Reproducibility of optical coherence tomography airway imaging

Optical coherence tomography (OCT) is a promising imaging technique to evaluate small airway remodeling. However, the short-term insertion-reinsertion reproducibility of OCT for evaluating the same bronchial pathway has yet to be established. We evaluated 74 OCT data sets from 38 current or former smokers twice within a single imaging session. Although the overall insertion-reinsertion airway wall thickness (WT) measurement coefficient of variation (CV) was moderate at 12%, much of the variability between repeat imaging was attributed to the observer; CV for repeated measurements of the same airway (intra-observer CV) was 9%. Therefore, reproducibility may be improved by introduction of automated analysis approaches suggesting that OCT has potential to be an in-vivo method for evaluating airway remodeling in future longitudinal and intervention studies. (C) 2015 Optical Society of Americ

Can HRCT be used as a marker of airway remodelling in children with difficult asthma?

BACKGROUND: Whole airway wall thickening on high resolution computed tomography (HRCT) is reported to parallel thickening of the bronchial epithelial reticular basement membrane (RBM) in adult asthmatics. A similar relationship in children with difficult asthma (DA), in whom RBM thickening is a known feature, may allow the use of HRCT as a non-invasive marker of airway remodelling. We evaluated this relationship in children with DA. METHODS: 27 children (median age 10.5 [range 4.1-16.7] years) with DA, underwent endobronchial biopsy from the right lower lobe and HRCT less than 4 months apart. HRCTs were assessed for bronchial wall thickening (BWT) of the right lower lobe using semi-quantitative and quantitative scoring techniques. The semi-quantitative score (grade 0-4) was an overall assessment of BWT of all clearly identifiable airways in HRCT scans. The quantitative score (BWT %; defined as [airway outer diameter - airway lumen diameter]/airway outer diameter x100) was the average score of all airways visible and calculated using electronic endpoint callipers. RBM thickness in endobronchial biopsies was measured using image analysis. 23/27 subjects performed spirometry and the relationships between RBM thickness and BWT with airflow obstruction evaluated. RESULTS: Median RBM thickness in endobronchial biopsies was 6.7(range 4.6-10.0) microm. Median qualitative score for BWT of the right lower lobe was 1(range 0-1.5) and quantitative score was 54.3 (range 48.2-65.6)%. There was no relationship between RBM thickness and BWT in the right lower lobe using either scoring technique. No relationship was found between FEV1 and BWT or RBM thickness. CONCLUSION: Although a relationship between RBM thickness and BWT on HRCT has been found in adults with asthma, this relationship does not appear to hold true in children with D

Quantitative Computed Tomography in COPD: Possibilities and Limitations

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease that is characterized by chronic airflow limitation. Unraveling of this heterogeneity is challenging but important, because it might enable more accurate diagnosis and treatment. Because spirometry cannot distinguish between the different contributing pathways of airflow limitation, and visual scoring is time-consuming and prone to observer variability, other techniques are sought to start this phenotyping process. Quantitative computed tomography (CT) is a promising technique, because current CT technology is able to quantify emphysema, air trapping, and large airway wall dimensions. This review focuses on CT quantification techniques of COPD disease components and their current status and role in phenotyping COPD

Multi-Nuclear Magnetic Resonance Imaging of Obstructive Lung Disease

Obstructive lung diseases such as chronic-obstructive-lung-disease (COPD), bronchiectasis, and asthma are characterized by airflow obstruction. They affect over six million Canadians costing the economy $12 billion/year. Despite decades of research, therapies that modify obstructive-lung-disease progression and control are lacking because patient diagnosis, monitoring, and response to therapy are currently made using airflow measurements that may conceal the independent contributions of underlying pathologies. One goal of obstructive-lung-disease research is to develop ways to identify patients with specific underlying pathological phenotypes to improve patient care and outcomes. Thoracic computed-tomography (CT) and magnetic-resonance-imaging (MRI) provide ways to regionally identify the underlying pathologies associated with obstructive-lung-disease, and offer quantitative biomarkers of obstructive-lung-disease (e.g. lung-density, airway dimensions, ventilation abnormalities, and lung microstructure). As the first step to identify patients with specific underlying pathological phenotypes, it is important to understand the physiological and clinical consequences of these imaging derived measurements. Accordingly, our objective was to evaluate lung structure and function using multi-nuclear pulmonary MRI in aging and obstructive-lung-disease to provide a better understanding of MR-derived biomarkers. In older never-smokers, the majority of subjects had 3He MR ventilation abnormalities that were not responsive to bronchodilation. 3He ventilation abnormalities were related to airflow obstruction and airways resistance, but not occupational exposure or exercise limitation. We then developed and evaluated ultra-short-echo-time MRI in COPD subjects with and without bronchiectasis. This work demonstrated that ultra-short-echo-time MR-derived measurements were reproducible and significantly related to CT tissue-density measurements. In the COPD subjects with bronchiectasis, ultra-short-echo-time signal-intensity was related to airway measurements. In COPD subjects without bronchiectasis, ultra-short-echo-time signal-intensity was related to the severity of emphysema. Finally, based on the ultra-short-echo-time MR biomarkers developed in patients with COPD and bronchiectasis, patients that share some of the airway and inflammatory features common in asthmatics, we produced ultra-short-echo-time MR measurements in asthma. These measurements not only provided similar information as CT, but also information about regional ventilation deficits. These results demonstrated that ultra-short-echo-time MR biomarkers may reflect ventilation heterogeneity and/or gas-trapping in asthma. These important findings indicate that multi-nuclear pulmonary MRI has the potential to quantitatively evaluate the different pathologies of obstructive-lung-disease

