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Although hyperpolarized (HP) 129 Xe ventilation MRI can be carried out within a breath hold, it is still challenging for many sick patients. Compressed sensing (CS) is a viable alternative to accelerate this approach. However, undersampled images with identical sampling ratios differ from one another. Twenty subjects (n = 10 healthy and n = 10 patients with asthma) were scanned using a GE MR750 3 T scanner, acquiring fully sampled 2D multi-slice HP 129 Xe lung ventilation images (10 s breath hold, 128 × 80 (FE × PE-frequency encoding × phase encoding) and 16 slices). Using fully sampled data, 500 variable-density Cartesian random undersampling patterns were generated, each at eight different sampling ratios from 10% to 80%. The parallel imaging and compressed sensing (PICS) command from BART was employed to reconstruct undersampled data. The signal to noise ratio (SNR), structural similarity index measurement (SSIM) and sidelobe to peak ratio of each were subsequently compared. There was a high degree of variation in both SNR and SSIM results from each of the 500 masks of each sampling rate. As the undersampling increases, there is more variation in the quantifying metrics, for both healthy and asthmatic individuals. Our study shows that random undersampling poses a significant challenge when applied at sampling ratios less than 60%, despite fulfilling CS's incoherency criteria. Such low sampling ratios will result in a large variety of undersampling patterns. Therefore, skipped segments of k-space cannot be allowed to happen randomly at low sampling rates. By optimizing the sampling pattern, CS will reach its full potential and be able to be applied to a highly undersampled 129 Xe lung dataset., (© 2024 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.)

The respiratory consequences of acute COVID-19 infection and related symptoms tend to resolve 4 weeks post-infection. However, for some patients, new, recurrent, or persisting symptoms remain beyond the acute phase and persist for months, post-infection. The symptoms that remain have been referred to as long-COVID. A number of research sites employed 129 Xe magnetic resonance imaging (MRI) during the pandemic and evaluated patients post-infection, months after hospitalization or home-based care as a way to better understand the consequences of infection on 129 Xe MR gas-exchange and ventilation imaging. A systematic review and comprehensive search were employed using MEDLINE via PubMed (April 2023) using the National Library of Medicine's Medical Subject Headings and key words: post-COVID-19, MRI, 129 Xe, long-COVID, COVID pneumonia, and post-acute COVID-19 syndrome. Fifteen peer-reviewed manuscripts were identified including four editorials, a single letter to the editor, one review article, and nine original research manuscripts (2020-2023). MRI and MR spectroscopy results are summarized from these prospective, controlled studies, which involved small sample sizes ranging from 9 to 76 participants. Key findings included: 1) 129 Xe MRI gas-exchange and ventilation abnormalities, 3 months post-COVID-19 infection, and 2) a combination of MRI gas-exchange and ventilation abnormalities alongside persistent symptoms in patients hospitalized and not hospitalized for COVID-19, 1-year post-infection. The persistence of respiratory symptoms and 129 Xe MRI abnormalities in the context of normal or nearly normal pulmonary function test results and chest computed tomography (CT) was consistent. Longitudinal improvements were observed in long-term follow-up of long-COVID patients but mean 129 Xe gas-exchange, ventilation heterogeneity values and symptoms remained abnormal, 1-year post-infection. Pulmonary functional MRI using inhaled hyperpolarized 129 Xe gas has played a role in detecting gas-exchange and ventilation abnormalities providing complementary information that may help develop our understanding of the root causes of long-COVID. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 5., (© 2023 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Hyperpolarized (HP) 129 Xe MRI uniquely images pulmonary ventilation, gas exchange, and terminal airway morphology rapidly and safely, providing novel information not possible using conventional imaging modalities or pulmonary function tests. As such, there is mounting interest in expanding the use of biomarkers derived from HP 129 Xe MRI as outcome measures in multi-site clinical trials across a range of pulmonary disorders. Until recently, HP 129 Xe MRI techniques have been developed largely independently at a limited number of academic centers, without harmonizing acquisition strategies. To promote uniformity and adoption of HP 129 Xe MRI more widely in translational research, multi-site trials, and ultimately clinical practice, this position paper from the 129 Xe MRI Clinical Trials Consortium (https://cpir.cchmc.org/XeMRICTC) recommends standard protocols to harmonize methods for image acquisition in HP 129 Xe MRI. Recommendations are described for the most common HP gas MRI techniques-calibration, ventilation, alveolar-airspace size, and gas exchange-across MRI scanner manufacturers most used for this application. Moreover, recommendations are described for 129 Xe dose volumes and breath-hold standardization to further foster consistency of imaging studies. The intention is that sites with HP 129 Xe MRI capabilities can readily implement these methods to obtain consistent high-quality images that provide regional insight into lung structure and function. While this document represents consensus at a snapshot in time, a roadmap for technical developments is provided that will further increase image quality and efficiency. These standardized dosing and imaging protocols will facilitate the wider adoption of HP 129 Xe MRI for multi-site pulmonary research., (© 2021 International Society for Magnetic Resonance in Medicine.)

