Khadija Sheikh

Ultra-short echo-time pulmonary MRI: evaluation and reproducibility in COPD subjects with and without bronchiectasis.

To evaluate ultra‐short‐echo‐time (UTE) MRI pulmonary signal‐intensity measurements and reproducibility in chronic obstructive pulmonary disease (COPD).

Globally optimal co-segmentation of three-dimensional pulmonary 1 H and hyperpolarized 3 He MRI with spatial consistence prior

Pulmonary imaging using hyperpolarized (3)He/(129)Xe gas is emerging as a new way to understand the regional nature of pulmonary ventilation abnormalities in obstructive lung diseases. However, the quantitative information derived is completely dependent on robust methods to segment both functional and structural/anatomical data. Here, we propose an approach to jointly segment the lung cavity from (1)H and (3)He pulmonary magnetic resonance images (MRI) by constraining the spatial consistency of the two segmentation regions, which simultaneously employs the image features from both modalities. We formulated the proposed co-segmentation problem as a coupled continuous min-cut model and showed that this combinatorial optimization problem can be solved globally and exactly by means of convex relaxation. In particular, we introduced a dual coupled continuous max-flow model to study the convex relaxed coupled continuous min-cut model under a primal and dual perspective. This gave rise to an efficient duality-based convex optimization algorithm. We implemented the proposed algorithm in parallel using general-purpose programming on graphics processing unit (GPGPU), which substantially increased its computational efficiency. Our experiments explored a clinical dataset of 25 subjects with chronic obstructive pulmonary disease (COPD) across a wide range of disease severity. The results showed that the proposed co-segmentation approach yielded superior performance compared to single-channel image segmentation in terms of precision, accuracy and robustness.

Pulmonary ventilation defects in older never-smokers

Hyperpolarized (3)He MRI previously revealed spatially persistent ventilation defects in healthy, older compared with healthy, younger never-smokers. To understand better the physiological consequences and potential relevance of (3)He MRI ventilation defects, we evaluated (3)He-MRI ventilation-defect percent (VDP) and the effect of deep inspiration (DI) and salbutamol on VDP in older never-smokers. To identify the potential determinants of ventilation defects in these subjects, we evaluated dyspnea, pulmonary function, and cardiopulmonary exercise test (CPET) measurements, as well as occupational and second-hand smoke exposure. Fifty-two never-smokers (71 ± 6 yr) with no history of chronic respiratory disease were evaluated. During a single visit, pulmonary function tests, CPET, and (3)He MRI were performed and the Burden of Obstructive Lung Disease questionnaire administered. For eight of 52 subjects, there was spirometry evidence of airflow limitation (Global Initiative for Chronic Obstructive Lung Disease-Unclassified, I, and II), and occupational exposure was reported in 13 of 52 subjects. In 13 of 52 (25%) subjects, there were no ventilation defects and in 39 of 52 (75%) subjects, ventilation defects were observed. For those subjects with ventilation defects, six of 39 showed a VDP response to DI/salbutamol. Ventilation heterogeneity and VDP were significantly greater, and forced expiratory volume in 1 s (FEV1)/forced vital capacity was significantly lower (P < 0.05) for subjects with ventilation defects with a response to DI/salbutamol than subjects with ventilation defects without a response to DI/salbutamol and subjects without ventilation defects. In a step-wise, forward multivariate model, FEV1, inspiratory capacity, and airway resistance significantly predicted VDP (R(2) = 0.45, P < 0.001). In conclusion, most never-smokers had normal spirometry and peripheral ventilation defects not reversed by DI/salbutamol; such ventilation defects were likely related to irreversible airway narrowing/collapse but not to dyspnea and decreased exercise capacity.

This is what COPD looks like.

Despite decades of research, and the growing healthcare and societal burden of chronic obstructive pulmonary disease (COPD), therapeutic COPD breakthroughs have not occurred. Sub‐optimal COPD patient phenotyping, an incomplete understanding of COPD pathogenesis and a scarcity of sensitive tools that provide patient‐relevant intermediate endpoints likely all play a role in the lack of new, efficacious COPD interventions. In other words, COPD patients are still diagnosed based on the presence of persistent airflow limitation measured using spirometry. Spirometry measurements reflect the global sum of all the different possible COPD pathologies and perhaps because of this, we lose sight of the different contributions of airway and parenchymal abnormalities. With recent advances in thoracic X‐ray computed tomography (CT) and magnetic resonance imaging (MRI), lung structure and function abnormalities may be regionally identified and measured. These imaging endpoints may serve as biomarkers of COPD that can be used to better phenotype patients. Therefore, here we review novel CT and MRI measurements that help reveal COPD phenotypes and what COPD really ‘looks’ like, beyond spirometric indices. We discuss MR and CT imaging approaches for generating reproducible and sensitive measurements of COPD phenotypes related to pulmonary ventilation and perfusion as well as airway and parenchyma anatomical and morphological features. These measurements may provide a way to advance the development and testing of new COPD interventions and therapies.

