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Pulmonary ventilation may be visualized and measured using hyperpolarized (3)He magnetic resonance imaging (MRI) while emphysema and its distribution can be quantified using thoracic computed tomography (CT). Our objective was to phenotype ex-smokers with COPD based on the apical-to-basal distribution of ventilation abnormalities and emphysema to better understand how these phenotypes change regionally as COPD progresses. We evaluated 100 COPD ex-smokers who provided written informed consent and underwent spirometry, CT and (3)He MRI. (3)He MRI ventilation imaging was used to quantify the ventilation defect percent (VDP) for whole-lung and individual lung lobes. Regional VDP was used to generate the apical-lung (AL)-to-basal-lung (BL) difference (ΔVDP); a positive ΔVDP indicated AL-predominant and negative ΔVDP indicated BL-predominant ventilation defects. Emphysema was quantified using the relative-area-of-the-lung ≤-950HU (RA950) of the CT density histogram for whole-lung and individual lung lobes. The AL-to-BL RA950 difference (ΔRA950) was generated with a positive ΔRA950 indicating AL-predominant emphysema and a negative ΔRA950 indicating BL-predominant emphysema. Seventy-two ex-smokers reported BL-predominant MRI ventilation defects and 71 reported AL-predominant CT emphysema. BL-predominant ventilation defects (AL/BL: GOLD I = 18%/82%, GOLD II = 24%/76%) and AL-predominant emphysema (AL/BL: GOLD I = 84%/16%, GOLD II = 72%/28%) were the major phenotypes in mild-moderate COPD. In severe COPD there was a more uniform distribution for ventilation defects (AL/BL: GOLD III = 40%/60%, GOLD IV = 43%/57%) and emphysema (AL/BL: GOLD III = 64%/36%, GOLD IV = 43%/57%). Basal-lung ventilation defects predominated in mild-moderate GOLD grades, and a more homogeneous distribution of ventilation defects was observed in more advanced grade COPD; these differences suggest that over time, regional ventilation abnormalities become more homogenously distributed during disease progression.

Purpose: To determine the role of imaging measurements of emphysema and airway disease in determining chronic obstructive pulmonary disease (COPD) symptoms and exercise limitation in patients with COPD, particularly in patients with mild-to-moderate disease., Materials and Methods: Participants (n = 116) with Global Initiative for Chronic Obstructive Lung Disease (GOLD) grade U (unclassified) or grade I-IV COPD provided informed consent to an ethics board-approved HIPAA-compliant protocol and underwent spirometry and plethysmography, completed the St George's Respiratory Questionnaire (SGRQ), completed a 6-minute walk test for the 6-minute walk distance (6MWD), and underwent hyperpolarized helium 3 ((3)He) magnetic resonance (MR) imaging and computed tomography (CT). Emphysema was estimated by using the MR imaging apparent diffusion coefficient (ADC) and the relative area of the CT attenuation histogram with attenuation of -950 HU or less (RA950). Airway disease was measured by using the CT airway wall thickness of airways with an internal perimeter of 10 mm and total airway count. Ventilation defect percentage at (3)He MR imaging was used to measure ventilation. Multivariable regression models for the 6MWD and SGRQ symptom subscore were used to evaluate the relationships between physiologic and imaging measurements., Results: Multivariate modeling for the 6MWD in 80 patients with GOLD grade U-II COPD showed that ADC (β = 0.34, P = .04), diffusing capacity of the lung for carbon monoxide (β = 0.60, P = .0008), and residual volume/total lung capacity (β = -0.26, P = .02) were significant variables, while forced expiratory volume in 1 second (FEV1) and airway disease measurements were not. In 36 patients with GOLD grade III or IV disease, FEV1 (β = 0.48, P = .01) was the only significant contributor in a multivariate model for 6MWD. MR imaging emphysema measurements also made the greatest relative contribution to symptoms in patients with milder (GOLD grade U-II) COPD (ADC: β = 0.60, P = .005; RA950: β = -0.52, P = .02; FEV1: β = -0.45, P = .0002) and in grade III or IV disease (ADC: β = 0.95, P = .01; RA950: β = -0.62, P = .07; airway count: β = -0.49, P = .01)., Conclusion: In patients with mild-to-moderate COPD, MR imaging emphysema measurements played a dominant role in the expression of exercise limitation, while both CT and MR imaging measurements of emphysema explained symptoms.

