Search

Computed tomography (CT) total-airway-count (TAC) and airway wall-thickness differ across chronic obstructive pulmonary disease (COPD) severities, but longitudinal insights are lacking. The aim of this study was to evaluate longitudinal CT airway measurements over three-years in ex-smokers. In this prospective convenience sample study, ex-smokers with (n = 50; 13 female; age = 70 ± 9 years; pack-years = 43 ± 26) and without (n = 40; 17 female; age = 69 ± 10 years; pack-years = 31 ± 17) COPD completed CT, 3He magnetic resonance imaging (MRI), and pulmonary function tests at baseline and three-year follow-up. CT TAC, airway wall-area (WA), lumen-area (LA), and wall-area percent (WA%) were generated. Emphysema was quantified as the relative-area-of-the-lung with attenuation < –950 Hounsfield-units (RA950). MRI ventilation-defect-percent (VDP) was also quantified. Differences over time were evaluated using paired-samples t tests. Multivariable prediction models using the backwards approach were generated. After three-years, forced-expiratory-volume in 1-second (FEV1) was not different in ex-smokers with (p = 0.4) and without (p = 0.5) COPD, whereas RA950 was (p < 0.001, p = 0.02, respectively). In ex-smokers without COPD, there was no change in TAC (p = 0.2); however, LA (p = 0.009) and WA% (p = 0.01) were significantly different. In ex-smokers with COPD, TAC (p < 0.001), WA (p = 0.04), LA (p < 0.001), and WA% (p < 0.001) were significantly different. In all ex-smokers, TAC was related to VDP (baseline: ρ = –0.30, p = 0.005; follow-up: ρ = –0.33, p = 0.002). In significant multivariable models, baseline airway wall-thickness was predictive of TAC worsening. After three-years, in the absence of FEV1 worsening, TAC diminished only in ex-smokers with COPD and airway walls were thinner in all ex-smokers. These longitudinal findings suggest that the evaluation of CT airway remodeling may be a useful clinical tool for predicting disease progression and managing COPD. Clinical trial registration:www.clinicaltrials.gov NCT02279329

Recent pulmonary functional MRI findings of spatially and temporally persistent ventilation abnormalities in patients with asthma contrast with previous in silico modeling studies that suggest that in asthma, ventilation defects may be randomly distributed. In a case study that used pulmonary MRI, CT imaging, and pulmonary function tests, we prospectively evaluated over the course of 7 years, nonidentical female adult twins, each with a lifelong history of asthma. We evaluated pulmonary function and MRI ventilation heterogeneity at baseline and follow-up after 7 years. In both twins, there was a spatially identical MRI ventilation defect and an abnormal subsegmental left-sided upper lobe airway that persisted in the same spatial location after 7 years. If ventilation defects are randomly distributed, this bears a probability of approximately one per 130,000 people. Our MRI observations in related patients with asthma suggest that ventilation abnormalities may not be randomly distributed in patients with asthma and persist distal to airway abnormalities for long periods of time.

Alpha-1 antitrypsin deficiency (AATD) leads to disabling chronic obstructive pulmonary disease (COPD). Current therapy aimed at slowing lung disease progression includes exogenous alpha-1 antitrypsin augmentation therapy, but there are few potential new treatments under development. Currently used measurements of AATD-related emphysema include the forced expiratory volume in 1 second (FEV1) and the diffusing capacity of carbon monoxide (DLCO); both are relatively insensitive to therapy, although computed tomography (CT) lung density measurements have been shown to worsen more slowly in treated patients.

RATIONALE AND OBJECTIVES: Ventilation heterogeneity is a hallmark feature of asthma. Our objective was to evaluate ventilation heterogeneity in patients with severe asthma, both pre- and post-salbutamol, as well as post-methacholine (MCh) challenge using the lung clearance index, free-breathing pulmonary MATERIALS AND METHODS: Sixteen severe asthmatics (49 ± 10 years) provided written informed consent to an ethics board-approved protocol. Spirometry, plethysmography, and multiple breath nitrogen washout to measure the lung clearance index were performed during a single visit within 15 minutes of MRI. Inhaled-gas MRI and FDMRI were performed pre- and post-bronchodilator to generate VDP. For asthmatics with forced expiratory volume in 1 second (FEV RESULTS: Hyperpolarized CONCLUSIONS: FDMRI VDP generated in free-breathing asthmatic patients was correlated with static inspiratory breath-hold

