Pulmonary Imaging Phenotypes of Chronic Obstructive Pulmonary Disease Using Multiparametric Response Maps.

Background Pulmonary imaging of chronic obstructive pulmonary disease (COPD) has focused on CT or MRI measurements, but these have not been evaluated in combination. Purpose To generate multiparametric response map (mPRM) measurements in ex-smokers with or without COPD by using volume-matched CT and hyperpolarized helium 3 (3He) MRI. Materials and Methods In this prospective study (https://clinicaltrials.gov, NCT02279329), participants underwent MRI and CT and completed pulmonary function tests, questionnaires, and the 6-minute walk test between December 2010 and January 2019. Disease status was determined by using Global initiative for chronic Obstructive Lung Disease (GOLD) criteria. The mPRM voxel values were generated by using co-registered MRI and CT labels. Kruskal-Wallis and Bonferroni tests were used to determine differences across disease severity, and correlations were determined by using Spearman coefficients. Results A total of 175 ex-smokers (mean age, 69 years ± 9 [standard deviation], 108 men) with or without COPD were evaluated. Ex-smokers without COPD had a larger fraction of normal mPRM voxels (60% vs 37%, 20%, and 7% for GOLD I, II, and III/IV disease, respectively; all P ≤ .001) and a smaller fraction of abnormal voxels, including small airways disease (normal CT, not ventilated: 5% vs 6% [not significant], 11%, and 19% [P ≤ .001 for both] for GOLD I, II, and III/IV disease, respectively) and mild emphysema (normal CT, abnormal apparent diffusion coefficient [ADC]: 33% vs 54%, 56%, and 54% for GOLD I, II, and III/IV disease respectively; all P ≤ .001). Normal mPRM measurements were positively correlated with forced expiratory volume in 1 second (FEV1) (r = 0.65, P < .001), the FEV1-to-forced vital capacity ratio (r = 0.81, P < .001), and diffusing capacity (r = 0.75, P < .001) and were negatively correlated with worse quality of life (r = -0.48, P < .001). Abnormal mPRM measurements of small airways disease (normal CT, not ventilated) and mild emphysema (normal CT, abnormal ADC) were negatively correlated with FEV1 (r = -0.65 and -0.42, respectively; P < .001) and diffusing capacity (r = -0.53 and -0.60, respectively; P < .001) and were positively correlated with worse quality of life (r = 0.45 and r = 0.33, respectively; P < .001), both of which were present in ex-smokers without COPD. Conclusion Multiparametric response maps revealed two abnormal structure-function results related to emphysema and small airways disease, both of which were unexpectedly present in ex-smokers with normal spirometry and CT findings. © RSNA, 2020 Online supplemental material is available for this article.

Chronic Obstructive Pulmonary Disease: Thoracic CT Texture Analysis and Machine Learning to Predict Pulmonary Ventilation.

Background Fixed airflow limitation and ventilation heterogeneity are common in chronic obstructive pulmonary disease (COPD). Conventional noncontrast CT provides airway and parenchymal measurements but cannot be used to directly determine lung function. Purpose To develop, train, and test a CT texture analysis and machine-learning algorithm to predict lung ventilation heterogeneity in participants with COPD. Materials and Methods In this prospective study (ClinicalTrials.gov: NCT02723474; conducted from January 2010 to February 2017), participants were randomized to optimization (n = 1), training (n = 67), and testing (n = 27) data sets. Hyperpolarized (HP) helium 3 (3He) MRI ventilation maps were co-registered with thoracic CT to provide ground truth labels, and 87 quantitative imaging features were extracted and normalized to lung averages to generate 174 features. The volume-of-interest dimension and the training data sampling method were optimized to maximize the area under the receiver operating characteristic curve (AUC). Forward feature selection was performed to reduce the number of features; logistic regression, linear support vector machine, and quadratic support vector machine classifiers were trained through fivefold cross validation. The highest-performing classification model was applied to the test data set. Pearson coefficients were used to determine the relationships between the model, MRI, and pulmonary function measurements. Results The quadratic support vector machine performed best in training and was applied to the test data set. Model-predicted ventilation maps had an accuracy of 88% (95% confidence interval [CI]: 88%, 88%) and an AUC of 0.82 (95% CI: 0.82, 0.83) when the HP 3He MRI ventilation maps were used as the reference standard. Model-predicted ventilation defect percentage (VDP) was correlated with VDP at HP 3He MRI (r = 0.90, P < .001). Both model-predicted and HP 3He MRI VDP were correlated with forced expiratory volume in 1 second (FEV1) (model: r = -0.65, P < .001; MRI: r = -0.70, P < .001), ratio of FEV1 to forced vital capacity (model: r = -0.73, P < .001; MRI: r = -0.75, P < .001), diffusing capacity (model: r = -0.69, P < .001; MRI: r = -0.65, P < .001), and quality-of-life score (model: r = 0.59, P = .001; MRI: r = 0.65, P < .001). Conclusion Model-predicted ventilation maps generated by using CT textures and machine learning were correlated with MRI ventilation maps (r = 0.90, P < .001). © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Fain in this issue.

Advanced pulmonary MRI to quantify alveolar and acinar duct abnormalities: Current status and future clinical applications.

