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Rationale and Objectives: The relationships between computed tomography (CT) pulmonary vascularity and MRI ventilation is not well-understood in chronic obstructive pulmonary disease (COPD) patients. Our objective was to evaluate CT pulmonary vascular and MRI ventilation measurements in ex-smokers and to investigate their associations and how such measurements change over time., Materials and Methods: Ninety ex-smokers (n = 41 without COPD 71 ± 10 years and n = 49 COPD 71 ± 8 years) provided written informed-consent to an ethics-board approved protocol and underwent imaging and pulmonary-function-tests twice, 31 ± 7 months apart. 3 He MRI was acquired to generate ventilation-defect-percent (VDP). CT measurements of the relative area-of-the-lung with attenuation <-950 Hounsfield units (RA 950 ), pulmonary vascular total-blood-volume (TBV) and percent of vessels with radius < one voxel (PV 1 ) were evaluated., Results: At baseline, there were significant differences in RA 950 (p = 0.0001), VDP (p = 0.0001), total-blood-volume (p = 0.0001) and PV 1 (p = 0.01) between ex-smokers and COPD participants as well as for VDP (p = 0.0001) in COPD participants with and without emphysema. The annual FEV 1 change (-40 ± 93 mL/year) was not different among participant subgroups (p = 0.87), but the annual RA 950 (p = 0.01) and PV 1 (p = 0.007) changes were significantly different in participants with an accelerated annual FEV 1 decline as compared to participants with a diminished annual FEV 1 decline. There were significant but weak relationships for PV 1 with FEV 1%pred (p = 0.02), FEV 1 /FVC (p = 0.001), and log RA 950 (p = 0.0001), but not VDP (p=0.20). The mean change in PV 1 was also weakly but significantly related to the change in RA 950 (p = 0.02)., Conclusion: CT pulmonary vascular measurements were significantly different in ex-smokers and participants with COPD and related to RA 950 but not VDP worsening over 2.5 years., (Copyright © 2020 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Background Longitudinal progression to irreversible airflow limitation occurs in approximately 10% of patients with asthma, but it is difficult to identify patients who are at risk for this transition. Purpose To investigate 6-year longitudinal changes in hyperpolarized helium 3 ( 3 He) MRI ventilation defects in study participants with mild-to-moderate asthma and identify predictors of longitudinal changes in postbronchodilator forced expiratory volume in 1 second (FEV 1 ) reversibility Materials and Methods Spirometry and hyperpolarized 3 He MRI were evaluated in participants with mild-to-moderate asthma in two prospectively planned visits approximately 6 years apart. Participants underwent methacholine challenge at baseline (January 2010 to April 2011) and pre- and postbronchodilator evaluations at follow-up (November 2016 to June 2017). FEV 1 and MRI ventilation defects, quantified as ventilation defect volume (VDV), were compared between visits by using paired t tests. Participants were dichotomized by postbronchodilator change in FEV 1 at follow-up, and differences between reversible and not-reversible groups were determined by using unpaired t tests. Multivariable models were generated to explain postbronchodilator FEV 1 reversibility at follow-up. Results Eleven participants with asthma (mean age, 42 years ± 9 [standard deviation]; seven men) were evaluated at baseline and after mean 78 months ± 7. Medications, exacerbations, FEV 1 (76% predicted vs 76% predicted; P = .91), and VDV (240 mL vs 250 mL; P = .92) were not different between visits. In eight of 11 participants (73%), MRI ventilation defects at baseline were at the same location in the lung at follow-up MRI. In the remaining three participants (27%), MRI ventilation defects worsened at the same lung locations as depicted at baseline methacholine-induced ventilation. At follow-up, postbronchodilator FEV 1 was not reversible in six of 11 participants; the concentration of methacholine to decrease FEV 1 by 20% (PC 20 ) was greater in FEV 1 -irreversible participants at follow-up ( P = .01). In a multivariable model, baseline MRI VDV helped to predict postbronchodilator reversibility at follow-up ( R  2 = 0.80; P < .01), but PC 20 , age, and FEV 1 did not ( R  2 = 0.63; P = .15). Conclusion MRI-derived, spatially persistent ventilation defects predict postbronchodilator reversibility 78 months ± 7 later for participants with mild-to-moderate asthma in whom there were no changes in lung function, medication, or exacerbations. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Stojanovska in this issue.

