San Jose Est{\'e}par, Ra{\'u}l and Han, MeiLan K and Loring, Stephen H and Silverman, Edwin K and Washko, George R and for the COPDGene Investigators}
}
@article {473241,
	title = {Automatic Airway Analysis for Genome-Wide Association Studies in Copd.},
	journal = {Proceedings / IEEE International Symposium on Biomedical Imaging: from nano to macro. IEEE International Symposium on Biomedical ImagingProceedings / IEEE International Symposium on Biomedical Imaging: from nano to macro. IEEE International Symposium on B},
	year = {2012},
	pages = {1467-1470},
	address = {Barcelona},
	abstract = {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. Those points are further clustered using connected components filtering to increase their specificity. Finally, we use the particle locations to perform airway wall detection using an edge detector based on the zero-crossing of the second order derivative. Given the airway wall locations, we compute three phenotypes for airway disease: wall thickening (Pi10,WA\%) and luminal remodeling (P\%). We validate the airway extraction technique and present results in 2,500 scans for the association of the extracted phenotypes with clinical outcomes that will be deployed as part of the COPDGene study GWAS analysis.},
	author = {San Jose Est{\'e}par, Ra{\'u}l and Ross, James C and Kindlmann, Gordon L and Diaz, Alejandro and Okajima, Yuka and Kikinis, Ron and Westin, Carl-Fredrik and Silverman, Edwin K and Washko, George G}
}
@article {473236,
	title = {Computational Vascular Morphometry for the Assessment of Pulmonary Vascular Disease Based on Scale-Space Particles.},
	journal = {Proceedings / IEEE International Symposium on Biomedical Imaging: from nano to macro. IEEE International Symposium on Biomedical ImagingProceedings / IEEE International Symposium on Biomedical Imaging: from nano to macro. IEEE International Symposium on B},
	year = {2012},
	pages = {1479-1482},
	address = {Barcelona},
	abstract = {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{\textquoteright}s scale. The biomarkers are based on the interrelation between vessel cross-section area and blood volume. We validate our vascular extraction method using simulated data with different complexity and we present results in 2,500 CT scans with different degrees of chronic obstructive pulmonary disease (COPD) severity. Results indicate that our CVM pipeline may track vascular remodeling present in COPD and it can be used in further clinical studies to assess the involvement of PVD in patient populations.},
	author = {San Jose Est{\'e}par, Ra{\'u}l and Ross, James C and Krissian, Karl and Schultz, Thomas and Washko, George R and Kindlmann, Gordon L}
}
@article {473246,
	title = {Emphysema Quantification in a Multi-Scanner Hrct Cohort Using Local Intensity Distributions.},
	journal = {Proceedings / IEEE International Symposium on Biomedical Imaging: from nano to macro. IEEE International Symposium on Biomedical ImagingProceedings / IEEE International Symposium on Biomedical Imaging: from nano to macro. IEEE International Symposium on B},
	year = {2012},
	pages = {474-477},
	address = {Barcelona},
	abstract = {This article investigates the suitability of local intensity distributions to analyze six emphysema classes in 342 CT scans obtained from 16 sites hosting scanners by 3 vendors and a total of 9 specific models in subjects with Chronic Obstructive Pulmonary Disease (COPD). We propose using kernel density estimation to deal with the inherent sparsity of local intensity histograms obtained from scarcely populated regions of interest. We validate our approach by leave-one-subject-out classification experiments and full-lung analyses. We compare our results with recently published LBP texture-based methodology. We demonstrate the efficacy of using intensity information alone in multi-scanner cohorts, which is a simpler, more intuitive approach.},
	author = {Mendoza, Carlos S and Washko, George and Ross, James and Diaz, Alejandro and Lynch, David and Crapo, James and Silverman, Edwin and Acha, Bego{\~n}a and Serrano, Carmen and San Jose Est{\'e}par, Ra{\'u}l}
}
@article {473206,
	title = {Genome-Wide Association Study For Local Histogram Emphysema Patterns Identifies Loci Near CHRNA3/5 And MMP12/MMP3},
	journal = {American journal of respiratory and critical care medicineAmerican journal of respiratory and critical care medicine},
	volume = {185},
	year = {2012},
	month = {Jun},
	pages = {A3808},
	abstract = {


