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

Purpose To compare hyperpolarized helium-3 (3He) and xenon-129 (129Xe) 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. 3He and 129Xe 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, 129Xe VDP (8 ± 5%) was significantly greater than 3He VDP (6 ± 5%, P = 0.003). Post-salbutamol, there was a significant improvement in both 129Xe (5 ± 4%, P < 0.0001) and 3He (4 ± 3%, P = 0.001) VDP, and the improvement in 129Xe VDP was significantly greater ( P = 0.008). 129Xe MRI COV (Pre: 0.309 ± 0.028, Post: 0.296 ± 0.036) was significantly greater than 3He 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 (129Xe, P = 0.002; 3He, P < 0.0001). For a single asthmatic, a sub-segmental 129Xe MRI ventilation defect that was visible only before salbutamol inhalation but not visible using 3He MRI was spatially related to a remodeled fourth generation sub-segmental airway (WA% = 78%, LA = 2.9 mm2). Conclusion In asthma, hyperpolarized 129Xe MRI may help reveal ventilation abnormalities before bronchodilation that are not observed using hyperpolarized 3He MRI. J. Magn. Reson. Imaging 2013;38:1521-1530. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Purpose The goal of this work was to investigate lung morphological changes associated with chronic obstructive pulmonary disease (COPD) using hyperpolarized 129Xe diffusion-weighted MRI. Methods Hyperpolarized 129Xe MRI was performed at three different nonzero diffusion sensitizations ( b-value = 12, 20, and 30 s/cm2) in the lungs of four subjects with COPD and four healthy volunteers. The image signal intensities were fit as a function of b-value to obtain anisotropic diffusion coefficient maps for all subjects. The image signal intensities were also fit to a morphological model allowing extraction of length scales associated with the terminal airways: external radius ( R), internal radius ( r), mean airspace chord length ( Lm), and depth of alveolar sleeve ( h). Results Longitudinal ( DL) and transverse ( DT) anisotropic diffusion coefficients were both significantly increased (both P= 0.004) in the COPD subjects (0.102 ± 0.02 cm2/s and 0.072 ± 0.02 cm2/s, respectively) compared with the healthy subjects (0.083 ± 0.011 cm2/s and 0.046 ± 0.017 cm2/s, respectively). Significant morphological differences were observed between the COPD subjects and healthy volunteers, specifically decreases in h (68 ± 36 µm vs. 95 ± 710 µm, respectively, P = 0.019) and increases in Lm (352 ± 57 µm vs. 253 ± 37 µm, respectively, P = 0.002) consistent with values obtained previously using hyperpolarized 3He MRI in similar subjects. Conclusions Diffusion-weighted hyperpolarized 129Xe MRI is a promising technique for mapping changes in human lung morphology and may be useful for early detection of emphysema associated with COPD. Magn Reson Med 70:1699-1706, 2013. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

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 (³He) MRI. The 6MWT distance (6MWD), SGRQ scores, ³He 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 ³He 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 ³He ADC compared with exsmokers with normal DLCO, providing evidence of the impact of mild or early stage emphysema and a better understanding of abnormal DLCO and hyperpolarised ³He MRI in ex-smokers without COPD. [ABSTRACT FROM AUTHOR]