Rationale and Objectives: Hyperpolarized (3)He magnetic resonance imaging (MRI) ventilation abnormalities are visible in ex-smokers without airflow limitation, but the clinical relevance of this is not well-understood. Our objective was to phenotype healthy ex-smokers with normal and abnormally elevated ventilation defect percent (VDP)., Materials and Methods: Sixty ex-smokers without airflow limitation provided written informed consent to (3)He MRI, computed tomography (CT), and pulmonary function tests in a single visit. (3)He MRI VDP and apparent diffusion coefficients (ADCs) were measured for whole-lung and each lung lobe as were CT measurements of emphysema (relative area [RA] with attenuation ≤-950 HU, RA950) and airway morphology (wall area percent [WA%], lumen area [LA] and LA normalized to body surface area [LA/BSA])., Results: In 42 ex-smokers, there was abnormally elevated VDP and no significant differences for pulmonary function, RA950, or airway measurements compared to 18 ex-smokers with normal VDP. Ex-smokers with abnormally elevated VDP reported significantly greater (3)He ADC in the apical lung (right upper lobe [RUL], P = .02; right middle lobe [RML], P = .04; and left upper lobe [LUL], P = .009). Whole lung (r = 0.40, P = .001) and lobar VDP (RUL, r = 0.32, P = .01; RML, r = 0.46, P = .002; right lower lobe [RLL], r = 0.38, P = .003; LUL, r = 0.35, P = .006; and left lower lobe, r = 0.37, P = .004) correlated with regional (3)He ADC. Although whole-lung VDP and CT airway morphology measurements were not correlated, regional VDP was correlated with RUL LA (r = -0.37, P = .004), LA/BSA (r = -0.42, P = .0008), RLL WA% (r = 0.28, P = .03), LA (r = -0.28, P = .03), and LA/BSA (r = -0.37, P = .004)., Conclusions: Abnormally elevated VDP in ex-smokers without airflow limitation was coincident with very mild emphysema detected using MRI and regional airway remodeling detected using CT representing a subclinical obstructive lung disease phenotype., (Copyright © 2015 AUR. Published by Elsevier Inc. All rights reserved.)

Purpose: Multi‐b diffusion‐weighted hyperpolarized inhaled‐gas MRI provides imaging biomarkers of terminal airspace enlargement including ADC and mean linear intercept (Lm), but clinical translation has been limited because image acquisition requires relatively long or multiple breath‐holds that are not well‐tolerated by patients. Therefore, we aimed to accelerate single breath‐hold 3D multi‐b diffusion‐weighted 129Xe MRI, using k‐space undersampling in imaging direction using a different undersampling pattern for different b‐values combined with the stretched exponential model to generate maps of ventilation, apparent transverse relaxation time constant (T2∗), ADC, and Lm values in a single, short breath‐hold; accelerated and non‐accelerated measurements were directly compared. Methods: We evaluated multi‐b (0, 12, 20, 30, and 45.5 s/cm2) diffusion‐weighted 129Xe T2∗/ADC/morphometry estimates using acceleration factor (AF = 1 and 7) and multi‐breath sampling in 3 volunteers (HV), and 6 participants with alpha‐1 antitrypsin deficiency (AATD). Results: For the HV subgroup, mean differences of 5%, 2%, and 8% were observed between fully sampled and undersampled k‐space for ADC, Lm, and T2∗ values, respectively. For the AATD subgroup, mean differences were 9%, 6%, and 12% between fully sampled and undersampled k‐space for ADC, Lm and T2∗ values, respectively. Although mean differences of 1% and 4.5% were observed between accelerated and multi‐breath sampled ADC and Lm values, respectively, mean ADC/Lm estimates were not significantly different from corresponding mean ADCM/LmM or mean ADCA/LmA estimates (all P > 0.60 , A = undersampled and M = multi‐breath sampled). Conclusions: Accelerated multi‐b diffusion‐weighted 129Xe MRI is feasible at AF = 7 for generating pulmonary ADC and Lm in AATD and normal lung. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: Thoracic x-ray computed tomography (CT) and hyperpolarized 3He magnetic resonance imaging (MRI) provide quantitative measurements of airspace enlargement in patients with emphysema. For patients with panlobular emphysema due to alpha-1 antitrypsin deficiency (AATD), sensitive biomarkers of disease progression and response to therapy have been difficult to develop and exploit, especially those biomarkers that correlate with outcomes like quality of life. Here, our objective was to generate and compare CT and diffusion-weighted inhaled-gas MRI measurements of emphysema including apparent diffusion coefficient (ADC) and MRI-derived mean linear intercept (Lm) in patients with AATD, chronic obstructive pulmonary disease (COPD) ex-smokers, and elderly never-smokers.Materials and Methods: We enrolled patients with AATD (n = 8; 57 ± 7 years), ex-smokers with COPD (n = 8; 77 ± 6 years), and a control group of never-smokers (n = 5; 64 ± 2 years) who underwent thoracic CT, MRI, spirometry, plethysmography, the St. George's Respiratory Questionnaire, and the 6-minute walk test during a single 2-hour visit. MRI-derived ADC, Lm, surface-to-volume ratio, and ventilation defect percent were generated for the apical, basal, and whole lung as was CT lung area ≤-950 Hounsfield units (RA950), low attenuating clusters, and airway count.Results: In patients with AATD, there was a significantly different MRI-derived ADC (P = .03), Lm (P < .0001), and surface-to-volume ratio (P < .0001), but not diffusing capacity of carbon monoxide, residual volume or total lung capacity, or CT RA950 (P > .05) compared to COPD ex-smokers with a significantly different St. George's Respiratory Questionnaire.Conclusions: In this proof-of-concept demonstration, we evaluated CT and MRI lung emphysema measurements and observed significantly worse MRI biomarkers of emphysema in patients with AATD compared to patients with COPD, although CT RA950 and diffusing capacity of carbon monoxide were not significantly different, underscoring the sensitivity of MRI measurements of AATD emphysema. [ABSTRACT FROM AUTHOR]