Purpose: To directly compare magnetic resonance (MR) imaging and computed tomography (CT) parametric response map (PRM) measurements of gas trapping and emphysema in ex-smokers both with and without chronic obstructive pulmonary disease (COPD)., Materials and Methods: Participants provided written informed consent to a protocol that was approved by a local research ethics board and Health Canada and was compliant with the HIPAA (Institutional Review Board Reg. #00000940). The prospectively planned study was performed from March 2014 to December 2014 and included 58 ex-smokers (mean age, 73 years ± 9) with (n = 32; mean age, 74 years ± 7) and without (n = 26; mean age, 70 years ± 11) COPD. MR imaging (at functional residual capacity plus 1 L), CT (at full inspiration and expiration), and spirometry or plethysmography were performed during a 2-hour visit to generate ventilation defect percent (VDP), apparent diffusion coefficient (ADC), and PRM gas trapping and emphysema measurements. The relationships between pulmonary function and imaging measurements were determined with analysis of variance (ANOVA), Holm-Bonferroni corrected Pearson correlations, multivariate regression modeling, and the spatial overlap coefficient (SOC)., Results: VDP, ADC, and PRM gas trapping and emphysema (ANOVA, P < .001) measurements were significantly different in healthy ex-smokers than they were in ex-smokers with COPD. In all ex-smokers, VDP was correlated with PRM gas trapping (r = 0.58, P < .001) and with PRM emphysema (r = 0.68, P < .001). VDP was also significantly correlated with PRM in ex-smokers with COPD (gas trapping: r = 0.47 and P = .03; emphysema: r = 0.62 and P < .001) but not in healthy ex-smokers. In a multivariate model that predicted PRM gas trapping, the forced expiratory volume in 1 second normalized to the forced vital capacity (standardized coefficients [βS] = -0.69, P = .001) and airway wall area percent (βS = -0.22, P = .02) were significant predictors. PRM emphysema was predicted by the diffusing capacity for carbon monoxide (βS = -0.29, P = .03) and VDP (βS = 0.41, P = .001). Helium 3 ADC values were significantly elevated in PRM gas-trapping regions (P < .001). The spatial relationship for ventilation defects was significantly greater with PRM gas trapping than with PRM emphysema in patients with mild (for gas trapping, SOC = 36% ± 28; for emphysema, SOC = 1% ± 2; P = .001) and moderate (for gas trapping, SOC = 34% ± 28; for emphysema, SOC = 7% ± 15; P = .006) COPD. For severe COPD, the spatial relationship for ventilation defects with PRM emphysema (SOC = 64% ± 30) was significantly greater than that for PRM gas trapping (SOC = 36% ± 18; P = .01)., Conclusion: In all ex-smokers, ADC values were significantly elevated in regions of PRM gas trapping, and VDP was quantitatively and spatially related to both PRM gas trapping and PRM emphysema. In patients with mild to moderate COPD, VDP was related to PRM gas trapping, whereas in patients with severe COPD, VDP correlated with both PRM gas trapping and PRM emphysema., ((©) RSNA, 2016 Online supplemental material is available for this article. An earlier incorrect version of this article appeared online. This article was corrected on January 12, 2016.)