Airway dimensions in COPD:relationships with clinical variables

SummaryBackgroundCOPD patients have varying degrees of airways disease and emphysema. CT scanning can differentiate these pathological subtypes. We evaluated airway dimensions and emphysema severity with low dose CT scanning in COPD patients to determine relationships with clinical features of the disease.MethodsFifty six patients with COPD had a low dose thoracic CT scan. Airways were analysed using novel software as either proximal (1st and 2nd generation) or distal (3rd to 6th generation); the extent of emphysema was assessed as the percentage of pixels less than −950 Hounsfield units. CT measures were related to clinical features of COPD.ResultsThicker walls in the proximal airways were associated with clinical features that may represent a bronchitic phenotype (MRC Bronchitis Score; β = 0.20, p = 0.003, Frequent Exacerbations; β = 0.14, p = 0.017, Total St George’s Score; β = 0.50, p = 0.001 and body mass index [BMI]; β = 0.26, p = 0.049); these associations were independent of emphysema. BMI was negatively correlated with the degree of emphysema (β = −0.41, p = 0.001). Airway wall thickness was negatively correlated with CT measured emphysema for both proximal and more distal airways (r = −0.30, p = 0.025 and r = −0.32, p = 0.015).ConclusionsCT measured airway dimensions are associated with several clinical measures of COPD; these are related to a bronchitic phenotype and the effect is independent of emphysema

Collapsible Silicone Tubes: An in Vitro Model for Tracheal Traction

Obstructive sleep apnea (OSA) is characterized by recurrent episodes of airway collapse and airflow limitation during sleep. Fragmented sleep and reductions in blood oxygen saturation lead to several comorbidities, including hypertension, cardiovascular disease, and cerebrovascular disease. Longitudinal forces (tracheal traction) acting on the soft tissues surrounding the upper airway have been proposed to play a significant role in stabilizing the airway and preventing collapse. However, the relative contribution of longitudinal forces as compared to other factors that affect airway stability (airway geometry, tissue properties, muscle activity) remains unclear. This in-vitro study aimed to investigate to what extent longitudinal forces can stabilize the upper airway against flow-induced collapse. Collapsible silicone tubes of varying lengths (L = 75 to 125mm), diameters (D = 12.70 to 31.75mm), and wall thicknesses (h = 0.98 to 2.22mm) were fabricated in-house. An experimental setup was developed that included a pressure catheter to measure air pressure in the tube lumen, a pump that generated sinusoidal bidirectional flow, and a laser line scanner to monitor deformations of the tube wall. The buckling pressure (pressure at which the tube collapses) was quantified as a function of tube geometry and longitudinal stretching. The silicone tubes collapsed at a similar range of transmural pressures (0 to 10 cmH2O) and flowrates (0 to 250ml/s) as observed in the human airway during sleep. Tube length had no clear effect on the buckling pressure, but mechanical stability increased when the wall-thickness-to-radius ratio ( = 2h/D) increased. The buckling pressured measured experimentally was in good agreement with the theory for tubes exposed to transmural pressure alone (zero flow), suggesting that tube collapse was determined primarily by the transmural pressure (rather than by fluid-structure interactions). Longitudinal stretching (5% strain) reduced the buckling pressure by 0.5 to 1.0 cmH2O, which was smaller than the effect of changes in tube diameter and wall thickness. Longitudinal stretching improved the stability of cylindrical silicone tubes, but its effect was smaller than the effect of changes in tube geometry

Pulmonary Structure and Function in Chronic Obstructive Pulmonary Disease Evaluated using Hyperpolarized Noble Gas Magnetic Resonance Imaging

Chronic obstructive pulmonary disease (COPD) is the 4th leading cause of death worldwide and accounts for the highest rate of hospital admissions in Canada. The need for sensitive regional and surrogate measurements of lung structure and function in COPD continues to motivate the development of non-radiation based and sensitive imaging approaches, such as hyperpolarized helium-3 (3He) and xenon-129 (129Xe) magnetic resonance imaging (MRI). The static ventilation images acquired using these approaches allows us to directly visualize lung regions accessed by the hyperpolarized gas during a breath-hold, as well as quantify the regions without signal referred to as the percentage of the thoracic cavity occupied by ventilation defects (VDP). The lung micro-structure can also be probed using diffusion-weighted imaging which takes advantage of the rapid diffusion of 3He and 129Xe atoms to generate surrogate measurements of alveolar size, referred to as the apparent diffusion coefficient (ADC). Here we evaluated COPD lung structure and function using hyperpolarized gas MRI measurements longitudinally, following treatment and in early disease. In COPD ex-smokers, we demonstrated 3He VDP and ADC worsened significantly in only 2 years although there was no change in age-matched healthy volunteers, suggestive of disease progression. We also evaluated COPD ex-smokers pre- and post-bronchodilator and showed regional improvements in gas distribution following bronchodilator therapy regardless of spirometry-based responder classification; the ADC measured in these same COPD ex-smokers also revealed significant reductions in regional gas trapping post-bronchodilator. Although 3He MRI has been more widely used, the limited global quantities necessitates the transition to hyperpolarized 129Xe, and therefore we directly compared 3He and 129Xe MRI in the same COPD ex-smokers and showed significantly greater gas distribution abnormalities for 129Xe compared to 3He MRI that were spatially and significantly related to lung regions with elevated ADC. Finally, we demonstrated that ex-smokers with normal spirometry but abnormal diffusion capacity of the lung for carbon monoxide (DLCO) had significantly worse symptoms, exercise capacity and 3He ADC than ex-smokers with normal DLCO. These important findings indicate that hyperpolarized gas MRI can be used to improve our understanding of lung structural and functional changes in COPD