ABSTRACT Background and objective: Spirometry is insensitive to small airway abnormalities in asthma. Our objective was to evaluate regional lung structure and function using hyperpolarized 3He magnetic resonance imaging (MRI) before, during and after a methacholine challenge (MCh). Methods: Twenty-five asthmatics (mean age = 34 ± 11 years) and eight healthy volunteers (HV) (mean age = 33 ± 11 years) underwent spirometry, plethysmography and hyperpolarized 3He MRI prior to a MCh. MRI was repeated following the MCh and again 25 min after salbutamol administration. 3He MRI gas distribution was quantified using semiautomated segmentation of the ventilation defect percent (VDP). Tissue microstructure was measured using the 3He apparent diffusion coefficient (ADC). Analysis of variance with repeated measures was used to evaluate changes at each time point as well as to determine interactions between regions of interest (ROI) and subject group. Pearson's correlations were performed to evaluate associations between 3He MRI measurements and established clinical measures. Results: In asthmatics, but not HV, whole-lung ADC was increased post-MCh ( P < 0.01). In asthmatics only, ADC was increased post-MCh in posterior ROI ( P < 0.01) and all ROI in the superior-inferior direction ( P < 0.01). VDP was increased in posterior and inferior ROI ( P < 0.001). There was a correlation between VDP and specific airway resistance ( r = 0.74, P < 0.0001), dyspnoea score ( r = 0.66, P < 0.01) and fractional exhaled nitric oxide ( r = 0.45, P < 0.05). Conclusions: We evaluated the regional pulmonary response to methacholine and salbutamol using 3He MRI and showed heterogeneous VDP and ADC consistent with bronchoconstriction and gas trapping, respectively, post-MCh. These regional alterations resolved post-salbutamol. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: To improve intra- and interobserver variability and enable the use of functional magnetic resonance imaging (MRI) for multicenter, multiobserver studies, we generated a semiautomated segmentation method for hyperpolarized helium-3 (3He) MRI. Therefore the objective of this study was to compare the reproducibility and spatial agreement of manual and semiautomated segmentation of 3He MRI ventilation defect volume (VDV) and ventilation volume (VV) in subjects with asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF). Materials and Methods: The multistep semiautomated segmentation method we developed employed hierarchical K-means clustering to classify 3He MRI pixel intensity values into five user-determined clusters ranging from signal void to hyperintense. A seeded region-growing algorithm was also used to segment the 1H MRI thoracic cavity for coregistration to the 3He cluster-map, generating VDV and VV. Results: We compared manual segmentation performed by an expert observer and semiautomated measurements of 3He MRI VDV and observed strong significant correlations between the volumes generated using each method (asthma, n = 5, r = 0.89, P < .0001; COPD, n = 5, r = 0.84, P < .0001; CF, n = 5, r = 0.89, P < .0001). Semiautomated VDV had high interobserver reproducibility (coefficient of variation [CV] = 7%, intraclass correlation coefficient [ICC] = 0.96); intraobserver reproducibility was significantly higher for semiautomated (CV = 5%, ICC = 1.00) compared to manual VDV (CV = 12%, ICC = 0.98). Spatial agreement for VV determined using the Dice coefficient (D) was also high for all disease states (asthma, D = 0.95; COPD, D = 0.88; CF, D = 0.90). Conclusions: Semiautomated segmentation 3He MRI provides excellent inter- and intraobserver precision with high spatial and quantitative agreement with manual measurements enabling its use in longitudinal studies. [ABSTRACT FROM AUTHOR]

Lung ventilation was mapped in five healthy Brown Norway rats (210-377 g) using both hyperpolarized 3He MRI and Xe-enhanced computed tomography (Xe-CT) under similar ventilator conditions. Whole-lung measurements of ventilation r obtained with 3He 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 3He 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. [ABSTRACT FROM AUTHOR]