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: To evaluate the predictive value of imaging and clinical and physiological measurements of chronic obstructive pulmonary disease ( COPD chronic obstructive pulmonary disease ) in patients monitored for more than 5 years for pulmonary exacerbations that required hospitalization., Materials and Methods: Exacerbations requiring hospitalization were monitored over 5 years in 91 subjects who provided written informed consent. Study was local research ethics board and Health Canada approved and HIPAA compliant. Subjects with COPD chronic obstructive pulmonary disease underwent spirometry, plethysmography, diffusing capacity of carbon monoxide, St George's Respiratory Questionnaire, 6-minute walk test, and imaging. Computed tomographic (CT) wall area and relative area with attenuation values less than -950 HU ( RA950 relative area with attenuation values less than -950 HU ), helium 3 ((3)He) magnetic resonance (MR) imaging ventilation defect percentage ( VDP ventilation defect percentage ), and apparent diffusion coefficient were generated. Zero-inflated Poisson model was used to compare number of hospitalizations with lung function and imaging measurements., Results: Twenty-four subjects were hospitalized 58 times and had significantly worse forced expiratory volume in 1 second ( FEV1 forced expiratory volume in 1 second ) (P < .0001), CT RA950 relative area with attenuation values less than -950 HU (P = .02), and (3)He VDP ventilation defect percentage (P < .0001) than values in 67 subjects who were not hospitalized. In mild to moderate COPD chronic obstructive pulmonary disease , nine hospitalized subjects had significantly worse FEV1 forced expiratory volume in 1 second (P = .02) and (3)He VDP ventilation defect percentage (P = .02) than values in 52 subjects who were not hospitalized. (3)He VDP ventilation defect percentage was quantitatively related to CT airway morphology (r = 0.26, P = .01) and quantitatively (r = 0.61, P < .0001) and spatially related to emphysema; this spatial relationship was significantly greater for hospitalized patients with COPD chronic obstructive pulmonary disease than unhospitalized patients (P = .0006). For all subjects, number of prior hospitalizations (P < .0001), 6-minute walk test distance (P < .0001), CT RA950 relative area with attenuation values less than -950 HU (P = .03), and (3)He VDP ventilation defect percentage (P = .002) were significantly related to number of hospitalizations. For 61 subjects with mild to moderate COPD chronic obstructive pulmonary disease , only (3)He VDP ventilation defect percentage was significantly associated with COPD chronic obstructive pulmonary disease exacerbations (P = .01)., Conclusion: (3)He MR imaging VDP ventilation defect percentage represents a mixed airways-emphysema phenotype and helps identify subjects with mild to moderate COPD chronic obstructive pulmonary disease who are at risk for exacerbation that requires hospitalization., (© RSNA, 2014.)

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.)

Objective: The aim of this study was to quantitatively evaluate the relationship between short echo time pulmonary (1)H magnetic resonance imaging (MRI) signal intensity (SI) and (3)He 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) (1)H and diffusion-weighted hyperpolarized (3)He MRI (b=1.6s/cm(2)) at 3.0T. In addition, for COPD subjects only, CT densitometry was also performed., Results: Mean (1)H SI was significantly greater for never-smokers (12.1 ± 1.1 arbitrary units (AU)) compared to COPD subjects (10.9 ± 1.3 AU, p=0.04). The (1)H SI AP-gradient was also significantly greater for never-smokers (0.40 AU/cm, R(2)=0.94) compared to COPD subjects (0.29 AU/cm, R(2)=0.968, p=0.05). There was a significant correlation between (1)H SI and (3)He ADC (r=-0.58, p=0.008) and significant correlations between (1)H 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 (1)H SI and (3)He ADC, as well as between (1)H SI and CT measurements of emphysema suggests that these imaging methods and measurements may be quantifying similar tissue changes in COPD and that pulmonary (1)H SI may be used to monitor emphysema as a complement to CT and noble gas MRI., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

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.)