Pulmonary ventilation may be visualized and measured using hyperpolarized3He magnetic resonance imaging (MRI) while emphysema and its distribution can be quantified using thoracic computed tomography (CT). Our objective was to phenotype ex-smokers with COPD based on the apical-to-basal distribution of ventilation abnormalities and emphysema to better understand how these phenotypes change regionally as COPD progresses. We evaluated 100 COPD ex-smokers who provided written informed consent and underwent spirometry, CT and3He MRI.3He MRI ventilation imaging was used to quantify the ventilation defect percent (VDP) for whole-lung and individual lung lobes. Regional VDP was used to generate the apical-lung (AL)-to-basal-lung (BL) difference (ΔVDP); a positive ΔVDP indicated AL-predominant and negative ΔVDP indicated BL-predominant ventilation defects. Emphysema was quantified using the relative-area-of-the-lung ≤−950HU (RA950) of the CT density histogram for whole-lung and individual lung lobes. The AL-to-BL RA950difference (ΔRA950) was generated with a positive ΔRA950indicating AL-predominant emphysema and a negative ΔRA950indicating BL-predominant emphysema. Seventy-two ex-smokers reported BL-predominant MRI ventilation defects and 71 reported AL-predominant CT emphysema. BL-predominant ventilation defects (AL/BL: GOLD I = 18%/82%, GOLD II = 24%/76%) and AL-predominant emphysema (AL/BL: GOLD I = 84%/16%, GOLD II = 72%/28%) were the major phenotypes in mild-moderate COPD. In severe COPD there was a more uniform distribution for ventilation defects (AL/BL: GOLD III = 40%/60%, GOLD IV = 43%/57%) and emphysema (AL/BL: GOLD III = 64%/36%, GOLD IV = 43%/57%). Basal-lung ventilation defects predominated in mild-moderate GOLD grades, and a more homogeneous distribution of ventilation defects was observed in more advanced grade COPD; these differences suggest that over time, regional ventilation abnormalities become more homogenously distributed during disease progression. [ABSTRACT FROM PUBLISHER]

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. [ABSTRACT FROM AUTHOR]