Background: Quantitative measurements of emphysema extracted from CT scan data are a useful tool in COPD phenotyping, but existing quantitative phenotypes such as low attenuation area (LAA) \% at -950HU have not found compelling genetic associations. Texture-based patterns of lung density in CT images may better characterize the amount and type of emphysema. Using a local histogram based emphysema classification method, we quantified the relative amounts of various types of emphysematous and normal lung tissue in CT scans from subjects in the COPDGene Study, and we performed a genome-wide association study on these quantitative phenotypes to identify genetic determinants of emphysema.\ 


},
	author = {Castaldi, Peter and San Jose Est{\'e}par, Ra{\'u}l and Sanchez Mendoza, Carlos and Cho, Michael H and Crapo, James and Lynch, David A and Beaty, Terri and Washko, George R and Silverman, Edwin K}
}
@article {473181,
	title = {Impact Of Differing Convolution Kernels On Quantitative CT Measures Of Lung Density And Correlation With Physiology In Smokers: B31f Vs B35f},
	journal = {American journal of respiratory and critical care medicineAmerican journal of respiratory and critical care medicine},
	volume = {185},
	year = {2012},
	month = {Jun},
	pages = {A2029},
	abstract = {


Rationale The purpose of this study is to evaluate whether quantitative CT (QCT) measures of emphysema (EMP) and gas trapping (GT) are significantly different when evaluated on images reconstructed with differing {\textquotedblleft}soft{\textquotedblright} convolution kernels, and to evaluate whether one kernel correlates better with physiology. Methods 


},
	author = {Zach, Jordan A. and Wilson, Carla and Williams, Andre and Stinson, Douglas and San Jose Est{\'e}par, Ra{\'u}l and Washko, George R and Sieren, Jered and Tschirren, Juerg and Hoffman, Eric A and Lynch, David A}
}
@article {473226,
	title = {Lung deflation and oxygen pulse in COPD: results from the NETT randomized trial.},
	journal = {Respiratory medicineRespiratory medicine},
	volume = {106},
	year = {2012},
	month = {Feb},
	pages = {109-119},
	abstract = {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. Medical and surgical patients were divided into "deflators" and "non-deflators" based on change in RV/TLC from baseline (∆RV/TLC). We defined deflation as the ∆RV/TLC experienced by 75\% of surgical patients. We examined changes in O(2) pulse at peak and similar (iso-work) exercise. Findings were validated in 718 patients who underwent CPET without ABGs.RESULTS:In the ABG substudy, surgical and medical deflators improved their RV/TLC and peak O(2) pulse (median ∆RV/TLC -18.0\% vs. -9.3\%, p=0.0003; median ∆O(2) pulse 13.6\% vs. 1.8\%, p=0.12). Surgical deflators also improved iso-work O(2) pulse (0.53 mL/beat, p=0.04 at 20 W). In the validation cohort, surgical deflators experienced a greater improvement in peak O(2) pulse than medical deflators (mean 18.9\% vs. 1.1\%). In surgical deflators improvements in O(2) pulse at rest and during unloaded pedaling (0.32 mL/beat, p\<0.0001 and 0.47 mL/beat, p\<0.0001, respectively) corresponded with significant reductions in HR and improvements in VO(2). On multivariate analysis, deflators were 88\% more likely than non-deflators to have an improvement in O(2) pulse (OR 1.88, 95\% CI 1.30-2.72, p=0.0008).CONCLUSION:In COPD, decreased hyperinflation through lung volume reduction is associated with improved O(2) pulse.},
	author = {Come, Carolyn E and Divo, Miguel J and San Jose Est{\'e}par, Ra{\'u}l and Sciurba, Frank C and Criner, Gerard J and Marchetti, Nathaniel and Scharf, Steven M and Mosenifar, Zab and Make, Barry J and Keller, Cesar A and Minai, Omar A and Martinez, Fernando J and Han, MeiLan K and Reilly, John J and Celli, Bartolome R and Washko, George R and NETT Research Group}
}
@article {473176,
	title = {Optimal Real-Time Estimation in Diffusion Tensor Imaging.},
	journal = {Magnetic resonance imagingMagnetic resonance imaging},
	volume = {30},
	year = {2012},
	month = {Jun 01},
	pages = {506-517},
	abstract = {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. In this paper, we propose an optimal real-time estimation framework for DTI reconstruction in single-coil acquisitions. By including an online estimation of the time-changing noise variance associated to the acquisition process, the proposed method achieves the sequential best linear unbiased estimator. Results on both synthetic and real data show that our method outperforms those so far proposed, reaching the best performance of the existing proposals by processing a substantially lower number of diffusion images.},
	author = {Casaseca-de-la-Higuera, Pablo and Trist{\'a}n-Vega, Antonio and Aja-Fernandez, Santiago and Alberola-Lopez, Carlos and Westin, Carl-Fredrik and San Jose Est{\'e}par, Ra{\'u}l}
}
@article {473196,
	title = {Pulmonary Vascular Remodeling Quantification In Inspiratory Volumetric CT Using Scale-Space Particles},
	journal = {American journal of respiratory and critical care medicineAmerican journal of respiratory and critical care medicine},
	volume = {185},
	year = {2012},
	month = {Jun},
	pages = {A4344},
	abstract = {