Background: The functional effects of abnormal diffusing capacity for carbon monoxide (DLCO) in ex-smokers without chronic obstructive pulmonary disease (COPD) are not well understood., Objective: We aimed to evaluate and compare well established clinical, physiological and emerging imaging measurements in ex-smokers with normal spirometry and abnormal DLCO with a group of ex-smokers with normal spirometry and DLCO and ex-smokers with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I COPD., Methods: We enrolled 38 ex-smokers and 15 subjects with stage I COPD who underwent spirometry, plethysmography, St George's Respiratory Questionnaire (SGRQ), 6 min Walk Test (6MWT), x-ray CT and hyperpolarised helium-3 ((3)He) MRI. The 6MWT distance (6MWD), SGRQ scores, (3)He MRI apparent diffusion coefficients (ADC) and CT attenuation values below -950 HU (RA950) were evaluated., Results: Of 38 ex-smokers without COPD, 19 subjects had abnormal DLCO with significantly worse ADC (p=0.01), 6MWD (p=0.008) and SGRQ (p=0.01) but not RA950 (p=0.53) compared with 19 ex-smokers with normal DLCO. Stage I COPD subjects showed significantly worse ADC (p=0.02), RA950 (p=0.0008) and 6MWD (p=0.005), but not SGRQ (p=0.59) compared with subjects with abnormal DLCO. There was a significant correlation for (3)He ADC with SGRQ (r=0.34, p=0.02) and 6MWD (r=-0.51, p=0.0002)., Conclusions: In ex-smokers with normal spirometry and CT but abnormal DLCO, there were significantly worse symptoms, 6MWD and (3)He ADC compared with ex-smokers with normal DLCO, providing evidence of the impact of mild or early stage emphysema and a better understanding of abnormal DLCO and hyperpolarised (3)He MRI in ex-smokers without COPD.

A chronic obstructive pulmonary disease (COPD) exsmoker underwent pulmonary function tests and hyperpolarized helium-3 ((3) He) magnetic resonance imaging (MRI) serially over 4 years, twice prior to and twice following an acute exacerbation (AE). About 2.5 years pre-AE, (3) He ventilation defect percent (VDP) was 16%, the apparent diffusion coefficient (ADC) was 0.34 cm(2) /s, and forced expiratory volume in 1 sec (FEV1 ) was 41%pred . Six months pre-AE, VDP and ADC were worse (29% and 0.38 cm(2) /s, respectively) without worsening FEV1 (47%pred ). After hospitalization and AE treatment, VDP was 20%, whereas FEV1 did not improve (45%pred ); 16 months post-AE, both VDP and ADC remained improved and similar to 4 years prior., (Copyright © 2012 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.

Purpose: To quantitatively compare hyperpolarized helium 3 (3He) and xenon 129 (129Xe) magnetic resonance (MR) images obtained within 5 minutes in healthy volunteers and patients with chronic obstructive pulmonary disease (COPD) and to evaluate the correlations between 3He and 129Xe MR imaging measurements and those from spirometry and plethysmography., Materials and Methods: This study was approved by an ethics board and compliant with HIPAA. Written informed consent was obtained from all subjects. Eight healthy volunteers and 10 patients with COPD underwent MR imaging, spirometry, and plethysmography. Ventilation defect percentages (VDPs) at 3He and 129Xe imaging were obtained by using semiautomated segmentation. Apparent diffusion coefficients (ADCs) were calculated from 3He (b=1.6 sec/cm2) and 129Xe (b=12 sec/cm2) diffusion-weighted images. VDPs at hyperpolarized 3He and 129Xe imaging were compared with a two-tailed Wilcoxon signed rank test and analysis of variance; Pearson correlation coefficients were used to evaluate the relationships among measurements., Results: 129Xe VDP was significantly greater than 3He VDP for patients with COPD (P<.0001) but not for healthy volunteers (P=.35), although 3He and 129Xe VDPs showed a significant correlation for all subjects (r=0.91, P<.0001). The forced expiratory volume in 1 second (FEV1) showed a similar and significant correlation with 3He VDP (r=-0.84, P<.0001) and 129Xe VDP (r=-0.89, P<.0001), although the correlation between the FEV1/forced vital capacity (FVC) ratio and 129Xe VDP (r=-0.95, P<.0001) was significantly greater (P=.01) than that for FEV1/FVC and 3He VDP (r=-0.84, P<.0001). A significant correlation was also observed for 3He and 129Xe ADC (r=0.97, P<.0001); 129Xe ADC was significantly correlated with diffusing capacity of lung for carbon monoxide (r=-0.79, P=.03) and computed tomographic emphysema measurements (areas with attenuation values in the 15th percentile: r=-0.91, P=.0003; relative areas with attenuation values of less than -950 HU: r=0.87, P=.001)., Conclusion: In patients with COPD, the VDP obtained with hyperpolarized 29Xe MR imaging was significantly greater than that with 3He MR imaging, suggesting incomplete or delayed filling of lung regions that may be related to the different properties of 129Xe gas and physiologic and/or anatomic abnormalities in COPD., (© RSNA, 2012)