Rationale: Inflammation and smooth muscle dysfunction are integral components of severe asthma that contribute to luminal obstruction causing airflow limitation, ventilation heterogeneity, and symptoms. This is important for guiding treatment decisions directed at the inflammatory (e.g., anti-T-helper cell type 2 monoclonal antibodies) and noninflammatory, smooth muscle-mediated (e.g., bronchial thermoplasty) components of severe asthma., Objectives: To investigate the contribution of eosinophilic bronchitis and smooth muscle dysfunction to magnetic resonance imaging (MRI) ventilation heterogeneity in patients with severe asthma., Methods: We measured the inhaled hyperpolarized gas MRI response to salbutamol as a marker of smooth muscle dysfunction, and sputum eosinophils as a marker of airway inflammation, and their contributions to ventilation heterogeneity (quantified as the ventilation defect percent [VDP]) in 27 patients with severe asthma. Spirometry and forced oscillation airway resistance measurements were also acquired pre- and postsalbutamol. Patients were dichotomized on the basis of sputum eosinophilia, and pre- and postsalbutamol VDP and physiological measurements were evaluated., Measurements and Main Results: MRI VDP improved with salbutamol inhalation in patients in whom sputum eosinophilia was uncontrolled (≥3%, n = 16) (P = 0.002) and in those in whom it was controlled (<3%, n = 11) (P = 0.02), independent of improvements in FEV 1 , indicating smooth muscle response. In those patients in whom sputum eosinophilia was uncontrolled, greater VDP persisted postsalbutamol (P = 0.004). Postsalbutamol VDP correlated with sputum eosinophils (r = 0.63; P = 0.005)., Conclusions: In patients with severe asthma, MRI regionally identifies the inflammatory and noninflammatory components of airway disease. Ventilation heterogeneity persists postsalbutamol in patients with uncontrolled eosinophilic bronchitis, which may be the functional consequence of airway inflammation.