Rationale: It is estimated that 30 to 70\% of subjects with advanced chronic obstructive pulmonary disease (COPD) have clinically significant pulmonary vascular disease (PVD). PVD is in part mediated by vascular remodeling including inflammation and endothelial dysfunction present even in smokers with normal lung function. Objective analysis of pulmonary vascular morphology on CT may provide robust metrics of vascular disease in smokers which are predictive of clinically meaningful processes.\ 


},
	author = {San Jose Est{\'e}par, Ra{\'u}l and Ross, James C and Kindlmann, Gordon L and Diaz, Alejandro and Kinney, Gregory and Hokanson, John and Silverman, Edwin K and Washko, George R}
}
@article {473191,
	title = {Quantifying Patterns Of Emphysema By Local Density Histogram In Chest CT Scans},
	journal = {American journal of respiratory and critical care medicineAmerican journal of respiratory and critical care medicine},
	volume = {185},
	year = {2012},
	month = {Jun},
	pages = {A4331},
	abstract = {


Rationale: A major limitation of global densitometry analysis for emphysema quantification is the lack of specificity for early stage disease and differentiation of patterns related to emphysema pathological types. Local approaches that attempt to classify different patterns of emphysema may better quantify the burden of disease and its progression. 


},
	author = {San Jose Est{\'e}par, Ra{\'u}l and Mendoza, Carlos S and Ross, James C and Diaz, Alejandro and Lynch, David A and Crapo, James and Silverman, Edwin K and Washko, George R}
}
@article {473171,
	title = {Real-time computed tomography-based augmented reality for natural orifice transluminal endoscopic surgery navigation.},
	journal = {The British journal of surgeryThe British journal of surgery},
	volume = {99},
	year = {2012},
	month = {Sep},
	pages = {1246-1253},
	abstract = {BACKGROUND:Natural orifice transluminal endoscopic surgery (NOTES) is technically challenging owing to endoscopic short-sighted visualization, excessive scope flexibility and lack of adequate instrumentation. Augmented reality may overcome these difficulties. This study tested whether an image registration system for NOTES procedures (IR-NOTES) can facilitate navigation.METHODS:In three human cadavers 15 intra-abdominal organs were targeted endoscopically with and without IR-NOTES via both transgastric and transcolonic routes, by three endoscopists with different levels of expertise. Ease of navigation was evaluated objectively by kinematic analysis, and navigation complexity was determined by creating an organ access complexity score based on the same data.RESULTS:Without IR-NOTES, 21 (11{\textperiodcentered}7 per cent) of 180 targets were not reached (expert endoscopist 3, advanced 7, intermediate 11), compared with one (1 per cent) of 90 with IR-NOTES (intermediate endoscopist) (P = 0{\textperiodcentered}002). Endoscope movements were significantly less complex in eight of the 15 listed organs when using IR-NOTES. The most complex areas to access were the pelvis and left upper quadrant, independently of the access route. The most difficult organs to access were the spleen (5 failed attempts; 3 of 7 kinematic variables significantly improved) and rectum (4 failed attempts; 5 of 7 kinematic variables significantly improved). The time needed to access the rectum through a transgastric approach was 206{\textperiodcentered}3 s without and 54{\textperiodcentered}9 s with IR-NOTES (P = 0{\textperiodcentered}027).CONCLUSION:The IR-NOTES system enhanced both navigation efficacy and ease of intra-abdominal NOTES exploration for operators of all levels. The system rendered some organs accessible to non-expert operators, thereby reducing one impediment to NOTES procedures. Copyright {\textcopyright} 2012 British Journal of Surgery Society Ltd. Published by John Wiley \& Sons, Ltd.},
	author = {Azagury, D E and Ryou, M and Shaikh, S N and San Jose Est{\'e}par, Ra{\'u}l and BI Lengyel and Jagadeesan, J and Vosburgh, KG and Thompson, CC}
}
@article {473186,
	title = {Statins And Interstitial Lung Abnormalities In Smokers},
	journal = {American journal of respiratory and critical care medicineAmerican journal of respiratory and critical care medicine},
	volume = {185},
	year = {2012},
	month = {Jun},
	pages = {A5170},
	abstract = {


Rationale: HMG-CoA reductase inhibitors (statins) have been implicated in the development of interstitial lung disease (ILD) but the relationship between statins and interstitial lung abnormalities (ILA) in smokers has not been assessed. 