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 ± 2 mo later (n = 15 subjects) using plethysmography, spirometry, and ³He MRI at 3.0 T. Total lung capacity, residual volume, and literature-based morphological parameters were used with alveolar volumes derived from ³He 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 ³He 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. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: Lung resection for primary bronchogenic carcinoma in the setting of chronic obstructive pulmonary disease often requires a detailed assessment of lung function to avoid perioperative complications and long-term disability. The aim of this study was to test the hypothesis that a novel technique of spiral computed tomographic (CT) subtraction imaging provides accuracy equal to the current standard of radioisotope perfusion scintigraphy in predicting postoperative lung function. Methods and Materials: Preoperative lung function, radioisotope perfusion scintigraphy, spiral CT subtraction imaging, and assessment of postoperative lung function were performed in 25 patients with surgically resectable primary bronchogenic carcinoma. Comparisons of predicted postoperative lung function between the two modalities and to true postoperative lung function were performed using Pearson''s correlation and linear regression analysis. Results: Among the 25 patients enrolled in the study, there was a high degree of agreement between the predicted value of postoperative forced expiratory lung volume in 1 second (FEV1) generated on novel contrast CT subtraction imaging and that on radioisotope perfusion scintigraphy (r = 0.96, P < .001). Furthermore, there was a strong correlation between the predicted and actual postoperative FEV1 values for both imaging modalities (r = 0.87, P < .001, and r = 0.88, P < .001, respectively), among the 14 patients completing the study protocol. Conclusion: A novel technique of CT subtraction imaging is equally accurate at predicting postoperative lung function as radioisotope perfusion scintigraphy, which may obviate the need for additional nuclear imaging in the context of the preoperative assessment of resectable lung cancer in high-risk patients. [Copyright &y& Elsevier]

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]

Rationale and Objectives: Hyperpolarized 3He magnetic resonance imaging ventilation defects have been observed in subjects with respiratory disorders. We quantified 3He ventilation defects in elderly and middle-aged subjects who had no history of smoking, respiratory, or cardiovascular disorders. Materials and Methods: Hyperpolarized 3He 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 cm3), whereas for same-day rescan, mean VDS was 2.5 (mean VDV 53 ± 35 cm3) and at 7-day rescan, mean VDS was 3.6 (mean VDV 48 ± 39 cm3). 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 3He studies of elderly subjects. [Copyright &y& Elsevier]

Reveals that the loss of hypoxic pulmonary vasoconstriction in chronic pneumonia is not mediated by nitric oxide. Hemodynamic monitoring; Response to exposure to hypoxic gas; Excess release of nitric oxide.

A reply to this letter has been published in Movement Disorders . [ABSTRACT FROM AUTHOR]

Pulmonary imaging measurements using magnetic resonance imaging (MRI) and computed tomography (CT) have the potential to deepen our understanding of chronic obstructive pulmonary disease (COPD) by measuring airway and parenchymal pathologic information that cannot be provided by spirometry. Currently, MRI and CT measurements are not included in mortality risk predictions, diagnosis, or COPD staging. We evaluated baseline pulmonary function, MRI and CT measurements alongside imaging texture-features to predict 10-year all-cause mortality in ex-smokers with (n = 93; 31 females; 70 ± 9years) and without (n = 69; 29 females, 69 ± 9years) COPD. CT airway and vessel measurements, helium-3 (3He) MRI ventilation defect percent (VDP) and apparent diffusion coefficients (ADC) were quantified. MRI and CT texture-features were extracted using PyRadiomics (version2.2.0). Associations between 10-year all-cause mortality and all clinical and imaging measurements were evaluated using multivariable regression model odds-ratios. Machine-learning predictive models for 10-year all-cause mortality were evaluated using area-under-receiver-operator-characteristic-curve (AUC), sensitivity and specificity analyses. DLCO (%pred) (HR = 0.955, 95%CI: 0.934-0.976, p < 0.001), MRI ADC (HR = 1.843, 95%CI: 1.260-2.871, p < 0.001), and CT informational-measure-of-correlation (HR = 3.546, 95% CI: 1.660-7.573, p = 0.001) were the strongest predictors of 10-year mortality. A machine-learning model trained on clinical, imaging, and imaging textures was the best predictive model (AUC = 0.82, sensitivity = 83%, specificity = 84%) and outperformed the solely clinical model (AUC = 0.76, sensitivity = 77%, specificity = 79%). In ex-smokers, regardless of COPD status, addition of CT and MR imaging texture measurements to clinical models provided unique prognostic information of mortality risk that can allow for better clinical management.Clinical Trial Registration: NCT02279329 [ABSTRACT FROM AUTHOR]