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 1 H magnetic resonance imaging (FDMRI), and inhaled-gas MRI ventilation defect percent (VDP)., 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 1 ) >70% predicted , MRI was also performed before and after MCh challenge. Wilcoxon signed-rank tests, Spearman correlations, and a repeated-measures analysis of variance were performed., Results: Hyperpolarized 3 He (P = .02) and FDMRI (P = .02) VDP significantly improved post-salbutamol and for four asthmatics who could perform MCh (n = 4). 3 He and FDMRI VDP significantly increased at the provocative concentration of MCh, resulting in a 20% decrease in FEV 1 (PC 20 ) and decreased post-bronchodilator (P = .02), with a significant difference between methods (P = .01). FDMRI VDP was moderately correlated with 3 He VDP (ρ = .61, P = .01), but underestimated VDP relative to 3 He VDP (-6 ± 9%). Whereas 3 He MRI VDP was significantly correlated with the lung clearance index, FDMRI was not (ρ = .49, P = .06)., Conclusions: FDMRI VDP generated in free-breathing asthmatic patients was correlated with static inspiratory breath-hold 3 He MRI VDP but underestimated VDP relative to 3 He MRI VDP. Although less sensitive to salbutamol and MCh, FDMRI VDP may be considered for asthma patient evaluations at centers without inhaled-gas MRI., (Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Purpose: To develop and assess ultrashort echo-time (UTE) magnetic resonance imaging (MRI) biomarkers of lung function in asthma patients., Materials and Methods: Thirty participants including 13 healthy volunteers and 17 asthmatics provided written informed consent to UTE and pulmonary function tests in addition to hyperpolarized-noble-gas 3T MRI and computed tomography (CT) for asthmatics only. The difference in MRI signal-intensity (SI) across four lung volumes (full-expiration, functional-residual-capacity [FRC], FRC+1L, and full-inspiration) was determined on a voxel-by-voxel basis to generate dynamic proton-density (DPD) maps. MRI ventilation-defect-percent (VDP), UTE SI, and DPD values as well as CT radiodensity were determined for whole lung and individual lobes., Results: Mean SI at full-expiration (P < 0.01), FRC (P < 0.05), and DPD (P < 0.01) were greater in healthy volunteers compared to asthmatics. In asthmatics, UTE SI at full-expiration and DPD were correlated with FEV 1 /FVC (SI r = 0.73/P = 0.002; DPD r = 0.75/P = 0.003), RV/TLC (SI r = -0.57/P = 0.02), or RV (DPD r = -0.62/P = 0.02), CT radiodensity (SI r = 0.83/P = 0.006; DPD r = 0.71/P = 0.01), and lobar VDP (SI r s  = -0.33/P = 0.02; DPD r s  = -0.47/P = 0.01)., Conclusion: In patients with asthma, UTE SI and dynamic proton-density were related to pulmonary function measurements, whole lung and lobar VDP, as well as CT radiodensity. Thus, UTE MRI biomarkers may reflect ventilation heterogeneity and/or gas-trapping in asthmatics using conventional equipment, making this approach potentially amenable for clinical use., Level of Evidence: 2 J. Magn. Reson. Imaging 2017;45:1204-1215., (© 2016 International Society for Magnetic Resonance in Medicine.)

In asthma patients, magnetic resonance imaging (MRI) and the lung clearance index (LCI) have revealed persistent ventilation heterogeneity, although its relationship to asthma control is not well understood. Therefore, our goal was to explore the relationship of MRI ventilation defects and the LCI with asthma control and quality of life in patients with severe, poorly controlled asthma.18 patients with severe, poorly controlled asthma (mean±sd 46±12 years, six males/12 females) provided written informed consent to an ethics board approved protocol, and underwent spirometry, LCI and (3)He MRI during a single 2-h visit. Asthma control and quality of life were evaluated using the Asthma Control Questionnaire (ACQ) and Asthma Quality of Life Questionnaire (AQLQ). Ventilation heterogeneity was quantified using the LCI and (3)He MRI ventilation defect percent (VDP).All participants reported poorly controlled disease (mean±sd ACQ score=2.3±0.9) and highly heterogeneous ventilation (mean±sd VDP=12±11% and LCI=10.5±3.0). While VDP and LCI were strongly correlated (r=0.86, p<0.0001), in a multivariate model that included forced expiratory volume in 1 s, VDP and LCI, VDP was the only independent predictor of asthma control (R(2)=0.38, p=0.01). There was also a significantly worse VDP, but not LCI in asthma patients with an ACQ score >2 (p=0.04) and AQLQ score <5 (p=0.04), and a trend towards worse VDP (p=0.053), but not LCI in asthma patients reporting ≥1 exacerbation in the past 6 months.In patients with poorly controlled, severe asthma MRI ventilation, but not LCI was significantly worse in those with worse ACQ and AQLQ., (Copyright ©ERS 2016.)