Oscillatory Positive Expiratory Pressure in Chronic Obstructive Pulmonary Disease

Abstract Evidence-based guidance for the use of airway clearance techniques (ACT) in chronic obstructive pulmonary disease (COPD) is lacking in-part because well-established measurements of pulmonary function such as the forced expiratory volume in 1s (FEV1) are relatively insensitive to ACT. The objective of this crossover study was to evaluate daily use of an oscillatory positive expiratory pressure (oPEP) device for 21–28 days in COPD patients who were self-identified as sputum-producers or non-sputum-producers. COPD volunteers provided written informed consent to daily oPEP use in a randomized crossover fashion. Participants completed baseline, crossover and study-end pulmonary function tests, St. Georges Respiratory Questionnaire (SGRQ), Patient Evaluation Questionnaire (PEQ), Six-Minute Walk Test and 3He magnetic resonance imaging (MRI) for the measurement of ventilation abnormalities using the ventilation defect percent (VDP). Fourteen COPD patients, self-identified as sputum-producers and 13 COPD-non-sputum-producers completed the study. Post-oPEP, the PEQ-ease-bringing-up-sputum was improved for sputum-producers (p = 0.005) and non-sputum-producers (p = 0.04), the magnitude of which was greater for sputum-producers (p = 0.03). There were significant post-oPEP improvements for sputum-producers only for FVC (p = 0.01), 6MWD (p = 0.04), SGRQ total score (p = 0.01) as well as PEQ-patient-global-assessment (p = 0.02). Clinically relevant post-oPEP improvements for PEQ-ease-bringing-up-sputum/PEQ-patient-global-assessment/SGRQ/VDP were observed in 8/7/9/6 of 14 sputum-producers and 2/0/3/3 of 13 non-sputum-producers. The post-oPEP change in 3He MRI VDP was related to the change in PEQ-ease-bringing-up-sputum (r = 0.65, p = 0.0004) and FEV1 (r = –0.50, p = 0.009). In COPD patients with chronic sputum production, PEQ and SGRQ scores, FVC and 6MWD improved post-oPEP. FEV1 and PEQ-ease-bringing-up-sputum improvements were related to improved ventilation providing mechanistic evidence to support oPEP use in COPD. Clinical Trials # NCT02282189 and NCT02282202.

Noninvasive quantification of alveolar morphometry in elderly never- and ex-smokers.

Diffusion‐weighted magnetic resonance imaging (MRI) provides a way to generate in vivo lung images with contrast sensitive to the molecular displacement of inhaled gas at subcellular length scales. Here, we aimed to evaluate hyperpolarized 3He MRI estimates of the alveolar dimensions in 38 healthy elderly never‐smokers (73 ± 6 years, 15 males) and 21 elderly ex‐smokers (70 ± 10 years, 14 males) with (n = 8, 77 ± 6 years) and without emphysema (n = 13, 65 ± 10 years). The ex‐smoker and never‐smoker subgroups were significantly different for FEV1/FVC (P = 0.0001) and DLCO (P = 0.009); while ex‐smokers with emphysema reported significantly diminished FEV1/FVC (P = 0.02) and a trend toward lower DLCO (P = 0.05) than ex‐smokers without emphysema. MRI apparent diffusion coefficients (ADC) and CT measurements of emphysema (relative area–CT density histogram, RA950) were significantly different (P = 0.001 and P = 0.007) for never‐smoker and ex‐smoker subgroups. In never‐smokers, the MRI estimate of mean linear intercept (260 ± 27 μm) was significantly elevated as compared to the results previously reported in younger never‐smokers (210 ± 30 μm), and trended smaller than in the age‐matched ex‐smokers (320 ± 72 μm, P = 0.06) evaluated here. Never‐smokers also reported significantly smaller internal (220 ± 24 μm, P = 0.01) acinar radius but greater alveolar sheath thickness (120 ± 4 μm, P < 0.0001) than ex‐smokers. Never‐smokers were also significantly different than ex‐smokers without emphysema for alveolar sheath thickness but not ADC, while ex‐smokers with emphysema reported significantly different ADC but not alveolar sheath thickness compared to ex‐smokers without CT evidence of emphysema. Differences in alveolar measurements in never‐ and ex‐smokers demonstrate the sensitivity of MRI measurements to the different effects of smoking and aging on acinar morphometry.