There are serious clinical gaps in our understanding of chronic lung disease that require novel, sensitive, and noninvasive in vivo measurements of the lung parenchyma to measure disease pathogenesis and progressive changes over time as well as response to treatment. Until recently, our knowledge and appreciation of the tissue changes that accompany lung disease has depended on ex vivo biopsy and concomitant histological and stereological measurements. These measurements have revealed the underlying pathologies that drive lung disease and have provided important observations about airway occlusion, obliteration of the terminal bronchioles and airspace enlargement, or fibrosis and their roles in disease initiation and progression. ex vivo tissue stereology and histology are the established gold standards and, more recently, micro-computed tomography (CT) measurements of ex vivo tissue samples has also been employed to reveal new mechanistic findings about the progression of obstructive lung disease in patients. While these approaches have provided important understandings using ex vivo analysis of excised samples, recently developed hyperpolarized noble gas MRI methods provide an opportunity to noninvasively measure acinar duct and terminal airway dimensions and geometry in vivo, and, without radiation burden. Therefore, in this review we summarize emerging pulmonary MRI morphometry methods that provide noninvasive in vivo measurements of the lung in patients with bronchopulmonary dysplasia and chronic obstructive pulmonary disease, among others. We discuss new findings, future research directions, as well as clinical opportunities to address current gaps in patient care and for testing of new therapies. Level of Evidence: 5 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2019;50:28-40.

Oscillometry and pulmonary magnetic resonance imaging in asthma and COPD.

Developed over six decades ago, pulmonary oscillometry has re-emerged as a noninvasive and effort-independent method for evaluating respiratory-system impedance in patients with obstructive lung disease. Here, we evaluated the relationships between hyperpolarized 3 He ventilation-defect-percent (VDP) and respiratory-system resistance, reactance and reactance area (AX ) measurements in 175 participants including 42 never-smokers without respiratory disease, 56 ex-smokers with chronic-obstructive-pulmonary-disease (COPD), 28 ex-smokers without COPD and 49 asthmatic never-smokers. COPD participants were dichotomized based on x-ray computed-tomography (CT) evidence of emphysema (relative-area CT-density-histogram ≤ 950HU (RA950 ) ≥ 6.8%). In asthma and COPD subgroups, MRI VDP was significantly related to the frequency-dependence of resistance (R5-19 ; asthma: ρ = 0.48, P = 0.0005; COPD: ρ = 0.45, P = 0.0004), reactance at 5 Hz (X5 : asthma, ρ = -0.41, P = 0.004; COPD: ρ = -0.38, P = 0.004) and AX (asthma: ρ = 0.47, P = 0.0007; COPD: ρ = 0.43, P = 0.0009). MRI VDP was also significantly related to R5-19 in COPD participants without emphysema (ρ = 0.54, P = 0.008), and to X5 in COPD participants with emphysema (ρ = -0.36, P = 0.04). AX was weakly related to VDP in asthma (ρ = 0.47, P = 0.0007) and COPD participants with (ρ = 0.39, P = 0.02) and without (ρ = 0.43, P = 0.04) emphysema. AX is sensitive to obstruction but not specific to the type of obstruction, whereas the different relationships for MRI VDP with R5-19 and X5 may reflect the different airway and parenchymal disease-specific biomechanical abnormalities that lead to ventilation defects.

Rapid single-breath hyperpolarized noble gas MRI-based biomarkers of airspace enlargement.

BACKGROUND: Multi-b diffusion-weighted hyperpolarized-gas MRI measures pulmonary airspace-enlargement using apparent diffusion coefficients (ADCs) and mean-linear-intercepts (Lm ). PURPOSE: To develop single-breath 3D multi-b diffusion-weighted 3 He and 129 Xe MRI using k-space undersampling. Rapid, cost-efficient, single-breath acquisitions may facilitate clinical translation. STUDY TYPE: Prospective. SUBJECTS: We evaluated 12 participants, including nine subjects (mean age = 69 ± 9) who were included in the retrospective experiment and three chronic pulmonary obstruction disease (COPD) patients (mean age = 81 ± 6) who participated in the prospective study. FIELD STRENGTH: A whole-body 3 T 2D/3D fast gradient recall echo (FGRE) sequence. ASSESSMENT: Hyperpolarized 3 He/129 Xe MRI, spirometry, plethysmography computed tomography (CT). We evaluated 129 Xe ADC/morphometry estimates by retrospectively undersampling previously acquired fully sampled multibreath, multi-b diffusion-weighted data. Next, we prospectively evaluated the feasibility of accelerated (AF = 7) 3 He MRI static-ventilation/T2 * (extra short-TE, b = 0 image) and ADC/morphometry (five b-values) maps using a single gas-dose and 16-second breath-hold. To conservatively evaluate cost-improvement, we compared total costs of single vs. multiple 129 Xe doses. STATISTICAL TESTS: Multivariate analysis of variance, independent t-tests and voxel-by-voxel basis difference test. RESULTS: For the retrospectively undersampled 129 Xe data, a nonsignificant mean difference for ADC/Lm of 14%/12%, 12%/8%, and 11%/9% was observed (all, P > 0.4) between the fully sampled and accelerated data for the never-smoker, COPD, and alpha-1 antitrypsin deficiency (AATD) groups, respectively. The control never-smoker group had significantly lower ADC (P < 0.001) and Lm (P < 0.001) than the COPD/AATD group for both fully sampled and accelerated data. For the prospectively acquired 3 He MRI data, static-ventilation, T2 *, ADC, and morphometry maps were acquired using a single 16-second breath-hold scan and single gas dose. Accelerated imaging resulted in cost savings of ~$US 1000/patient, a conservative estimate based on 129 Xe MRI dose savings (single vs. five doses). DATA CONCLUSION: This is a proof-of-concept demonstration of accelerated (7×) morphometry that shows that less cost- and time-efficient multibreath methods that lead to variability and patient fatigue may be avoided in the future. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2018.