The objective of this study was to evaluate the regional effects of bronchodilator administration in chronic obstructive pulmonary disease (COPD) using hyperpolarized helium-3 ((3)He) MRI apparent diffusion coefficient (ADC). Ten COPD ex-smokers provided written, informed consent and underwent diffusion-weighted, hyperpolarized (3)He MRI, spirometry, and plethysmography before and 25 ± 2 min after bronchodilator administration. Pre- and postsalbutamol whole-lung (WL) ADC maps were generated and registered together to identify the lung regions containing the (3)He signal at both time points, and mean ADC within those regions of interest (ROI) was determined for a measurement of previously ventilated ROI ADC (ADC(P)). Lung ROI with (3)He signal at both time points was used as a binary mask on postsalbutamol WL ADC maps to obtain an ADC measurement for newly ventilated ROI (ADC(N)). Postsalbutamol, no significant differences were detected in WL ADC (P = 0.516). There were no significant differences between ADC(N) and ADC(P) postsalbutamol (P = 1.00), suggesting that the ADC(N) lung regions were not more emphysematous than the lung ROI participating in ventilation before bronchodilator administration. Postsalbutamol, a statistically significant decrease in ADC(P) (P = 0.01) was detected, and there were significant differences between ADC(P) in the most anterior and most posterior image slices (P = 0.02), suggesting a reduction in regional gas trapping following bronchodilator administration. Regional evaluation of tissue microstructure using hyperpolarized (3)He MRI ADC provides insights into lung alterations that accompany improvements in regional (3)He gas distribution after bronchodilator administration.

Lung ventilation was mapped in five healthy Brown Norway rats (210-377 g) using both hyperpolarized (3)He MRI and Xe-enhanced computed tomography (Xe-CT) under similar ventilator conditions. Whole-lung measurements of ventilation r obtained with (3)He MRI were not significantly different from those obtained from Xe-CT (p = 0.1875 by Wilcoxon matched pairs test). The ventilation parameter r is defined as the fraction of refreshed gas per unit volume per breath. Regional ventilation was also measured in four regions of the lung using both methods. A two-tailed paired t-test was performed for each region, yielding p > 0.05 for all but the upper portion of the right lung. The distribution of regional ventilation was evaluated by calculating ventilation gradients in the superior/inferior (S/I) direction. The average S/I gradient obtained using the (3)He MRI method was found to be 0.17 ± 0.04 cm(-1) , whereas the average S/I gradient obtained using the Xe-CT method was found to be 0.016 ± 0.005 cm(-1) . In general, S/I ventilation gradients obtained from both methods were significantly different from each other (p = 0.0019 by two-tailed paired t-test). These regional differences in ventilation measurements may be caused by the manner in which the gas contrast agents distribute physiologically and/or by the imaging modality., (Copyright © 2011 John Wiley & Sons, Ltd.)

During the past several years there has been extensive development and application of hyperpolarized helium-3 (HP (3)He) magnetic resonance imaging (MRI) in clinical respiratory indications such as asthma, chronic obstructive pulmonary disease, cystic fibrosis, radiation-induced lung injury, and transplantation. This review focuses on the state-of-the-art of HP (3)He MRI and its application to clinical pulmonary research. This is not an overview of the physics of the method, as this topic has been covered previously. We focus here on the potential of this imaging method and its challenges in demonstrating new types of information that has the potential to influence clinical research and decision making in pulmonary medicine. Particular attention is given to functional imaging approaches related to ventilation and diffusion-weighted imaging with applications in chronic obstructive pulmonary disease, cystic fibrosis, asthma, and radiation-induced lung injury. The strengths and challenges of the application of (3)He MRI in these indications are discussed along with a comparison to established and emerging imaging techniques., (Copyright © 2010 Wiley-Liss, Inc.)