Pulmonary Abnormalities and Carotid Atherosclerosis in Ex-Smokers without Airflow Limitation

Abstract It is well-established that COPD patients have a burden of vascular disease that cannot be fully-explained by smoking history but the mechanistic links between atherosclerosis and pulmonary disease in COPD patients are not well-understood. Moreover, in ex-smokers without symptoms or other evidence of COPD, subclinical pulmonary and vascular disease, although potentially present, has not been described or evaluated. Hence our aim was to use sensitive three-dimensional (3D) pulmonary and carotid imaging to quantify pulmonary airway/parenchyma abnormalities and atherosclerosis in ex-smokers without airflow limitation or symptoms consistent with COPD. We evaluated 61 subjects without airflow limitation including 34 never- (72 ± 6 years) and 27 ex-smokers (73 ± 9 years), who provided written informed consent to spirometry, plethysmography, 3He magnetic resonance imaging (MRI) and carotid ultrasound (US) and, for ex-smokers alone, thoracic X-ray computed tomography (CT). Ex-smokers had significantly greater 3He ventilation defect percent (VDP = 7%, p = 0.001) and carotid total plaque volume (TPV = 250 mm3, p = 0.002) than never-smokers, although there were no significant differences for spirometry or plethysmography, and CT airway and emphysema measurements were normal. There were univariate relationships for 3He VDP with carotid intima media thickness (IMT, r = 0.42, p = 0.004), TPV (r = 0.41, p = 0.006) and vessel wall volume (VWV, r = 0.40, p = 0.007). Multivariate models that included age, BMI, FEV1, DLCO and VDP showed that only VDP significantly predicted IMT (β = 0.41, p = 0.001), VWV (β = 0.45, p = 0.003) and TPV (β = 0.38, p = 0.005). In summary, there was imaging evidence of mild airways disease and carotid plaque burden that were related and significantly greater in ex-smokers without airflow limitation than in never-smokers.

Anatomical pulmonary magnetic resonance imaging segmentation for regional structure-function measurements of asthma

PURPOSE Pulmonary magnetic-resonance-imaging (MRI) and x-ray computed-tomography have provided strong evidence of spatially and temporally persistent lung structure-function abnormalities in asthmatics. This has generated a shift in their understanding of lung disease and supports the use of imaging biomarkers as intermediate endpoints of asthma severity and control. In particular, pulmonary (1)H MRI can be used to provide quantitative lung structure-function measurements longitudinally and in response to treatment. However, to translate such biomarkers of asthma, robust methods are required to segment the lung from pulmonary (1)H MRI. Therefore, their objective was to develop a pulmonary (1)H MRI segmentation algorithm to provide regional measurements with the precision and speed required to support clinical studies. METHODS The authors developed a method to segment the left and right lung from (1)H MRI acquired in 20 asthmatics including five well-controlled and 15 severe poorly controlled participants who provided written informed consent to a study protocol approved by Health Canada. Same-day spirometry and plethysmography measurements of lung function and volume were acquired as well as (1)H MRI using a whole-body radiofrequency coil and fast spoiled gradient-recalled echo sequence at a fixed lung volume (functional residual capacity + 1 l). We incorporated the left-to-right lung volume proportion prior based on the Potts model and derived a volume-proportion preserved Potts model, which was approximated through convex relaxation and further represented by a dual volume-proportion preserved max-flow model. The max-flow model led to a linear problem with convex and linear equality constraints that implicitly encoded the proportion prior. To implement the algorithm, (1)H MRI was resampled into ∼3 × 3 × 3 mm(3) isotropic voxel space. Two observers placed seeds on each lung and on the background of 20 pulmonary (1)H MR images in a randomized dataset, on five occasions, five consecutive days in a row. Segmentation accuracy was evaluated using the Dice-similarity-coefficient (DSC) of the segmented thoracic cavity with comparison to five-rounds of manual segmentation by an expert observer. The authors also evaluated the root-mean-squared-error (RMSE) of the Euclidean distance between lung surfaces, the absolute, and percent volume error. Reproducibility was measured using the coefficient of variation (CoV) and intraclass correlation coefficient (ICC) for two observers who repeated segmentation measurements five-times. RESULTS For five well-controlled asthmatics, forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) was 83% ± 7% and FEV1 was 86 ± 9%pred. For 15 severe, poorly controlled asthmatics, FEV1/FV C = 66% ± 17% and FEV1 = 72 ± 27%pred. The DSC for algorithm and manual segmentation was 91% ± 3%, 92% ± 2% and 91% ± 2% for the left, right, and whole lung, respectively. RMSE was 4.0 ± 1.0 mm for each of the left, right, and whole lung. The absolute (percent) volume errors were 0.1 l (∼6%) for each of right and left lung and ∼0.2 l (∼6%) for whole lung. Intra- and inter-CoV (ICC) were <0.5% (>0.91%) for DSC and <4.5% (>0.93%) for RMSE. While segmentation required 10 s including ∼6 s for user interaction, the smallest detectable difference was 0.24 l for algorithm measurements which was similar to manual measurements. CONCLUSIONS This lung segmentation approach provided the necessary and sufficient precision and accuracy required for research and clinical studies.

Pulmonary MRI morphometry modeling of airspace enlargement in chronic obstructive pulmonary disease and alpha-1 antitrypsin deficiency.

We generated lung morphometry measurements using single‐breath diffusion‐weighted MRI and three different acinar duct models in healthy participants and patients with emphysema stemming from chronic obstructive lung disease (COPD) and alpha‐1 antitrypsin deficiency (AATD).

Ultrashort echo time MRI biomarkers of asthma.

To develop and assess ultrashort echo‐time (UTE) magnetic resonance imaging (MRI) biomarkers of lung function in asthma patients.