Rationale and Objectives: Pulmonary functional magnetic resonance imaging provides a way to quantify ventilation and its heterogeneity-a hallmark finding in chronic obstructive pulmonary disease (COPD). Unfortunately, the etiology and physiological meaning of ventilation defects and their relationship to pulmonary function and symptoms in COPD are not well understood. Another biomarker of ventilation heterogeneity is provided by the "poorly communicating fraction" (PCF), and is calculated as the ratio of total lung capacity to alveolar volume made using whole-body plethysmography. Our objective was to compare ventilation heterogeneity using hyperpolarized (3)He magnetic resonance imaging (MRI) and PCF measurements in elderly never-smokers and in ex-smokers with COPD., Materials and Methods: One hundred forty-six participants (71 ± 8 years, range = 48-87 years) provided written informed consent including 45 elderly never-smokers (71 ± 6 years, range = 61-84 years) and 101 ex-smokers with COPD (71 ± 8 years, range = 48-87 years). During a single 2-hour visit, spirometry, plethysmography, and hyperpolarized (3)He MRI were acquired. The MRI-derived ventilation defect percent (VDP) and plethysmography measurements were acquired and PCF values were calculated. Linear regression, Pearson correlations, and Bland-Altman analysis were used to evaluate the relationships for PCF and MRI VDP., Results: PCF (P < 0.001) and VDP (P < 0.001) were significantly increased with increasing COPD severity. There was a significant relationship for VDP and PCF (r = 0.68, P < 0.001) in all subjects and COPD subjects alone (r = 0.61, P < 0.001). Bland-Altman analysis showed that PCF and VDP were significantly different (mean bias = 9.7, upper limit = 32, lower limit = -13, P < 0.001), and in severe-grade COPD, PCF overestimates of VDP were significantly greater., Conclusions: In elderly never-smokers and in ex-smokers with COPD, PCF and VDP are moderately correlated estimates of COPD ventilation heterogeneity that may be reflecting similar pathophysiology., (Copyright © 2016 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

In patients with asthma, magnetic resonance imaging (MRI) provides direct measurements of regional ventilation heterogeneity, the etiology of which is not well-understood, nor is the relationship of ventilation abnormalities with lung mechanics. In addition, respiratory resistance and reactance are often abnormal in asthmatics and the frequency dependence of respiratory resistance is thought to reflect ventilation heterogeneity. We acquiredMRIventilation defect maps, forced expiratory volume in one-second (FEV1), and airways resistance (Raw) measurements, and used a computational airway model to explore the relationship of ventilation defect percent (VDP) with simulated measurements of respiratory system resistance (Rrs) and reactance (Xrs).MRIventilation defect maps were experimentally acquired in 25 asthmatics before, during, and after methacholine challenge and these were nonrigidly coregistered to the airway tree model. Using the model coregistered to ventilation defect maps, we narrowed proximal (9th) and distal (14th) generation airways that were spatially related to theMRIventilation defects. The relationships forVDPwith Raw measured using plethysmography (r = 0.79), and model predictions of Rrs>14(r = 0.91,P < 0.0001) and Rrs>9(r = 0.88,P < 0.0001) were significantly stronger (P = 0.005;P = 0.03, respectively) than withFEV1(r = -0.68,P = 0.0001). The slopes for the relationship ofVDPwith simulated lung mechanics measurements were different (P < 0.0001); among these, the slope for theVDP-Xrs0.2relationship was largest, suggesting thatVDPwas dominated by peripheral airway heterogeneity in these patients. In conclusion, as a first step toward understanding potential links between lung mechanics and ventilation defects, impedance predictions were made using a computational airway tree model with simulated constriction of airways related to ventilation defects measured in mild-moderate asthmatics., (© 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.)

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. George's Respiratory Questionnaire (SGRQ), Patient Evaluation Questionnaire (PEQ), Six-Minute Walk Test and (3)He 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 (3)He 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.

Background: To evaluate ultra-short-echo-time (UTE) MRI pulmonary signal-intensity measurements and reproducibility in chronic obstructive pulmonary disease (COPD)., Methods: A two-dimensional sequence (echo-time = 0.05 ms; acquisition-time = 13 s) with interleaved half-pulse excitation and radial ramp-sampling was used with compressed-sensing to reconstruct UTE images from under-sampled data. Five healthy volunteers and 15 subjects with COPD provided written informed consent to imaging and pulmonary-function-tests. Healthy volunteers underwent MRI at four lung volumes: full-expiration, functional-residual-capacity (FRC), FRC+1L, and full-inhalation; COPD patients underwent computed-tomography (CT) and MRI at FRC+1L. Three-week reproducibility was evaluated and the relative area of the density histogram ≤ -950 HU (RA950 ) was compared with mean MRI signal-intensity. The 15th percentile of signal-intensity-histogram (SI15 ) was compared with the 15th percentile of the CT-density-histogram (HU15 )., Results: In healthy subjects, signal-intensity correlated with the inverse of lung volume (r = 0.99; P = 0.007). Contrast-to-noise and signal-to-noise ratios were significantly improved for 32-channel UTE (P < 0.01). The coefficient of variation for 3-week repeated measurements was 4%. There were significant correlations for signal-intensity with RA950 (r = -0.71; P = 0.005), FEV1 /FVC (r = 0.59; P = 0.02), and for SI15 with HU15 (r = 0.62; P = 0.01)., Conclusion: Pulmonary signal-intensity is reproducible and related to tissue density. In COPD subjects with and without bronchiectasis, signal-intensity was also related to pulmonary function and CT measurements., (© 2014 Wiley Periodicals, Inc.)