RATIONALE AND OBJECTIVES: In this proof-of-concept demonstration, we aimed to quantitatively and qualitatively compare pulmonary ventilation abnormalities derived from Fourier decomposition of free-breathing (1)H magnetic resonance imaging (FDMRI) to hyperpolarized (3)He MRI in subjects with chronic obstructive pulmonary disease (COPD) and bronchiectasis. MATERIALS AND METHODS: All subjects provided written informed consent to a protocol approved by a local research ethics board and Health, Canada, and they underwent MRI, computed tomography (CT), spirometry, and plethysmography during a single 2-hour visit. Semiautomated segmentation was used to generate ventilation defect measurements derived from FDMRI and (3)He MRI, and these were compared using analysis of variance and Pearson correlations. RESULTS: Twenty-six subjects were evaluated including 12 COPD subjects (67 ± 9 years) and 14 bronchiectasis subjects (70 ± 11 years). For COPD subjects, FDMRI and (3)He MRI ventilation defect percent (VDP) was 7 ± 6% and 24 ± 14%, respectively (P < .001; bias = -16 ± 9%). In COPD subjects, FDMRI was significantly correlated with (3)He MRI VDP (r = .88; P = .0001), (3)He MRI apparent diffusion coefficient (r = .71; P < .05), airways resistance (r = .60; P < .05), and RA950 (r = .80; P < .01). In subjects with bronchiectasis, FDMRI VDP (5 ± 3%) and (3)He MRI VDP (18 ± 9%) were significantly different (P < .001) and not correlated (P > .05). The Dice similarity coefficient (DSC) for FDMRI and (3)He MRI ventilation was 86 ± 7% for COPD and 86 ± 4% for bronchiectasis subjects (P > .05); the DSC for FDMRI ventilation defects and CT RA950 was 19 ± 20% in COPD and 2 ± 3% in bronchiectasis subjects (P < .01). CONCLUSIONS: FDMRI and (3)He MRI VDP were strongly related in COPD but not in bronchiectasis subjects. In COPD only, FDMRI ventilation defects were spatially related with (3)He ventilation defects and emphysema.

Although the human and societal burden and cost of COPD is staggering, there are few clinical tools that provide earlier diagnoses or a means to regionally monitor disease in a way that might lead to improved therapies and outcomes. In acknowledgement of the current gaps in COPD therapy, the objective of the Thoracic Imaging Network of Canada (TINCan) is to improve COPD patient phenotyping through imaging, to provide methods and imaging-based intermediate endpoints for the development of new treatments, and to evaluate disease progression and patient-based outcomes in COPD patients and those at risk of COPD. Here we summarize and outline the TINCan study protocol and describe our objectives. TINCan is a prospective study that aims to identify and quantify novel COPD phenotypes from thoracic computed tomography (CT) and thoracic hyperpolarized noble gas magnetic resonance imaging (MRI) in 200 ex-smokers, 50 years of age or greater, including asymptomatic ex-smokers with normal pulmonary function and Global initiative for chronic Obstructive Lung Disease (GOLD) Unclassified (U) , and GOLD stages I-IV patients. Baseline and 2-year follow-up measurements will be acquired using spirometry, plethysmography, diffusing capacity of the lung for carbon monoxide (DL

PURPOSE: To compare hyperpolarized helium-3 ((3) He) and xenon-129 ((129) Xe) MRI in asthmatics before and after salbutamol inhalation. MATERIALS AND METHODS: Seven asthmatics provided written informed consent and underwent spirometry, plethysmography, and MRI before and after salbutamol inhalation. (3) He and (129) Xe ventilation defect percent (VDP) and ventilation coefficient of variation (COV) were measured. To characterize the airways spatially related to ventilation defects, wall area percent (WA%) and lumen area (LA) were evaluated for two subjects who had thoracic x-ray computed tomography (CT) acquired 1 year before MRI. RESULTS: Before salbutamol inhalation, (129) Xe VDP (8 ± 5%) was significantly greater than (3) He VDP (6 ± 5%, P = 0.003). Post-salbutamol, there was a significant improvement in both (129) Xe (5 ± 4%, P < 0.0001) and (3) He (4 ± 3%, P = 0.001) VDP, and the improvement in (129) Xe VDP was significantly greater (P = 0.008). (129) Xe MRI COV (Pre: 0.309 ± 0.028, Post: 0.296 ± 0.036) was significantly greater than (3) He MRI COV (Pre: 0.282 ± 0.018, Post: 0.269 ± 0.024), pre- (P < 0.0001) and post-salbutamol (P < 0.0001) and the decrease in COV post-salbutamol was significant ((129) Xe, P = 0.002; (3) He, P < 0.0001). For a single asthmatic, a sub-segmental (129) Xe MRI ventilation defect that was visible only before salbutamol inhalation but not visible using (3) He MRI was spatially related to a remodeled fourth generation sub-segmental airway (WA% = 78%, LA = 2.9 mm(2) ). CONCLUSION: In asthma, hyperpolarized (129) Xe MRI may help reveal ventilation abnormalities before bronchodilation that are not observed using hyperpolarized (3) He MRI.