Noble gas pulmonary magnetic resonance imaging ( MRI) is transitioning away from 3He to 129Xe gas, but the physiological/clinical relevance of 129Xe apparent diffusion coefficient ( ADC) parenchyma measurements is not well understood. Therefore, our objective was to generate 129Xe MRI ADC for comparison with 3He ADC and with well-established measurements of alveolar structure and function in older never-smokers and ex-smokers with chronic obstructive pulmonary disease ( COPD). In four never-smokers and 10 COPD ex-smokers, 3He ( b = 1.6 sec/cm2) and 129Xe ( b = 12, 20, and 30 sec/cm2) ADC, computed tomography ( CT) density-threshold measurements, and the diffusing capacity for carbon monoxide (DLCO) were measured. To understand regional differences, the anterior-posterior ( APG) and superior-inferior (∆ SI) ADC differences were evaluated. Compared to never-smokers, COPD ex-smokers showed greater 3He ADC ( P = 0.006), 129Xe ADCb12 ( P = 0.006), and ADCb20 ( P = 0.006), but not for ADCb30 ( P > 0.05). Never-smokers and COPD ex-smokers had significantly different APG for 3He ADC ( P = 0.02), 129Xe ADCb12 ( P = 0.006), and ADCb20 ( P = 0.01), but not for ADCb30 ( P > 0.05). ∆ SI for never- and ex-smokers was significantly different for 3He ADC ( P = 0.046), but not for 129Xe ADC ( P > 0.05). There were strong correlations for DLCO with 3He ADC and 129Xe ADCb12 (both r = −0.95, P < 0.05); in a multivariate model 129Xe ADCb12 was the only significant predictor of DLCO ( P = 0.049). For COPD ex-smokers, CT relative area <−950 HU ( RA950) correlated with 3He ADC ( r = 0.90, P = 0.008) and 129Xe ADCb12 ( r = 0.85, P = 0.03). In conclusion, while 129Xe ADCb30 may be appropriate for evaluating subclinical or mild emphysema, in this small group of never-smokers and ex-smokers with moderate-to-severe emphysema, 129Xe ADCb12 provided a physiologically appropriate estimate of gas exchange abnormalities and alveolar microstructure. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: High-resolution computed tomography (CT) measurements of emphysema typically use Hounsfield unit (HU) density histogram thresholds or observer scores based on regions of low x-ray attenuation. Our objective was to develop an automated measurement of emphysema using principal component analysis (PCA) of the CT density histogram. Materials and Methods: Ninety-seven ex-smokers, including 53 subjects with chronic obstructive pulmonary disease (COPD) and 44 asymptomatic subjects (AEs), provided written informed consent to imaging as well as plethysmography and spirometry. We applied PCA to the CT density histogram to generate whole lung and regional density histogram principal components including the first and second components and the sum of both principal components (density histogram principal component score [DHPCS]). Significant relationships for DHPCS with single HU thresholds, pulmonary function measurements, an expert''s emphysema score, and hyperpolarized 3He magnetic resonance imaging apparent diffusion coefficients (ADCs) were determined using linear regression and Pearson coefficients. Receiver operator characteristics analysis was performed using forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) as the independent diagnostic. Results: There was a significant difference (P < .0001) between AE and COPD subjects for DHPCS; FEV1/FVC; diffusing capacity of lung for carbon monoxide%predicted; attenuation values below −950, −910, and −856 HU; and 3He ADCs. There were significant correlations for DHPCS with FEV1/FVC (r = −0.85, P < .0001); diffusing capacity of lung for carbon monoxide%predicted (r = −0.67, P < .0001); attenuation values below −950/−910/−856 HU (r = 0.93/0.96/0.76, P < .0001); and 3He ADCs (r = 0.85, P < .0001). Receiver operator characteristics analysis showed a 91% classification rate for DHPCS. Conclusions: We generated an automated emphysema score using PCA of the CT density histogram with a 91% COPD classification rate that showed strong and significant correlations with pulmonary function tests, single HU thresholds, and 3He magnetic resonance imaging ADCs. [Copyright &y& Elsevier]

In subjects with chronic obstructive pulmonary disease (COPD), hyperpolarized xenon-129 (129Xe) magnetic resonance imaging (MRI) reveals significantly greater ventilation defects than hyperpolarized helium-3 (³He) MRI. The physiological and/or morphological determinants of ventilation defects and the differences observed between hyperpolarized ³He and 129Xe MRI are not yet understood. Here we aimed to determine the structural basis for the differences in ventilation observed between ³He and 129Xe 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. ³He and 129Xe 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 ³He 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 ³He gas only, mean ³He ADCHO was significantly greater than for regions accessed by both gases (ADCHO = 0.503 ± 0.119 cm²/s, ADCHX = 0.470 ± 0.125 cm²/s, P < 0.0001). The difference between ³He and 129Xe ventilation volume was significantly correlated with CT HU15% (r = -65, P = 0.04) and ³He 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 129Xe MRI ventilation compared with ³He MRI, and these regions of decreased 129Xe ventilation were spatially and significantly correlated with regions of increased pulmonary emphysema, but not airway wall thickness. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: We assessed subjects with stage II and stage III chronic obstructive pulmonary disease (COPD) and age-matched healthy volunteers at a single center using 3He magnetic resonance imaging (MRI) at 3.0 T. Measurements of the 3He apparent diffusion coefficient (ADC) and center coronal slice 3He ventilation defect volume (VDV) were examined for same-day and 7-day reproducibility as well as subgroup comparisons. Materials and Methods: Twenty-four subjects who provided written informed consent (15 males; mean age 67 ±7 years) with stage II (n = 9), stage III COPD (n = 7), and age-matched healthy volunteers (n = 8) were enrolled based on their age and pulmonary function test results. All subjects underwent plethysmography, spirometry, and MRI at 3.0 T. The time frame between scans was 7 ± 2 minutes (same-day rescan) and again 7 ± 2 days later (7-day rescan). 3He ADC and VDV reproducibility was evaluated using linear regression, intraclass correlation coefficients (ICC) and Lin''s concordance correlation coefficients (CCC). Results: ADC reproducibility was high for same-day rescan (r2 = 0.934) and 7-day rescan (r2 = 0.960, ICC and CCC of 0.96 and 0.98, respectively). Same-day rescan VDV reproducibility evaluated using the ICC and CCC (0.97 and 0.98, respectively) as well as linear regression (r2 = 0.941) was also high, but VDV 7-day rescan reproducibility was lower and significantly different (r2 = 0.576, P < .001, ICC 0.74, CCC 0.75, P < .01). Conclusions: Hyperpolarized 3He MRI was well-tolerated in subjects with stage II and stage III COPD. Seven-day repeated scanning was highly reproducible for ADC and moderately reproducible for VDV. [Copyright &y& Elsevier]