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., (Copyright © 2015 AUR. Published by Elsevier Inc. All rights reserved.)

Rationale and Objectives: Hyperpolarized (3)He magnetic resonance imaging (MRI) previously revealed the temporal and spatial heterogeneity of ventilation defects in asthmatics, but these findings have not been used in treatment studies or to guide personalized therapy. Our objective was to exploit the temporal and spatial information inherent to (3)He MRI and develop image processing methods to generate pulmonary ventilation temporal-spatial maps that could be used to measure, optimize, and guide asthma therapy., Materials and Methods: In this proof-of-concept study, seven asthmatics provided written informed consent to an approved protocol and underwent spirometry and (3)He MRI on three occasions, each 5 ± 2 days apart. A registration and segmentation pipeline was developed to generate three-dimensional, temporal-spatial, pulmonary function maps. Briefly, (3)He ventilation images were segmented to generate ventilation masks that were coregistered and voxels classified according to their temporal behavior. This enabled the regional mapping of temporally persistent and intermittent ventilation defects that were normalized to the (1)H MRI thoracic cavity volume to generate persistent ventilation defect percent (VDPP) and intermittent ventilation defect percent (VDPI)., Results: (3)He temporal-spatial pulmonary function maps identified temporally persistent and intermittent ventilation defects. VDP(I) was significantly greater in the posterior (P = .04) and inferior (P = .04) lung as compared to the anterior and superior lung. Persistent and intermittent ventilation defect percent were strongly correlated with forced expiratory volume in one second/forced vital capacity (VDP(P): r = -0.87, P = .01; VDP(I): r = -0.96, P = .0008)., Conclusions: Temporal-spatial pulmonary maps generated from (3)He MRI can be used to quantify temporally persistent and intermittent ventilation defects as asthma intermediate end points and targets for therapy., (Copyright © 2014 AUR. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2014 the American Physiological Society.)

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., (Copyright © 2013 Wiley Periodicals, Inc.)

In subjects with chronic obstructive pulmonary disease (COPD), hyperpolarized xenon-129 ((129)Xe) magnetic resonance imaging (MRI) reveals significantly greater ventilation defects than hyperpolarized helium-3 ((3)He) MRI. The physiological and/or morphological determinants of ventilation defects and the differences observed between hyperpolarized (3)He and (129)Xe MRI are not yet understood. Here we aimed to determine the structural basis for the differences in ventilation observed between (3)He and (129)Xe MRI in subjects with COPD using apparent diffusion coefficients (ADC) and computed tomography (CT). Ten COPD ex-smokers provided written, informed consent and underwent MRI, CT, spirometry, and plethysmography. (3)He and (129)Xe MRI ventilation volume was generated using semiautomated segmentation, and ADC maps were registered to generate ADC values for lung regions of interest ventilated by both gases (ADCHX) and by (3)He gas only (ADCHO). CT wall area percentage and the lowest 15th percentile point of the CT lung density histogram (HU15%) were also evaluated. For lung regions accessed by (3)He gas only, mean (3)He ADCHO was significantly greater than for regions accessed by both gases (ADCHO = 0.503 ± 0.119 cm(2)/s, ADCHX = 0.470 ± 0.125 cm(2)/s, P < 0.0001). The difference between (3)He and (129)Xe ventilation volume was significantly correlated with CT HU15% (r = -65, P = 0.04) and (3)He ADCHO (r = 0.70, P = 0.02), but not CT wall area percentage (r = -0.34, P = 0.33). In conclusion, in this small study in COPD subjects, we observed significantly decreased (129)Xe MRI ventilation compared with (3)He MRI, and these regions of decreased (129)Xe ventilation were spatially and significantly correlated with regions of increased pulmonary emphysema, but not airway wall thickness.