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. 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.
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.
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.
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 “soft” convolution kernels, and to evaluate whether one kernel correlates better with physiology. Methods
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.
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.
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.
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.
Washko GR, Hatabu H, Fernandez I, Nishino M, Okajima Y, Yamashiro T, Ross J, San Jose Estépar R, Diaz A, Himes B, Come C, D'Aco K, Martinez FJ, Han MLK, Lynch DA, Crapo J, Silverman EK, Rosas IO, Hunninghake GM. Statins And Interstitial Lung Abnormalities In Smokers. American journal of respiratory and critical care medicineAmerican journal of respiratory and critical care medicine 2012;185: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.
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’s image might be used as an internal reference standard for CT lung densitometry.
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.
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).
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 (11·7 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 = 0·002). 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 206·3 s without and 54·9 s with IR-NOTES (P = 0·027). 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.