We aimed to evaluate the potential for the use of hyperpolarized helium-3 magnetic resonance imaging (MRI) apparent diffusion coefficient (ADC) surrogates of alveolar size, together with literature-based morphological parameters in a theoretical model of lung mechanics to simulate noninvasive transpulmonary pressure-volume curves. Fourteen ex-smokers with chronic obstructive pulmonary disease (COPD) (n = 8 stage II, n = 6 stage III/IV COPD) and five age-matched never-smokers, provided written, informed consent and were evaluated at baseline and 26 + or - 2 mo later (n = 15 subjects) using plethysmography, spirometry, and (3)He MRI at 3.0 T. Total lung capacity, residual volume, and literature-based morphological parameters were used with alveolar volumes derived from (3)He ADC to simulate noninvasive pressure-volume curves. The resultant anterior-posterior transpulmonary pressure gradient was significantly decreased for stage II COPD (P < 0.01) and stage III COPD subjects (P < 0.001) compared with healthy volunteers. Both COPD subgroups showed increased alveolar radius compared with healthy subjects (P < 0.01, stage II COPD; P < 0.001, stage III COPD). In addition, surface area and surface tension were significantly increased in stage III COPD compared with healthy volunteers (P < 0.01). These results suggest that (3)He MRI provides a potential noninvasive approach to evaluate lung mechanics regionally and further supports the use of ADC values as a regional noninvasive probe of pulmonary microstructure and compliance.

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 (3)He magnetic resonance imaging (MRI) at 3.0 T. Measurements of the (3)He apparent diffusion coefficient (ADC) and center coronal slice (3)He 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). (3)He 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 (r(2) = 0.934) and 7-day rescan (r(2) = 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 (r(2) = 0.941) was also high, but VDV 7-day rescan reproducibility was lower and significantly different (r(2) = 0.576, P < .001, ICC 0.74, CCC 0.75, P < .01)., Conclusions: Hyperpolarized (3)He 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.

Rationale and Objectives: Hyperpolarized (3)He magnetic resonance imaging ventilation defects have been observed in subjects with respiratory disorders. We quantified (3)He ventilation defects in elderly and middle-aged subjects who had no history of smoking, respiratory, or cardiovascular disorders., Materials and Methods: Hyperpolarized (3)He magnetic resonance imaging ventilation defect volume (VDV) and ventilation defect score (VDS) were assessed in eight elderly healthy volunteers (mean 67+/-6 years) scanned twice within 7+/-2 minutes and again 7+/-2 days later. A younger cohort of 24 subjects (mean 44+/-10 years) was also scanned for direct comparison. Four observers blinded to scan timepoint and subject identity scored VDS and manually segmented VDV in all center coronal slices., Results: Center coronal slice ventilation defects were observed in six of eight elderly subjects (ages 63-74 years, 5 males) in all scans acquired and in no middle-aged subjects. At the scan timepoint, mean VDS was 2.7 (mean VDV 52+/-34 cm(3)), whereas for same-day rescan, mean VDS was 2.5 (mean VDV 53+/-35 cm(3)) and at 7-day rescan, mean VDS was 3.6 (mean VDV 48+/-39 cm(3)). Interscan coefficients of variation (COV) for mean VDV was 1.8% (same-day rescan) and 5.3% (7-day rescan) and interobserver COV ranged from 10-12%., Conclusion: Elderly subjects have ventilation defects that are reproducible in same-day scanning and 7-day scanning visits. The observation of reproducible pulmonary ventilation defects in otherwise healthy elderly volunteers suggests caution must be used in interpreting results from (3)He studies of elderly subjects.