},
	author = {Washko, George R and Hatabu, Hiroto and Fernandez, Isis and Nishino, Mizuki and Okajima, Yuka and Yamashiro, Tsuneo and Ross, James and San Jose Est{\'e}par, Ra{\'u}l and Diaz, Alejandro and Himes, Blanca and Come, Carolyn and D\'Aco, Katherine and Martinez, Fernando J and Han, MeiLan K and Lynch, David A and Crapo, James and Silverman, Edwin K and Rosas, Ivan O and Hunninghake, Gary M}
}
@article {473201,
	title = {Trachea Air: Internal Reference Standard For CT Lung Densitometry},
	journal = {American journal of respiratory and critical care medicineAmerican journal of respiratory and critical care medicine},
	volume = {185},
	year = {2012},
	month = {Jun},
	pages = {A2037},
	abstract = {


RATIONALE: The nominal CT number of air is -1000HU. In contemporary multi-slice CT scanners, the CT number of air in the trachea is greater than -1000HU. Consequently, the value of trachea air CT number of an individual subject{\textquoteright}s image might be used as an internal reference standard for CT lung densitometry. 


},
	author = {Judy, Philip F and San Jose Est{\'e}par, Ra{\'u}l and Ross, James C and Washko, George R and Silverman, Edwin K and Lynch, David A and the COPDGene Investigators, \&}
}
@article {470131,
	title = {Quantitative pulmonary imaging using computed tomography and magnetic resonance imaging},
	journal = {Respirology},
	volume = {17},
	number = {3},
	year = {2012},
	month = {2012 Apr},
	pages = {432-44},
	abstract = {Measurements of lung function, including spirometry and body plethesmography, are easy to perform and are the current clinical standard for assessing disease severity. However, these lung functional techniques do not adequately explain the observed variability in clinical manifestations of disease and offer little insight into the relationship of lung structure and function. Lung imaging and the image-based assessment of lung disease has matured to the extent that it is common for clinical, epidemiologic and genetic investigation to have a component dedicated to image analysis. There are several exciting imaging modalities currently being used for the non-invasive study of lung anatomy and function. In this review, we will focus on two of them; X-ray computed tomography and magnetic resonance imaging. Following a brief introduction of each method, we detail some of the most recent work being done to characterize smoking-related lung disease and the clinical applications of such knowledge.},
	keywords = {Airway Remodeling, Asthma, Cystic Fibrosis, Emphysema, Female, Humans, Lung, Lung Diseases, Lung Diseases, Interstitial, Magnetic Resonance Imaging, Male, Pulmonary Disease, Chronic Obstructive, Tomography, X-Ray Computed},
	issn = {1440-1843},
	doi = {10.1111/j.1440-1843.2011.02117.x},
	author = {Washko, George R and Parraga, Grace and Coxson, Harvey O}
}
@article {470121,
	title = {Statins and pulmonary fibrosis: the potential role of NLRP3 inflammasome activation},
	journal = {Am J Respir Crit Care Med},
	volume = {185},
	number = {5},
	year = {2012},
	month = {2012 Mar 01},
	pages = {547-56},
	abstract = {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. Next, we evaluated the effect of statin pretreatment on bleomycin-induced fibrosis in mice and explored the mechanism behind these observations in vitro.

MEASUREMENTS AND MAIN RESULTS: In COPDGene, 38\% of subjects with ILA were taking statins compared with 27\% of subjects without ILA. Statin use was positively associated in ILA (odds ratio, 1.60; 95\% confidence interval, 1.03-2.50; P = 0.04) after adjustment for covariates including a history of high cholesterol or coronary artery disease. This association was modified by the hydrophilicity of statin and the age of the subject. Next, we demonstrate that statin administration aggravates lung injury and fibrosis in bleomycin-treated mice. Statin pretreatment enhances caspase-1-mediated immune responses in vivo and in vitro; the latter responses were abolished in bone marrow-derived macrophages isolated from Nlrp3(-/-) and Casp1(-/-) mice. Finally, we provide further insights by demonstrating that statins enhance NLRP3-inflammasome activation by increasing mitochondrial reactive oxygen species generation in macrophages.