PURPOSE: The goal of this work was to investigate lung morphological changes associated with chronic obstructive pulmonary disease (COPD) using hyperpolarized (129) Xe diffusion-weighted MRI. METHODS: Hyperpolarized (129) Xe MRI was performed at three different nonzero diffusion sensitizations (b-value = 12, 20, and 30 s/cm(2) ) in the lungs of four subjects with COPD and four healthy volunteers. The image signal intensities were fit as a function of b-value to obtain anisotropic diffusion coefficient maps for all subjects. The image signal intensities were also fit to a morphological model allowing extraction of length scales associated with the terminal airways: external radius (R), internal radius (r), mean airspace chord length (Lm ), and depth of alveolar sleeve (h). RESULTS: Longitudinal (DL ) and transverse (DT ) anisotropic diffusion coefficients were both significantly increased (both P= 0.004) in the COPD subjects (0.102 ± 0.02 cm(2) /s and 0.072 ± 0.02 cm(2) /s, respectively) compared with the healthy subjects (0.083 ± 0.011 cm(2) /s and 0.046 ± 0.017 cm(2) /s, respectively). Significant morphological differences were observed between the COPD subjects and healthy volunteers, specifically decreases in h (68 ± 36 µm vs. 95 ± 710 µm, respectively, P = 0.019) and increases in Lm (352 ± 57 µm vs. 253 ± 37 µm, respectively, P = 0.002) consistent with values obtained previously using hyperpolarized (3) He MRI in similar subjects. CONCLUSIONS: Diffusion-weighted hyperpolarized (129) Xe MRI is a promising technique for mapping changes in human lung morphology and may be useful for early detection of emphysema associated with COPD.

BACKGROUND AND OBJECTIVE: Spirometry is insensitive to small airway abnormalities in asthma. Our objective was to evaluate regional lung structure and function using hyperpolarized (3)He magnetic resonance imaging (MRI) before, during and after a methacholine challenge (MCh). METHODS: Twenty-five asthmatics (mean age = 34 ± 11 years) and eight healthy volunteers (HV) (mean age = 33 ± 11 years) underwent spirometry, plethysmography and hyperpolarized (3)He MRI prior to a MCh. MRI was repeated following the MCh and again 25 min after salbutamol administration. (3)He MRI gas distribution was quantified using semiautomated segmentation of the ventilation defect percent (VDP). Tissue microstructure was measured using the (3)He apparent diffusion coefficient (ADC). Analysis of variance with repeated measures was used to evaluate changes at each time point as well as to determine interactions between regions of interest (ROI) and subject group. Pearson's correlations were performed to evaluate associations between (3)He MRI measurements and established clinical measures. RESULTS: In asthmatics, but not HV, whole-lung ADC was increased post-MCh (P < 0.01). In asthmatics only, ADC was increased post-MCh in posterior ROI (P < 0.01) and all ROI in the superior-inferior direction (P < 0.01). VDP was increased in posterior and inferior ROI (P < 0.001). There was a correlation between VDP and specific airway resistance (r = 0.74, P < 0.0001), dyspnoea score (r = 0.66, P < 0.01) and fractional exhaled nitric oxide (r = 0.45, P < 0.05). CONCLUSIONS: We evaluated the regional pulmonary response to methacholine and salbutamol using (3)He MRI and showed heterogeneous VDP and ADC consistent with bronchoconstriction and gas trapping, respectively, post-MCh. These regional alterations resolved post-salbutamol.

A 73-year-old exsmoker with Global initiative for chronic Obstructive Lung Disease stage III chronic obstructive pulmonary disease underwent airway bypass (AB) as part of the Exhale Airway Stents for Emphysema (EASE) trial, and was the only EASE subject to undergo hyperpolarized 3He magnetic resonance imaging for evaluation of lung function pre- and post-AB. 3He magnetic resonance imaging was acquired twice previously (32 and eight months pre-AB) and twice post-AB (six and 12 months post-AB). Six months post-AB, his increase in forced vital capacity was

RATIONALE AND OBJECTIVES: Emphysema and small airway obstruction are the pathological hallmarks of chronic obstructive pulmonary disease (COPD). The aim of this pilot study in a small group of chronic obstructive pulmonary disease (COPD) patients was to quantify hyperpolarized helium-3 ((3)He) magnetic resonance imaging (MRI) functional and structural measurements and to explore the potential role for (3)He MRI in detecting the lung structural and functional COPD phenotypes. MATERIALS AND METHODS: We evaluated 20 ex-smokers with stage I (n=1), stage II (n=9) and stage III COPD (n=10). All subjects underwent same-day plethysmography, spirometry, (1)H MRI and hyperpolarized (3)He MRI at 3.0T. (3)He ventilation defect percent (VDP) was generated from (3)He static ventilation images and (1)H thoracic images and the (3)He apparent diffusion coefficient (ADC) was derived from diffusion-weighted MRI. RESULTS: Based on the relative contribution of normalized ADC and VDP, there was evidence of a predominant (3)He MRI measurement in seven patients (n=3 mainly ventilation defects or VDP dominant (VD), n=4 mainly increased ADC or ADC dominant (AD)). Analysis of variance (ANOVA) showed significantly lower ADC for subjects with predominantly elevated VDP (p=0.02 compared to subjects with predominantly elevated ADC; p=0.008 compared to mixed group) and significantly decreased VDP for subjects with predominantly elevated ADC (p=0.003, compared to mixed group). CONCLUSION: In this small pilot study, a preliminary analysis shows the potential for (3)He MRI to categorize or phenotype COPD ex-smokers, providing good evidence of feasibility for larger prospective studies.