We measured hyperpolarized 3He magnetic resonance imaging (MRI) apparent diffusion coefficients (ADC) and quantified ADC gradients in each three- by-three voxel region of interest (ROl). Such local ADC gradients can be represented in vector maps showing the magnitude (∣G3x3∣) and direction of ADC gradients, providing a qualitative visualization tool and quantitative measurement of airway and air space heterogeneity. Twenty-four subjects (15 male, mean age = 67 ± 7 yr) with global initiative for chronic obstructive lung disease (GOLD) stage II (n = 9, mean age 68 ± 6 yr), GOLD stage III chronic obstructive pulmonary disease (COPD; n = 7, mean age 67 ± 8 yr), and age-matched healthy volunteers (n = 8, mean age 67 ± 6 yr) were enrolled based on their age and spirometry results. Hyperpolarized 3He MRI was performed on a whole body 3.0 Tesla system. Mean 3He ADC and ADC standard deviation were calculated for the center coronal slice, and the mean magnitude and direction of the ADC gradient vectors were calculated for each three-by-three voxel matrix (∣G3x3∣). While the 3He ADC standard deviation was not significantly different, mean ∣G3x3∣ was significantly different between subjects with stage 11(0.14 ± 0.03 cm/s) and stage III COPD (0.19 ± 0.03 cm/s; P <0.005) and between healthy subjects (0.12 ± 0.03 cm/s) and those with stage II COPD (P < 0.02). The second order statistic ∣G3x3∣ may provide a sensitive measure of ADC heterogeneity for ROT representing 9.4 X 9.4 X 30 mm or 2.6 cm3 of lung tissue. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to quantitatively evaluate the relationship between short echo time pulmonary 1H magnetic resonance imaging (MRI) signal intensity (SI) and 3He MRI apparent diffusion coefficients (ADC), high-resolution computed tomography (CT) measurements of emphysema, and pulmonary function measurements. Materials and methods: Nine healthy never-smokers and 11 COPD subjects underwent same-day plethysmography, spirometry, short echo time ((TE)=1.2ms) 1H and diffusion-weighted hyperpolarized 3He MRI (b =1.6s/cm2) at 3.0T. In addition, for COPD subjects only, CT densitometry was also performed. Results: Mean 1H SI was significantly greater for never-smokers (12.1±1.1 arbitrary units (AU)) compared to COPD subjects (10.9±1.3AU, p =0.04). The 1H SI AP-gradient was also significantly greater for never-smokers (0.40AU/cm, R 2 =0.94) compared to COPD subjects (0.29AU/cm, R 2 =0.968, p =0.05). There was a significant correlation between 1H SI and 3He ADC (r =−0.58, p =0.008) and significant correlations between 1H MR SI and CT measurements of emphysema (RA950, r =−0.69, p =0.02 and HU15, r =0.66, p =0.03). Conclusions: The significant and moderately strong relationship between 1H SI and 3He ADC, as well as between 1H SI and CT measurements of emphysema suggests that these imaging methods and measurements may be quantifying similar tissue changes in COPD and that pulmonary 1H SI may be used to monitor emphysema as a complement to CT and noble gas MRI. [ABSTRACT FROM AUTHOR]

Abstract: 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 (3He) magnetic resonance imaging (MRI) functional and structural measurements and to explore the potential role for 3He 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, 1H MRI and hyperpolarized 3He MRI at 3.0T. 3He ventilation defect percent (VDP) was generated from 3He static ventilation images and 1H thoracic images and the 3He 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 3He 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 3He MRI to categorize or phenotype COPD ex-smokers, providing good evidence of feasibility for larger prospective studies. [Copyright &y& Elsevier]