CONCLUSIONS: Statin use is associated with ILA among smokers in the COPDGene study and enhances bleomycin-induced lung inflammation and fibrosis in the mouse through a mechanism involving enhanced NLRP3-inflammasome activation. Our findings suggest that statins may influence the susceptibility to, or progression of, ILD. Clinical trial registered with www.clinicaltrials.gov (NCT 00608764).},
	keywords = {Animals, Bleomycin, Carrier Proteins, Caspase 1, Drug Synergism, Female, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Idiopathic Pulmonary Fibrosis, Inflammasomes, Lung, Male, Mice, Mice, Inbred C57BL, NLR Family, Pyrin Domain-Containing 3 Protein, Pulmonary Fibrosis, Regression Analysis, Smoking},
	issn = {1535-4970},
	doi = {10.1164/rccm.201108-1574OC},
	author = {Xu, Jin-Fu and Washko, George R and Nakahira, Kiichi and Hatabu, Hiroto and Patel, Avignat S and Fernandez, Isis E and Nishino, Mizuki and Okajima, Yuka and Yamashiro, Tsuneo and Ross, James C and San Jos{\'e} Est{\'e}par, Ra{\'u}l and Diaz, Alejandro A and Li, Hui-Ping and Qu, Jie-Ming and Himes, Blanca E and Come, Carolyn E and D{\textquoteright}Aco, Katherine and Martinez, Fernando J and Han, MeiLan K and Lynch, David A and Crapo, James D and Morse, Danielle and Ryter, Stefan W and Silverman, Edwin K and Rosas, Ivan O and Choi, Augustine M K and Hunninghake, Gary M}
}
@article {444366,
	title = {Real-time computed tomography-based augmented reality for natural orifice transluminal endoscopic surgery navigation.},
	journal = {Br J Surg},
	volume = {99},
	number = {9},
	year = {2012},
	month = {2012 Sep},
	pages = {1246-53},
	abstract = {BACKGROUND: Natural orifice transluminal endoscopic surgery (NOTES) is technically challenging owing to endoscopic short-sighted visualization, excessive scope flexibility and lack of adequate instrumentation. Augmented reality may overcome these difficulties. This study tested whether an image registration system for NOTES procedures (IR-NOTES) can facilitate navigation. METHODS: In three human cadavers 15 intra-abdominal organs were targeted endoscopically with and without IR-NOTES via both transgastric and transcolonic routes, by three endoscopists with different levels of expertise. Ease of navigation was evaluated objectively by kinematic analysis, and navigation complexity was determined by creating an organ access complexity score based on the same data. RESULTS: Without IR-NOTES, 21 (11{\textperiodcentered}7 per cent) of 180 targets were not reached (expert endoscopist 3, advanced 7, intermediate 11), compared with one (1 per cent) of 90 with IR-NOTES (intermediate endoscopist) (P = 0{\textperiodcentered}002). Endoscope movements were significantly less complex in eight of the 15 listed organs when using IR-NOTES. The most complex areas to access were the pelvis and left upper quadrant, independently of the access route. The most difficult organs to access were the spleen (5 failed attempts; 3 of 7 kinematic variables significantly improved) and rectum (4 failed attempts; 5 of 7 kinematic variables significantly improved). The time needed to access the rectum through a transgastric approach was 206{\textperiodcentered}3 s without and 54{\textperiodcentered}9 s with IR-NOTES (P = 0{\textperiodcentered}027). CONCLUSION: The IR-NOTES system enhanced both navigation efficacy and ease of intra-abdominal NOTES exploration for operators of all levels. The system rendered some organs accessible to non-expert operators, thereby reducing one impediment to NOTES procedures.},
	keywords = {Abdominal Wall, Adult, Cadaver, Computer Simulation, Computer Systems, Digestive System, Female, Humans, Male, Natural Orifice Endoscopic Surgery, Pelvic Floor, Tomography, X-Ray Computed},
	issn = {1365-2168},
	doi = {10.1002/bjs.8838},
	author = {Azagury, D E and Ryou, M and Shaikh, S N and San Jos{\'e} Est{\'e}par, R and BI Lengyel and Jagadeesan, J and Vosburgh, KG and Thompson, CC}
}
@article {8619,
	title = {BBB},
	journal = {CCC},
	volume = {1},
	number = {1},
	year = {2012},
	pages = {2},
	author = {BBB}
}